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Physical exercise for people with Parkinson’s disease: a systematic

review and network meta-analysis (Review)

Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A,
Roheger M, Eggers C, Skoetz N, Kalbe E

Ernst M, Folkerts A-K, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C, Skoetz N,
Kalbe E.
Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis.
Cochrane Database of Systematic Reviews 2023, Issue 1. Art. No.: CD013856.
DOI: 10.1002/14651858.CD013856.pub2.

www.cochranelibrary.com

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review)
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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TABLE OF CONTENTS
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 4
BACKGROUND.............................................................................................................................................................................................. 9
OBJECTIVES.................................................................................................................................................................................................. 11
METHODS..................................................................................................................................................................................................... 11
RESULTS........................................................................................................................................................................................................ 16
Figure 1.................................................................................................................................................................................................. 17
Figure 2.................................................................................................................................................................................................. 21
Figure 3.................................................................................................................................................................................................. 26
Figure 4.................................................................................................................................................................................................. 28
Figure 5.................................................................................................................................................................................................. 29
Figure 6.................................................................................................................................................................................................. 30
Figure 7.................................................................................................................................................................................................. 32
Figure 8.................................................................................................................................................................................................. 33
Figure 9.................................................................................................................................................................................................. 34
Figure 10................................................................................................................................................................................................ 35
Figure 11................................................................................................................................................................................................ 39
Figure 12................................................................................................................................................................................................ 40
Figure 13................................................................................................................................................................................................ 42
Figure 14................................................................................................................................................................................................ 45
Figure 15................................................................................................................................................................................................ 46
Figure 16................................................................................................................................................................................................ 47
Figure 17................................................................................................................................................................................................ 48
Figure 18................................................................................................................................................................................................ 49
Figure 19................................................................................................................................................................................................ 50
DISCUSSION.................................................................................................................................................................................................. 55
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 63
ACKNOWLEDGEMENTS................................................................................................................................................................................ 65
REFERENCES................................................................................................................................................................................................ 66
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 93
ADDITIONAL TABLES.................................................................................................................................................................................... 318
APPENDICES................................................................................................................................................................................................. 328
WHAT'S NEW................................................................................................................................................................................................. 354
HISTORY........................................................................................................................................................................................................ 355
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 355
DECLARATIONS OF INTEREST..................................................................................................................................................................... 355
SOURCES OF SUPPORT............................................................................................................................................................................... 355
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 355
INDEX TERMS............................................................................................................................................................................................... 356

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[Intervention Review]

Physical exercise for people with Parkinson’s disease: a systematic

review and network meta-analysis

Moritz Ernst1, Ann-Kristin Folkerts2, Romina Gollan2, Emma Lieker2, Julia Caro-Valenzuela1, Anne Adams3, Nora Cryns1, Ina Monsef1,
Antje Dresen4, Mandy Roheger5, Carsten Eggers6,7, Nicole Skoetz1, Elke Kalbe2

1Cochrane Haematology, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf,
Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 2Medical Psychology, Neuropsychology
and Gender Studies and Center for Neuropsychological Diagnostics and Intervention (CeNDI), Faculty of Medicine and University
Hospital Cologne, University of Cologne, Cologne, Germany. 3Institute of Medical Statistics and Computational Biology, Faculty of
Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. 4Institute of Medical Sociology, Health Services
Resarch, and Rehabilitation Science (IMVR), Faculty of Human Sciences and Faculty of Medicine and University Hospital Cologne,
University of Cologne, Cologne, Germany. 5Ambulatory Assessment in Psychology, Department of Psychology, Carl von Ossietzky
University Oldenburg, Oldenburg, Germany. 6Department of Neurology, University Hospital Marburg, Marburg, Germany. 7Department of
Neurology, Knappschaftskrankenhaus Bottrop GmbH, Bottrop, Germany

Contact: Moritz Ernst, [email protected].

Editorial group: Cochrane Movement Disorders Group.

Publication status and date: Edited (no change to conclusions), published in Issue 5, 2023.

Citation: Ernst M, Folkerts A-K, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, Cryns N, Monsef I, Dresen A, Roheger M, Eggers C,
Skoetz N, Kalbe E. Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis. Cochrane
Database of Systematic Reviews 2023, Issue 1. Art. No.: CD013856. DOI: 10.1002/14651858.CD013856.pub2.

Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Editorial note: Key results from the network meta-analysis are also available as an interactive summary of findings table, produced in
collaboration with MAGIC.

ABSTRACT

Background
Physical exercise is effective in managing Parkinson's disease (PD), but the relative benefit of different exercise types remains unclear.

Objectives
To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the
occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs).

Search methods
An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other
databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date.

Selection criteria
We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise,
a control group, or both.

Data collection and analysis

Two review authors independently extracted data. A third author was involved in case of disagreements.

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We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility
and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk
of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and
QoL. We consulted a third review author to resolve any disagreements.

Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using
the GRADE approach.

Main results
We included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The
number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included
data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data.
Here, we present the main results.

We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group.
The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale
(UPDRS-M) and the Parkinson's Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom
burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for
PDQ-39).

Severity of motor signs

The evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor
signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional,
and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27
to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The
evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs
(mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have
a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the
effects of strength/resistance training and "Lee Silverman Voice training BIG" (LSVT BIG) on the severity of motor signs (strength/resistance:
MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence).

Quality of life
The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on
QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate
beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD
-9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low
confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG,
and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance:
MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95%
CI -11.45 to 13.92; very low confidence).

Adverse events
Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs)
occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were
falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events
(very low confidence).

Across outcomes, we observed little evidence of differences between exercise types.

Authors' conclusions
We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD
included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of
physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary.
Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific
programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in
our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional
studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings
to a broader range of people with PD.

PLAIN LANGUAGE SUMMARY

Physical exercise for people with Parkinson's disease: what type of exercise works best?

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Background

Parkinson's disease (PD) is a progressive disorder of the nervous system that mostly affects people over 60. Symptoms begin gradually
and include movement issues, such as trembling, stiffness, slowness of movement and balance, and coordination issues. People with PD
can also have emotional and mood problems, fatigue, sleep problems, and thinking difficulties. The disorder cannot be cured, but the
symptoms can be relieved, for example, with medicine or surgery. Moreover, people with PD may benefit from physiotherapy or other
forms of physical exercise, such as dancing. But it remains unclear if some of these exercise types work better than others.

What was our aim?

We wanted to find out what type of physical exercise works best to improve movement and quality of life for people with PD. We also
wanted to find out what type of exercise causes the least unwanted effects.

What did we do?

We searched for studies that compared physical exercise with no physical exercise or with another physical exercise type. We compared
and summarized their short-term results, and rated our confidence in the evidence, based on factors such as study methods and number
of people included. We only studied short-term results.

What did we find?

We found 156 studies on different physical exercise types for people with PD. The studies included a total of 7939 people. The smallest
study was conducted with 10 people and the biggest with 474 people. The average participant age was between 60 and 74 years. The
studies were conducted in countries around the world, with the highest number (34) in the USA. Of the included studies, 71 (3196 people)
provided information on movement; 55 (3283 people) provided information on quality of life, and 85 (5192 people) provided information
on unwanted effects.

What are the key results?

Many types of physical exercise worked well for people with PD compared to no physical exercise.

Dance has a moderate beneficial effect on movement. Aqua-based training, gait/balance/functional training, and training that consists of
several exercise types (i.e. multi-domain training) might have a moderate beneficial effect on movement. Mind-body (e.g. tai chi or yoga)
and endurance training might have a small beneficial effect on movement. Flexibility training might have little to no effect on movement.
We are very uncertain about the effects of strength/resistance training and the PD-specific physical therapy "Lee Silverman Voice training
BIG" (LSVT BIG) on movement.

Aqua-based training probably has a large beneficial effect on quality of life. Endurance training might have a moderate, and gait/balance/
functional and multi-domain training might have a small beneficial effect on quality of life. We are very uncertain about the effects of mind-
body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on quality of life.

Our confidence in the effects ranged from high to very low. When our confidence was reduced, it was often because of two reasons. First,
not all of the studies provided information on movement or quality of life from all the people who participated. Second, studies were very
small.

Only 85 studies provided some information about unwanted effects, and mostly only for the physical exercise groups, not the groups who
did not do exercise. No unwanted effects were reported in 40 studies. No serious unwanted effects were reported in four studies. Unwanted
effects were reported in 28 studies. The unwanted effects reported most frequently were falls (18 studies) and pain (10 studies). We could
not say what type of exercise causes the least unwanted effects because studies did not provide information about everything we needed.
That is why we are very uncertain about the results on unwanted effects.

What does this mean?

We found that many types of physical exercise can help improve movement and quality of life for people with PD. We found scant evidence
that certain exercise types work better than others. Therefore, for movement and quality of life, we think physical exercise is important,
but the exact exercise type might be less important. Still, it is possible that some symptoms may be relieved best with specific types of
training made for people with PD. The types of training we included seemed to be quite safe.

Larger, well-designed studies are needed to increase our confidence in the evidence. Also, more research is required to understand the
features that influence the effects of exercise. More studies involving people who have worse symptoms could help extend the results to
more people with PD.

How up to date is this review?

The evidence is up to date to May 2021.

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SUMMARY OF FINDINGS

Summary of findings 1. Network estimates of effects and confidence in the evidence for physical exercise in people
with Parkinson’s disease on the severity of motor signs

Patient or population: people with Parkinson's disease

Interventions: physical exercise including: aqua-based training, dance, endurance training, flexibility training, gait/balance/func-
tional training, gaming, LSVT BIG, mind-body training, multi-domain training, and strength/resistance training
Comparison: passive control group (mean [median] UPDRS-M score = 21.34 [19.80])*
Outcome: severity of motor signs, reported as UPDRS-M scores, scale from 0 to 108 (worse)
Settings: inpatient and outpatient care

Total studies: 71 RCTs Estimated ab- Estimated Confidence in Interpretation***

solute effects absolute ef- the evidence
Total participants: on severity of fects on sever- (CINeMA)
3196 motor signs ity of motor
(SMD and 95% signs (MD and
CI) 95% CI), MCID
for improve-
ment/worsen-
ing: -2.5/2.5**

Dance -0.77 (-1.16 to -10.32 (-15.54 to ⊕⊕⊕⊕ Dance has a moderate beneficial effect on
-0.37) -4.96) the severity of motor signs.
(5 RCTs; 169 partici- High
pants)

Aqua-based training -0.58 (-0.99 to -7.77 (-13.27 to ⊕⊕OOa,d Aqua-based training might have a moder-
-0.17) -2.28) Low ate beneficial effect on the severity of motor
(2 RCTs; 30 participants) signs.

Gait/balance/functional -0.55 (-0.85 to -7.37 (-11.39 to ⊕⊕OOa,d Gait/balance/functional training might have
training -0.25) -3.35) Low a moderate beneficial effect on the severity
of motor signs.
(3 RCTs; 137 partici-
pants)

Multi-domain training -0.52 (-0.77 to -6.97 (-10.32 to ⊕⊕OOa,d Multi-domain training might have a moder-
-0.27) -3.62) Low ate beneficial effect on the severity of motor
(7 RCTs; 271 partici- signs.
pants)

Strength/resistance -0.52 (-0.89 to -6.97 (-11.93 to ⊕OOOa,d,e The effect of strength/resistance training
training -0.15) -2.01) Very low might have a moderate beneficial effect on
the severity of motor signs, but the evidence
(2 RCTs; 52 participants) is very uncertain.

Mind-body training -0.49 (-0.76 to -6.57 (-10.18 to ⊕⊕OOa,d Mind-body training might have a small ben-
-0.21) -2.81) Low eficial effect on the severity of motor signs.
(10 RCTs; 323 partici-
pants)

Endurance training -0.48 (-0.8 to -6.43 (-10.72 to ⊕⊕OOb,d Endurance training might have a small ben-
-0.17) -2.28) Low eficial effect on the severity of motor signs.
(5 RCTs; 227 partici-
pants)

LSVT BIG -0.41 (-1.1 to -5.49 (-14.74 to ⊕OOOb,c LSVT BIG might have a small beneficial ef-
0.27) 3.62) Very low fect on the severity of motor signs, but the
(1 RCT; 39 participants) evidence is very uncertain.

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Flexibility training 0.15 (-0.36 to 2.01 (-4.82 to ⊕⊕OOc,f,g Flexibility training might have a trivial or no
0.67) 8.98) Low effect on the severity of motor signs.
(No direct evidence, in-
direct evidence only)

Gaming Not applica- Not applica- Not applica- Not applicable****

ble**** ble**** ble****
(No direct or indirect
evidence)

CI: confidence interval; MCID: minimal clinically important difference; MD: mean difference; PI: prediction interval; SD: standard de-
viation; SMD: standardized mean difference; UPDRS-M: Unified Parkinson Disease Rating Scale - motor scale

CINeMA grades of evidence (derived from the GRADE Working Group grades of evidence)
High confidence: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate confidence: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the
effect, but there is a possibility that it is substantially different.
Low confidence: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of
the effect.
Very low confidence: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from
the estimate of the effect.

* We calculated scores based on mean UPDRS-M scores (post-intervention), reported in 23 studies (317 participants) included in the
network meta-analysis.
** We rescaled scores from SMDs to MDs of the UPDRS-M using an SD of 13.4 (Shulman 2010). Minimal clinically important difference for
improvement: -2.5 (Shulman 2010).
*** We based the classification of effect sizes on the SMDs following Cohen 1988 (i.e. small, unimportant: < 0.2; small, important: 0.2 to
0.5; moderate: 0.5 to 0.8; large: > 0.8).
**** None of the studies provided data on the effect of gaming on the severity of motor signs.
aLarge contribution of studies at high risk of bias and inconsistency between results of primary analysis and sensitivity analysis limited to
studies at low risk of bias (downgraded by 1 level for risk of bias).
bLarge contribution of studies with at least some concerns regarding risk of bias; no sensitivity analysis limited to studies at low risk of bias
available (downgraded by 1 level for risk of bias).
cCI includes effects in both directions (downgraded by 2 levels for imprecision).
dWhile CI includes effect in favor of the intervention (i.e. aqua-based, endurance, gait/balance/functional, mind-body, multi-domain, and
strength/resistance training), PI includes effects in both directions (i.e. PI extends beyond range of equivalence on the opposite side of line
of no effect favoring the passive control group) (downgraded by 1 level for heterogeneity).
eWhile CI of direct estimate includes effect in favor of strength/resistance training, CI of indirect estimate extends into range of equivalence
across line of no effect (downgraded by 1 level for incoherence).
fEstimates are based on indirect evidence only and global approach to assess incoherence is significant, P < 0.05, I2 = 58.4% (downgraded
by 2 levels for incoherence).
gThe overall level of confidence was downgraded by no more than 2 levels in order to avoid downgrading more than once for related
concerns (i.e. imprecision, heterogeneity, and incoherence).
Additionally, we present key results from the network meta-analysis in an interactive summary of findings table.

Summary of findings 2. Network estimates of effects and confidence in the evidence for physical exercise in people
with Parkinson’s disease on quality of life

Patients or population: people with Parkinson's disease

Interventions: physical exercise including aqua-based training, dance, endurance training, flexibility training, and gait/bal-
ance/functional training, gaming, LSVT BIG, mind-body training, multi-domain training, and strength/resistance training
Comparison: passive control group (mean [median] PDQ-39 score = 32.72 [29.50])*

Outcome: quality of life, reported as PDQ-39 scores, scale from 0 to 100 (worse)

Settings: inpatient and outpatient care

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Total studies: 55 RCTs Estimated ab- Estimated ab- Confidence in Interpretation***

solute effects solute effects the evidence
Total participants: on quality of life on quality of (CINeMA)
3283 (SMD and 95% life (MD and
CI) 95% CI), MCID
for improve-
ment/worsen-
ing: -4.72/4.22**

Aqua-based training -0.85 (-1.32 to -14.98 (-23.26 to ⊕⊕⊕Oa Aqua-based training probably has a large
-0.37) -6.52) beneficial effect on quality of life.
(1 RCT; 18 participants) Moderate

Endurance training -0.52 (-0.89 to -9.16 (-15.68 to ⊕⊕OOa,e Endurance training might have a moderate
-0.16) -2.82) Low beneficial effect on quality of life.
(3 RCTs; 90 participants)

Mind-body training -0.50 (-0.83 to -8.81 (-14.62 to ⊕OOOb,e Mind-body training might have a moderate
-0.17) -3.00) Very low beneficial effect on quality of life, but the ev-
(5 RCTs; 155 partici- idence is very uncertain.
pants)

Gaming -0.40 (-1.05 to -7.05 (-18.50 to ⊕OOOb,c,g,h Gaming might have a small beneficial effect
0.25) 4.41) Very low on quality of life, but the evidence is very
(No direct evidence, in- uncertain.
direct evidence only)

Strength/resistance -0.36 (-0.70 to -6.34 (-12.33 to ⊕OOOa,e,f,h Strength/resistance training might have a
training -0.02) -0.35) Very low small beneficial effect on quality of life, but
the evidence is very uncertain.
(3 RCTs; 87 participants)

Gait/balance/functional -0.32 (-0.57 to -5.64 (-10.04 to ⊕⊕OOa,e Gait/balance/functional training might have
training -0.07) -1.23) Low a small beneficial effect on quality of life.

(5 RCTs; 745 partici-

pants)

Multi-domain training -0.30 (-0.53 to -5.29 (-9.34 to ⊕⊕OOa,e Multi-domain training might have a small
-0.06) -1.06) Low beneficial effect on quality of life.
(7 RCTs; 575 partici-
pants)

Dance -0.23 (-0.64 to -4.05 (-11.28 to ⊕OOOb,d Dance might have a small beneficial effect
0.17) 3.00) Very low on quality of life, but the evidence is very
(4 RCTs; 130 partici- uncertain.
pants)

LSVT BIG 0.13 (-0.91 to 2.29 (-16.03 to ⊕OOOa,c,g,h LSVT BIG might have a trivial or no effect on
1.16) 20.44) Very low quality of life, but the evidence is very un-
(No direct evidence, in- certain.
direct evidence only)

Flexibility training 0.07 (-0.65 to 1.23 (-11.45 to ⊕OOOb,c,g,h Flexibility training might have a trivial or no
0.79) 13.92) Very low effect on quality of life, but the evidence is
(No direct evidence, in- very uncertain.
direct evidence only)

CI: confidence interval; MCID: minimal clinically important difference; MD: mean difference; PDQ-39: Parkinson's Disease Question-
naire 39; PI: prediction interval; SD: standard deviation; SMD: standardized mean difference

CINeMA grades of evidence (derived from the GRADE Working Group grades of evidence)

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High confidence: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate confidence: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the
effect, but there is a possibility that it is substantially different.
Low confidence: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of
the effect.
Very low confidence: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from
the estimate of the effect.

* We calculated scores based on mean PDQ-39 scores (post-intervention) reported in 21 studies (642 participants) included in the network
meta-analysis.
** We rescaled scores from SMDs to MDs of the PDQ-39 using an SD of 17.62 (Peto 2001). Minimal clinically important difference for
improvement/worsening: -4.72/4.22 (Horvath 2017).
*** We based the classification of effect sizes on the SMDs following Cohen 1988 (i.e. small, unimportant: < 0.2; small, important: 0.2 to
0.5; moderate: 0.5 to 0.8; large: > 0.8).
aHigh risk of bias in measurement of the outcome due to the nature of self-reported questionnaires (i.e. the subjectivity of the assessment)
(downgraded by 1 level for risk of bias).
bLarge contribution of studies at high risk of bias even when considering only domains that are not affected by the subjectivity of the
assessment (downgraded by 2 levels for risk of bias).
cCI includes effects in both directions (downgraded by 2 levels for imprecision).
dEstimate favors dance and CI extends into range of equivalence across line of no effect (downgraded by 1 level for imprecision).
eWhile CI includes effect in favor of the intervention (i.e. endurance, gait/balance/functional, mind-body, multi-domain, and strength/
resistance training), PI includes effects in both directions (i.e. PI extends beyond range of equivalence on the opposite site of line of no
effect favoring the passive control group) (downgraded by 1 level for heterogeneity).
f While CI of direct estimate includes effect in favor of strength/resistance training, CI of indirect estimate includes effects in favor of both
interventions (i.e. CI extends beyond range of equivalence on the opposite side of line of no effect favoring the passive control group)
(downgraded by 2 levels for incoherence).
gEstimates are based on indirect evidence only and global approach to assess incoherence is significant, P < 0.05, I2 = 60.0% (downgraded
by 2 levels for incoherence).
hThe overall level of confidence was very low even when avoiding downgrading more than once for related concerns (i.e. imprecision,
heterogeneity, and incoherence).
Additionally, we present key results from the network meta-analysis in an interactive summary of findings table.

Summary of findings 3. Estimates of effects and confidence in the evidence for physical exercise in people with
Parkinson’s disease on adverse events

Patient or population: people with Parkinson's disease

Interventions: physical interventions including aqua-based training, dance, endurance training, flexibility training, gait/bal-
ance/functional training, gaming, LSVT BIG, mind-body training, multi-domain training, and strength/resistance training
Comparison: passive control group

Outcome: adverse events (number of participants with any adverse event)

Settings: inpatient and outpatient care

Outcome Impact Number of par- Confidence in Interpretation

ticipants (stud- the evidence
ies) (GRADE)

Adverse events Among 156 studies, only 85 provided some kind of 5192 (85) ⊕OOOa,b The evidence is
safety data (i.e. occurrence or absence of events Very low very uncertain
mostly described as adverse events). Most stud- about the effect
ies reported events for the intervention groups on- of physical exer-
ly. No adverse events occurred in 40 studies. No cise on the risk of
serious or major adverse events occurred in four adverse events.
studies. Adverse events occurred in 28 studies.
The most frequently reported events were falls (18
studies) and pain (10 studies).

GRADE Working Group grades of evidence

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High confidence: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate confidence: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the
effect, but there is a possibility that it is substantially different.
Low confidence: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of
the effect.
Very low confidence: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from
the estimate of the effect.

aReporting of adverse events was highly heterogeneous and frequently incomplete (downgraded by 2 levels for risk of bias).
bEffects could not be estimated using quantitative analysis (downgraded by 1 level for imprecision).

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BACKGROUND widely investigated intervention that is demonstrated to be

effective for some people with PD (Aum 2018).
Description of the condition
Recently, an increasing number of studies has been
Parkinsonian syndromes include idiopathic Parkinson’s disease investigating the potential of non-pharmacological and non-
(PD) and atypical Parkinsonian syndromes, the latter of which surgical interventions, including primarily physiotherapy, but also
are rare diseases and comprise only 5% to 7% of all types of other types of physical exercise, in managing motor and non-motor
parkinsonism (Bower 1997; Rajput 1984). PD is the second most symptoms in PD. In systematic reviews and clinical guidelines,
common neurodegenerative disease for people over 60 years of age physical exercise interventions for people with PD are defined as
(De Lau 2006). interventions that focus on the enhancement of muscle strength,
aerobic capacity, balance, gait, and functional mobility by means of
PD is associated with loss of dopaminergic neurons in the
cueing, cognitive movement strategies, and physical exercises (e.g.
substantia nigra and the presence of Lewy bodies (Damier
Keus 2014; Tomlinson 2013).
1999). The precise mechanisms of neurodegeneration are unclear
but most likely involve both genetic and environmental factors Positive effects of a variety of types of physical exercise in
(Ascherio 2016). PD is primarily characterized by progressive people with PD have been observed in systematic reviews.
motor symptoms, including bradykinesia, muscular rigidity, rest These include short-term benefits of physiotherapy on motor
tremor, and postural instability (Hughes 1992). These features impairment and activities of daily living (Tomlinson 2013), positive
cause impairment in various aspects of mobility, such as gait, effects of Nordic walking on motor and non-motor symptoms
transfers, balance, and posture (Keus 2007). Furthermore, non- (Bombieri 2017), and improved balance and well-being through
motor symptoms such as anxiety, depression, fatigue, sleep tai chi training (Ćwiękała-Lewis 2017). Additionally, more recent
disturbance, and sensory symptoms (Shulman 2001), frequently systematic reviews have demonstrated the potential to improve
occur in people with PD, as well as cognitive dysfunctions which can outcomes, such as severity of motor signs, quality of life, freezing
potentially occur at any disease stage and range from mild cognitive of gait, or functional mobility and balance, for people with PD
impairment to PD dementia (Aarsland 2021; Muslimović 2005). through several types of physical exercise. These include, for
Motor and non-motor symptoms cause substantial functional example, aquatic therapy (Cugusi 2019; Gomes Neto 2020), dance
limitations and a reduction in the quality of life (QoL) of people (Carapellotti 2020; Chen 2020), mind-body training (Jin 2019),
with PD and their caregivers (Aarsland 2021; Martinez-Martin 2011). physiotherapy (Consentino 2020), exercises targeted at freezing of
There has been a vast discussion about different subtypes of gait (Gilat 2021), and strength/resistance and endurance training
the disease; however, so far there has been no final conclusion (Gamborg 2022).
about distinct subtypes and their potential respective courses of
symptomatology (Bloem 2021). PD remains a clinical diagnosis Evidence of beneficial effects of physical exercise for people with
typically based on the presence of a combination of cardinal motor PD was also provided by recent systematic reviews with network
features, associated and exclusionary symptoms, and response to meta-analyses (NMAs). Álvarez-Bueno and colleagues analyzed the
dopaminergic treatment (Postuma 2015). effects of nine types of exercise (namely, endurance, resistance,
combined, balance, dance, alternative exercises such as yoga or
Incidence rates of PD based on prospective population-based tai chi, body weight supported, and sensorimotor interventions
studies range from 8 to 18 per 100,000 person-years. Incidence of including or not including endurance exercise) on motor symptoms,
PD is rare before 50 years of age and increases sharply after 60 using an NMA (Álvarez-Bueno 2021). They identified evidence of
years of age (De Lau 2006). Epidemiological studies suggest that positive effects on the severity of motor signs for dance, endurance,
men have a higher risk than women of developing PD (De Lau resistance, and sensorimotor training with or without endurance
2006; Moisan 2016). In most people with PD, life expectancy is not exercise compared with a control group, but no evidence of
severely reduced (Bäckström 2018). differences between the interventions. The authors concluded that
interventions "including more complex and demanding activities
The European Union-wide burden for PD is estimated to be
seem to be the most effective [...]" (Álvarez-Bueno 2021). In another
70 disability-adjusted life years (Deuschl 2020). There is also a
NMA that was part of a review of exercise interventions comprising
huge health economic burden, with mean annual costs of 20,095
tai chi, qigong, resistance training, aerobic exercise, multimodal
euros (EUR) per person with PD in Germany (Winter 2010). With
exercise training, dance, tango, and yoga, the authors found
approximately 6.1 million people with PD worldwide, the global
evidence of beneficial effects on the severity of motor signs for
burden of the disease has more than doubled over the past
dance and tango, and evidence of beneficial effects on functional
generation, and it is likely to increase further due to demographic
mobility and balance for dance, tango, multimodal exercises, and
change (Dorsey 2018).
tai chi (Tang 2019). The only evidence of differences between the
Description of the intervention interventions was observed in comparisons including a single study
each (e.g. superiority in the effect of tango on severity of motor
Pharmacological agents, such as levodopa, dopamine agonists, signs compared to tai chi). Tang and colleagues concluded by
and monoamine oxidase B inhibitors, have been central to the highlighting tango as an effective option to improve the functional
treatment of motor symptoms in PD (Rizek 2016). When the mobility of people with PD. Kwok and colleagues conducted
disease progresses, the efficacy of levodopa can decline and a systematic review with NMA on behavioral interventions,
fluctuate throughout the day, which is referred to as switching including obstacle training, gait training on a treadmill, and action
between the 'on'- (i.e. symptoms are controlled) and 'off'- (i.e. observation training, for the management of freezing of gait (Kwok
symptoms worsen) medication state (Ramirez-Zamora 2014). 2022). They provided evidence of statistically significant effects
Surgical treatment, especially deep brain stimulation, is another on freezing of gait compared to usual care or no treatment

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for obstacle training, gait training with a treadmill, and general ganglia. For example, dopamine neurotransmission increases
exercise, and further beneficial effects for action observation through enhanced vesicular release and decreasing dopamine
training and conventional physiotherapy after controlling for the clearance in the synaptic cleft due to reduced dopamine reuptake
baseline severity of freezing of gait (Kwok 2022). Similar to the (Petzinger 2007). Furthermore, the efficacy of neurotransmission
results of Tang and colleagues (Tang 2019), little evidence of increases because of enhanced dopamine D2 receptor expression
differences between the interventions was observed in the Kwok in remaining dopaminergic neurons and their targets (Yin 2009).
2022 review: only comparisons involving obstacle training (for
which only a single study provided data) indicated superiority on Integrating findings from neuroimaging studies on healthy-aging
freezing of gait over the effects of most other interventions (Kwok adults and people with PD and focusing on the beneficial effects
2022). of exercise on mobility and cognition, Bonavita hypothesizes that
exercise-induced prefrontal activation may drive improvements in
Investigations of the long-term effects of different types of physical cognitive performances and gait control (Bonavita 2020). Also, it is
exercise (including multimodal physical therapy, progressive suggested that resistance training may facilitate neuroplasticity in
resistance training, aerobic training, gait and balance training, tai the basal ganglia and corticomotor networks associated with gait
chi, and dance) found that these interventions modify long-term performance (Bonavita 2020).
motor symptoms and physical functioning in people with PD, with
balance training having the longest carry-over effects, followed by In addition to the evidence of neurobiological changes induced
gait and tai chi training (Mak 2017). by exercise, several systematic reviews documented the positive
impact of exercise programs on measures of functional and related
Physical exercise appears to be relatively safe. Although data on capabilities, such as physical functioning, balance, gait, strength,
adverse events were rare in most studies included in previous and activities of daily living (Goodwin 2008; Mak 2017; Radder
systematic reviews on physical exercise for PD, studies that 2020; Wu 2021). Focusing on long-term effects of exercise, Mak
provided data on this outcome reported either no, or no serious, and colleagues observed that, by sustained training, some of these
adverse events (Bombieri 2017; Ćwiękała-Lewis 2017; Tomlinson effects may persist for up to 12 months after completing training
2013). Mak and colleagues conducted a review of long-term effects (Mak 2017).
of exercise and physical activity for PD that included 46 studies
(Mak 2017). They reported that adverse events were reported in 25 Finally, people with PD may benefit not only from the functional
studies, of which 10 reported injuries that were sustained during effects of exercise, but also from the opportunities for social
training; 28 studies noted falls and minor injuries that did not interaction during group or partnered exercise programs.
require medical attention. Further adverse events reported were
hypotension, lightheadedness or dizziness, joint pain or muscle Why it is important to do this review
soreness, injury-induced shoulder pain, fatigue, and discomfort The increasing number of trials assessing physical exercise
due to devices (i.e. due to the harness of a robotic gait trainer in demonstrates the growing interest in non-pharmacological and
one study). Given the total number of participants in the 25 studies non-surgical interventions for the treatment of PD. There are
(792 participants), the authors regarded the overall risk of adverse several systematic reviews and meta-analyses focusing on one type
events as low and the interventions as safe and well tolerated (Mak (e.g. Bombieri 2017; Ćwiękała-Lewis 2017; Dockx 2016; Dos Santos
2017). 2017), as well as some that focus on several types of physical
exercise (e.g. Tomlinson 2013; Tomlinson 2014). Moreover, recent
Nevertheless, it has to be noted that adverse events may have
systematic reviews have investigated the comparative efficacy of
occurred in studies without being recorded or reported, potentially
different types of exercise for people with PD using network meta-
leading to an overestimation of the safety of physical exercise.
analyses (NMAs) and demonstrated the potential of several exercise
programs to improve outcomes for people with PD (Álvarez-Bueno
How the intervention might work
2021; Kwok 2022; Tang 2019). However, two of these reviews
There is a vast amount of evidence that physical exercise focused on only one outcome domain (Álvarez-Bueno 2021; Kwok
substantially induces neuroplasticity and enhances brain health 2022), and none of them performed safety analyses. Furthermore,
in both motor and cognitive circuits in PD. Neuroplasticity is the some reviews provided only limited information on the methods
brain's ability to modify existing neural networks; for example, by used (e.g. statistical analyses (Tang 2019); methods used to account
adding or reorganizing synapses. for trial design when combining RCTs and non-randomized studies
(Álvarez-Bueno 2021); whether all relevant steps were performed
Evidence from a systematic review on studies in humans suggests in duplicate by independent reviewers (Tang 2019); detailed
that physical exercise may lead to changes in various markers of information on the assessments of risk of bias (Álvarez-Bueno 2021;
neuroplasticity, as indicated by changes in brain function and brain Kwok 2022; Tang 2019); or the confidence in the evidence (Álvarez-
structure (Johansson 2020). Bueno 2021; Kwok 2022)); did not assess the confidence in the
evidence (Tang 2019); or had other methodological limitations (e.g.
Evidence from studies in both animals and humans suggests that
addressing a limited number of interventions, and limiting the
physical activity may induce specific structural and functional brain
study selection to English articles (Tang 2019)). Thus, the relative
changes relevant for people with PD (Bonavita 2020; Voss 2013).
benefit of a broad range of exercise programs in improving several
In rodent models of PD, forced or voluntary physical exercises core outcomes – including the severity of motor signs, QoL, and the
have neuroprotective effects as the release of neurotrophic factors risk of adverse events – in people with PD remains unclear.
(e.g. brain-derived neurotrophic factor, glial-derived neurotrophic
We conducted a comprehensive systematic review comparing
factor) increases (Cohen 2003). These animal models also showed
all types of physical exercise in a network meta-analysis
compensatory changes in dopaminergic neurons of the basal
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combining direct and indirect evidence. When the methodological and have incorporated diverse training devices (e.g. treadmill,
assumptions are met, network meta-analyses allow the estimation physiotherapy, aerobic exercises, qigong, bicycle exercises,
of metrics for all possible comparisons in the same model and strength training, Lee Silverman Voice Training BIG (LSVT BIG),
enable analyses of direct and indirect evidence simultaneously. Nordic walking, virtual reality exercises, dance, balance training,
Such analyses potentially enable ranking of different treatments gait training, aqua-based exercises, yoga, tai chi). We included
for specific outcomes. Such ranking could be highly relevant for interventions: conducted in either a group or an individual setting;
people with PD and clinicians when making clinical decisions on lasting for at least five sessions under direct (i.e. excluding remote)
non-pharmacological and non-surgical PD treatment, and when supervision; and consisting of either continuous training or interval
people with PD wish to integrate more physical training in their training. We included combined interventions only when physical
daily life. training was the main component of the intervention. Concomitant
supportive treatment should not have differed between study
OBJECTIVES arms.

To compare the effects of different types of physical exercise in We grouped similar interventions based on an adaptation of the
adults with Parkinson's disease (PD) on the severity of motor signs, ProFaNE taxonomy (a naming and classification system developed
quality of life (QoL) and the occurrence of adverse events, and to for falls-prevention interventions; Lamb 2011). As recommended
generate a clinically meaningful treatment ranking using network by authors of a Cochrane Review who applied the taxonomy to
meta-analyses (NMAs). categorize exercise interventions for falls prevention (Sherrington
2019), we have provided information on our operationalization
METHODS of the taxonomy in Appendix 1. Please note that the type of
exercise or control group derived from this taxonomy was pivotal
Criteria for considering studies for this review in determining the eligibility of a study for inclusion in our review.
Types of studies For example, we included a study if it compared two different
interventions categorized as the same exercise type.
We included randomized controlled trials (RCTs). We included
both full-text and abstract publications as long as they Two review authors (ME, AF, RG, EL, JCV) categorized the
provided sufficient information on study design, characteristics of interventions based on all available information describing
participants, and interventions. We included trials with participants the interventions' characteristics (e.g. exercise components and
performing physical exercise in at least one treatment arm. In the their relative proportion, intensity, setting). We categorized
case of cross-over trials, we analyzed only the first period of the interventions according to the dominant exercise category. We
trial. We imposed no limitations with respect to length of follow-up. assigned all study arms to one of the ten possible exercise
categories or one of the two possible categories of control groups,
We excluded cluster-RCTs in order to preserve as much regardless of how study authors labeled the study arms. As a result,
methodological homogeneity across trials as possible. We we may have assigned a study arm that was designated as a control
also excluded non-randomized trials, case reports, and clinical arm to an exercise category (e.g. we may have assigned a study
observations. arm with an intervention comprising stretching exercises to the
flexibility training category, although it was designated as a control
Types of participants
arm to study the efficacy of tai chi). When we were unable to reach a
We included trials involving adults (≥ 18 years of age) with a consensus about category assignment, we consulted a third review
confirmed diagnosis of idiopathic Parkinson's disease (at least 90% author (ME, AF) for the final decision.
of the sample with idiopathic Parkinson's disease). We included
participants of all cognitive stages (without cognitive impairment, Our decision set included all interventions that used structured
with mild cognitive impairment, with dementia). We did not exercise. We assigned them to the following categories:
impose any restrictions regarding sex or educational level of the
• aqua-based training;
participants.
• dance;
We excluded trials involving participants with atypical • endurance training;
parkinsonism (e.g. drug-induced parkinsonism, vascular • flexibility training;
parkinsonism).
• gait/balance/functional training;
We assume that participants who fulfilled the inclusion criteria • gaming;
were equally eligible to be randomized to any of the interventions • LSVT BIG;
we compared. • mind-body training;
Types of interventions • multi-domain training; and
• strength/resistance training.
We included trials comparing different types of physical exercise
with each other, with a control group, or both. For more details on the interventions, please see Appendix 1.

We included trials involving physical training as one main We expected that many studies would use an active or a passive
component of the intervention. Interventions needed to comprise control group as comparators against the interventions included
structured exercise. Interventions may have included various in our decision set. We included these interventions in our
training content, have been delivered in various environments, supplementary set in order to improve inference among the

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interventions in the decision set, as described in Chapter 11 of • Functional mobility and balance (measured with the Timed Up
the Cochrane Handbook for Systematic Reviews of Interventions and Go (TUG), which measures the time taken in seconds for a
(Chaimani 2022). person to get up from a chair, walk a certain distance (usually
three meters), turn around, and walk back to the chair and sit
We defined 'active control' groups as groups receiving a structured, down, Podsiadlo 1991).
supervised, non-physical intervention (e.g. communication • Adverse events (number of participants with any adverse event).
training). We defined 'passive control' groups as groups not
receiving a structured, supervised intervention (e.g. wait-list, no Timing of outcome assessment
treatment, usual care, advice only, unstructured physical activity).
We evaluated outcomes assessed shortly (≤ six weeks) after the
When no direct evidence from RCTs existed, and we considered the intervention. When multiple assessments within this interval were
trials sufficiently similar with respect to the participant population reported, we evaluated the assessment closest to the end of the
to ensure the transitivity assumption of network meta-analysis, we intervention. We gave preference to data on the severity of motor
obtained indirect estimates of intervention effects via the network signs assessed during the on-medication state.
calculations.
We evaluated adverse events measured at any time after initiation
Types of outcome measures of the intervention.
We included all trials fulfilling our inclusion criteria, irrespective Search methods for identification of studies
of whether they reported the outcomes of interest listed below
(Primary outcomes; Secondary outcomes). These outcomes are Electronic searches
consistent with a proposed consensus set of outcomes for people We adapted search strategies as suggested in Chapter 4 of
with Parkinson's disease (De Roos 2017). the Cochrane Handbook for Systematic Reviews of Interventions
(Lefebvre 2020). We applied no language restrictions to reduce
We estimated the relative ranking of the competing interventions
language bias. We used medical subject headings (MeSH) or
according to the outcomes described below. We produced network
equivalent and text word terms.
plots for each outcome displaying the amount of evidence.
We conducted searches tailored to each of the following databases
We only considered outcomes measured using standardized and
and trial registries:
validated instruments. When studies reported multiple outcome
measures, we gave preference according to the order in which they • CENTRAL via The Cochrane Register of Studies Online (inception
are listed below. to 17 May 2021) (Appendix 2);
Primary outcomes • MEDLINE via OvidSP (inception to 17 May 2021) (Appendix 3);
• Embase via OvidSP (inception to 17 May 2021) (Appendix 4);
• Severity of motor signs (measured, for example, with: the
Movement Disorder Society-Sponsored Revision of the Unified • CINAHL via EBSCO (inception to 17 May 2021) (Appendix 5);
Parkinson’s Disease Rating Scale (MDS-UPDRS-M, motor score, • SPORTDiscus via EBSCO (inception to 17 May 2021) (Appendix 6);
Goetz 2008); the Unified Parkinson's Disease Rating Scale • AMED (Allied and Complementary Medicine) via OvidSP
(UPDRS-M, motor score, designed to assess motor impairment (inception to 17 May 2021) (Appendix 7);
and disability in Parkinson's disease, Fahn 1987); the Hoehn • REHABDATA via www.naric.com/?q=en/rehabdata (18 May 2021)
and Yahr scale (used to describe how symptoms of Parkinson's (Appendix 8);
disease progress, Hoehn 1967); the Webster Rating Scale • PEDro (Physiotherapy Evidence Database) via
(assessment of severity of disease and clinical impairment www.pedro.org.au (18 May 2021) (Appendix 9);
against 10 items, Webster 1968); or the Columbia University
• EU Clinical Trials Register via www.clinicaltrialsregister.eu/ctr-
Rating Scale (assessment of motor impairment and activities
search/search (20 May 2021) (Appendix 10);
of daily living against 13 items, Yahr 1969); or other validated
scales. • World Health Organization International Clinical Trials Registry
Platform via www.who.int/ictrp/search/en (20 May 2021)
• Quality of life (QoL; measured, for example, with: the Parkinson’s
(Appendix 10);
Disease Questionnaire 39 (PDQ-39, a Parkinson's disease-
specific health-related QoL questionnaire containing 39 items • ClinicalTrials.gov via www.clinicaltrials.gov (20 May 2021)
divided among eight domains, Jenkinson 1997b; Peto 1995); (Appendix 10);
Parkinson's Disease Questionnaire 8 - short-form of the PDQ-39, • ISRCTN registry via www.isrctn.com (20 May 2021) (Appendix
Jenkinson 1997a); EuroQol (EQ-5D), a generic QoL questionnaire 10).
containing five items, EuroQol Group 1990); or other validated
instruments). These searches were complemented by a handsearch of abstracts
covering the following conferences (2019, 2020):
Secondary outcomes
• International Congress of Parkinson's Disease & Movement
• Freezing of gait (measured with the Freezing of Gait Disorders;
Questionnaire (FOG-Q, Giladi 2000) or the New Freezing of Gait • American Academy of Neurology;
Questionnaire (NFOG-Q, Nieuwboer 2009). Both measure the
• European Academy of Neurology;
freezing of gait in people with Parkinson's disease).
• International Association of Parkinsonism and Related
Disorders.
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Searching other resources • participant characteristics: participant details (baseline

demographics such as age, sex), number of participants
We handsearched references of all identified trials, relevant review
recruited, allocated, or evaluated, participants lost to follow-up,
articles, and current treatment guidelines for further literature. We
disease severity, cognitive stage, physical capability;
contacted authors of relevant studies for unpublished material or
further information on ongoing studies. • intervention: type, frequency, setting, supervision;
• outcomes: motor outcomes (motor function, freezing of gait,
Data collection and analysis functional mobility and balance), QoL, adverse events;
Selection of studies • notes: sponsorship or funding for trial and notable conflicts of
interest of authors, trial registry record information (e.g. NCT
One review author (ME) screened the results and removed titles numbers).
that clearly did not satisfy the inclusion criteria. Following this
initial screening, two review authors (ME, AF) independently We collated multiple reports of the same study, so that each study
screened the remaining results for eligibility by reading the rather than each report was the unit of interest in the review.
abstracts, and obtained full-text copies of potentially eligible We collected characteristics of the included studies in sufficient
studies. In the case of disagreement or when it was unclear whether detail to populate a table of Characteristics of included studies
we should include an abstract or not, we assessed the full-text in the full review. For the outcomes, when both effect sizes with
publication for further discussion. If we were still unable to reach standard deviations (SDs) or standard errors (SEs) and raw data
consensus, a third author (MR) would have adjudicated. were reported, we collected the effect sizes with SDs or SEs
originally reported by the authors of the trial. We evaluated the
We did not anonymize the studies before assessment. We include impact of potential effect modifiers (see Subgroup analysis and
a Preferred Reporting Items for Systematic Reviews and Meta- investigation of heterogeneity section).
Analyses (PRISMA) flow chart that shows the status of identified
studies (Moher 2009), as recommended in Chapter 3 of the Assessment of risk of bias in included studies
Cochrane Handbook for Systematic Reviews of Interventions (Page We used the Cochrane Risk of Bias 2 tool (RoB 2; beta version 7;
2020a). We report the review in accordance with the PRISMA Sterne 2019) to assess risk of bias for the severity of motor signs and
extension for network meta-analysis (Hutton 2015). QoL.
We included studies in the Characteristics of included studies table We assessed the effect of assignment to intervention (the intention-
irrespective of whether measured outcome data were reported in to-treat effect).
a 'usable' way. There were no language restrictions, and articles
were translated if not published in English. Volunteers recruited The tool implements signaling questions for each domain, leading
via Cochrane's TaskExchange platform translated seven articles: six to 'low', 'high', or 'some concerns' for risk of bias. The answers
of these were published in Chinese (Gu 2013; Guan 2016; Wang to these signaling questions are available in a supplementary file
2017; Wang 2018; Zhang 2018; Zhu 2011), and one was published (see Risk of bias in included studies). Additionally, we created plots
in Persian (Taheri 2011). We included five of these studies in this visualizing the judgments using the robvis tool (McGuinness 2020).
review (Gu 2013; Guan 2016; Taheri 2011; Wang 2017; Zhu 2011).
We addressed the following domains covering all types of bias that
We recorded excluded studies in the Characteristics of excluded can affect results of randomized trials:
studies table.
• bias arising from the randomization process;
Data extraction and management • bias due to deviations from intended interventions;
Two review authors (ME, AF, RG, EL, JCV) extracted data using a • bias due to missing outcome data;
standardized data extraction form. When authors were unable to • bias in measurement of the outcome;
reach a consensus, we consulted a third review author (ME, AF) for • bias in selection of the reported result.
the final decision. If required, we contacted the authors of specific
studies for supplementary information (Li 2020). After reaching an For adverse events, retrieving effect estimates for a network meta-
agreement, we entered data into Review Manager Web (RevMan analysis and conducting a formal assessment of risk of bias was not
Web; RevMan Web 2022). feasible. Therefore, we made an informal judgment of the risk of
bias for this outcome.
We extracted the following information:
Two review authors (ME, AF) independently assessed risk of bias
• general information: author, title, source, publication date, for each outcome. If we were unable to reach a consensus, we
country, language, duplicate publication; consulted a third review author for a final decision.
• quality assessment: sequence generation, allocation
concealment, blinding (participants, personnel, outcome Measures of treatment effect
assessors), incomplete outcome data, selective outcome
Relative treatment effects
reporting, other sources of bias;
• study characteristics: trial design, setting, source of participants, We gave preference to intention-to-treat data to calculate
statistical methods (power calculations, subgroup analysis), treatment effects. For continuous outcomes, we calculated mean
treatment cross-overs, compliance with assigned treatment, differences (MDs), including 95% confidence intervals (CIs), when
discontinuation, time point of randomization, length of follow- assessed with the same instrument; otherwise we calculated
up; standardized mean differences (SMDs), including 95% CIs. For the
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continuous outcomes included in the summary of findings tables mean change scores based on SDs of pre and post mean
and analyzed using network meta-analyses (i.e. the severity of scores, as described in Chapter 6 of the Cochrane Handbook for
motor signs and quality of life), we also calculated 95% prediction Systematic Reviews of Interventions (6.5.2.8 (2); Higgins 2020b).
intervals (PIs) that were considered among CIs in the assessment Imputation was conducted using a correlation coefficient of r =
of the confidence in the evidence. For these outcomes, we also 0.5.
converted SMDs back to MDs on the most frequently reported • For two studies reporting data on QoL (Schmitz-Hubsch 2006)
scale and interpreted findings with respect to a minimum clinically or functional mobility and balance (Nieuwboer 2007), for which
important difference (MCID) on the respective scale (e.g. 2.5 points we received individual patient data from the study authors, we
on the UPDRS-M (Shulman 2010)). For the remaining outcomes calculated post mean scores and SDs for each group and we
(i.e. freezing of gait and functional mobility and balance), we also imputed missing data for one participant each using the last
presented the results along with the MCID on the most frequently observation carried forward method.
reported scale, or, when the MCID was not retrievable, the minimum
detectable change (i.e. 3.5 seconds on the TUG (Huang 2011)). We estimated data from figures as data were not reported
numerically from: five studies reporting the severity of motor signs
Relative treatment ranking (Colgrove 2012, 13 participants; De Assis 2018, 12 participants;
We obtained a treatment hierarchy using P-scores (Rücker 2015). Reuter 2011, 90 participants; Ridgel 2019, 16 participants; Shen
P-scores allow ranking treatments on a continuous 0 to 1 scale in 2021, 30 participants), one study each reporting QoL (Poliakoff
a frequentist network meta-analysis. Since ranking according to 2013, 30 participants), and freezing of gait (Duncan 2012, 52
P-scores is a probability ranking, we report not only P-scores but participants); and two studies reporting functional mobility and
also network estimates along with corresponding 95% CIs. The use balance (Corcos 2013, 38 participants; Ridgel 2019, 16 participants).
of P-scores allows us, separately for each outcome of interest, to
Assessment of heterogeneity
answer the question of which treatment has the highest proportion
of competitors that it beats (Salanti 2021). Assessment of clinical and methodological heterogeneity within
treatment comparisons
Unit of analysis issues
To evaluate the presence of clinical heterogeneity, we generated
Studies with multiple treatment groups summary statistics for the important clinical and methodological
As recommended in Chapter 23.3.4 of the Cochrane Handbook for characteristics across all included studies. Within each pairwise
Systematic Reviews of Interventions (Higgins 2020a), for studies comparison, we assessed the presence of clinical heterogeneity by
with multiple treatment groups, we combined arms as long as visually inspecting the similarity of these characteristics (see Effects
they could be regarded as subtypes of the same intervention type. of interventions).
When arms could not be pooled this way, we included multi-arm
Assessment of transitivity across treatment comparisons
trials using a network meta-analysis approach that accounts for the
within-study correlation between the effect sizes by reweighting all To check if the assumption of transitivity held, we assessed whether
comparisons of each multi-arm study (Rücker 2012; Rücker 2014). the included interventions were similar when they were evaluated
in RCTs with different designs. Furthermore, we compared the
Dealing with missing data distribution of the potential effect modifiers across the different
As suggested in Chapter 10 of the Cochrane Handbook for pairwise comparisons. For each set of studies, grouped by
Systematic Reviews of Interventions (Deeks 2020), we took the treatment comparison, we created a table of important clinical
following steps to deal with missing data. Whenever possible, and methodological characteristics (e.g. age, sex, and cognitive
we contacted the original investigators to request relevant stage of participants, length of intervention, disease duration,
missing data. When the number of participants evaluated for disease severity, physical capability; see Effects of interventions).
a given outcome was not reported, we used the number of We visually inspected the similarity of these factors, including the
participants randomized per treatment arm as the denominator. inclusion and exclusion criteria of every trial in the network. Despite
When estimates for means and SDs were missing, we calculated the diversity of the investigated interventions in the network, we
these statistics from reported data whenever possible, using assumed transitivity across our treatment comparisons based on
approaches described in Chapter 10 of the Cochrane Handbook predefined, narrow inclusion criteria, similarity of inclusion and
for Systematic Reviews of Interventions (Deeks 2020). When data exclusion criteria of the included studies, and balanced distribution
were not reported numerically but graphically, two review authors of clinical and methodological characteristics across comparisons.
(ME, JCV) independently estimated missing data from figures. We
Assessment of statistical heterogeneity and inconsistency
addressed the potential impact of missing data on findings of the
review in the Discussion section. To evaluate the presence of heterogeneity and inconsistency in the
entire network, we report the generalised heterogeneity statistic
We did not need to calculate SDs according to a validated Qtotal and the generalised I2 statistic as described in Schwarzer
imputation method (Furukawa 2006), as these statistics were either
2015. We used the decomp.design command in the R package
available or retrievable based on other statistics (e.g. standard
netmeta version 1.0-1 or decomposition of the heterogeneity
errors).
statistic into a Q statistic for assessing the heterogeneity between
We imputed data as follows. studies with the same design (netmeta 2021; R), and a Q
statistic for assessing the designs' inconsistency to identify the
• For one study reporting data on functional mobility and balance amount of heterogeneity or inconsistency within as well as
(Hackney 2009, 61 participants), we imputed missing SDs of between designs. To evaluate the presence of inconsistency locally,

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we compared direct and indirect treatment estimates of each effects in multi-arm studies. We assumed a common estimate for
treatment comparison. This can serve as a check for consistency the heterogeneity variance across the different comparisons. To
of a network meta-analysis (Dias 2010). For this purpose, we evaluate the extent to which treatments are connected, we provide
used the netsplit function in the R package netmeta version a network plot for our outcomes. For each comparison, we report
1.0-1, which enabled us to split the network evidence into direct the estimated treatment effect along with its 95% CI. We graphically
and indirect contributions (netmeta 2021; R). For each treatment present the results using forest plots, with the passive control group
comparison, we present direct and indirect treatment estimates as reference treatment. We used the R package netmeta version
plus the network estimate using forest plots. In addition, for each 1.0-1 for statistical analyses (netmeta 2021; R).
comparison, we report the Z value and P value of the test for
disagreement (direct versus indirect). We considered a P value of Subgroup analysis and investigation of heterogeneity
less than 0.05 significant for this test. However, it should be noted We planned to perform subgroup analyses using the following
that in a network of evidence there may be many loops, and with characteristics, which might have an effect on the outcomes:
multiple testing there is an increased likelihood that we might find
an inconsistent loop by chance. Therefore, we were cautious when • age (< 50 years, ≥ 50 years);
deriving conclusions from this approach. • sex (male, female);
When finding substantive heterogeneity or inconsistency, we • cognitive stage (participants without cognitive impairment,
reviewed the evidence base, reconsidered inclusion criteria, and participants with cognitive impairment);
discussed the potential role of unmeasured effect modifiers to • length of intervention (< 12 weeks, ≥ 12 weeks).
identify further sources.
Given the distribution of these characteristics across studies, we
We interpreted I2 values according to Chapter 9.5.2 of the Cochrane were only able to perform subgroup analyses by the length of
Handbook for Systematic Reviews of Interventions as follows (Deeks intervention. We conducted these for all outcomes included in the
2020): NMAs (i.e. the severity of motor signs, QoL, freezing of gait, and
functional mobility and balance).
• 0% to 40% might not be important;
Sensitivity analysis
• 30% to 60% may represent moderate heterogeneity;
• 50% to 90% may represent substantial heterogeneity; We performed sensitivity analyses to test the robustness of our
• 75% to 100% represents considerable heterogeneity. results by analyzing trial results at low overall risk of bias, as judged
by using the RoB 2 tool only (Sterne 2019). We conducted sensitivity
We used the P value of the Chi2 test only for describing the extent analyses for the primary outcomes included in the NMAs (i.e. the
of heterogeneity and not for determining statistical significance. In severity of motor signs and QoL).
addition, we report Tau2, the between-study variance in random-
Summary of findings and assessment of the certainty of the
effects meta-analysis. In the event of excessive heterogeneity that
evidence
was unexplained by subgroup analyses, we did not report outcome
results as the pooled effect estimate of the network meta-analysis Confidence in the evidence
but provided a narrative description of the results of each study.
Two review authors (ME, AF) independently rated their confidence
Assessment of reporting biases in the evidence in the results of the network meta-analyses
using the Confidence in Network Meta-Analysis (CINeMA) approach
In pairwise comparisons with at least 10 trials, we examined (Nikolakopoulou 2020).
the presence of small-study effects graphically by generating
funnel plots. We used linear regression tests to test for CINeMA identifies six domains to be judged:
funnel plot asymmetry (Egger 1997). We considered a P value
of less than 0.1 significant for this test (Page 2020b). We • within-study bias;
additionally considered comparison-adjusted funnel plots and • reporting bias;
the accompanying regression test to assess selection bias. We • indirectness;
examined the presence of small-study effects for the primary
• imprecision;
outcomes only. Moreover, we searched study registries to identify
completed but not published trials. • heterogeneity;
• incoherence.
Data synthesis
We considered the judgments for all domains and avoided
Methods for direct treatment comparisons downgrading by more than two levels for related concerns (i.e.
Pairwise comparisons are part of the NMA; thus, we did not perform imprecision, heterogeneity, and incoherence).
additional pairwise meta-analyses.
We rated our confidence in the evidence in the results on adverse
Methods for indirect and mixed comparisons events, which we reported narratively, using the GRADE approach
(Schünemann 2022).
As the data were considered sufficiently similar to be combined,
we performed an NMA using the frequentist weighted least- Summary of findings tables
squares approach described by Rücker 2012. We used a random-
We included summary of findings tables to present the main
effects model, taking into account the correlated treatment
findings in a transparent and simple tabular format for outcomes
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prespecified at protocol stage (Roheger 2021). In particular, reference lists and review articles, and one reference of a study
we included key information concerning the confidence in the awaiting classification during the peer review process, resulting in
evidence, the magnitude of effect of the interventions examined, 21,982 records in total.
and the sum of available data on the severity of motor signs
(Summary of findings 1), QoL (Summary of findings 2), and At the initial screening stage, we removed 2556 duplicates, and one
adverse events (Summary of findings 3). Additionally, we created author (ME) excluded 16,129 references due to lack of conformity
an interactive summary of findings table using the MATCH-IT tool with the inclusion criteria, leaving 3297 records. Two review
(MATCH-IT) to present key results from the network meta-analyses. authors (ME, AF) independently screen these and excluded another
2854 records not meeting the inclusion criteria.
Quality of life
We further evaluated the remaining 314 studies (443 references),
Due to the nature of self-reported questionnaires and the either as full-text publications or, if not available, as abstract
corresponding subjectivity of the assessment, we judged all study publications or study registry entries. This led to the exclusion of 32
results on QoL to be at high risk of bias (i.e. due to high risk of bias in studies. In addition, we identified 58 ongoing studies which may be
measurement of the outcome as assessed by domain 4 of the RoB 2 completed by 2024. Sixty-eight studies are awaiting classification,
tool; Sterne 2019). Therefore, when assessing the confidence in the including one identified during the peer review process.
evidence for QoL, by default, we downgraded by one level for risk of
bias for all comparisons. Additionally, we downgraded by another We finally included 156 studies, with a total of 7939 participants,
level for risk of bias when the effect estimates were highly affected which evaluated physical exercise for people with Parkinson's
by studies that we judged to be at high risk of bias when considering disease (PD) in this systematic review. We included 109 of these
only domains not affected by self-reporting of the outcome (i.e. studies, providing data on 4394 participants, in our network meta-
excluding domain 4 of the RoB 2 tool). analyses (NMAs).

RESULTS We report the overall numbers of references identified, screened,

selected, excluded, and included in a PRISMA flow diagram (see
Description of studies Figure 1).
Results of the search
Our literature search yielded 21,965 potentially relevant references.
Additionally, we identified 16 references via handsearching

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Figure 1.

21965 records 17 records

identified through identified through
database searching other sources

19426 records
after duplicates
removed

19426 records 16129 records

screened (initial excluded (initial
screening) screening)

3297 records 2854 records

screened excluded (double
(double-screening) screening)

32 studies
(34 references) excluded,
with reasons:

• Similar
interventions (n = 16)
• No RCT (n = 10)
314 studies (443 • No supervision or <
references) 5 supervised training
assessed for sessions (n = 3)
eligibility • Terminated (n = 2)
• Cluster RCT (n = 1)

68 studies
(77 references) awaiting
classification
58 ongoing studies (59
references)

156 studies (273

references)
included in
qualitative
synthesis

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156 studies (273

Figure 1. (Continued)
references)
included in
qualitative
synthesis

109 studies
included in
quantitative
synthesis (network
meta-analysis)

Included studies Ferrazzoli 2018; Ferreira 2018; Fietzek 2014; Fil-Balkan 2018; Fisher
2008; Frazzitta 2012; Frazzitta 2014; Frazzitta 2015; Ganesan 2014;
For a detailed description of the studies, see the Characteristics
Gao 2014; Gobbi 2021; Goodwin 2011; Gu 2013; Guan 2016; Hackney
of included studies table. Here we provide a brief overview of the
2007; Hackney 2009; Harvey 2019; Hass 2012; Hirsch 2003; Hubble
included studies.
2018; Johansson 2018; Kanegusuku 2017; King 2013; King 2020;
Published full-text articles were available for all of the 156 included Kunkel 2017; Kurt 2018; Kurtais 2008; Kwok 2019; Landers 2016;
studies. We included 151 studies whose full-text articles were Lee HJ 2018; Lehman 2005; Li 2012; Liao 2015; Liu 2016; Mak 2008;
published in English. We also included five studies not published Mak 2021; Martin 2015; Medijainen 2019; Michels 2018; Miyai 2000;
in English: four were published in Chinese (Gu 2013; Guan 2016; Miyai 2002; Morris 2009; Morris 2015; Morris 2017; Muller 1997;
Wang 2017; Zhu 2011), and one in Persian (Taheri 2011). Volunteers Mulligan 2018; Myers 2020; Nadeau 2014; Ni 2016; Nieuwboer 2007;
recruited via Cochrane's TaskExchange platform translated these Ortiz-Rubio 2018; Palmer 1986; Park 2014; Paul 2014; Pazzaglia
studies' articles. 2020; Pedreira 2013; Peloggia Cursino 2018; Pérez de la Cruz 2017;
Picelli 2016; Pohl 2013; Pohl 2020; Poier 2019; Poliakoff 2013;
We contacted study authors of 51 studies for additional Protas 2005; Qutubuddin 2013; Reuter 2011; Ribas 2017; Ridgel
information. We received a response including additional trial 2019; Rios Romenets 2015; Santos 2017a; Santos 2017b; Santos
information or outcome data from the authors of 23 studies 2017c; Santos 2019; Schaible 2021; Schenkman 1998; Schenkman
(Bridgewater 1996; Burini 2006; Capato 2020a; Carroll 2018; 2012; Schenkman 2018; Schilling 2010; Schlenstedt 2015; Schmitz-
Ebersbach 2010; Gobbi 2021; Goodwin 2011; Hackney 2009; Hubsch 2006; Sedaghati 2016; Shahmohammadi 2017; Shanahan
Johansson 2018; King 2020; Mak 2021; Morris 2009; Nieuwboer 2017; Shen 2021; Shulman 2013; Silva 2019; Silva-Batista 2018;
2007; Paul 2014; Pérez de la Cruz 2017; Pohl 2013; Pohl 2020; Silveira 2018; Smania 2010; Solla 2019; Sparrow 2016; Stack 2012;
Santos 2017a; Santos 2017b; Schenkman 2012; Schmitz-Hubsch Stozek 2016; Sujatha 2019; Szefler-Derela 2020; Szymura 2020;
2006; Terrens 2020; Yuan 2020). We received no response from Taheri 2011; Terrens 2020; Tollar 2018; Tollar 2019; Toole 2000; Van
authors of 28 studies (Agosti 2016; Arfa-Fatollahkhani 2019; Cheng Puymbroeck 2018; Vergara-Diaz 2018; Vivas 2011; Volpe 2013; Volpe
2017; Cheung 2018; Claesson 2018; Corcos 2013; Daneshvar 2019; 2014; Volpe 2017a; Volpe 2017b; Wan 2021; Wang 2017; Winward
Dashtipour 2015; Dipasquale 2017; Ferrazzoli 2018; Ferreira 2018; 2012; Wong-Yu 2015; Yang 2010; Yen 2011; Youm 2020; Yuan 2020;
Harvey 2019; Hubble 2018; Liu 2016; Pazzaglia 2020; Pedreira 2013; Zhang 2015; Zhu 2011). Ten of these trials had a cross-over design
Picelli 2016; Reuter 2011; Ribas 2017; Santos 2019; Shanahan 2017; (Burini 2006; Ellis 2005; Fietzek 2014; Gobbi 2021; King 2020; Martin
Shen 2021; Smania 2010; Sparrow 2016; Stack 2012; Sujatha 2019; 2015; Miyai 2000; Nieuwboer 2007; Sparrow 2016; Yuan 2020).
Szefler-Derela 2020; Volpe 2013).
The number of trial arms per study that were relevant to this review
Design ranged between two and four. The majority (127 studies) included
two relevant arms (Agosti 2016; Allen 2010; Amano 2013; Arfa-
We included data from 156 randomized controlled trials (RCTs) Fatollahkhani 2019; Ashburn 2007; Ashburn 2018; Avenali 2021;
(Agosti 2016; Allen 2010; Almeida 2012; Amano 2013; Arfa- Bridgewater 1996; Burini 2006; Cakit 2007; Canning 2012; Canning
Fatollahkhani 2019; Ashburn 2007; Ashburn 2018; Avenali 2021; 2015; Carroll 2018; Cherup 2021; Cheung 2018; Choi 2013; Cholewa
Bridgewater 1996; Burini 2006; Cakit 2007; Canning 2012; Canning 2013; Claesson 2018; Colgrove 2012; Conradsson 2015; Corcos
2015; Capato 2020a; Carroll 2018; Carvalho 2015; Chaiwanichsiri 2013; Cugusi 2015; Daneshvar 2019; Dashtipour 2015; da Silva
2011; Cheng 2017; Cherup 2021; Cheung 2018; Choi 2013; Cholewa Rocha Paz 2019; De Assis 2018; De Moraes Filho 2020; Dipasquale
2013; Claesson 2018; Colgrove 2012; Conradsson 2015; Corcos 2013; 2017; Duncan 2012; Ellis 2005; Feng 2019; Ferrazzoli 2018; Ferreira
Cugusi 2015; Daneshvar 2019; Dashtipour 2015; da Silva Rocha 2018; Fietzek 2014; Fil-Balkan 2018; Frazzitta 2012; Frazzitta 2014;
Paz 2019; De Assis 2018; De Moraes Filho 2020; Dipasquale 2017; Frazzitta 2015; Gao 2014; Goodwin 2011; Gu 2013; Guan 2016;
Duncan 2012; Ebersbach 2010; Ellis 2005; Feng 2019; Ferraz 2018; Hackney 2007; Harvey 2019; Hass 2012; Hirsch 2003; Hubble 2018;

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Johansson 2018; Kanegusuku 2017; King 2013; King 2020; Kunkel 2019; Kunkel 2017; Poliakoff 2013; Stack 2012; Winward 2012);
2017; Kurt 2018; Kurtais 2008; Kwok 2019; Lee HJ 2018; Lehman five studies each in Spain (Ortiz-Rubio 2018; Pérez de la Cruz
2005; Liu 2016; Mak 2021; Martin 2015; Medijainen 2019; Michels 2017; Santos 2017a; Santos 2017c; Vivas 2011), Sweden (Claesson
2018; Miyai 2000; Miyai 2002; Morris 2009; Morris 2017; Muller 1997; 2018; Conradsson 2015; Johansson 2018; Pohl 2013; Pohl 2020),
Mulligan 2018; Myers 2020; Nieuwboer 2007; Ortiz-Rubio 2018; Iran (Arfa-Fatollahkhani 2019; Daneshvar 2019; Sedaghati 2016;
Palmer 1986; Park 2014; Paul 2014; Pazzaglia 2020; Pedreira 2013; Shahmohammadi 2017; Taheri 2011), and Taiwan (Cheng 2017; Liao
Pérez de la Cruz 2017; Picelli 2016; Pohl 2013; Pohl 2020; Poier 2019; 2015; Yang 2010; Yen 2011; Yuan 2020); four studies each in Canada
Poliakoff 2013; Protas 2005; Qutubuddin 2013; Ribas 2017; Ridgel (Almeida 2012; Nadeau 2014; Rios Romenets 2015; Silveira 2018),
2019; Rios Romenets 2015; Santos 2017a; Santos 2017b; Santos Poland (Cholewa 2013; Stozek 2016; Szefler-Derela 2020; Szymura
2017c; Schaible 2021; Schenkman 1998; Schenkman 2012; Schilling 2020) and Turkey (Cakit 2007; Fil-Balkan 2018; Kurt 2018; Kurtais
2010; Schlenstedt 2015; Schmitz-Hubsch 2006; Shahmohammadi 2008); three studies each in Hong Kong (Kwok 2019; Mak 2008; Mak
2017; Shanahan 2017; Shen 2021; Silva 2019; Smania 2010; Solla 2021) and Korea (Choi 2013; Lee HJ 2018; Youm 2020); and two
2019; Sparrow 2016; Stack 2012; Stozek 2016; Sujatha 2019; studies each in Hungary (Tollar 2018; Tollar 2019), India (Ganesan
Szefler-Derela 2020; Szymura 2020; Taheri 2011; Toole 2000; Van 2014; Sujatha 2019), Ireland (Carroll 2018; Shanahan 2017), Japan
Puymbroeck 2018; Vergara-Diaz 2018; Vivas 2011; Volpe 2013; Volpe (Miyai 2000; Miyai 2002) and New Zealand (Martin 2015; Mulligan
2014; Volpe 2017a; Volpe 2017b; Wan 2021; Wang 2017; Winward 2018). One study each was conducted in Belgium (Nieuwboer 2007),
2012; Wong-Yu 2015; Yang 2010; Youm 2020; Yuan 2020; Zhang 2015; Estonia (Medijainen 2019), the Netherlands (Capato 2020a), and
Zhu 2011). Twenty-eight studies included three arms (Almeida Thailand (Chaiwanichsiri 2011), and one study was conducted in
2012; Capato 2020a; Carvalho 2015; Chaiwanichsiri 2011; Cheng the Netherlands and the USA (Ellis 2005).
2017; Ebersbach 2010; Ferraz 2018; Fisher 2008; Ganesan 2014;
Gobbi 2021; Li 2012; Liao 2015; Mak 2008; Morris 2015; Nadeau Of the included studies, 139 were conducted in single centers
2014; Ni 2016; Peloggia Cursino 2018; Reuter 2011; Santos 2019; and 15 studies were conducted at multiple centers (Ashburn
Schenkman 2018; Sedaghati 2016; Shulman 2013; Silva-Batista 2007; Ashburn 2018; Ellis 2005; Goodwin 2011; Kwok 2019; Morris
2018; Silveira 2018; Terrens 2020; Tollar 2018; Tollar 2019; Yen 2011), 2015; Nieuwboer 2007; Paul 2014; Poliakoff 2013; Santos 2017a;
and two studies included four arms of interest (Hackney 2009; Schenkman 1998; Schenkman 2012; Shanahan 2017; Volpe 2017a;
Landers 2016). Zhu 2011). For two studies (Reuter 2011; Sedaghati 2016), it was not
clear whether they were conducted in a single center or in multiple
Sample sizes centers.
The number of randomized participants ranged between 10 in Miyai The exercise intervention did not include a home-based
2000 to 474 in Ashburn 2018, with a mean number of 51 participants component in the majority of studies (122 studies: Agosti 2016;
randomized per study. For the studies included in the network Almeida 2012; Amano 2013; Arfa-Fatollahkhani 2019; Bridgewater
meta-analysis, data were provided for a mean number of 21 1996; Burini 2006; Cakit 2007; Capato 2020a; Carroll 2018; Carvalho
participants per trial arm, ranging from between four participants 2015; Cheng 2017; Cheung 2018; Conradsson 2015; Corcos 2013;
in Michels 2018 to 115 participants in Canning 2015 per trial arm. Cugusi 2015; Dashtipour 2015; da Silva Rocha Paz 2019; De Assis
2018; Dipasquale 2017; Duncan 2012; Ebersbach 2010; Ellis 2005;
Location
Feng 2019; Ferraz 2018; Ferrazzoli 2018; Ferreira 2018; Fietzek
Most studies were conducted in the USA (34 studies: Amano 2013; 2014; Fil-Balkan 2018; Fisher 2008; Frazzitta 2012; Frazzitta 2014;
Cherup 2021; Cheung 2018; Colgrove 2012; Corcos 2013; Dashtipour Frazzitta 2015; Ganesan 2014; Gao 2014; Guan 2016; Hackney 2007;
2015; Duncan 2012; Fisher 2008; Hackney 2007; Hackney 2009; Hass Hackney 2009; Harvey 2019; Hass 2012; Hirsch 2003; Hubble 2018;
2012; Hirsch 2003; King 2013; King 2020; Landers 2016; Lehman Kanegusuku 2017; King 2013; Kunkel 2017; Kurt 2018; Landers 2016;
2005; Li 2012; Michels 2018; Myers 2020; Ni 2016; Palmer 1986; Lehman 2005; Li 2012; Liao 2015; Liu 2016; Mak 2008; Medijainen
Park 2014; Protas 2005; Qutubuddin 2013; Ridgel 2019; Schenkman 2019; Michels 2018; Miyai 2000; Miyai 2002; Morris 2009; Muller 1997;
1998; Schenkman 2012; Schenkman 2018; Schilling 2010; Shulman Mulligan 2018; Myers 2020; Nadeau 2014; Ni 2016; Nieuwboer 2007;
2013; Sparrow 2016; Toole 2000; Van Puymbroeck 2018; Vergara- Ortiz-Rubio 2018; Palmer 1986; Park 2014; Paul 2014; Pazzaglia
Diaz 2018), followed by Italy (17 studies: Agosti 2016; Avenali 2020; Pedreira 2013; Peloggia Cursino 2018; Pérez de la Cruz 2017;
2021; Burini 2006; Cugusi 2015; Dipasquale 2017; Ferrazzoli 2018; Picelli 2016; Pohl 2013; Pohl 2020; Poier 2019; Poliakoff 2013;
Frazzitta 2012; Frazzitta 2014; Frazzitta 2015; Pazzaglia 2020; Picelli Protas 2005; Qutubuddin 2013; Reuter 2011; Ribas 2017; Ridgel
2016; Smania 2010; Solla 2019; Volpe 2013; Volpe 2014; Volpe 2019; Santos 2017a; Santos 2017b; Santos 2017c; Santos 2019;
2017a; Volpe 2017b), Brazil (15 studies: Carvalho 2015; da Silva Schenkman 1998; Schenkman 2012; Schenkman 2018; Schilling
Rocha Paz 2019; De Assis 2018; De Moraes Filho 2020; Ferraz 2010; Schlenstedt 2015; Schmitz-Hubsch 2006; Sedaghati 2016;
2018; Ferreira 2018; Gobbi 2021; Kanegusuku 2017; Pedreira 2013; Shahmohammadi 2017; Shen 2021; Shulman 2013; Silva 2019;
Peloggia Cursino 2018; Ribas 2017; Santos 2017b; Santos 2019; Silva-Batista 2018; Silveira 2018; Smania 2010; Solla 2019; Sparrow
Silva 2019; Silva-Batista 2018), China (11 studies: Feng 2019; 2016; Stack 2012; Stozek 2016; Sujatha 2019; Szefler-Derela 2020;
Gao 2014; Gu 2013; Guan 2016; Liu 2016; Shen 2021; Wan 2021; Szymura 2020; Taheri 2011; Terrens 2020; Tollar 2018; Toole 2000;
Wang 2017; Wong-Yu 2015; Zhang 2015; Zhu 2011), Australia (10 Van Puymbroeck 2018; Vivas 2011; Volpe 2014; Volpe 2017a; Volpe
studies: Allen 2010; Bridgewater 1996; Canning 2012; Canning 2015; 2017b; Wan 2021; Wang 2017; Winward 2012; Yang 2010; Yen 2011;
Hubble 2018; Morris 2009; Morris 2015; Morris 2017; Park 2014; Youm 2020; Yuan 2020; Zhang 2015). The exercise intervention
Terrens 2020). Eight studies each were conducted in Germany was conducted at home or had a home-based component in 29
(Ebersbach 2010; Fietzek 2014; Muller 1997; Poier 2019; Reuter studies (Allen 2010; Ashburn 2007; Ashburn 2018; Canning 2012;
2011; Schaible 2021; Schlenstedt 2015; Schmitz-Hubsch 2006) and Canning 2015; Chaiwanichsiri 2011; Choi 2013; Cholewa 2013;
the UK (Ashburn 2007; Ashburn 2018; Goodwin 2011; Harvey Claesson 2018; Colgrove 2012; Goodwin 2011; Gu 2013; Johansson

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2018; Kurtais 2008; Kwok 2019; Lee HJ 2018; Mak 2021; Martin Tollar 2018; Tollar 2019; Van Puymbroeck 2018; Vivas 2011; Volpe
2015; Morris 2015; Morris 2017; Nieuwboer 2007; Schaible 2021; 2013; Volpe 2014; Volpe 2017a; Wan 2021; Wang 2017; Wong-Yu
Shanahan 2017; Stack 2012; Tollar 2019; Vergara-Diaz 2018; Volpe 2015; Yen 2011; Youm 2020; Yuan 2020; Zhang 2015);
2013; Wong-Yu 2015; Zhu 2011). Whether a home-based component • 27 studies included people without cognitive impairment, or
was included was unclear for five studies (Avenali 2021; Cherup with mild cognitive impairment, or both (Ashburn 2007; Cakit
2021; Daneshvar 2019; De Moraes Filho 2020; Gobbi 2021). 2007; Carvalho 2015; Choi 2013; Claesson 2018; De Assis 2018;
De Moraes Filho 2020; Fietzek 2014; Johansson 2018; King 2013;
Participants King 2020; Kurtais 2008; Kwok 2019; Lee HJ 2018; Michels
The 156 studies included in our review represented adults (≥ 18 2018; Muller 1997; Pedreira 2013; Poier 2019; Poliakoff 2013;
years of age) with a confirmed diagnosis of idiopathic PD. Protas 2005; Qutubuddin 2013; Ribas 2017; Rios Romenets 2015;
Shanahan 2017; Silva 2019; Silveira 2018; Stack 2012);
The age of the participants, reported as mean or median, ranged • one study included people with mild cognitive impairment
between 59.9 years in Park 2014 to 74 years in Stack 2012. (Avenali 2021);
Three studies included only men (Chaiwanichsiri 2011; Protas • six studies included people for whom the cognitive stage ranged
2005; Shahmohammadi 2017). The remaining 153 studies included from no cognitive impairment to suspected dementia (Harvey
women and men. For these studies, the proportion of men ranged 2019; Kunkel 2017; Picelli 2016; Pohl 2020; Schlenstedt 2015;
between 31% in Mak 2021 to 90% in Agosti 2016. More men than Volpe 2017b);
women were included in the majority of studies (77%) which may • for 23 studies, we were not able to make a judgment on the
reflect the increased risk of men developing PD. participants' cognitive stage (Almeida 2012; Bridgewater 1996;
Carroll 2018; Cherup 2021; Daneshvar 2019; da Silva Rocha
Based on a judgment we derived from the inclusion criteria and Paz 2019; Duncan 2012; Ferrazzoli 2018; Goodwin 2011; Hass
cognitive screening results that were reported by the study authors, 2012; Hirsch 2003; Kanegusuku 2017; Palmer 1986; Park 2014;
for most of the studies, the samples were limited to people without Pohl 2013; Ridgel 2019; Stozek 2016; Sujatha 2019; Toole 2000;
severe cognitive impairment or dementia: Vergara-Diaz 2018; Winward 2012; Yang 2010; Zhu 2011).

• 99 studies included people without cognitive impairment The disease severity, assessed with the original or modified Hoehn
(Agosti 2016; Allen 2010; Amano 2013; Arfa-Fatollahkhani 2019; and Yahr scale (HY, Hoehn 1967), ranged between one and four.
Ashburn 2018; Burini 2006; Canning 2012; Canning 2015; Capato Participants with HY stages that ranged beyond stage three were
2020a; Chaiwanichsiri 2011; Cheng 2017; Cheung 2018; Cholewa included in 17 studies (Ashburn 2007; Ashburn 2018; Canning 2015;
2013; Colgrove 2012; Conradsson 2015; Corcos 2013; Cugusi Gao 2014; King 2013; Landers 2016; Li 2012; Mak 2008; Morris
2015; Dashtipour 2015; Dipasquale 2017; Ebersbach 2010; Ellis 2015; Morris 2017; Nieuwboer 2007; Pohl 2013; Schmitz-Hubsch
2005; Feng 2019; Ferraz 2018; Ferreira 2018; Fil-Balkan 2018; 2006; Smania 2010; Stack 2012; Wan 2021; Winward 2012). In 11
Fisher 2008; Frazzitta 2012; Frazzitta 2014; Frazzitta 2015; studies (Allen 2010; Almeida 2012; Liu 2016; Mulligan 2018; Palmer
Ganesan 2014; Gao 2014; Gobbi 2021; Gu 2013; Guan 2016; 1986; Pazzaglia 2020; Poier 2019; Poliakoff 2013; Qutubuddin 2013;
Hackney 2007; Hackney 2009; Hubble 2018; Kurt 2018; Landers Silveira 2018; Sujatha 2019), HY stages were not reported.
2016; Lehman 2005; Li 2012; Liao 2015; Liu 2016; Mak 2008;
Mak 2021; Martin 2015; Medijainen 2019; Miyai 2000; Miyai 2002; The mean or median duration of disease of the participants, which
Morris 2009; Morris 2015; Morris 2017; Mulligan 2018; Myers 2020; was usually reported at study arm-level as years since diagnosis
Nadeau 2014; Ni 2016; Nieuwboer 2007; Ortiz-Rubio 2018; Paul of PD, ranged between 0.3 years in Schenkman 2018 ("time since
2014; Pazzaglia 2020; Peloggia Cursino 2018; Pérez de la Cruz diagnosis") to 13.3 years in Fietzek 2014 ("disease duration", not
2017; Reuter 2011; Santos 2017a; Santos 2017b; Santos 2017c; further specified).
Santos 2019; Schaible 2021; Schenkman 1998; Schenkman
2012; Schenkman 2018; Schilling 2010; Schmitz-Hubsch 2006; Interventions
Sedaghati 2016; Shahmohammadi 2017; Shen 2021; Shulman For details on the categories of interventions and control groups,
2013; Silva-Batista 2018; Smania 2010; Solla 2019; Sparrow 2016; please see Appendix 1. The network graph of the ideal network
Szefler-Derela 2020; Szymura 2020; Taheri 2011; Terrens 2020; comparing all interventions is displayed in Figure 2.

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Figure 2. Overview of the ideal network

The studies included in our review comprised the following types 2017b; Wang 2017; Wong-Yu 2015; Yang 2010; Yen 2011; Yuan
of physical exercise: 2020);
• gaming (5 studies: Ferraz 2018; Pazzaglia 2020; Pedreira 2013;
• aqua-based training (11 studies: Carroll 2018; De Assis 2018; Kurt Santos 2019; Zhu 2011);
2018; Pérez de la Cruz 2017; Shahmohammadi 2017; Silva 2019;
Vivas 2011; Volpe 2014; Volpe 2017a; Volpe 2017b; Wang 2017); • LSVT BIG (3 studies: Dashtipour 2015; Ebersbach 2010; Schaible
2021);
• dance (13 studies: Duncan 2012; Hackney 2007; Hackney 2009;
Kunkel 2017; Michels 2018; Pohl 2013; Pohl 2020; Poier 2019; Rios • mind-body training (23 studies: Amano 2013; Burini 2006;
Cherup 2021; Cheung 2018; Choi 2013; Colgrove 2012; Guan
Romenets 2015; Shanahan 2017; Solla 2019; Terrens 2020; Volpe
2016; Hackney 2009; Kwok 2019; Lee HJ 2018; Li 2012; Liu 2016;
2013);
Myers 2020; Ni 2016; Palmer 1986; Poier 2019; Schmitz-Hubsch
• endurance training (20 studies: Arfa-Fatollahkhani 2019; Burini 2006; Shen 2021; Van Puymbroeck 2018; Vergara-Diaz 2018; Wan
2006; Cakit 2007; Canning 2012; Carvalho 2015; Cugusi 2015; da 2021; Zhang 2015; Zhu 2011);
Silva Rocha Paz 2019; Daneshvar 2019; Ebersbach 2010; Ferraz
2018; Fisher 2008; Mak 2021; Nadeau 2014; Reuter 2011; Ridgel • multi-domain training (60 studies: Ashburn 2007; Avenali 2021;
Bridgewater 1996; Carvalho 2015; Cheng 2017; Cholewa 2013;
2019; Schenkman 2018; Silveira 2018; Sujatha 2019; Szefler-
Corcos 2013; da Silva Rocha Paz 2019; Dashtipour 2015;
Derela 2020; Tollar 2018);
Dipasquale 2017; Ellis 2005; Feng 2019; Ferrazzoli 2018; Fil-
• flexibility (10 studies: Agosti 2016; Li 2012; Palmer 1986; Peloggia Balkan 2018; Fisher 2008; Frazzitta 2012; Frazzitta 2014; Frazzitta
Cursino 2018; Qutubuddin 2013; Reuter 2011; Ridgel 2019; 2015; Gao 2014; Gobbi 2021; Goodwin 2011; Hackney 2007;
Schenkman 2012; Shen 2021; Taheri 2011); Hirsch 2003; King 2013; King 2020; Kurt 2018; Kwok 2019; Liao
• gait/balance/functional training (58 studies: Allen 2010; 2015; Mak 2008; Medijainen 2019; Miyai 2000; Miyai 2002; Morris
Almeida 2012; Ashburn 2018; Canning 2015; Capato 2020a; 2009; Morris 2017; Mulligan 2018; Nadeau 2014; Park 2014;
Chaiwanichsiri 2011; Cheng 2017; Cherup 2021; Claesson 2018; Pedreira 2013; Pérez de la Cruz 2017; Poliakoff 2013; Ribas
Conradsson 2015; Daneshvar 2019; Dipasquale 2017; Feng 2019; 2017; Santos 2019; Schaible 2021; Schenkman 1998; Schenkman
Ferraz 2018; Fietzek 2014; Fil-Balkan 2018; Ganesan 2014; Gobbi 2012; Shulman 2013; Silveira 2018; Smania 2010; Sujatha 2019;
2021; Gu 2013; Hirsch 2003; Hubble 2018; Johansson 2018; Szefler-Derela 2020; Terrens 2020; Tollar 2019; Toole 2000; Vivas
King 2013; Kurtais 2008; Landers 2016; Lehman 2005; Mak 2008; 2011; Volpe 2013; Volpe 2017a; Winward 2012; Yang 2010; Youm
Martin 2015; Miyai 2000; Miyai 2002; Morris 2009; Morris 2015; 2020; Zhang 2015);
Muller 1997; Nieuwboer 2007; Pazzaglia 2020; Peloggia Cursino • strength/resistance training (17 studies: Carvalho 2015; Corcos
2018; Picelli 2016; Protas 2005; Ribas 2017; Santos 2017b; Santos 2013; De Moraes Filho 2020; Ferreira 2018; Harvey 2019; Hass
2017c; Schlenstedt 2015; Sedaghati 2016; Shahmohammadi 2012; Kanegusuku 2017; Li 2012; Morris 2015; Ni 2016; Ortiz-
2017; Shulman 2013; Smania 2010; Sparrow 2016; Stack 2012; Rubio 2018; Paul 2014; Santos 2017a; Santos 2017b; Schilling
Stozek 2016; Szymura 2020; Tollar 2018; Volpe 2014; Volpe 2010; Schlenstedt 2015; Silva-Batista 2018).

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These interventions were compared to another type of physical 2012; Corcos 2013; Cugusi 2015; da Silva Rocha Paz 2019; De Assis
exercise or, as specified below, to an active control group or a 2018; Ebersbach 2010; Ellis 2005; Feng 2019; Fil-Balkan 2018; Fisher
passive control group: 2008; Frazzitta 2014; Ganesan 2014; Gao 2014; Gu 2013; Hackney
2007; Hackney 2009; Kurt 2018; Lee HJ 2018; Miyai 2002; Morris
• active control group (13 studies: Capato 2020a; Chaiwanichsiri 2015; Muller 1997; Ni 2016; Park 2014; Pérez de la Cruz 2017;
2011; Fisher 2008; Gobbi 2021; Johansson 2018; King 2020; Mak Pohl 2013; Poliakoff 2013; Qutubuddin 2013; Reuter 2011; Ridgel
2021; Michels 2018; Morris 2015; Morris 2017; Muller 1997; Ortiz- 2019; Santos 2017b; Schaible 2021; Schenkman 2012; Schlenstedt
Rubio 2018; Wong-Yu 2015); 2015; Schmitz-Hubsch 2006; Shen 2021; Shulman 2013; Solla 2019;
• passive control group (91 studies: Agosti 2016; Allen 2010; Terrens 2020; Vergara-Diaz 2018; Volpe 2013; Volpe 2014; Volpe
Almeida 2012; Amano 2013; Arfa-Fatollahkhani 2019; Ashburn 2017a; Volpe 2017b; Wang 2017; Youm 2020; Zhang 2015; Zhu 2011).
2007; Ashburn 2018; Avenali 2021; Bridgewater 1996; Cakit 2007; Twelve studies reported data on the motor score of the Movement
Canning 2012; Canning 2015; Carroll 2018; Cheung 2018; Choi Disorder Society-Sponsored Revision of the Unified Parkinson’s
2013; Cholewa 2013; Claesson 2018; Colgrove 2012; Conradsson Disease Rating Scale (MDS-UPDRS-M, Goetz 2008) (Avenali 2021;
2015; Cugusi 2015; De Assis 2018; De Moraes Filho 2020; Duncan Duncan 2012; King 2020; Kwok 2019; Mak 2021; Michels 2018; Morris
2012; Ebersbach 2010; Ellis 2005; Ferrazzoli 2018; Ferreira 2017; Nadeau 2014; Rios Romenets 2015; Santos 2017a; Schenkman
2018; Fietzek 2014; Frazzitta 2012; Frazzitta 2014; Frazzitta 2018; Van Puymbroeck 2018). Two studies reported data on the
2015; Ganesan 2014; Gao 2014; Goodwin 2011; Gu 2013; Guan 14-item version of the UPDRS-M (Cheng 2017; Li 2012). One study
2016; Hackney 2009; Harvey 2019; Hass 2012; Hubble 2018; reported data on the Hoehn and Yahr scale (HY, Hoehn 1967)
Kanegusuku 2017; Kunkel 2017; Kurtais 2008; Landers 2016; (Smania 2010). Fifty-one studies reported the severity of motor
Lee HJ 2018; Lehman 2005; Liao 2015; Liu 2016; Mak 2008; signs during the on-medication state (Almeida 2012; Amano 2013;
Martin 2015; Medijainen 2019; Mulligan 2018; Myers 2020; Ni Avenali 2021; Burini 2006; Canning 2012; Capato 2020a; Carroll
2016; Nieuwboer 2007; Park 2014; Paul 2014; Picelli 2016; Pohl 2018; Cheng 2017; Cholewa 2013; Cugusi 2015; De Assis 2018;
2013; Pohl 2020; Poliakoff 2013; Protas 2005; Qutubuddin 2013; Ebersbach 2010; Ellis 2005; Feng 2019; Fisher 2008; Frazzitta 2014;
Rios Romenets 2015; Santos 2017a; Santos 2017c; Schenkman Ganesan 2014; Gu 2013; Hackney 2007; Hackney 2009; Kurt 2018;
1998; Schenkman 2018; Schilling 2010; Schmitz-Hubsch 2006; Kwok 2019; Lee HJ 2018; Li 2012; Mak 2021; Michels 2018; Miyai
Sedaghati 2016; Shanahan 2017; Silva 2019; Silva-Batista 2018; 2002; Morris 2015; Morris 2017; Muller 1997; Ni 2016; Pohl 2013;
Silveira 2018; Solla 2019; Sparrow 2016; Stack 2012; Stozek 2016; Poliakoff 2013; Qutubuddin 2013; Ridgel 2019; Rios Romenets 2015;
Szymura 2020; Taheri 2011; Tollar 2018; Tollar 2019; Toole 2000; Santos 2017a; Santos 2017b; Schaible 2021; Schenkman 2012;
Van Puymbroeck 2018; Vergara-Diaz 2018; Wan 2021; Winward Schlenstedt 2015; Schmitz-Hubsch 2006; Shen 2021; Shulman 2013;
2012; Yen 2011; Youm 2020; Yuan 2020). Smania 2010; Solla 2019; Terrens 2020; Volpe 2014; Volpe 2017a;
Youm 2020; Zhang 2015). Five studies reported the outcome during
For three studies (Santos 2019; Schaible 2021; Schenkman 2012), the off-medication state (Duncan 2012; King 2020; Pérez de la Cruz
we did not include all study arms in our analyses. They included 2017; Schenkman 2018; Vergara-Diaz 2018). One study provided
treatments that did not fulfill the criteria for being categorized as an data for both the on- and off-medication states (Corcos 2013). The
eligible intervention or comparator as clearly as other interventions timing of assessment relative to the medication state was unclear
of the same (potential) category (e.g. in terms of the components of for 14 studies (Carvalho 2015; Choi 2013; Colgrove 2012; da Silva
the training or the degree of supervision). We excluded these study Rocha Paz 2019; Fil-Balkan 2018; Gao 2014; Nadeau 2014; Park 2014;
arms from our analyses in order to preserve homogeneity within Reuter 2011; Van Puymbroeck 2018; Volpe 2013; Volpe 2017b; Wang
our categories (for details, see Characteristics of included studies). 2017; Zhu 2011).
The length of intervention ranged between two weeks (Fietzek Quality of life
2014; Lehman 2005; Morris 2009) and two years (Corcos 2013; Tollar
2019), with a mean length of 11.9 weeks. Quality of life (QoL) was reported in 55 studies. Fifty studies
reported data on the Parkinson’s Disease Questionnaire 39
The duration of a single training session ranged between 15 (PDQ-39, Jenkinson 1997b; Peto 1995) (Allen 2010; Amano 2013;
minutes (Shulman 2013; duration increased over the course of the Ashburn 2018; Burini 2006; Canning 2012; Canning 2015; Carroll
intervention) and two hours (Morris 2015; Stozek 2016; Wong-Yu 2018; Cheng 2017; Cholewa 2013; Corcos 2013; Daneshvar 2019;
2015). Ferraz 2018; Ferrazzoli 2018; Ferreira 2018; Gobbi 2021; Johansson
2018; King 2020; Kunkel 2017; Liao 2015; Michels 2018; Morris
Outcomes 2009; Morris 2015; Morris 2017; Nadeau 2014; Ni 2016; Nieuwboer
2007; Pedreira 2013; Peloggia Cursino 2018; Pohl 2013; Pohl 2020;
Of the 156 studies included in our review, 109 studies reported
Poier 2019; Poliakoff 2013; Qutubuddin 2013; Rios Romenets 2015;
data we included in our network meta-analyses. Eighty-five studies
Santos 2017a; Santos 2017b; Schaible 2021; Schenkman 2012;
provided information on adverse events. All outcomes included in
Schlenstedt 2015; Schmitz-Hubsch 2006; Shulman 2013; Terrens
our network meta-analysis were assessed shortly (≤ six weeks) after
2020; Tollar 2018; Tollar 2019; Vergara-Diaz 2018; Volpe 2013;
the intervention.
Volpe 2014; Volpe 2017a; Volpe 2017b; Winward 2012). Two studies
Severity of motor signs reported data on the Parkinson's Disease Questionnaire 8, i.e. the
short-form of the PDQ-39 (PDQ-8, Jenkinson 1997a) (Kwok 2019;
The severity of motor signs was reported in 71 studies. Of these, Li 2012). Two studies reported data on the Parkinson’s Disease
56 studies reported data on the motor score of the Unified Quality of Life Questionnaire (PDQ-L, De Boer 1996) (Lee HJ 2018;
Parkinson's Disease Rating Scale (UPDRS-M, Fahn 1987) (Almeida Shahmohammadi 2017). One study reported data on the EuroQol
2012; Amano 2013; Burini 2006; Canning 2012; Capato 2020a; (EQ-5D) questionnaire (EuroQol Group 1990) (Goodwin 2011).
Carroll 2018; Carvalho 2015; Choi 2013; Cholewa 2013; Colgrove

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Freezing of gait some studies certain harms were described as adverse events,
Freezing of gait was reported in 20 studies. Sixteen studies reported in other studies, the same harms were recorded as reasons for
data on the Freezing of Gait Questionnaire (FOG-Q, Giladi 2000) dropout (i.e. narratively or in a flow chart) instead of adverse
(Allen 2010; Canning 2015; Carroll 2018; Cheng 2017; Duncan 2012; events. Furthermore, few studies provided data that were available
Hackney 2007; Hackney 2009; Medijainen 2019; Nieuwboer 2007; for, and reported separately by, all trial arms. In particular, the
Pohl 2020; Rios Romenets 2015; Santos 2017a; Santos 2017c; documentation of adverse events in control groups was often
Schlenstedt 2015; Van Puymbroeck 2018; Volpe 2013). Four studies missing or reduced in comparison to the report of adverse events
reported data on the New Freezing of Gait Questionnaire (NFOG-Q, in experimental groups. Therefore, conducting a quantitative
Nieuwboer 2009) (Capato 2020a; King 2020; Martin 2015; Paul 2014). synthesis on the number of participants with any adverse event
using a network meta-analysis was not possible. As a result, we
Functional mobility and balance provide a narrative report of the data on adverse events.
Functional mobility and balance was reported in 54 studies. Fifty- Conflicts of interest
three studies reported data on the Timed Up and Go test (TUG,
Podsiadlo 1991), which measures time taken in seconds for a Exclusively non-commercial funding sources were reported in
person to get up from a chair, walk a certain distance (usually 92 studies (Agosti 2016; Allen 2010; Almeida 2012; Amano
three meters), turn around, and walk back to the chair and 2013; Ashburn 2007; Ashburn 2018; Avenali 2021; Bridgewater
sit down (Almeida 2012; Arfa-Fatollahkhani 2019; Capato 2020a; 1996; Canning 2012; Canning 2015; Capato 2020a; Chaiwanichsiri
Chaiwanichsiri 2011; Cheng 2017; Cherup 2021; Choi 2013; Corcos 2011; Cheng 2017; Cheung 2018; Claesson 2018; Colgrove 2012;
2013; Cugusi 2015; da Silva Rocha Paz 2019; De Moraes Filho 2020; Conradsson 2015; Corcos 2013; Daneshvar 2019; Duncan 2012;
Ebersbach 2010; Feng 2019; Ferreira 2018; Fil-Balkan 2018; Gao Ebersbach 2010; Feng 2019; Fietzek 2014; Fisher 2008; Gobbi 2021;
2014; Guan 2016; Hackney 2007; Hackney 2009; Kunkel 2017; Kurt Goodwin 2011; Gu 2013; Hackney 2007; Hackney 2009; Hubble
2018; Kwok 2019; Li 2012; Liao 2015; Liu 2016; Mak 2021; Michels 2018; Johansson 2018; Kanegusuku 2017; King 2013; King 2020;
2018; Morris 2009; Morris 2015; Ni 2016; Nieuwboer 2007; Paul Kunkel 2017; Kurt 2018; Kwok 2019; Landers 2016; Lee HJ 2018; Li
2014; Pérez de la Cruz 2017; Pohl 2013; Ridgel 2019; Rios Romenets 2012; Liao 2015; Mak 2021; Medijainen 2019; Miyai 2000; Miyai 2002;
2015; Santos 2019; Schilling 2010; Schlenstedt 2015; Sedaghati Morris 2015; Morris 2017; Muller 1997; Myers 2020; Nadeau 2014;
2016; Shen 2021; Shulman 2013; Silva 2019; Solla 2019; Tollar 2019; Nieuwboer 2007; Park 2014; Paul 2014; Pedreira 2013; Pohl 2013;
Vergara-Diaz 2018; Volpe 2014; Volpe 2017a; Volpe 2017b; Wan Pohl 2020; Poier 2019; Poliakoff 2013; Rios Romenets 2015; Santos
2021; Wang 2017; Wong-Yu 2015; Zhang 2015). One study reported 2017a; Santos 2017b; Santos 2019; Schenkman 1998; Schenkman
data on the TUG with a distance of 2.44 meters to be covered (Youm 2012; Schenkman 2018; Schlenstedt 2015; Schmitz-Hubsch 2006;
2020). Shanahan 2017; Shen 2021; Shulman 2013; Silva 2019; Silva-
Batista 2018; Silveira 2018; Smania 2010; Solla 2019; Sparrow 2016;
Adverse events (number of participants with any adverse event) Stack 2012; Szymura 2020; Tollar 2018; Tollar 2019; Toole 2000;
Van Puymbroeck 2018; Vergara-Diaz 2018; Vivas 2011; Wan 2021;
Of the 156 included studies, 85 studies provided information
Winward 2012; Wong-Yu 2015; Yang 2010; Yen 2011; Youm 2020;
on adverse events (i.e. occurrence or absence) (Allen 2010;
Yuan 2020; Zhang 2015).
Ashburn 2007; Ashburn 2018; Canning 2012; Canning 2015; Cakit
2007; Capato 2020a; Carroll 2018; Chaiwanichsiri 2011; Cheng Four studies were funded or supported (i.e. provision of equipment
2017; Cherup 2021; Cheung 2018; Claesson 2018; Colgrove 2012; or facilities) by a commercial entity (Harvey 2019, "Speedflex
Conradsson 2015; Corcos 2013; Cugusi 2015; Dashtipour 2015; Europe Ltd"; Pazzaglia 2020, "BTS Spa, Garbagnate Milanese";
Dipasquale 2017; Ferraz 2018; Fietzek 2014; Fisher 2008; Frazzitta Schilling 2010, "Life Fitness, Inc"; Terrens 2020, "Lee Silverman
2015; Ganesan 2014; Gao 2014; Goodwin 2011; Hackney 2009; Voice Treatment small student grant").
Harvey 2019; Hass 2012; Hubble 2018; Johansson 2018; King 2013;
King 2020; Kunkel 2017; Kwok 2019; Lee HJ 2018; Li 2012; Liao In one study, funding sources included an association of
2015; Mak 2021; Martin 2015; Michels 2018; Morris 2009; Morris physiotherapists (Martin 2015, "Physiotherapy New Zealand’s Older
2015; Morris 2017; Myers 2020; Nadeau 2014; Ni 2016; Nieuwboer Adult and Neurology Special Interest Groups").
2007; Ortiz-Rubio 2018; Park 2014; Paul 2014; Pérez de la Cruz
2017; Picelli 2016; Pohl 2013; Pohl 2020; Poier 2019; Poliakoff In 17 studies, it was explicitly reported that no specific funding
2013; Reuter 2011; Ribas 2017; Rios Romenets 2015; Santos 2017a; or financial support was received (Cherup 2021; Fil-Balkan 2018;
Schaible 2021; Schenkman 1998; Schenkman 2012; Schenkman Frazzitta 2012; Frazzitta 2014; Frazzitta 2015; Gao 2014; Ni
2018; Sedaghati 2016; Shanahan 2017; Shulman 2013; Silva-Batista 2016; Ortiz-Rubio 2018; Pérez de la Cruz 2017; Schaible 2021;
2018; Smania 2010; Solla 2019; Sparrow 2016; Szefler-Derela 2020; Shahmohammadi 2017; Smania 2010; Szefler-Derela 2020; Volpe
Terrens 2020;Tollar 2018; Tollar 2019; Vergara-Diaz 2018; Volpe 2014; Volpe 2017a), or no funding sources were declared (Arfa-
2013; Volpe 2014; Volpe 2017b; Wong-Yu 2015; Yang 2010; Yen 2011; Fatollahkhani 2019, "none declared"; Michels 2018, "N/A"; Peloggia
Yuan 2020; Zhang 2015). Cursino 2018, "nothing to declare").

Adverse events were measured and reported heterogeneously. The Forty-two studies provided no information on funding sources
reports varied, for example, in the selection and specification of (Arfa-Fatollahkhani 2019; Burini 2006; Cakit 2007; Carroll 2018;
adverse event, in the way the events were counted (i.e. report Carvalho 2015; Choi 2013; Cholewa 2013; Cugusi 2015; Dashtipour
of the number of events or report of the number of participants 2015; da Silva Rocha Paz 2019; De Assis 2018; De Moraes Filho 2020;
with adverse events), and in the timing of their assessment Dipasquale 2017; Ellis 2005; Ferraz 2018; Ferrazzoli 2018; Ferreira
(i.e. collection of data only during delivery of the intervention 2018; Ganesan 2014; Guan 2016; Hass 2012; Hirsch 2003; Kurtais
or during the whole course of the study). Moreover, while in 2008; Lehman 2005; Liu 2016; Mak 2008; Morris 2009; Mulligan 2018;

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 23
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
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Picelli 2016; Protas 2005; Qutubuddin 2013; Reuter 2011; Ribas reviewed and managed by the Brigham and Women’s Hospital
2017; Ridgel 2019; Santos 2017c; Sedaghati 2016; Stozek 2016; and Partner’s HealthCare in accordance with their conflict of
Sujatha 2019; Taheri 2011; Volpe 2013; Volpe 2017b; Wang 2017; Zhu interest policies".
2011).
Forty-seven studies provided no information on conflicts of interest
In 90 studies, the authors declared that there were no conflicts (Amano 2013; Arfa-Fatollahkhani 2019; Bridgewater 1996; Burini
of interest (Agosti 2016; Almeida 2012; Ashburn 2007; Avenali 2006; Cakit 2007; Capato 2020a; Carroll 2018; Choi 2013; Colgrove
2021; Canning 2012; Carvalho 2015; Chaiwanichsiri 2011; Cheng 2012; Cugusi 2015; da Silva Rocha Paz 2019; Ellis 2005; Feng 2019;
2017; Cherup 2021; Cheung 2018; Cholewa 2013; Claesson 2018; Ferreira 2018; Gu 2013; Guan 2016; Hackney 2007; Hackney 2009;
Conradsson 2015; Daneshvar 2019; Dashtipour 2015; De Assis King 2013; Kurtais 2008; Lee HJ 2018; Lehman 2005; Mak 2008;
2018; De Moraes Filho 2020; Dipasquale 2017; Duncan 2012; Ferraz Muller 1997; Palmer 1986; Park 2014; Pedreira 2013; Picelli 2016;
2018; Ferrazzoli 2018; Fietzek 2014; Fil-Balkan 2018; Fisher 2008; Poliakoff 2013; Protas 2005; Reuter 2011; Ribas 2017; Schenkman
Frazzitta 2012; Frazzitta 2014; Frazzitta 2015; Ganesan 2014; Gao 1998; Schenkman 2012; Schilling 2010; Schmitz-Hubsch 2006;
2014; Gobbi 2021; Hass 2012; Hirsch 2003; Hubble 2018; Johansson Sedaghati 2016; Shanahan 2017; Stack 2012; Sujatha 2019; Taheri
2018; Kanegusuku 2017; Kunkel 2017; Kurt 2018; Kwok 2019; 2011; Terrens 2020; Toole 2000; Volpe 2017b; Wang 2017; Yen 2011;
Landers 2016; Li 2012; Liao 2015; Liu 2016; Mak 2021; Martin 2015; Zhu 2011).
Medijainen 2019; Miyai 2000; Miyai 2002; Morris 2009; Morris 2015;
Morris 2017; Mulligan 2018; Myers 2020; Nadeau 2014; Ni 2016; Ongoing studies
Ortiz-Rubio 2018; Pazzaglia 2020; Peloggia Cursino 2018; Pérez de We classified 58 studies as ongoing because this was indicated
la Cruz 2017; Pohl 2013; Poier 2019; Qutubuddin 2013; Santos by the study publication, the study completion date reported in
2017a; Santos 2017b; Santos 2017c; Santos 2019; Schenkman the trial registry was 2020 or later, or relevant changes have been
2018; Schlenstedt 2015; Shahmohammadi 2017; Shen 2021; Silva made in the trial registry indicating that the trial was ongoing
2019; Silva-Batista 2018; Silveira 2018; Smania 2010; Solla 2019; (ACTRN12617001057370; ACTRN12620001135909; Bevilacqua
Sparrow 2016; Stozek 2016; Szymura 2020; Tollar 2018; Tollar 2019; 2020; ChiCTR1900022621; ChiCTR2000029025; ChiCTR2000029135;
Van Puymbroeck 2018; Vivas 2011; Volpe 2013; Volpe 2014; Volpe ChiCTR2000036306; ChiCTR2000037178; ChiCTR2000037305;
2017a; Winward 2012; Wong-Yu 2015; Yang 2010; Youm 2020; Yuan ChiCTR2000037384; CTRI/2018/05/014241; CTRI/2019/06/019618;
2020Zhang 2015). CTRI/2020/06/025794; DRKS00018841; Gooßes 2020; Hackney
2020; Li 2021; Lima 2020; Mayoral-Moreno 2021; NCT02457832;
Eleven studies declared potential conflicts of interest, including
NCT03244813; NCT03343574; NCT03560089; NCT03563807;
relationships with commercial entities (e.g. pharmaceutical
NCT03582371; NCT03711955; NCT03751371; NCT03833349;
companies), that were not directly related to the study (Allen 2010;
NCT03860649; NCT03882879; NCT03960931; NCT03972969;
Canning 2015; Corcos 2013; Ebersbach 2010; Harvey 2019; Michels
NCT03974529; NCT03983785; NCT04000360; NCT04046276;
2018; Paul 2014; Rios Romenets 2015; Schaible 2021; Shulman 2013;
NCT04063605; NCT04122690; NCT04135924; NCT04194762;
Szefler-Derela 2020).
NCT04215900; NCT04379778; NCT04558879; NCT04613141;
Three studies declared potential conflicts of interest that were NCT04644367; NCT04665869; NCT04699617; NCT04863118;
limited to relationships with non-commercial entities (e.g. NCT04872153; NCT04878679; RBR-26kn3b; RBR-277fqv;
universities) (Ashburn 2018; Goodwin 2011; Wan 2021). RBR-5r5dhf; RBR-5yjyr7; RBR-74683n; RBR-8s5v5f; RBR-9v7gj4;
TCTR20201009001). One of these studies was suspended due to
Five studies declared the following potential conflicts of interest COVID-19 but may be continued (NCT04215900).
related to the study.
Studies awaiting classification
• King 2020: "(The last author) has an equity interest in APDM, a
We listed 68 studies (including published full-text articles,
company that may have a commercial interest in the results of
abstracts, and trial registry records) as "awaiting classification"
this study. This potential conflict of interest has been reviewed
due to insufficient information to judge eligibility. According to the
and managed by the Research & Development Committee at the
available information, these studies were completed or potentially
VA Portland Health Care System and Oregon Health & Science
could have been completed.
University. They have put in place a plan to help ensure that this
research study is not affected by the financial interest". We contacted the authors of 14 studies in order to receive
• Nieuwboer 2007: "The proceeds of the sale of the CD-Rom will be additional information to allow a judgment on their eligibility,
used to fund completion of analysis of the full RESCUE dataset. but received either no response or insufficient information
We may be involved in this further work". for clarification (Amara 2020; de Oliveira 2017; Huang 2020;
• Pohl 2020: "(The first author) is a non-practicing certified Kargarfard 2012; Khongprasert 2019; Koli 2018; Lee G 2018; Lee
practitioner of the Ronnie Gardiner Method. She was blind to the 2019; Mohammadpour 2018; Ogundele 2018; Rosenfeldt 2021;
results of the outcome evaluations of all patients and did not Shen 2014; Stozek 2017; Swarnakar 2019). One study providing
take part in the interviews". insufficient information to judge eligibility was identified during
• Ridgel 2019: "(The first author) is a co-inventor on two patents the peer review process for this review (Wroblewska
́ 2019). We
which are related to the device used in this study: “Bike System will contact the study authors in order to clarify eligibility in a
for Use in Rehabilitation of a Patient,” US 10,058,736 and US future update of this review. For 53 studies identified through
9,802,081. No royalties have been distributed from this patent". registry searches, we were not able to make a judgment on
their eligibility or to identify published or unpublished data
• Vergara-Diaz 2018: "(The last author) is the founder and sole
linked to the study, or the study completion date reported
owner of the Tree of Life Tai Chi Center. (His) interests were
in the trial registry was 2019 or before and there have been
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no updates in the trial registry indicating that the trial was • two studies were terminated (NCT03637023; NCT04291027); and
ongoing (ACTRN12605000566639; ACTRN12609000900213; • one study was a cluster-RCT (Munneke 2010).
ACTRN12612001016820; ACTRN12618000923268p;
ChiCTR1800019534; ChiCTR-INR-17011340; ChiCTR- Risk of bias in included studies
IOR-16009065; ChiCTR-IPR-17011875; ChiCTR-TRC-14004549;
CTRI/2017/08/009471; DRKS00008732; IRCT2015040616830N4; Using the RoB 2 tool, we assessed the risk of bias for 93 RCTs that
IRCT2016071228885N1; IRCT20171030037099N1; NCT00004760; contributed results to our primary outcomes which are included
NCT00029809; NCT00167453; NCT00387218; NCT01014663; in Summary of findings 1 and Summary of findings 2 (Allen 2010;
NCT01076712; NCT01246700; NCT01427062; NCT01439022; Almeida 2012; Amano 2013; Ashburn 2018; Avenali 2021; Burini
NCT01562496; NCT01757509; NCT01835652; NCT01960985; 2006; Canning 2012; Canning 2015; Capato 2020a; Carroll 2018;
NCT02017938; NCT02267785; NCT02419768; NCT02476240; Carvalho 2015; Cheng 2017; Choi 2013; Cholewa 2013; Colgrove
NCT02476266; NCT02615548; NCT02656355; NCT02674724; 2012; Corcos 2013; Cugusi 2015; da Silva Rocha Paz 2019; Daneshvar
NCT02745171; NCT02816619; NCT02999997; NCT03212014; 2019; De Assis 2018; Duncan 2012; Ebersbach 2010; Ellis 2005; Feng
NCT03406728; NCT03443752; NCT03568903; NCT03618901; 2019; Ferraz 2018; Ferrazzoli 2018; Ferreira 2018; Fil-Balkan 2018;
NCT03689764; NCT04012086; RBR-34d7jm; RBR-3vm7bf; Fisher 2008; Frazzitta 2014; Ganesan 2014; Gao 2014; Gobbi 2021;
RBR-3z39v3; RBR-4m3k2c; RBR-6rngmb; RBR-7xfkpx; Goodwin 2011; Gu 2013; Hackney 2007; Hackney 2009; Johansson
TCTR20180111003; TCTR20180530004). 2018; King 2020; Kunkel 2017; Kurt 2018; Kwok 2019; Lee HJ 2018;
Li 2012; Liao 2015; Mak 2021; Michels 2018; Miyai 2002; Morris
Excluded studies 2009; Morris 2015; Morris 2017; Muller 1997; Nadeau 2014; Ni 2016;
Nieuwboer 2007; Park 2014; Pedreira 2013; Peloggia Cursino 2018;
After screening of titles/abstracts, we excluded 18,967 records that Pérez de la Cruz 2017; Pohl 2013; Pohl 2020; Poier 2019; Poliakoff
did not match our inclusion criteria. We evaluated reports of 32 2013; Qutubuddin 2013; Reuter 2011; Ridgel 2019; Rios Romenets
studies in more detail, which were finally excluded for one or more 2015; Santos 2017a; Santos 2017b; Schaible 2021; Schenkman
of the following reasons (see Characteristics of excluded studies 2012; Schenkman 2018; Schlenstedt 2015; Schmitz-Hubsch 2006;
table): Shahmohammadi 2017; Shen 2021; Shulman 2013; Smania 2010;
Solla 2019; Terrens 2020; Tollar 2018; Tollar 2019; Van Puymbroeck
• 16 studies compared interventions that were too similar; that
2018; Vergara-Diaz 2018; Volpe 2013; Volpe 2014; Volpe 2017a; Volpe
is, they would have been categorized as the same type of
2017b; Wang 2017; Winward 2012; Youm 2020; Zhang 2015; Zhu
intervention according to our adapted version of the ProFaNE
2011). These studies contributed 71 study results to the severity
taxonomy (Lamb 2011) (Antunes Marques 2019; Cancela 2020;
of motor signs, and 55 study results to quality of life. The RoB 2
Capato 2020b; Combs 2013; Granziera 2021; Melo 2018; Moon
judgments for all study results per outcomes and for all domains
2020; Passos-Monteiro 2020; Picelli 2012; Sahu 2018; Serrao
are available in a supplementary file (Ernst 2022). Traffic light plots
2019; Silva-Batista 2020; Soke 2021; Van Wegen 2015; Wang
(domain-level judgments for each individual result) and summary
2018; Zhu 2020);
plots (distribution of judgments within each domain) are displayed
• 10 studies were not RCTs (Hashimoto 2015; Israel 2018; Kalyani for study results on the severity of motor signs in Figure 3 and Figure
2019; Maciel 2020; Rawson 2019; Sage 2009; Segura 2020; Yousefi 4, and for study results on quality of life in Figure 5 and Figure 6,
2009; Yu 1998; Zhang 2018); respectively. We summarize the judgments below.
• three studies did not include any or fewer than five supervised
training sessions (Laupheimer 2011; Thaut 1996; Xiao 2016);

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Figure 3. Risk of bias traffic light plot for severity of motor signs.

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Figure 3. (Continued)

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Figure 3. (Continued)

Figure 4. Risk of bias summary plot for severity of motor signs.

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Figure 5. Risk of bias summary plot for quality of life.

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Figure 5. (Continued)

Figure 6. Risk of bias traffic light plot for quality of life.

Since the reporting of adverse events was highly heterogeneous Severity of motor signs
and frequently incomplete, retrieving effect estimates for a network
For the severity of motor signs, we judged the overall risk of bias
meta-analysis and conducting a formal assessment of risk of bias
as low for seven study results (9.9%, Capato 2020a; Cheng 2017;
was not feasible. Therefore, we made an informal judgment of the
Colgrove 2012; Corcos 2013; Li 2012; Volpe 2013; Volpe 2014). We
risk of bias for this outcome.
had some concerns regarding overall risk of bias for 29 study results

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(40.9%). We judged 35 study results (49.3%) to be at high overall 2015; Shahmohammadi 2017; Shulman 2013; Terrens 2020; Tollar
risk of bias. Most frequently, we had concerns regarding bias due to 2019; Vergara-Diaz 2018).
deviations from the intended interventions, as the results reported
by trialists frequently lacked data from a substantial proportion of Risk of bias by comparison
participants who had been randomized. For the effects of six interventions (i.e. aqua-based, endurance,
gait/balance/functional training, LSVT BIG, multi-domain, and
Risk of bias by comparison
strength/resistance training versus a passive control group), we had
We had no concerns regarding risk of bias for the effects of two some concerns regarding risk of bias that were due to self-reporting
interventions versus a passive control group. For the comparison of the outcome (i.e. high risk in domain 4: "bias in measurement of
of dance with a passive control group, the effect estimate was the outcome"). Considering only the domains that are not affected
dominated by 'high risk of bias' studies with a weight of around by self-reporting of the outcome, the effect estimates were highly
70% in the primary analysis. However, both the primary analysis affected by studies at low risk of bias or studies with some concerns
and the sensitivity analysis, which was limited to 'low risk of bias' regarding risk of bias.
studies, suggested an effect in favor of dance. For the comparison
of flexibility training with a passive control group, 'high risk of bias' We had serious concerns regarding risk of bias for the effects
studies accounted for around 30% of the effect estimate. Effects of dance, flexibility training, gaming, and mind-body training
within equivalence of flexibility training and a passive control group versus a passive control group, because the effect estimates were
were suggested by both the primary and the sensitivity analysis. highly affected by 'high risk of bias' studies even when bias in
measurement of the outcome was not taken into account.
For the effects of the remaining interventions versus a passive
control group, we had some concerns regarding risk of bias. For the Adverse events
comparisons of aqua-based, gait/balance/functional, mind-body, Reporting of adverse events was highly heterogeneous and
multi-domain, and strength/resistance training with a passive frequently incomplete: most studies did not report events for all
control group, the contribution of 'high risk of bias' studies to the groups. Therefore, we judged the risk of bias for this outcome to be
effect estimates ranged between around 40% and 60%. While the high.
primary analysis suggested effects in favor of the interventions,
the confidence intervals included effects within equivalence with Effects of interventions
a passive control group in the sensitivity analysis limited to 'low
risk of bias' studies. For the comparisons of endurance training and See: Summary of findings 1 Network estimates of effects and
LSVT BIG with a passive control group, the effect estimates were confidence in the evidence for physical exercise in people with
highly affected by study results that were at least of some concern Parkinson’s disease on the severity of motor signs; Summary of
regarding risk of bias, while 'low risk of bias' studies contributed findings 2 Network estimates of effects and confidence in the
only little weight to the estimates (i.e. below 5%). The sensitivity evidence for physical exercise in people with Parkinson’s disease
analysis did not include data on the effects of endurance training on quality of life; Summary of findings 3 Estimates of effects and
and LSVT BIG versus a passive control group. confidence in the evidence for physical exercise in people with
Parkinson’s disease on adverse events
Quality of life
We present our main findings from the NMAs for each comparison
Due to the nature of self-reported questionnaires and the of interventions included in our decision set with a passive control
corresponding subjectivity of the assessment of quality of life, we group, which was the most common comparator, in Summary
judged all study results to be at high overall risk of bias. of findings 1 and Summary of findings 2. Results for other
comparisons are reported below and in the additional tables and
Considering the domains that are not affected by self-reporting of
figures. Additionally, we present key results from the NMAs in an
the outcome only (i.e. excluding domain 4: "bias in measurement
interactive summary of findings table. We present our main findings
of the outcome"), we judged eight study results (14.5%) to be at
on the occurrence of adverse events in Summary of findings 3.
low risk of bias (Cheng 2017; Corcos 2013; Liao 2015; Morris 2009;
Nieuwboer 2007; Tollar 2018; Volpe 2013; Volpe 2014). For 20 study Pairwise comparisons
results (36.4%), we had some concerns regarding risk of bias (Allen
2010; Canning 2012; Canning 2015; Daneshvar 2019; Ferrazzoli Pairwise comparisons are part of the NMAs, and we did not perform
2018; Goodwin 2011; Johansson 2018; Michels 2018; Morris 2015; additional pairwise meta-analyses. The direct effect estimates for
Morris 2017; Poier 2019; Rios Romenets 2015; Santos 2017a; Santos all pairwise comparisons are presented in the upper triangle of each
2017b; Schaible 2021; Schenkman 2012; Schmitz-Hubsch 2006; league table (Table 1; Table 2; Table 3; Table 4).
Volpe 2017a; Volpe 2017b; Winward 2012), and we judged 27 study
For the comparison of the effects on the severity of motor signs
results (49.1%) to be at high risk of bias (Amano 2013; Ashburn 2018;
between mind-body training and a passive control group, funnel
Burini 2006; Carroll 2018; Cholewa 2013; Ferraz 2018; Ferreira 2018;
plot analysis did not suggest asymmetry (P = 0.47; Figure 7). Since
Gobbi 2021; King 2020; Kunkel 2017; Kwok 2019; Lee HJ 2018; Li
this was the only pairwise comparison across outcomes, with a
2012; Nadeau 2014; Ni 2016; Pedreira 2013; Peloggia Cursino 2018;
minimum of 10 studies, we did not conduct further funnel plot
Pohl 2013; Pohl 2020; Poliakoff 2013; Qutubuddin 2013; Schlenstedt
analyses.

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Figure 7. Funnel plot for the comparison of the effects on severity of motor signs between mind-body training and a
passive control group.

Transitivity Rocha Paz 2019; De Assis 2018; Duncan 2012; Ebersbach 2010;
Ellis 2005; Feng 2019; Fil-Balkan 2018; Fisher 2008; Frazzitta 2014;
As the clinical and methodological characteristics that could
Ganesan 2014; Gao 2014; Gu 2013; Hackney 2007; Hackney 2009;
potentially affect the relative treatment effects were similar across
King 2020; Kurt 2018; Kwok 2019; Lee HJ 2018; Li 2012; Mak 2021;
the included trials, we assumed that the transitivity assumption
Michels 2018; Miyai 2002; Morris 2015; Morris 2017; Muller 1997;
holds. Distributions of potential effect modifiers across the
Nadeau 2014; Ni 2016; Park 2014; Pérez de la Cruz 2017; Pohl
different pairwise comparisons are displayed in a supplementary
2013; Poliakoff 2013; Qutubuddin 2013; Reuter 2011; Ridgel 2019;
file (Ernst 2022).
Rios Romenets 2015; Santos 2017a; Santos 2017b; Schaible 2021;
Severity of motor signs Schenkman 2012; Schenkman 2018; Schlenstedt 2015; Schmitz-
Hubsch 2006; Shen 2021; Shulman 2013; Smania 2010; Solla 2019;
Data on the severity of motor signs were reported in 71 studies, Terrens 2020; Van Puymbroeck 2018; Vergara-Diaz 2018; Volpe 2013;
of which seven had three arms (3196 participants; Almeida 2012; Volpe 2014; Volpe 2017a; Volpe 2017b; Wang 2017; Youm 2020;
Amano 2013; Avenali 2021; Burini 2006; Canning 2012; Capato Zhang 2015; Zhu 2011). The fully-connected network was based
2020a; Carroll 2018; Carvalho 2015; Cheng 2017; Choi 2013; on 85 pairwise comparisons and included data on all interventions
Cholewa 2013; Colgrove 2012; Corcos 2013; Cugusi 2015; da Silva except for gaming (Figure 8).

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Figure 8. Network graph for severity of motor signs. Treatments are connected by a line when there is at least one
study comparing the two treatments.
Line width: number of studies. Node width: number of participants.

A league table with results for all pairwise comparisons, including 95% CI -0.77 to -0.27; strength/resistance training: SMD -0.52, 95%
network estimates and direct estimates, is displayed in Table 1. CI -0.89 to -0.15; mind-body training: SMD -0.49, 95% CI -0.76 to
Please note that higher scores denote higher severity of motor -0.21; endurance training: SMD -0.48, 95% CI -0.80 to -0.17). For
signs. Therefore, negative estimates reflect improvement. Also, the same interventions, the evidence also suggests decreases in
please note that the minimum clinically important difference for the severity of motor signs compared to flexibility training (dance:
improvement of -2.5 points on the UPDRS-M corresponds to an SMD SMD -0.92, 95% CI -1.55 to -0.29; aqua-based training: SMD -0.73,
of -0.19 (Shulman 2010). 95% CI -1.36 to -0.11; gait/balance/functional training: SMD -0.70,
95% CI -1.25 to -0.16; multi-domain training: SMD -0.68, 95% CI
The evidence suggests that the severity of motor signs was -1.20 to -0.16; strength/resistance training: SMD -0.67, 95% CI -1.22
decreased for seven interventions compared to a passive control to -0.13; mind-body training: SMD -0.64, 95% CI -1.14 to -0.14;
group (dance: SMD -0.77, 95% CI -1.16 to -0.37; aqua-based training: endurance training: SMD -0.64, 95% CI -1.14 to -0.13). Moreover, for
SMD -0.58, 95% CI -0.99 to -0.17; gait/balance/functional training: dance and gait/balance/functional training, the evidence suggests
SMD -0.55, 95% CI -0.85 to -0.25; multi-domain training: SMD -0.52, that the severity of motor signs was decreased compared to an

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active control group (dance: SMD -0.59, 95% CI -1.11 to -0.08; gait/ resistance training: SMD -0.35, 95% CI -0.79 to 0.10; endurance
balance/functional training: SMD -0.38, 95% CI -0.75 to -0.01). We training: SMD -0.31, 95% CI -0.73 to 0.10).
did not identify evidence for further statistically significant effects.
However, we observed that several interventions may also have The highest-ranked interventions were dance (P-score: 0.88), aqua-
beneficial effects on the severity of motor signs compared to an based training (P-score: 0.69), and gait/balance/functional training
active control group, but the CIs extended across the line of no (P-score: 0.67). The lowest-ranked interventions were flexibility
effect (e.g. aqua-based training: SMD -0.41, 95% CI -0.90 to 0.09; training (P-score: 0.05), a passive control group (P-score: 0.10), and
multi-domain training: SMD -0.35, 95% CI -0.71 to 0.01; strength/ an active control group (P-score: 0.23) (Figure 9).

Figure 9. Forest plot for severity of motor signs.

Reference treatment: passive control. Treatment effects are expressed as standardized mean differences (SMD) with
95% confidence intervals (CI). Treatments are ordered by P-score (descending). Please note that severity of motor
signs is labelled 'clinician-rated impairment and disability' (CRID), a term we had originally used for this outcome,
but ultimately discarded for the sake of higher accuracy and better readability.

Cochran's Q test and I2 statistics indicated moderate to substantial Flexibility training might have a trivial or no effect on the severity
heterogeneity between the studies (Qtotal = 163.38, degrees of of motor signs (low confidence). The evidence is very uncertain
freedom (df) = 68, P < 0.001; Qwithin = 87.87, df = 40, P < 0.001; about the effects of strength/resistance training and LSVT BIG on
Qbetween = 75.51, df = 28, P < 0.001; I2 = 58.4%, Tau2 = 0.1501). the severity of motor signs (very low confidence).

The most common limitations to our confidence in the effects on

For the severity of motor signs, we judged 35 study results (49.3%)
the severity of motor signs were either: (a) a large proportion of
to be at high overall risk of bias. Most frequently, we had concerns
'high risk of bias' studies and inconsistency between results of the
regarding bias due to deviations from the intended interventions,
primary analysis and sensitivity analysis limited to 'low risk of bias'
as the results reported by trialists frequently lacked data from a
studies (downgraded by one level for risk of bias for the effects
substantial proportion of participants who had been randomized,
of aqua-based, gait/balance/functional, multi-domain, strength/
which may lead to an overestimation of effects.
resistance, and mind-body training); or (b) a large proportion of
We rated the confidence in the evidence for the severity of motor studies with at least some concerns regarding risk of bias while
signs using the CINeMA approach (Nikolakopoulou 2020), for the no sensitivity analysis could be conducted (downgraded by one
comparison of each intervention included in our decision set, level for risk of bias for the effect of LSVT BIG), and inconsistencies
except gaming, with a passive control group. The evidence suggests between the effects observed when considering only confidence
that dance has a moderate beneficial effect on the severity of motor intervals and when additionally considering prediction intervals
signs (high confidence), and aqua-based, gait/balance/functional, (downgraded by one level for heterogeneity for the effects of aqua-
and multi-domain training might have a moderate beneficial effect based, endurance, gait/balance/functional, mind-body, multi-
on the severity of motor signs (low confidence). Furthermore, we domain, and strength/resistance training). Prediction intervals are
found that mind-body and endurance training might have a small provided in Appendix 11. Details on reasons for downgrading are
beneficial effect on the severity of motor signs (low confidence). provided in Summary of findings 1.
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Tests for inconsistencies in closed loops indicated disagreements balance/functional training with mind-body training (P = 0.002),
between direct and indirect estimates for the comparisons of gait/ and strength/resistance training with a passive control group (P =
0.046) (Table 5, Figure 10).

Figure 10. Comparison of direct and indirect evidence (in closed loops) for severity of motor signs. Treatment
effects are expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Please note that

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severity of motor signs is labelled 'clinician-rated impairment and disability' (CRID), a term we had originally used
for this outcome, but ultimately discarded for the sake of higher accuracy and better readability.

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Figure 10. (Continued)

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Figure 10. (Continued)

Quality of life 2009; Morris 2015; Morris 2017; Nadeau 2014; Ni 2016; Nieuwboer
2007; Pedreira 2013; Peloggia Cursino 2018; Pohl 2013; Pohl 2020;
Data on quality of life (QoL) were reported in 55 studies, of
Poier 2019; Poliakoff 2013; Qutubuddin 2013; Rios Romenets 2015;
which six had three arms (3283 participants; Allen 2010; Amano
Santos 2017a; Santos 2017b; Schaible 2021; Schenkman 2012;
2013; Ashburn 2018; Burini 2006; Canning 2012; Canning 2015;
Schlenstedt 2015; Schmitz-Hubsch 2006; Shahmohammadi 2017;
Carroll 2018; Cheng 2017; Cholewa 2013; Corcos 2013; Daneshvar
Shulman 2013; Terrens 2020; Tollar 2018; Tollar 2019; Vergara-Diaz
2019; Ferraz 2018; Ferrazzoli 2018; Ferreira 2018; Gobbi 2021;
2018; Volpe 2013; Volpe 2014; Volpe 2017a; Volpe 2017b; Winward
Goodwin 2011; Johansson 2018; King 2020; Kunkel 2017; Kwok
2012). The fully-connected network was based on 67 pairwise
2019; Lee HJ 2018; Li 2012; Liao 2015; Michels 2018; Morris
comparisons and included data on all interventions (Figure 11).

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Figure 11. Network graph for quality of life. Treatments are connected by a line when there is at least one study
comparing the two treatments.
Line width: number of studies. Node width: number of participants.

A league table with results for all pairwise comparisons, including -0.02; gait/balance/functional training: SMD -0.32, 95% CI -0.57 to
network estimates and direct estimates, is displayed in Table -0.07; multi-domain training: SMD -0.30, 95% CI -0.53 to -0.06). For
2. Please note that higher scores denote lower QoL. Therefore, three interventions, the evidence also suggests increases in QoL
negative estimates reflect improvement. Also, please note that the compared to an active control group (aqua-based training: SMD
minimum clinically important difference for improvement of -4.72 -0.90, 95% CI -1.47 to -0.33; endurance training: SMD -0.58, 95% CI
points on the PDQ-39 corresponds to an SMD of -0.27 (Horvath -1.07 to -0.08; mind-body training: SMD -0.55, 95% CI -1.03 to -0.07).
2017). Moreover, for aqua-based training, the evidence suggests that QoL
was increased compared to gait/balance/functional training (SMD
The evidence suggests that QoL was increased for six interventions -0.53, 95% CI -0.99 to -0.07), multi-domain training (SMD -0.55, 95%
compared to a passive control group (aqua-based training: SMD CI -1.02 to -0.09), and flexibility training (SMD -0.92, 95% CI -1.76
-0.85, 95% CI -1.32 to -0.37; endurance training: SMD -0.52, 95% to -0.08). There was no further evidence of statistically significant
CI -0.89 to -0.16; mind-body training: SMD -0.50, 95% CI -0.83 effects. However, we observed that several interventions may also
to -0.17; strength/resistance training: SMD -0.36, 95% CI -0.70 to have beneficial effects on QoL compared to an active control group,

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but the CIs extended across the line of no effect (e.g. multi-domain an active control group included both inferiority and superiority of
training: SMD -0.55, 95% CI -1.03 to -0.07; strength/resistance LSVT BIG (LSVT BIG compared to flexibility: SMD 0.06, 95% CI -1.18
training: SMD -0.41, 95% CI -0.87 to 0.04; gait/balance/functional to 1.30; LSVT BIG compared to an active control group: SMD 0.07,
training: SMD -0.37, 95% CI -0.76 to 0.02). Furthermore, the effect 95% CI -1.00 to 1.15).
of aqua-based training on QoL may be increased compared to
dance (SMD -0.61, 95% CI -1.22 to 0.00) and strength/resistance The highest-ranked interventions were aqua-based training (P-
training (SMD -0.49, 95% CI -1.03 to 0.06), but the CIs touched or score: 0.95), endurance training (P-score: 0.77), and mind-body
extended across the line of no effect. Also, the CIs related to some training (P-score: 0.75). The lowest-ranked interventions were an
comparisons that involved LSVT BIG were very wide. That is, the CIs active control group (P-score: 0.17), a passive control group (P-
of the effects of LSVT BIG on QoL compared to flexibility training and score: 0.19), and flexibility training (P-score: 0.22) (Figure 12).

Figure 12. Forest plot for quality of life. Reference treatment: passive control. Treatment effects are expressed
as standardized mean differences (SMD) with 95% confidence intervals (CI). Treatments are ordered by P-score
(descending).

Cochran's Q test and I2 statistics indicated moderate to substantial moderate beneficial effect, while gait/balance/functional and
heterogeneity between the studies (Qtotal = 125.02, df = 50, P < multi-domain training might have a small beneficial effect on
0.001; Qwithin = 71.91, df = 26, P < 0.001; Qbetween = 53.11, df = 24, P quality of life (low confidence). The evidence is very uncertain about
< 0.001; I2 = 60.0%, Tau2 = 0.1210). the effects of mind-body training, gaming, strength/resistance
training, dance, LSVT BIG, and flexibility training on QoL (very low
For QoL, we judged all study results to be at high overall risk confidence).
of bias due to the subjectivity of the assessment. Moreover, we
frequently had concerns regarding bias due to deviations from A primary limitation to our confidence in the effects was due
the intended interventions, as the results reported by trialists to the self-report of QoL and the corresponding risk of bias in
frequently lacked data from a substantial proportion of participants the measurement of the outcome as assessed by domain 4 of
who had been randomized. Both self-report of the outcome and the RoB 2 tool (Sterne 2019). Therefore, for all comparisons,
failure to report data for the intention-to-treat sample may lead to we downgraded by one level for risk of bias. For the effects
an overestimation of effects. of mind-body training, gaming, dance, and flexibility training on
QoL compared to a passive control group, we downgraded by
Again, we rated the confidence in the evidence for QoL using the a total number of two levels for risk of bias, because the effect
CINeMA approach for the comparison of each intervention included estimates were highly affected by studies that were judged to be
in our decision set with a passive control group (Nikolakopoulou at high risk of bias considering only the domains that are not
2020). The evidence suggests that aqua-based training probably affected by self-reporting of the outcome (i.e. excluding domain
has a large beneficial effect on QoL (moderate confidence). 4 of the RoB 2 tool). The second most common limitation to
Furthermore, we found that endurance training might have a our confidence in the evidence were inconsistencies between the
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effects observed when considering only confidence intervals and Tests for inconsistencies in closed loops indicated disagreement
when additionally considering prediction intervals (downgraded between direct and indirect estimates for the comparison of
by one level for heterogeneity for the effects of endurance, strength/resistance training with a passive control group (P = 0.031)
gait/balance/functional, mind-body, multi-domain, and strength/ (Table 6, Figure 13).
resistance training). Prediction intervals are provided in Appendix
12. Details on reasons for downgrading are provided in Summary of
findings 2.

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Figure 13. Comparison of direct and indirect evidence (in closed loops) for quality of life. Treatment effects are
expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). QoL = quality of life

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Figure 13. (Continued)

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Figure 13. (Continued)

Freezing of gait Pohl 2020; Rios Romenets 2015; Santos 2017a; Santos 2017c;
Schlenstedt 2015; Van Puymbroeck 2018; Volpe 2013). All studies
Data on freezing of gait were reported in 20 studies (1048
had two arms. The fully-connected network was based on 20
participants; Allen 2010; Canning 2015; Capato 2020a; Carroll 2018;
pairwise comparisons and included data on all interventions except
Cheng 2017; Duncan 2012; Hackney 2007; Hackney 2009; King
for endurance training, flexibility training, gaming, and LSVT BIG
2020; Martin 2015; Medijainen 2019; Nieuwboer 2007; Paul 2014;
(Figure 14).

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Figure 14. Network graph for freezing of gait. Treatments are connected by a line when there is at least one study
comparing the two treatments.
Line width: number of studies. Node width: number of participants.

A league table with results for all pairwise comparisons including 95% CI -1.45 to 0.05; dance: SMD -0.55, 95% CI -1.18 to 0.08; gait/
network estimates and direct estimates is displayed in Table balance/functional training: SMD -0.50, 95% CI -1.02 to 0.01). Gait/
3. Please note that higher scores denote increased freezing of balance/functional training may also have a beneficial effect on
gait. Therefore, negative estimates reflect improvement. Also, freezing of gait compared to a passive control group, but again,
please note that the minimum clinically important difference for the CI extended across the line of no effect (SMD -0.20, 95% CI
improvement of -3 points on the FOG-Q corresponds to an SMD of -0.49 to 0.10). Also, the CIs related to some comparisons that
-0.64 (Fietzek 2020). involved aqua-based training were very wide. That is, the CIs of
the effects of aqua-based training on freezing of gait compared
We did not identify evidence for statistically significant effects to strength/resistance training and mind-body training included
on freezing of gait. However, according to the estimates, some both inferiority and superiority of aqua-based training (strength/
interventions may have beneficial effects on freezing of gait resistance training compared to aqua-based training: SMD 0.06,
compared to an active control group, but the CIs extended across 95% CI -1.13 to 1.25; aqua-based training compared to mind-body
the line of no effect (e.g. strength/resistance training: SMD -0.70, training: SMD -0.14, 95% CI -1.54 to 1.25).

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The highest-ranked interventions were strength/resistance training a passive control group (P-score: 0.31) (Figure 15). However, the
(P-score: 0.75), aqua-based training (P-score: 0.70), and dance (P- ranking of the interventions should be interpreted very carefully
score: 0.64). The lowest-ranked interventions were an active control given the large size of the confidence intervals of the effect
group (P-score: 0.10), multi-domain training (P-score: 0.30), and estimates.

Figure 15. Forest plot for freezing of gait. Reference treatment: passive control. Treatment effects are expressed
as standardized mean differences (SMD) with 95% confidence intervals (CI). Treatments are ordered by P-score
(descending).

The presence of moderate heterogeneity between the studies as Tests for inconsistencies in closed loops indicated disagreements
indicated by I2 statistics was not found to be statistically significant between direct and indirect estimates for the comparisons of both
according to Cochran's Q test (Qtotal = 22.36, df = 13, P = 0.050; gait/balance/functional training and a passive control group with
Qwithin = 14.83, df = 9, P = 0.10; Qbetween = 7.53, df = 4, P = 0.11; I2 strength/resistance training (P = 0.0395) (Table 7, Figure 16).
= 41.9%, Tau2 = 0.0632).

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Figure 16. Comparison of direct and indirect evidence (in closed loops) for freezing of gait. Treatment effects are
expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). FOG = freezing of gait

Functional mobility and balance Liao 2015; Liu 2016; Mak 2021; Michels 2018; Morris 2009; Morris
2015; Ni 2016; Nieuwboer 2007; Paul 2014; Pérez de la Cruz 2017;
Data on functional mobility and balance were reported in 54
Pohl 2013; Ridgel 2019; Rios Romenets 2015; Santos 2019; Schilling
studies, of which six had three arms (2546 participants; Almeida
2010; Schlenstedt 2015; Sedaghati 2016; Shen 2021; Shulman 2013;
2012; Arfa-Fatollahkhani 2019; Capato 2020a; Chaiwanichsiri 2011;
Silva 2019; Solla 2019; Tollar 2019; Vergara-Diaz 2018; Volpe 2014;
Cheng 2017; Cherup 2021; Choi 2013; Corcos 2013; Cugusi 2015; da
Volpe 2017a; Volpe 2017b; Wan 2021; Wang 2017; Wong-Yu 2015;
Silva Rocha Paz 2019; De Moraes Filho 2020; Ebersbach 2010; Feng
Youm 2020; Zhang 2015). The fully-connected network was based
2019; Ferreira 2018; Fil-Balkan 2018; Gao 2014; Guan 2016; Hackney
on 64 pairwise comparisons and included data on all interventions
2007; Hackney 2009; Kunkel 2017; Kurt 2018; Kwok 2019; Li 2012;
(Figure 17).

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Figure 17. Network graph for functional mobility and balance. Treatments are connected by a line when there is at
least one study comparing the two treatments.
Line width: number of studies. Node width: number of participants.

A league table with results for all pairwise comparisons, including CI -1.40 to -0.18; gait/balance/functional training: SMD -0.77, 95%
network estimates and direct estimates, is displayed in Table 4. CI -1.20 to -0.35; strength/resistance training: SMD -0.69, 95% CI
Please note that higher scores denote more time to complete the -1.15 to -0.23; multi-domain training: SMD -0.63, 95% CI -1.07 to
Timed Up and Go test (TUG) and thus, worse functionality and -0.20). Moreover, for aqua-based training, the evidence suggests
balance. Therefore, negative estimates reflect improvement. Also, that functional mobility and balance were increased compared
please note that the minimum detectable change of -3.5 seconds to gait/balance/functional training (SMD -0.63, 95% CI -1.19 to
on the TUG corresponds to an SMD of -0.86 (Huang 2011). -0.06), strength/resistance training (SMD -0.71, 95% CI -1.40 to
-0.01), multi-domain training (SMD -0.77, 95 % CI -1.33 to -0.20),
The evidence suggests that functional mobility and balance were an active control group (SMD -1.07, 95% CI -1.83 to -0.32), and
increased for seven interventions compared to a passive control flexibility training (SMD -1.33, 95% CI -2.29 to -0.37). We also
group (aqua-based training: SMD -1.40, 95% CI -2.01 to -0.79; identified evidence suggesting that functional mobility and balance
mind-body training: SMD -0.88, 95% CI -1.27 to -0.48; dance: SMD were increased for mind-body training compared to flexibility
-0.84, 95% CI -1.39 to -0.30; endurance training: SMD -0.79, 95% training (SMD -0.81, 95% CI -1.58 to -0.04). There was no further

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evidence of statistically significant effects. However, we observed on functional mobility and balance in relation to other types of
that gait/balance/functional training may have a beneficial effect physical exercise. For example, the CIs included both inferiority
on functional mobility and balance compared to an active control and superiority of the effects of gaming on functional mobility and
group, but the CIs extended across the line of no effect (SMD -0.45, balance compared to LSVT BIG (LSVT BIG compared to gaming: SMD
95% CI -0.99 to 0.10). Similarly, LSVT BIG may have a large beneficial -0.50, 95% CI -2.35 to 1.35), or multi-domain training (multi-domain
effect on functional mobility and balance compared to a passive training compared to gaming: SMD -0.13, 95% CI -1.50 to 1.25).
control group, but the CI extended across the line of no effect
(SMD -1.01, 95% CI -2.18 to 0.17). The CIs related to comparisons The highest-ranked interventions were aqua-based training (P-
that involved gaming were very wide. For example, the estimate of score: 0.94), LSVT BIG (P-score: 0.69), and mind-body training (P-
the effect of gaming on functional mobility and balance compared score: 0.68), while the lowest-ranked interventions were a passive
to an active control group included both benefit and harm (SMD control group (P-score: 0.08), flexibility training (P-score: 0.15), and
-0.18, 95% CI -1.69 to 1.34). This also applies to effects of gaming an active control group (P-score: 0.25) (Figure 18).

Figure 18. Forest plot for functional mobility and balance. Reference treatment: passive control. Treatment effects
are expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Treatments are ordered
by P-score (descending).

Cochran's Q test and I2 statistics indicated substantial to Tests for inconsistencies in closed loops indicated disagreements
considerable heterogeneity between the studies (Qtotal = 204.30, df between direct and indirect estimates for the comparisons of dance
= 48, P < 0.001; Qwithin = 108.31, df = 27, P < 0.001; Qbetween = 95.99, with a passive control group (P = 0.015), dance with multi-domain
df = 21, P < 0.001; I2 = 76.5%, Tau2 = 0.3436). training (P = 0.0495), and multi-domain training with a passive
control group (P = 0.007) (Table 8, Figure 19).

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Figure 19. Comparison of direct and indirect evidence (in closed loops) for functional balance and mobility.
Treatment effects are expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). TUG =
Timed Up & Go test

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Figure 19. (Continued)

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Figure 19. (Continued)

Adverse events (number of participants with any adverse serious or major adverse events (Dashtipour 2015; Li 2012; Shulman
event) 2013; Volpe 2017b). Twenty-eight studies reported that adverse
events occurred (Allen 2010; Ashburn 2007; Ashburn 2018; Canning
Due to heterogeneity in the measurement and report of adverse
2015; Cheng 2017; Claesson 2018; Conradsson 2015; Corcos 2013;
events, we did not conduct a quantitative synthesis on the number
Fietzek 2014; Harvey 2019; Johansson 2018; King 2013; King 2020;
of participants with any adverse event using an NMA. Instead, we
Kunkel 2017; Kwok 2019; Michels 2018; Morris 2015; Nieuwboer
provide a narrative report of the data. For the sake of consistency,
2007; Poier 2019; Poliakoff 2013; Reuter 2011; Rios Romenets
we summarize the harms that were described as adverse events
2015; Schenkman 2012; Sparrow 2016; Terrens 2020; Vergara-Diaz
by the trialists, while we do not report harms recorded as reasons
2018; Volpe 2013; Yen 2011). Twenty studies reported the events,
for dropout unless trialists described them elsewhere as adverse
separated by all groups (Ashburn 2007; Ashburn 2018; Claesson
events.
2018; Conradsson 2015; Corcos 2013; Harvey 2019; King 2013;
Among the 156 included studies, 85 studies (5192 participants) Kunkel 2017; Kwok 2019; Michels 2018; Nieuwboer 2007; Poier 2019;
provided some kind of safety information (i.e. occurrence or Poliakoff 2013; Reuter 2011; Rios Romenets 2015; Schenkman 2012;
absence of events mostly described as adverse events; Allen 2010; Sparrow 2016; Terrens 2020; Vergara-Diaz 2018; Volpe 2013), and
Ashburn 2007; Ashburn 2018; Canning 2012; Canning 2015; Cakit eight studies reported the events either only for selected groups
2007; Capato 2020a; Carroll 2018; Chaiwanichsiri 2011; Cheng or combined for the groups (Allen 2010; Canning 2015; Cheng
2017; Cherup 2021; Cheung 2018; Claesson 2018; Colgrove 2012; 2017; Fietzek 2014; Johansson 2018; King 2020; Morris 2015; Yen
Conradsson 2015; Corcos 2013; Cugusi 2015; Dashtipour 2015; 2011). The events reported by studies were: pain, falls, tendency
Dipasquale 2017; Ferraz 2018; Fietzek 2014; Fisher 2008; Frazzitta to fall, fractures, soreness, adverse events without specification,
2015; Ganesan 2014; Gao 2014; Goodwin 2011; Hackney 2009; fatigue, hospitalization, injuries, surgeries, death, dizziness, drop in
Harvey 2019; Hass 2012; Hubble 2018; Johansson 2018; King 2013; blood pressure, heart problems, hypotension after intense walking
King 2020; Kunkel 2017; Kwok 2019; Lee HJ 2018; Li 2012; Liao uphill in hot weather, illness, lightheadedness, muscle cramps,
2015; Mak 2021; Martin 2015; Michels 2018; Morris 2009; Morris panic attack, respiratory infection, serious adverse events without
2015; Morris 2017; Myers 2020; Nadeau 2014; Ni 2016; Nieuwboer specification, slipped disc, sprain/strain, sprained ankle, stiffness,
2007; Ortiz-Rubio 2018; Park 2014; Paul 2014; Pérez de la Cruz and twisted ankle. Most studies reported events for the intervention
2017; Picelli 2016; Pohl 2013; Pohl 2020; Poier 2019; Poliakoff groups only.
2013; Reuter 2011; Ribas 2017; Rios Romenets 2015; Santos 2017a;
In summary, only 85 studies provided some kind of safety data,
Schaible 2021; Schenkman 1998; Schenkman 2012; Schenkman
mostly only for the intervention groups. No adverse events
2018; Sedaghati 2016; Shanahan 2017; Shulman 2013; Silva-Batista
occurred in 40 studies. No serious or major adverse events occurred
2018; Smania 2010; Solla 2019; Sparrow 2016; Szefler-Derela 2020;
in four studies. Adverse events occurred in 28 studies. The most
Terrens 2020;Tollar 2018; Tollar 2019; Vergara-Diaz 2018; Volpe
frequently reported events were falls (18 studies) and pain (10
2013; Volpe 2014; Volpe 2017b; Wong-Yu 2015; Yang 2010; Yen
studies).
2011; Yuan 2020; Zhang 2015). Seventy-one studies (46%) did
not provide any information on adverse events. Thirteen studies Retrieving effect estimates for a network meta-analysis was
reported falls, but did not label them as adverse events (Cakit not feasible because reporting of adverse events was highly
2007; Ferraz 2018; Gao 2014; Goodwin 2011; Hackney 2009; Martin heterogeneous and frequently incomplete. Therefore, we judged
2015; Morris 2017; Paul 2014; Schenkman 2018; Sedaghati 2016; the risk of bias for this outcome to be high.
Smania 2010; Volpe 2014; Wong-Yu 2015). Forty studies reported
that there were no adverse events (Canning 2012; Capato 2020a; We rated the confidence in the evidence for adverse events using
Carroll 2018; Chaiwanichsiri 2011; Cherup 2021; Cheung 2018; the GRADE approach (Schünemann 2022). We downgraded our
Colgrove 2012; Cugusi 2015; Dipasquale 2017; Fisher 2008; Frazzitta confidence in the evidence by two levels for risk of bias due to highly
2015; Ganesan 2014; Hass 2012; Hubble 2018; Lee HJ 2018; Liao heterogeneous and frequently incomplete reporting of safety data.
2015; Mak 2021; Morris 2009; Myers 2020; Nadeau 2014; Ni 2016; We downgraded by one level for imprecision, as we could not
Ortiz-Rubio 2018; Park 2014; Pérez de la Cruz 2017; Picelli 2016; estimate the effects using quantitative analyses. As a result, the
Pohl 2013; Pohl 2020; Ribas 2017; Santos 2017a; Schaible 2021; evidence is very uncertain about the effect of physical exercise on
Schenkman 1998; Shanahan 2017; Silva-Batista 2018; Solla 2019; the risk of adverse events.
Szefler-Derela 2020; Tollar 2018; Tollar 2019; Yang 2010; Yuan
2020; Zhang 2015), and four studies reported that there were no

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Subgroup analyses 95% CI -1.24 to 0.00; mind-body training: SMD -0.48, 95% CI -1.03 to
0.08), but the CIs touched or extended across the line of no effect.
We conducted subgroup analyses by the length of intervention (<
Also, the effect of dance on the severity of motor signs may be
12 weeks, ≥ 12 weeks) for all outcomes included in the NMAs. Due
superior to the effect of mind-body training, but the CI extended
to the distribution of characteristics of the included studies and
across the line of no effect (SMD -0.47, 95% CI -1.02, 0.08).
participants, we were not able to perform subgroup analyses by the
age (< 50 years, ≥ 50 years), sex (male, female), or cognitive stage In the analysis of studies with an intervention lasting less than
(without cognitive impairment, with cognitive impairment) of the 12 weeks using a passive control group as reference treatment,
participants. We describe the results of the NMAs for each outcome, the highest-ranked interventions were mind-body training (P-
separated by the length of intervention, below (data not shown). score: 0.78), aqua-based training (P-score: 0.77), and gait/balance/
Please note that there is no formal statistical test for the presence functional training (P-score: 0.71). The lowest-ranked interventions
of subgroup differences in NMAs. Therefore, we have reported the were flexibility training (P-score: 0.06), a passive control group (P-
results of the subgroup analyses narratively; these results should score: 0.17), and an active control group (P-score: 0.30).
be interpreted with caution (see also 'Impact of the length of the
intervention' section in the Summary of main results). In the analysis of studies with an intervention lasting for 12
weeks or longer using a passive control group as reference
Severity of motor signs treatment, the highest-ranked interventions were dance (P-score:
From 71 studies reporting the severity of motor signs, the length of 0.89), endurance training (P-score: 0.70), and strength/resistance
intervention was less than 12 weeks for 41 studies, and 12 weeks training (P-score: 0.68). The lowest-ranked interventions were a
or longer for 30 studies. The network of studies (1514 participants) passive control group (P-score: 0.15), flexibility training (P-score:
with interventions lasting less than 12 weeks included data on 0.16), and an active control group (P-score: 0.33).
all interventions included in the full analysis (i.e. all interventions
Cochran's Q test and I2 statistics indicated that there was moderate
except for gaming), while no data on aqua-based training, LSVT
to substantial heterogeneity between the studies in the subgroup
BIG, and gaming were included in the network of studies (1032
analyses (< 12 weeks: Qtotal = 93.57, df = 34, P < 0.001; Qwithin =
participants) with interventions lasting for 12 weeks or longer. Both
networks were fully connected. 53.09, df = 19, P < 0.001; Qbetween = 40.48, df = 15; P < 0.001; I2 =
63.7%, Tau2 = 0.1925; and ≥ 12 weeks: Qtotal = 60.11, df = 25, P <
Analyzing studies with an intervention length of less than 12 weeks, 0.001; Qwithin = 23.18, df = 13, P = 0.040; Qbetween = 36.94, df = 12, P
we found evidence suggesting that the severity of motor signs was < 0.001; I2 = 58.4%, Tau2 = 0.1593).
decreased for four interventions compared to a passive control
group (mind-body training: SMD -0.65, 95% CI -1.17 to -0.12; aqua- Quality of life
based training: SMD -0.63, 95% CI -1.12 to -0.14; gait/balance/
functional training: SMD -0.56, 95% CI -0.94 to -0.18; multi-domain From 55 studies reporting QoL, the length of intervention was less
training: SMD -0.52, 95% CI -0.88 to -0.18). We did not identify than 12 weeks for 35 studies, and 12 weeks or longer for 20 studies.
evidence for further statistically significant effects. However, we The network of studies (1826 participants) with interventions
observed that several interventions may also have beneficial lasting for less than 12 weeks included data on all interventions
effects on the severity of motor signs compared to an active control included in the full analysis except for flexibility training, while
group, but the CIs extended across the line of no effect (aqua-based no data on gaming, dance, and LSVT BIG were included in the
training: SMD -0.48, 95% CI -1.05 to 0.09; gait/balance/functional network of studies (1457 participants) with interventions lasting for
training: SMD -0.40, 95% CI -0.83 to 0.02; multi-domain training: 12 weeks or longer. Both networks were fully connected.
SMD -0.36, 95% CI -0.80 to 0.07). Similarly, some interventions may
Analyzing studies with an intervention length of less than 12 weeks,
have beneficial effects on the severity of motor signs compared
we found evidence suggesting that QoL was increased for three
to flexibility training, but, again, the CIs extended across the line
interventions compared to a passive control group (aqua-based
of no effect (mind-body training: SMD -1.48, 95% CI -2.99 to 0.02;
training: SMD -1.01, 95% CI -1.61 to -0.42; endurance training: SMD
aqua-based training: SMD -1.47, 95% CI -2.98 to 0.05; gait/balance/
-0.57, 95% CI -1.04 to -0.10; strength/resistance training: SMD -0.58,
functional training: SMD -1.39, 95% CI -2.87 to 0.09).
95% CI -1.15 to -0.01). No further statistically significant effects
Analyzing studies with an intervention length of 12 weeks or longer, were observed. Gait/balance/functional training lasting for up to 12
we found evidence suggesting that the severity of motor signs was weeks may have a beneficial effect on QoL compared to a passive
decreased for five interventions compared to a passive control control group, but the CI extended across the line of no effect (SMD
group (dance: SMD -0.93, 95% CI -1.42 to -0.43; endurance training: -0.37, 95% CI -0.77 to 0.02). Furthermore, the effect of aqua-based
SMD -0.66, 95% CI -1.12 to -0.20; strength/resistance training: SMD training may be superior to the effects of other types of physical
-0.64, 95% CI -1.18 to -0.11; multi-domain training: SMD -0.60, exercise - for example, gait/balance/functional training (SMD -0.64,
95% CI -0.99 to -0.21; mind-body training: SMD -0.46, 95% CI -0.80 95% CI -1.19 to -0.09) or LSVT BIG (SMD -1.24, 95% CI -2.48 to 0.00) -
to -0.11). Also, the evidence suggests that the severity of motor but the CIs extended across or touched the line of no effect.
signs was decreased for three interventions compared to flexibility
Analyzing studies with an intervention length of 12 weeks or longer,
training (dance: SMD -0.95, 95% CI -1.67 to 0.22; endurance training:
we found evidence suggesting that QoL was increased for four
SMD -0.68, 95% CI -1.28 to -0.07; strength/resistance training: SMD
interventions compared to a passive control group (dance: SMD
-0.66, 95% CI -1.29 to -0.03). Similar to the interventions lasting less
-0.68, 95% CI -1.29 to -0.08; mind-body training: SMD -0.51, 95%
than 12 weeks, some interventions lasting longer than 12 weeks
CI -0.88 to -0.14; multi-domain training: SMD -0.37, 95% CI -0.66
may also have beneficial effects on the severity of motor signs
to -0.08; gait/balance/functional training: SMD -0.29, 95% CI -0.55
compared to flexibility training (multi-domain training: SMD -0.62,
to -0.02). The evidence also suggests that QoL was increased

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compared to an active control group for seven interventions the CIs crossed the line of no effect (strength/resistance training:
(dance: SMD -1.45, 95% CI -2.26 to -0.63; mind-body training: SMD SMD -0.86, 95% CI -1.73 to 0.02; gait/balance/functional training:
-1.27, 95% CI -1.95 to -0.59; endurance training: SMD -1.24, 95% SMD -0.45, 95% CI -0.96 to 0.06).
CI -2.01 to -0.48; multi-domain training: SMD -1.13, 95% CI -1.70
to -0.57; aqua-based training: SMD -1.05, 95% CI -2.09 to -0.01; Similarly to the full analysis, in the analysis of studies with
gait/balance/functional training: SMD -1.05, 95% CI -1.61 to -0.48; an intervention length of less than 12 weeks, the highest-
strength/resistance training: SMD -1.00, 95% CI -1.68 to -0.32) as ranked interventions using a passive control group as reference
well as for a passive control group (SMD -76, 95% CI -1.35 to treatment were strength/resistance training (P-score: 0.77), aqua-
-0.17). Moreover, we observed evidence suggesting that QoL was based training (P-score: 0.68), and dance (P-score: 0.64), and the
increased for mind-body training compared to flexibility training lowest-ranked interventions were an active control group (P-score:
(SMD -0.63, 95% CI -1.12 to -0.14). None of the remaining effects 0.09), a passive control group (P-score: 0.34), and multi-domain
were statistically significant. However, the effects of both dance and training (P-score: 0.38).
multi-domain training on QoL may be increased compared to the
In the analysis of studies with an intervention lasting for 12
effect of flexibility training, but the CIs touched or extended across
weeks or longer using a passive control group as reference
the line of no effect (dance: SMD -0.81, 95% CI -1.62 to 0.00; multi-
treatment, the highest-ranked intervention was gait/balance/
domain training: SMD -0.50, 95% CI -1.09 to 0.10).
functional training (P-score: 0.78) followed by dance (P-score: 0.58),
For the analysis of studies with an intervention length of less than strength/resistance training (P-score: 0.58), a passive control group
12 weeks, the presence of moderate to substantial heterogeneity (P-score: 0.38), and multi-domain training (P-score: 0.18). However,
between the studies, as indicated by I2 statistics, was not found to as for the full analysis, the ranking of the interventions should be
be statistically significant according to Cochran's Q test (Qtotal = interpreted very carefully given the large size of the confidence
75.33, df = 28, P < 0.001; Qwithin = 51.44, df = 12, P < 0.001; Qbetween intervals of the effect estimates and the absence of evidence for
effects in the subgroup analyses.
= 23.88, df = 16, P = 0.09; I2 = 52.8%, Tau2 = 0.1670). There was no
evidence of important heterogeneity in the analysis of studies with Cochran's Q test and I2 statistics did not indicate that there
an intervention lasting for 12 weeks or longer (Qtotal = 21.92, df = 14, was important heterogeneity in the analysis of studies with an
P = 0.08; Qwithin = 11.69, df = 7, P = 0.111; Qbetween = 10.24, df = 7, P intervention length of less than 12 weeks (Qtotal = 6.12, df = 4, P
= 0.18; I2 = 36.1%, Tau2 = 0.0839). = 0.19; Qwithin = 0.31, df = 1, P = 0.58; Qbetween = 5.81, df = 3, P
= 0.12; I2 = 34.6%, Tau2 = 0.0594). However, there was evidence of
In the analysis of studies with an intervention lasting less than 12
moderate to substantial heterogeneity in the analysis of studies
weeks using a passive control group as reference treatment, the
with an intervention lasting for 12 weeks or longer (Q = 13.37, df =
highest-ranked interventions were aqua-based training (P-score:
5, P = 0.02; I2 = 62.6%, Tau2 = 0.1601).
0.96), endurance training (P-score: 0.75), and strength/resistance
training (P-score: 0.74). The lowest-ranked interventions were a Functional mobility and balance
passive control group (P-score: 0.19), LSVT BIG (P-score: 0.19), and
dance (P-score: 0.26). From 54 studies reporting functional mobility and balance, the
length of intervention was less than 12 weeks for 31 studies, and
In the analysis of studies with an intervention lasting for 12 weeks 12 weeks or longer for 23 studies. The network of studies (1514
or longer using a passive control group as reference treatment, participants) with interventions lasting for less than 12 weeks
the highest-ranked interventions were dance (P-score: 0.86), mind- included data on all interventions, while no data on aqua-based
body training (P-score: 0.78), and endurance training (P-score: training, gaming, and LSVT BIG were included in the network
0.72). The lowest-ranked interventions were an active control group of studies with interventions lasting 12 weeks or longer (1032
(P-score: 0.01), flexibility training (P-score: 0.20), and a passive participants). Both networks were fully connected.
control group (P-score: 0.24).
Analyzing studies with an intervention length of less than 12
Freezing of gait weeks, we found evidence for differences in functional mobility
and balance in favor of mind-body training compared with gait/
From 20 studies reporting freezing of gait, the length of intervention
balance/functional training (SMD -1.40, 95% CI -2.61 to -0.20),
was less than 12 weeks for 11 studies, and 12 weeks or longer
strength/resistance training (SMD -1.41, 95% CI -2.78 to -0.05),
for nine studies. The network of studies (1457 participants) with
multi-domain training (SMD -1.42, 95% CI -2.54 to -0.30), dance
interventions lasting for less than 12 weeks included data on all
(SMD -1.67, 95% CI -3.09 to -0.24), endurance training (SMD -1.78,
interventions included in the full analysis (i.e. all interventions
95% CI -3.38 to -0.17), an active control group (SMD -1.97, 95% CI
except for endurance, flexibility training, gaming, and LSVT BIG),
-3.32 to -0.63), a passive control group (SMD -2.14, 95% CI -3.32 to
while the network of studies (505 participants) with interventions
-0.95), and flexibility training (SMD -2.77, 95% CI -5.10 to -0.45). Also,
lasting for 12 weeks or longer only included data on gait/balance/
the evidence suggests that functional mobility and balance were
functional training, dance, strength/resistance, and multi-domain
increased for aqua-based training compared with gait/balance/
training, and a passive control group. Both networks were fully
functional training (SMD -0.68, 95% CI -1.34 to -0.03), multi-domain
connected.
training (SMD -0.70, 95% CI -1.37 -0.03), an active control group
No statistically significant effects were observed in the subgroup (SMD -1.26, 95% CI -2.16 to -0.35), and a passive control group
analyses. However, analyzing studies with an intervention length of (SMD -1.42, 95% CI -2.18 to -0.65), and for gait/balance/functional
less than 12 weeks, as for the full analysis, both strength/resistance training compared with a passive control group (SMD -0.73, 95% CI
training and gait/balance/functional training may have beneficial -1.32 to -0.14). We did not observe evidence for further statistically
effects on freezing of gait compared to an active control group, but significant effects. Aqua-based training may have a large effect on

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functional mobility and balance compared to flexibility training, nine pairwise comparisons, and included data on all interventions
but the CI crossed the line of no effect (SMD -2.06, 95% CI -4.19 included in the full analysis except for endurance training and LSVT
to 0.08). Similarly, both strength/resistance training and multi- BIG.
domain training may have beneficial effects on functional mobility
and balance compared to a passive control group, but the CIs The evidence suggests that the severity of motor signs was
crossed the line of no effect (strength/resistance training: SMD decreased for dance compared to a passive control group (SMD
-0.72, 95% CI 1.52 to 0.07; multi-domain training: SMD -0.72, 95% CI -1.69, 95% CI -3.31 to -0.06). In comparison to an active control
-1.46 to 0.02). group, the evidence suggests that the severity of motor signs was
decreased for dance (SMD -1.65, 95% CI -2.87 to -0.42), and for
In the analysis of studies with an intervention length of 12 weeks or gait/balance/functional training (SMD -0.88, 95% CI -1.24 to -0.53).
longer, we observed evidence suggesting differences in functional Moreover, the evidence suggests decreases in the severity of motor
mobility and balance in favor of endurance training compared with signs compared to flexibility training for dance (SMD -1.49, 95% CI
flexibility training (SMD -1.54, 95% CI -2.90 to -0.17), and a passive -2.58 to -0.41), mind-body training (-0.84, 95% CI -1.20 to -0.48),
control group (SMD -1.62, 95% CI -2.68 to -0.55), as well as for and strength/resistance training (SMD -0.60, 95% CI -0.95 to -0.24).
dance compared with flexibility training (SMD -1.22, 95% -2.38 to Furthermore, the evidence suggests that the severity of motor signs
-0.06) and a passive control group (SMD -1.30, 95% CI -2.11 to was decreased for dance compared to multi-domain training (SMD
-0.50). Moreover, the evidence suggests that functional mobility -0.99, 95% CI -1.85 to -0.14). No more statistically significant effects
and balance were increased in comparison with a passive control were observed. However, the CIs of many comparisons were wide
group for gait/balance/functional training (SMD -1.06, 95% -1.95 and included up to large effects while crossing the line of no effect
to -0.17), multi-domain training (SMD -0.94, 95% CI -1.55 to -0.33), (e.g. dance compared to strength/resistance training: SMD -0.90,
mind-body training (SMD -0.79, 95% CI -1.23 to -0.34), and strength/ 95% CI -1.92 to 0.13; mind-body training compared to a passive
resistance training (SMD -0.67, 95% CI -1.27 to -0.08). The effect of control group: SMD -1.03, 95% CI -2.25 to 0.18; mind-body training
an active control group on functional mobility and balance may be compared to strength/resistance training: SMD -0.24, 95% CI -0.59
increased compared to the effect of a passive control group, but the to 0.10), or large effects in both directions (e.g. multi-domain
very wide CI, including a large effect in favor of the active control training compared to aqua-based training: SMD -0.01, 95% CI -1.06
group, crossed the line of no effect (SMD -1.59, 95% CI -3.21 to 0.04). to 1.04).

Using a passive control group as reference treatment, mind-body The highest-ranked interventions were dance (P-score: 0.95),
training (P-score: 0.97), aqua-based training (P-score: 0.86), and mind-body training (P-score: 0.76), and gait/balance/functional
gait/balance/functional training (P-score: 0.58) were the highest- training (P-score: 0.67). The lowest-ranked interventions were an
ranked interventions, and flexibility training (P-score: 0.13), a active control group (P-score: 0.14), a passive control group (P-
passive control group (P-score: 0.18), and an active control group score: 0.19), and flexibility training (P-score: 0.20). Aqua-based
(P-score: 0.26) were the lowest-ranked interventions in the NMA of training, which was ranked second among 11 interventions in the
studies with an intervention lasting for less than 12 weeks. full analysis, was ranked sixth among nine interventions in the
sensitivity analysis.
In the NMA of studies with an intervention lasting 12 weeks or
longer, the highest-ranked interventions were endurance training Please note that the results of the sensitivity analysis should be
(P-score: 0.84), an active control group (P-score: 0.78) and dance interpreted with caution, given the limited amount of data and the
(P-score: 0.74). The lowest-ranked interventions were a passive large confidence intervals in the effect estimates.
control group (P-score: 0.06), flexibility training (P-score: 0.11), and
strength/resistance training (P-score: 0.37). DISCUSSION

Cochran's Q test and I2 statistics indicated that there was Summary of main results
substantial to considerable heterogeneity between the studies in
Our objectives were to compare the effects of different types of
the subgroup analyses (< 12 weeks: Qtotal = 116.39, df = 22, P < 0.001;
physical exercise in adults with Parkinson's disease (PD) on the
Qwithin = 34.07, df = 13, P = 0.001; Qbetween = 82.32, df = 9, P < 0.001; severity of motor signs, quality of life (QoL), and the occurrence of
I2 = 81.1%, Tau2 = 0.4526; and ≥ 12 weeks: Qtotal = 67.18, df = 18, P < adverse events, and to generate a clinically meaningful treatment
0.001; Qwithin = 11.72, df = 7, P = 0.11; Qbetween = 55.46, df = 11, P < ranking using network meta-analyses (NMAs).
0.001; I2 = 73.2%, Tau2 = 0.3271).
We identified 156 randomized controlled trials (RCTs) which
Sensitivity analysis evaluated physical exercise for people with PD. We included 109
studies, providing data on 4394 participants, in our NMAs. The
We used the Risk of Bias 2 tool (RoB 2) to assess risk of bias for studies comprised various types of physical exercise which we
the study results on the severity of motor signs and QoL (Sterne categorized into 10 groups of exercise based on an adapted version
2019). We performed sensitivity analyses to test the robustness of of the ProFaNE taxonomy (Lamb 2011):
our results by analyzing trial results at low overall risk of bias. Since
we judged all study results on QoL to be at high risk of bias, we only • aqua-based training;
performed a sensitivity analysis for study results on the severity of • dance;
motor signs.
• endurance training;
The sensitivity analysis on the severity of motor signs included • flexibility training;
seven study results judged to be at low risk of bias (492 • gait/balance/functional training;
participants). The fully-connected network was based on only • gaming;
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• LSVT BIG; • The fully-connected network for the effects on freezing of

• mind-body training; gait included data from 20 studies (1048 participants) on all
• multi-domain training; and interventions except for endurance training, flexibility training,
gaming, and LSVT BIG. Gait/balance/functional training may
• strength/resistance training.
have a beneficial effect on freezing of gait, but the CI extended
These interventions were compared to another type of physical across the line of no effect. The intervention with the highest
exercise, an active control group, or, most frequently, to a passive rank was strength/resistance training, followed by aqua-based
control group. training and dance. The lowest-ranked interventions were an
active control group, followed by multi-domain training and a
Effects on severity of motor signs, quality of life, freezing of passive control group.
gait, and functional mobility and balance • The fully-connected network for the effects on functional
mobility and balance included data from 54 studies (2546
We conducted NMAs for the severity of motor signs, QoL, freezing
participants) on all interventions. The evidence suggests that
of gait, and functional mobility and balance. For each of these
functional mobility and balance were increased for seven
outcomes, we generated a treatment ranking based on a fully-
interventions compared to a passive control group (i.e. aqua-
connected network. Due to heterogeneity in measuring and
based training, mind-body training, dance, endurance training,
reporting of safety outcomes, we were not able to conduct an NMA
gait/balance/functional training, strength/resistance training,
on adverse events.
and multi-domain training). LSVT BIG may have a beneficial
We report the results and our confidence in the evidence for effect on functional mobility and balance, but the confidence
the effects of each type of physical exercise compared to a interval (CI) extended across the line of no effect. The
passive control group, on the severity of motor signs and QoL, in intervention with the highest rank was aqua-based training,
Summary of findings 1 and Summary of findings 2, respectively. We followed by LSVT BIG and mind-body training. The lowest-
summarize below the results for the effects of each type of physical ranked interventions were a passive control group, followed by
exercise compared to a passive control group, and for differences in flexibility training and an active control group.
the effects between exercise types, on all outcomes.
Across outcomes, we observed only little evidence of differences in
We observed evidence of beneficial effects for several types of the effects between different types of physical exercise, as follows.
physical exercise compared to a passive control group:
• The evidence suggests that the effect of aqua-based training
• The fully-connected network for the effects on the severity of on QoL was superior to the effects of gait/balance/functional
motor signs included data from 71 studies (3196 participants) training and multi-domain training. The effect of aqua-based
on all interventions except for gaming. The evidence suggests training on QoL may also be increased compared to dance and
that dance has a moderate beneficial effect on the severity of strength/resistance training, but the CIs touched or extended
motor signs (high confidence), and aqua-based, gait/balance/ across the line of no effect. The evidence also suggests that the
functional, and multi-domain training might have a moderate effect of aqua-based training on functional mobility and balance
beneficial effect on the severity of motor signs (low confidence). was superior to the effects of gait/balance/functional training,
We also found that mind-body and endurance training might strength/resistance training, and multi-domain training.
have a small beneficial effect on the severity of motor signs • We observed evidence suggesting that the effects of flexibility
(low confidence). Flexibility training might have a trivial or training were inferior to the effects of one or more types of
no effect on the severity of motor signs (low confidence). physical exercise in each analysis that included data on this
The evidence is very uncertain about the effects of strength/ intervention (i.e. severity of motor signs, QoL, and functional
resistance training and LSVT BIG on the severity of motor mobility and balance).
signs (very low confidence). The intervention with the highest
rank was dance, followed by aqua-based and gait/balance/ In summary, we observed evidence of beneficial effects on various
functional training. The lowest-ranked interventions were outcomes for several types of physical exercise, but little evidence
flexibility training, followed by a passive and an active control of differences between these interventions.
group.
Effects on adverse events
• The fully-connected network for the effects on QoL included
data from 55 studies (3283 participants) on all interventions. The The measurement and reporting of adverse events was highly
evidence suggests that aqua-based training probably has a large heterogeneous and frequently incomplete. Among 156 studies
beneficial effect on QoL (moderate confidence). The evidence included in this review, 85 studies (5192 participants) provided
also suggests that endurance training might have a moderate some kind of safety data; that is, data on events described as
beneficial effect, and that gait/balance/functional and multi- adverse events. Forty trials reported that there were no adverse
domain training might have a small beneficial effect on QoL (low events and four trials reported that there were no serious or major
confidence). The evidence is very uncertain about the effects adverse events. Twenty-eight studies reported that adverse events
of mind-body training, gaming, strength/resistance training, occurred. The most frequently reported events were falls (reported
dance, LSVT BIG, and flexibility training on QoL (very low in 18 studies) and pain (reported in 10 studies). Most studies
confidence). The intervention with the highest rank was aqua- reported events for the intervention groups only. The evidence is
based training, followed by endurance and mind-body training. very uncertain about the effect of physical exercise on the risk of
The lowest-ranked interventions were an active control group, adverse events (very low confidence).
followed by a passive control group and flexibility training.

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Impact of the length of the intervention categorized as an eligible intervention or comparator as clearly as
other interventions of the same category.
The pattern of evidence we observed in subgroup analyses
separated by the length of the intervention was similar to the Second, we did not include some types of physical exercise, such
pattern observed in the full analysis including all studies. First, as as boxing, in this review. As a result, we did not include the entire
in the full analysis, we found evidence of statistically significant landscape of studies on physical exercise for people with PD.
effects on the severity of motor signs, QoL, and functional mobility
and balance in favor of several types of physical exercise, but no Third, for those exercise types we did include, we may have masked
evidence of statistically significant effects on freezing of gait in the the impact of potential effect modifiers. For example, our taxonomy
subgroup analyses. Second, we observed only little evidence of led us to categorize both tango and waltz/foxtrot as 'dance' types
differences between the interventions. In particular, we observed of physical exercise. However, if certain features that vary between
evidence of statistically significant effects on the severity of motor these dance styles are important for the effects of exercise - as
signs, QoL, and functional mobility and balance, in favor of suggested by Hackney and colleagues who compared tango, waltz/
an intervention compared with a passive control group, more foxtrot, and no intervention, and identified evidence of differences
frequently in the analyses of studies with an intervention lasting in the effects of the dance styles (Hackney 2009) - we would have
for 12 weeks or longer compared to the analyses of studies with an masked the impact of those features.
intervention lasting for a shorter period. Therefore, the observation
of beneficial effects for people with PD might be facilitated by Fourth, it should be noted that our ability confidently to categorize
longer training periods. We seldom observed evidence suggesting interventions according to the dominant exercise category varied
that there were statistically significant differences between the for different exercise types. For example, we were more certain
interventions with regard to their effect on QoL and functional in categorizing interventions as dance or mind-body training
mobility and balance, but we observed such evidence more than we were categorizing interventions that comprised treadmill
frequently in the analyses of studies with an intervention length training, for example, which could have been categorized either
of less than 12 weeks compared to the analyses of studies with as gait/balance/functional training, endurance training, or even
an intervention lasting for 12 weeks or longer. The results of the multi-domain training based on the information describing this
subgroup analyses should be interpreted with caution. First, since intervention.
there is no formal statistical test for the presence of subgroup
differences, our observation of a potentially positive impact of the Finally, our definition of some categories was quite narrow. We
intervention length should be regarded as exploratory. Second, considered interventions that deliver the 'Lee Silverman Voice
differences between the interventions should be interpreted Training BIG' (LSVT BIG) as a separate exercise category, as we
carefully due to the lack of full data on all interventions in some were particularly interested in this intervention. However, we
subgroup analyses, and large confidence intervals in the effect included data from only three trials with this intervention in
estimates. Third, it should be noted that, in addition to the effects this review, which limited our confidence in the effects of this
described above, we observed further estimates with CIs that program. Also, our 'gaming' category included interventions that
included beneficial effects of interventions but crossed the line of involve structured, physical exercises delivered via video-games,
no effect in both the full analyses and the subgroup analyses. virtual reality applications, or both. We limited this category to
interventions not already categorized as any of the other exercise
Overall completeness and applicability of evidence types. As a result, this category included data from only five trials,
and does not cover the various interventions for people with PD
Types of physical exercise in this systematic review that employ video-games, virtual reality applications, or related
We adapted the ProFaNE taxonomy developed in Lamb 2011 to technology. Combining these interventions would have required
categorize physical exercise, based on all the information available us to use a broader definition (e.g. virtual-reality-supported
describing the interventions' characteristics, according to the interventions, 'exergaming').
dominant exercise category, and irrespective of how the study
In conclusion, the approach we employed to define and compare
authors labeled the interventions (e.g. whether they described
the interventions should be regarded as an approximation of
interventions as an experimental or a control arm). This procedure
the full landscape of exercise programs available for people with
allowed us to group similar interventions and compare their effects
PD, and as a tool used to discriminate between groups of these
on people with PD in NMAs. However, we acknowledge that it also
interventions.
entailed making a series of decisions about study inclusion and
intervention classification that inevitably involved judgment and Flexibility training
trade-offs. We outline the main considerations below.
We did not observe any evidence of beneficial effects of flexibility
First, applying the ProFaNE taxonomy in the way we did required training. However, the flexibility training interventions included in
us to exclude studies comparing interventions that were too similar our review were usually used by trialists as a control group without
to be grouped into different categories of our taxonomy. Similarly, the intention to show any positive effects. Therefore, we cannot
we pooled arms of interventions that fell into the same category rule out that well-designed flexibility training might have beneficial
according to our taxonomy, but may have varied in features effects for people with PD.
irrelevant to the taxonomy (e.g. intensity), allowing a certain
degree of heterogeneity within the categories. Moreover, in order Timing of assessment of motor signs
to preserve homogeneity within our categories, for three studies, For the sake of consistency, we prioritised data on the severity
we did not include all study arms in our analyses because the of motor signs (e.g. scores of the UPDRS-M) measured during
studies included treatments that did not fulfill the criteria for being the on-medication state, which was reported by most studies.

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However, one included study reported data for both the on- of motor signs for the majority of exercise types included in the
and off-medication states (Corcos 2013). The Corcos 2013 study sensitivity analysis (i.e. dance, mind-body training, gait/balance/
provided evidence of between-group differences when UPDRS- functional training, and strength/resistance training). The results of
M scores were measured during the off-medication state but no the sensitivity analysis should be interpreted with caution, given
evidence of statistically significant effects when measured during the limited amount of data and the large confidence intervals in the
the on-medication state. Similar results were observed in a study effect estimates. In order to test the robustness of the main results
of 130 participants with PD by Van der Kolk and colleagues, who based on more data in future evidence syntheses, we will consider
compared an endurance training with a control group instructed extending the sensitivity analyses to the inclusion of trial results
to do stretching, flexibility, and relaxation exercises, and found with 'some concerns' regarding risk of bias.
evidence of a beneficial effect of endurance training on MDS-
UPDRS-M scores only when measured during the off-medication Adverse events
state (Van der Kolk 2019). While this study was not eligible for Almost half of the studies (46%) did not provide any safety data.
inclusion in this review, as the number of supervised sessions was Reporting was highly heterogeneous and frequently incomplete
below five (i.e. the minimum level of supervision required), it is in those studies that reported data on adverse events. Moreover,
in line with the study by Corcos and colleagues suggesting that we only summarized harms described as adverse events by the
the timing of assessment with respect to the medication state trialists, but not harms recorded as reasons for dropout unless
could be a confounder (Corcos 2013). Therefore, combining data they were described elsewhere as adverse events by the trialists.
measured during the on-medication state with data measured Thus, given that trialists have different definitions of relevant
during the off-medication state across trials may have masked the adverse events, we cannot rule out that potentially relevant events
potential impact of this confounder and increased heterogeneity in occurred, but were not reported, either at the study-level or at
our results. the level of our synthesis. Therefore, the evidence is likely to be
incomplete, and judgments about the safety of physical exercise for
Study population in this systematic review
people with PD based on our review remain very uncertain.
Most studies included only people with mild to moderate PD and
without major cognitive impairment. Therefore, the applicability Ongoing studies and studies awaiting classification
of our results to people with advanced disease severity, major In addition to the studies included in our review, we identified
cognitive impairment, or both, might be limited. numerous records of trials that are potentially eligible for inclusion
in our review. We identified 68 trials as awaiting classification and
Inconsistency, heterogeneity
58 ongoing trials. However, most of these references are records
Investigating the presence of heterogeneity and inconsistency, from trial registries with limited information, and we derived our
both locally and globally, we identified some disagreements judgment of 'potentially eligible' using a high level of sensitivity
between direct and indirect estimates, as well as heterogeneity and a low level of specificity in order to capture any relevant
in both pairwise comparisons and the entire networks. When trials for a future update of this review. Given the specificity of
reviewing the evidence base, we usually found discrepancies to our inclusion criteria (e.g. interventions need to be designed and
be explained by the distribution of potential effect modifiers, such compared appropriately to match our categorization of exercise
as the intensity of the intervention (as indicated by the frequency types or control groups), we assume that the number of trials that
and duration of exercise sessions, the length of the intervention, are actually eligible for inclusion in our review is only a fraction of
or both), or by outlying effects of single studies that may have these numbers. Therefore, we do not think that our analyses miss a
occurred due to the generally small number of participants in relevant amount of data at this time. Nevertheless, including data
the included studies. Moreover, we had generally expected to from these studies in a future update of this review may change our
see some degree of heterogeneity given the number and variety results.
of interventions for people with PD included in our review. We
accounted for inconsistency and heterogeneity in our ratings of Despite all these limitations, we were able to identify a large
confidence in the evidence. number of trials comparing a variety of physical exercise types with
each other and with control groups considering several efficacy
Sensitivity analysis outcomes. In our NMAs, which were exclusively based on fully-
connected networks, we were able to include data from up to 3283
We assessed the risk of bias only for study results on our primary
participants with PD, emphasizing the overall completeness and
outcomes; namely, the severity of motor signs and QoL. Since we
applicability of our findings.
judged all study results on QoL to be at high risk of bias, we only
performed a sensitivity analysis for the study results on the severity Quality of the evidence
of motor signs. Thus, we tested the robustness of our results by
analyzing trial results at low overall risk of bias only to a limited Risk of bias
extent. The results of the sensitivity analysis on the severity of
We assessed risk of bias for each study result on the severity of
motor signs were fairly comparable to the results of the full analysis.
motor signs and QoL. Overall, a large number of study results had
First, we identified evidence of effects on the severity of motor
a high risk of bias. For the severity of motor signs, we judged 35
signs in favor of several types of physical exercise compared to
study results (49%) to be at high risk of bias. Due to the nature of
a control group. As compared to the full analysis, we observed
self-reported questionnaires and the corresponding subjectivity of
evidence of effects on the severity of motor signs compared to a
the assessment of QoL, we judged all study results to be at high
passive control group for fewer interventions. However, when also
overall risk of bias (i.e. due to high risk of "bias in measurement
considering the comparisons with an active control group and with
of the outcome", as assessed with domain 4 of the Risk of Bias 2
flexibility training, the evidence suggests decreases in the severity
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tool (RoB 2; Sterne 2019). When only considering domains that are multi-domain training, dance, LSVT BIG, and flexibility training) on
not affected by self-reporting of the outcome, we judged 27 study QoL by default. Additionally, we downgraded by a second level for
results (49%) on QoL to be at high risk of bias. Most frequently, we risk of bias for the effects of mind-body training, gaming, dance,
judged the overall risk of bias to be high, because we had concerns and flexibility training on QoL, because the effects have a large
regarding domain 2 of the RoB tool (i.e. "bias due to deviations contribution from studies at high risk of bias even when considering
from intended interventions"). In particular, the results reported only domains that are not affected by the subjectivity of the
by trialists frequently lacked data from a substantial proportion assessment. The CIs corresponding to the effects of gaming, LSVT
of participants (≥ 10%) who had been randomized. Therefore, we BIG, and flexibility training on QoL include effects in both directions.
often saw the potential for a substantial impact on the result due to Therefore, we downgraded by two levels for imprecision. We
the failure to include these participants in the analyses. downgraded by one level for imprecision for the effect of dance
on QoL, because the estimate favors the intervention and the
Using an informal assessment of risk of bias, we judged the risk of CI extends into the range of equivalence across the line of
bias for results on adverse events to be high, because reporting of no effect. For the effects of endurance training, gait/balance/
safety data was highly heterogeneous and frequently incomplete. functional training, mind-body training, multi-domain training, and
strength/resistance training on QoL, we downgraded by one level
Confidence in the evidence
for heterogeneity, because the PIs include effects in both directions
We rated our confidence in the evidence for the effects on (i.e. the PIs extend beyond the range of equivalence on the opposite
the severity of motor signs and QoL of each type of physical side of the line of no effect favoring the passive control group), while
exercise compared with a passive control group. The most common the CIs include effects in favor of the interventions. We downgraded
limitations to our confidence in the effects were a large proportion by two levels for incoherence for the effect of strength/resistance
of studies at high risk of bias and large prediction intervals. training on QoL, because the CI of the indirect estimate includes
effects in favor of both interventions (i.e. the CI extends beyond
For the effects of aqua-based training, gait/balance/functional the range of equivalence on the opposite side of the line of no
training, multi-domain training, strength/resistance training, and effect favoring the passive control group), while the CI of the direct
mind-body training on the severity of motor signs, we downgraded estimate includes an effect in favor of strength/resistance training.
by one level for risk of bias due to the large contribution of studies at We also downgraded by two levels for incoherence for the effects
high risk of bias, and inconsistency between results of the primary of gaming, LSVT BIG, and flexibility training, because the estimates
analysis and the sensitivity analysis limited to studies at low risk are based on indirect evidence only and the global approach to
of bias. For the effects of endurance training and LSVT BIG on the assess incoherence is significant (P < 0.05, I2 = 60.0%). For the effects
severity of motor signs, we downgraded by one level for risk of of gaming, strength/resistance training, LSVT BIG, and flexibility
bias due to the large contribution of studies with at least some training, the overall level of confidence was very low even when
concerns regarding risk of bias. No sensitivity analysis limited to avoiding downgrading more than once for related concerns (i.e.
studies at low risk of bias was available for these effects. We imprecision, heterogeneity, and incoherence).
downgraded by two levels for imprecision for the effects of LSVT
BIG and flexibility training on the severity of motor signs because We also rated the confidence in the evidence in the results on
the confidence intervals (CIs) include effects in both directions. adverse events, which we reported narratively. We downgraded the
For the effects of aqua-based training, gait/balance/functional confidence in the evidence by two levels for risk of bias due to highly
training, multi-domain training, strength/resistance training, mind- heterogeneous and frequently incomplete reporting of safety data,
body training, and endurance training on the severity of motor and we downgraded by one level for imprecision, as we could not
signs, we downgraded by one level for heterogeneity, because the estimate the effects using quantitative analyses.
prediction intervals (PIs) include effects in both directions (i.e. PI
extends beyond the range of equivalence on the opposite side of Potential biases in the review process
the line of no effect favoring the passive control group), while the We performed an in-depth literature search based on a sensitive
CIs include effects in favor of the interventions. We downgraded search strategy developed by an experienced information specialist
by one level for incoherence for the effect of strength/resistance (IM). The electronic database searches were complemented by
training on the severity of motor signs, because the CI of the searches of the proceedings of relevant international conferences
indirect estimate extends into the range of equivalence across and study registries, which allowed us to identify performed but
the line of no effect, while the CI of the direct estimate includes not published studies in order to detect potential publication bias.
an effect in favor of the intervention. Finally, since the estimates Moreover, we were in close collaboration with clinical experts and
for the effect of flexibility training on the severity of motor signs are therefore confident that we have identified all studies relevant
are based on indirect evidence only and the global approach to to the review question.
assess incoherence is significant (P < 0.05, I2 = 58.4%), we would
have downgraded by two levels for incoherence. However, in order In light of the large number of search results, one review authors
to avoid downgrading more than once for related concerns (i.e. (ME) performed the initial screening of titles and abstracts for
imprecision, heterogeneity, and incoherence), we downgraded the clearly irrelevant results (e.g. animal studies, pharmacological
overall level of confidence by no more than two levels. studies, single-arm studies). Two review authors (ME, AF) then
screened the remaining results in duplicate and independently.
Due to the nature of self-reported questionnaires and the Although we tried to maintain a high level of sensitivity during
corresponding subjectivity of the assessment, we downgraded by the initial screening, we recognize that this approach bears a
one level for risk of bias for the effects of all interventions (i.e. aqua- higher risk of missing relevant records compared to two authors
based training, endurance training, mind-body training, gaming, independently screening in duplicate at the initial screening
strength/resistance training, gait/balance/functional training, stage. Other relevant tasks were performed fully in duplicate and
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independently in order to minimize bias arising in the conduct of 920 participants (Tang 2019). The review authors found evidence
this review (i.e. data collection, assessment of risk of bias and the of beneficial effects on the severity of motor signs only for
confidence of the evidence). dance and tango, and evidence of beneficial effects on functional
mobility and balance for dance, tango, multimodal exercises, and
Both the risk of bias tool and the CINeMA approach are sensitive tai chi. No evidence of effects on QoL were observed. The only
to subjective assessments; thus, our judgments may diverge evidence of differences between the interventions was observed
from those of other review authors. Given the large number of in comparisons including a single study each (e.g. superiority
study results, we made a special effort to apply the criteria for in the effect of tango on severity of motor signs compared to
our judgments consistently. This approach may have produced tai chi). The review authors concluded by highlighting tango
judgments that were differently sensitive to specific studies and the as an effective option to improve the functional mobility for
way trialists reported them. people with PD. Given several methodological limitations (e.g.
the search strategy was non-comprehensive, addressing a limited
Agreements and disagreements with other studies or number of interventions; the study selection was limited to English
reviews articles; it was unclear whether all relevant steps were performed
To our knowledge, this is the largest and most comprehensive in duplicate by independent review authors; the reporting of
systematic review with NMAs comparing different types of physical statistical analyses and risk of bias judgments was unclear), we
exercise for people with PD. In general, the results of our review are think that comparability to our review is limited. Nevertheless,
largely consistent with the results of previous efforts to synthesize our results are in agreement with the ones observed by Tang and
the evidence on the efficacy and safety of physical exercise for colleagues as they found evidence of beneficial effects of different
people with PD. interventions, particularly for tango and dance, but also for other
interventions such as multimodal exercise, on the severity of motor
Evidence from systematic reviews with network meta- signs and functional mobility and balance. Moreover, consistent
analyses with our results, Tang and colleagues observed only little evidence
of differences between the interventions. In contrast to this review,
This section reflects on results on the severity of motor signs, we also identified evidence of beneficial effects for QoL for several
quality of life, freezing of gait, and functional mobility and balance. interventions.
The results of our review are, to a large extent, consistent with the
results of other systematic reviews with NMAs on physical exercise Kwok and colleagues' systematic review with NMA included
for people with PD, although comparability is limited due to several controlled clinical trials of a broad range of behavioral
methodological differences (Álvarez-Bueno 2021; Kwok 2022; Tang interventions for the management of freezing of gait (Kwok 2022).
2019). They included training programs that were eligible for inclusion in
our review (e.g. gait training on treadmill and mind-body exercises)
Alvarez-Bueno and colleagues conducted a systematic review as well as interventions we did not include (e.g. action observation
with NMA analyzing the effect of exercise programs on motor training and real-time biofeedback) (Kwok 2022). The NMA on
symptoms in people with PD (Álvarez-Bueno 2021). The review freezing of gait included data from 35 studies (1454 participants).
included 56 studies providing data from 2470 participants. Evidence of statistically significant effects on freezing of gait
The review authors categorized the interventions using nine compared to usual care or no treatment were found for obstacle
types of exercise (i.e. endurance, resistance, combined, balance, training, gait training with treadmill, and general exercise. Further
dance, alternative exercises such as yoga or tai chi, body- beneficial effects were found for action observation training
weight supported, and sensorimotor interventions including or and conventional physiotherapy after controlling for the baseline
not including endurance exercise). As in our review, the authors severity of freezing of gait. Evidence of differences between
identified evidence of positive effects on the severity of motor the behavioral interventions was observed only for comparisons
signs for several interventions compared with a control group involving obstacle training; that is, the effect of obstacle training on
(i.e. dance, endurance, resistance, sensorimotor training with or freezing of gait was superior to the effects of any other intervention
without endurance exercise). Based on the ranking and the effect except psycho-education. It should be noted that data on obstacle
sizes of the interventions, the authors concluded that interventions training were provided by only one small study (33 participants)
"including more complex and demanding activities (sensorimotor and CIs were large.
training including endurance, resistance, and dance) seem to be
the most effective..." (Álvarez-Bueno 2021). In line with our results, Several methodological differences limit the comparability of
however, the effect sizes had large confidence intervals (CIs), and the results from Kwok 2022 and our results. For example, we
there was no evidence of differences between the interventions. only included randomized controlled trials, while Kwok and
In contrast to our results, the authors did not identify evidence of colleagues also included a non-randomized study. Moreover, the
positive effects on the severity of motor signs for balance, body- authors' approach to categorizing interventions varied significantly
weight support, and combined exercises, although it should be from ours. For example, general exercises included aqua-based
noted that these CIs were also large and point estimates favored the training; mind-body exercises included dance; and conventional
interventions. Consistent with our results, there was no evidence of physiotherapy included strength/resistance training. In contrast,
differences between the interventions. we considered aqua-based training, dance, and strength/resistance
training as separate, stand-alone, exercise types. Furthermore, in
Tang and colleagues authored a review and NMA of exercise contrast to our review, covariates such as baseline severity of
interventions, including tai chi, qigong, resistance training, aerobic freezing of gait were statistically controlled for in the NMAs.
exercise, multimodal exercise training, dance, tango, and yoga,
for people with PD (Tang 2019). They included 19 studies with

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Despite these methodological differences, some of the results the effects of gait/balance/functional training and multi-domain
described by Kwok and colleagues may be considered as fairly training. Thus, including more recent data, combining both direct
similar to our results. First, in our review, we observed that and indirect evidence using an NMA, and applying a more nuanced
gait/balance/functional training may have a beneficial effect on concept of exercises delivered in a non-aquatic setting, our review
freezing of gait compared to both active and passive control confirms the potential of aqua-based training for people with PD to
groups. Although the CIs extended across the line of no effect reduce the severity of motor signs compared with a control group,
for both comparisons, descriptively, this pattern is consistent and adds to the evidence indicating that aqua-based training might
with Kwok and colleagues' observation of beneficial effects of be particularly beneficial in improving functional mobility and
obstacle training and gait training with treadmill compared to usual balance and QoL.
care. Second, Kwok and colleagues - who considered strength/
resistance training as a subtype of general exercise - found evidence Carapellotti and colleagues conducted a systematic review on the
of a beneficial effect of this exercise group on freezing of gait effects of several styles and techniques of dance (e.g. tango, Irish
compared to usual care. Similarly, we observed that strength/ set dancing, and ballet) for people with PD (Carapellotti 2020).
resistance training may have beneficial effects on freezing of gait They included sixteen trials (638 participants), and performed
compared to an active control group, although the CIs extended meta-analysis on nine trials. These results of Carapellotti 2020
across the line of no effect. We also found that dance may have a are comparable to ours to some degree. In line with our results,
beneficial effect on freezing of gait compared to an active control Carapellotti and colleagues found evidence of a positive effect of
group, although, again, the effect was not statistically significant. dance on the severity of motor signs compared with no exercise,
In contrast, Kwok and colleagues considered dance as a subtype but no evidence of differences in the effects of dance and other
of mind-body exercises and found no evidence of an effect on exercises. As observed in our review, Carapellotti and colleagues
freezing of gait for this exercise group. It should be kept in mind also found a positive effect of dance compared with no exercise
that the differences in how we defined exercise types limit the on functional mobility and balance, but no evidence of an effect
interpretability of these comparisons. on QoL. However, in contrast to our results, the review authors
also found evidence suggesting that the effects of dance on both
Evidence from systematic reviews with pairwise meta- QoL and functional mobility and balance were superior to the
analyses effects of an active control group (i.e. another exercise or physical
activity), although both results were based on data from only two
This section reflects on results on the severity of motor signs,
small studies. In summary, their results are consistent with our
quality of life, and functional mobility and balance. The results of
results indicating the potential of dance to reduce the severity of
our review are also, to a large extent, in agreement with the results
motor signs and improve functional mobility for people with PD.
of systematic reviews with pairwise meta-analyses on exercises
On the other hand, in contrast to our findings, Carapellotti 2020
such as aqua-based training or dance for people with PD.
observed some evidence that dance might be superior to other
Our results correspond to the results of a systematic review by active interventions.
Gomes Neto and colleagues that compared water-based exercise
In another review published in 2020, Chen and colleagues focused
(i.e. aerobic and strength exercises delivered in water) with land-
on the effects of several exercise types, including dance, on QoL for
based exercise or usual care (Gomes Neto 2020). They including
people with PD (Chen 2020). Based on data from 20 studies (1143
data on 435 participants from 15 studies. As observed in our
participants), they found evidence of a positive effect of dance on
review, Gomes Neto and colleagues identified evidence of a positive
QoL, compared with usual care or no exercise (Chen 2020). Please
effect on functional mobility and balance for water-based exercise
note that these differences may be due to inclusion of a small non-
compared with a passive control group receiving usual care.
randomized study (15 participants) with a large effect in favor of
Moreover, the review authors found that the effects on both QoL
dance, which we excluded from our review due to the study design.
and functional mobility and balance observed for water-based
exercise were superior to the effects of land-based exercise. Similar More similarities can be observed when comparing our results
effects had been observed previously by Cugusi and colleagues, with the results of systematic reviews on other types of physical
who also conducted a systematic review on RCTs for people with exercise, focusing on either a specific type or several types of
PD comparing aquatic exercise programs with land-based exercise exercise for people with PD. For example, in agreement with
or with a control group (Cugusi 2019). They included data from our results, Jin and colleagues - whose review included data
six studies (159 participants). Cugusi and colleagues analyzed from 21 RCTs and one non-randomized trial (1199 participants)
effects on the severity of motor signs, and identified evidence of - identified beneficial effects of mind-body training (including
a positive effect of aqua-based exercise compared with a control tai chi, yoga, and qigong) compared with a control group on
group, but no evidence of a difference in the effects between the severity of motor signs, QoL, and functional mobility and
aqua-based exercises and land-based exercises. Although we did balance (Jin 2019). In another review, Choi and colleagues included
not combine all comparator interventions as land-based exercises, data from 18 studies (1144 participants) (Choi 2020). Consistent
as described in these reviews (Gomes Neto 2020; Cugusi 2019), with our results, they found beneficial effects of several exercise
but instead used several exercise categories, the results of these therapies - including walking exercise, strength and flexibility
reviews are consistent with ours. First, analyzing the effects on exercise, balancing exercise, aerobic exercise, and complex exercise
the severity of motor signs, we also observed a beneficial effect (which comprised two types of exercise - compared to no exercise
of aqua-based training, while we did not observe evidence of or regular activity on the severity of motor signs and functional
any differences between the effects of different types of physical mobility and balance (Choi 2020).
exercise. Second, we identified evidence of positive effects of aqua-
based training on both QoL and functional mobility and balance Beneficial effects of resistance training on QoL and functional
that were superior to a passive control group, and superior to mobility and balance compared to a control group, as observed in
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our review, were also reported in a systematic review by Gamborg exercise, although these effects might be rather small compared to
and colleagues (Gamborg 2022). They including data from 33 the effects on other outcomes, such as the severity of motor signs,
studies (1266 participants) on intensive exercise therapy with a QoL, and functional mobility and balance. Importantly, our review
focus on resistance training and endurance training (Gamborg and the approach we adopted to derive exercise categories was
2022). For endurance training, Gamborg and colleagues identified not specifically designed to compare interventions based on their
evidence of beneficial effects on functional mobility and balance, as impact on freezing of gait.
found in our review. In contrast to our review, the review authors did
not identify evidence of a beneficial effect of endurance training on A more nuanced approach to address this question was provided
QoL. Moreover, while we found evidence of statistically significant by Gilat and colleagues, who conducted a systematic review
beneficial effects of both resistance training and endurance training on interventions that were divided into three subcategories
on the severity of motor signs, the corresponding evidence according to their relevance to freezing of gait (Gilat 2021).
observed by Gamborg and colleagues was mixed. For endurance These comprised freezing-of-gait-specific (e.g. action-observation
training, meta-analyses were conducted and the CIs extended training and fall prevention training), freezing-of-gait-relevant (e.g.
slightly across the line of no effect for both severity of motor cognitive training, balance training, and curved treadmill training),
signs measured during the "on"-, and the "off"-state. However, for and generic exercises (e.g. dance, yoga, aquatic training, tai chi and
resistance training, the authors indicated that there was no change physiotherapy not aimed at freezing of gait). The primary meta-
in the outcome. Please note that comparability of these findings analysis on the effect of exercise compared with a control group
with our results may be limited due to methodological differences. included data from 41 studies (1838 participants) and indicated
These included differences in measurement of the outcome (in that both freezing-of-gait-specific and freezing of-gait-relevant
contrast to Gamborg and colleagues, we combined data on the exercises reduced freezing of gait, while generic exercises did
severity of motor signs measured during the "on"- and the "off- not, indicating that targeted training (i.e. training that addresses
state) and selection of studies (e.g. the authors included a study specific symptoms or impairments of people with PD, e.g. gait) is
that was ineligible for inclusion in our review as it compared two needed to address freezing of gait in people with PD. Assuming
interventions, which we considered as similar types of strength/ that specificity of exercise is crucial to affect freezing of gait, the
resistance training). However, other evidence syntheses identified fact that we categorized interventions based on the dominant
evidence of statistically significant beneficial effects on the severity exercise mode may have masked potential differences in the
of motor signs for endurance training or aerobic exercise compared effects of the interventions. On the other hand, it is likely that we
to a control group, consistent with the results of our review. These categorized most exercises that, in theory, could target freezing
included a systematic review with NMA on exercise programs of gait as gait/balance/functional training, and we observed that
(Álvarez-Bueno 2021), and a systematic review with pairwise meta- this type of exercise may have a beneficial effect on freezing of
analyses on exercise therapies (Choi 2020). gait compared to control groups. Although the effects were not
statistically significant, they may be regarded as consistent with the
Evidence of effects on freezing of gait superiority of targeted exercises suggested by Gilat and colleagues.
In contrast, while the authors reported that generic exercises did
Previous efforts to synthesize the evidence on the efficacy of
not affect freezing of gait, we observed that strength/resistance
physical exercise for people with PD provided mixed results with
training and dance - that is, exercises considered as generic - may
respect to the effects on freezing of gait. For example, there was a
also have beneficial effects on freezing of gait compared to an active
lack of evidence of statistically significant effects on freezing of gait
control group. Again, it should be noted that these effects were not
in the systematic review by Carapellotti and colleagues, comparing
statistically significant. This is fairly in line with results from the
dance with no intervention (Carapellotti 2020). Similarly, Cugusi
Kwok 2022 systematic review with NMA on behavioral interventions
and colleagues did not find evidence of a statistically significant
for the management of freezing of gait. It provided evidence of
effect of aquatic exercise programs on freezing of gait, compared
statistically significant effects on freezing of gait compared to
with land-based exercise or with a control group (Cugusi 2019).
usual care or no treatment for obstacle training, gait training with
However, evidence of statistically significant beneficial effects on
treadmill, and general exercise, and also for action-observation
freezing of gait was observed in other systematic reviews: namely,
training and conventional physiotherapy, when controlling for the
in a systematic review focusing on the effects of physiotherapy
baseline severity of freezing of gait (Kwok 2022).
compared to no treatment or a control group (Consentino 2020),
as well as in a systematic review comparing physiotherapy with In conclusion, while specificity of exercise may be particularly
placebo or no intervention (Tomlinson 2013). The interventions important to address freezing of gait, we cannot rule out that
included in both of these reviews comprised several types of people with PD may also benefit from some interventions not
exercise, including aquatic exercise and dance; some of the targeted at this outcome.
corresponding analyses were based on a limited number of studies
and participants. Combining the findings of these reviews with Evidence of adverse events
our results, the exact impact of physical exercise on freezing of
In accordance with the limited and heterogeneous reporting of
gait remains inconclusive. While none of the effects we observed
adverse events (AEs) observed in the studies included in our review,
were statistically significant, the CIs included beneficial effects on
authors of only a few systematic reviews on physical exercise for
freezing of gait for several interventions compared to a control
people with PD synthesized safety information. Review authors
group. This applies to the effects of strength/resistance training,
concluded that the interventions are relatively safe, given that
dance and gait/balance/functional training compared to an active
when studies reported AEs, they were only minor (e.g. Choi 2020;
control group, and to the effect of gait/balance/functional training
Cugusi 2019; Gamborg 2022; Tomlinson 2014). This corresponds to
compared to a passive control group. Therefore, we cannot rule out
the synthesis of safety data in this review. Therefore, although our
that freezing of gait could be improved by some types of physical
review pointed out the difficulties in synthesizing the evidence on
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the comparative safety of different types of physical exercise, our or (b) they compared interventions that were not sufficiently
results are consistent with previous research suggesting that, in different to represent distinct exercise types as defined for our
general, physical exercise seems to be relatively safe for people with categories (e.g. aqua-based training with and without additional
PD. land-based rehabilitation in Gomes Neto 2020, or different dance
styles or dance with or without a partner in Carapellotti 2020).
Evidence of the impact of the length of intervention Moreover, despite an overlap in the categorization of interventions
Consistent with our results, authors of other systematic reviews and control groups applied in our review and in other reviews, our
also identified evidence suggesting that the length of intervention approach to categorizing both exercise types and control groups
might have a positive impact on the beneficial effects of exercise. diverged to some degree from the approaches of other review
Combining all exercise types in a systematic review on the effects of authors, resulting in differences in the selection of interventions
physical exercise on QoL, Chen and colleagues identified evidence and the corresponding analyses. For example, Carapellotti and
of a positive relation of the effects on QoL and the length colleagues divided groups that were compared to dance into
of intervention (Chen 2020). Specifically, positive effects were groups receiving no intervention, and "active control" groups
observed for interventions lasting for 12 weeks or longer, but not receiving exercise or physical activity (Carapellotti 2020). In
for interventions lasting for less than 12 weeks. Similarly, in their contrast, we considered some of these interventions as distinct
systematic review with NMA on the effect of exercise programs on physical interventions, some as active control groups (i.e. a
motor symptoms, Álvarez-Bueno and colleagues provided evidence structured, supervised, non-physical intervention), and some as
suggesting that the length of interventions (in weeks) influenced passive control groups (i.e. no intervention, or unstructured
the impact of the intervention on the severity of motor signs interventions without supervision, including general physical
(Álvarez-Bueno 2021). However, this evidence was only found for activity, or usual care). This also applies to other systematic
dance, and analyses were only performed for comparisons with reviews; for example, the Gilat 2021 systematic review focused on
at least six studies (Álvarez-Bueno 2021). These results are in line the management of freezing of gait and categorized interventions
with our observation of more beneficial effects on the severity of according to their relevance to this outcome. Furthermore, across
motor signs, QoL, but also on functional mobility and balance, the systematic reviews mentioned in the Discussion section, other
in the analyses limited to interventions with a minimum length methodological differences occurred: for example, in the selection
of 12 weeks compared to the analyses of interventions with a and application of tools used to assess risk of bias and the
shorter length. In a narrative review including different types confidence in the evidence; in the comprehensiveness of the
of physical exercise (multi-modal physical therapy, progressive search strategies (e.g. limitation to English-language articles); in
resistance training, aerobic training, gait and balance training, the measurement of the outcomes (e.g. limitation to data on the
tai chi, and dance), Mak and colleagues focused on long-term severity of motor signs measured with the UPDRS-M); and in the
effects, which they defined as effects lasting at least 12 weeks (Mak study inclusion criteria (e.g. inclusion of non-randomized studies).
2017). They found that physical exercise could modify long-term
motor symptoms and physical functioning in people with PD, with
AUTHORS' CONCLUSIONS
balance training having the longest carry-over effects, followed
Implications for practice
by gait and tai chi training (Mak 2017). The authors wrote that
"a minimum of 4 weeks of gait training or 8 weeks of balance We provide evidence of beneficial effects on the severity of motor
training can have positive effects that persist for 3–12 months signs, quality of life (QoL), and functional mobility and balance
after treatment completion" and that "sustained strength training, for most types of physical exercise for people with Parkinson's
aerobic training, tai chi or dance therapy lasting at least 12 weeks" disease (PD) included in this systematic review. We also observed
could "produce long-term beneficial effects" (Mak 2017). Finally, evidence of superiority in some effects of aqua-based training
they recommended that training periods should last for at least 12 compared to effects of other interventions (i.e. an effect on
weeks in order to achieve clinically meaningful improvements in QoL superior to the effects of gait/balance/functional training
UPDRS-M scores. As we only analyzed outcomes assessed shortly and multi-domain training; and an effect on functional mobility
after the intervention, our review does not allow us to draw and balance superior to the effects of gait/balance/functional
conclusions on the sustainability of the effects of physical exercise. training, strength/resistance training, and multi-domain training).
Nevertheless, our observation of more beneficial effects on the We did not identify any further evidence of differences between
severity of motor signs, QoL, and on functional mobility and the exercise types. Also, while some interventions were among
balance in studies with interventions lasting 12 weeks or longer the three highest-ranked exercise types multiple times (i.e. aqua-
corresponds with the authors' emphasis on a sufficiently long based training, dance, mind-body training, and strength/resistance
duration of exercise programs. training), these results should be interpreted carefully due to the
lack of full data on all interventions in some analyses, and large
Methodological differences to other systematic reviews confidence intervals in the effect estimates.
There was usually a large overlap in the selection of eligible
In summary, the overall pattern of results across outcomes
studies between our review and other systematic reviews on either
and interventions provides only little evidence of differences
several or specific types of exercise for people with PD. However,
between the exercise types included in this review. Thus,
we excluded some studies eligible for inclusion in other reviews
our systematic review highlights the importance of physical
because: (a) they investigated interventions that did not fulfill
exercise for people with PD in general, while the exact exercise
our criteria to be considered as structured physical exercise (e.g.
type might be secondary with respect to the rather global
because physical exercise was not the primary component of the
outcome measures severity of motor signs and QoL. Therefore,
intervention, or supervision was not provided for a minimum of five
the personal preferences of people with PD should be given
training sessions, or the training lacked a certain level of structure);
special consideration. Nevertheless, fundamental principles of
Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 63
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
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exercise should be taken into account when establishing an not be investigated, it might be helpful in maintaining the individual
individual training routine. For example, the World Health training routine.
Organization (WHO) guidelines for physical activity for adults
living with disability recommend that a variety of exercise When interpreting the results of this systematic review, it should be
types are undertaken, including aerobic physical activity, muscle- recognized that network meta-analyses cannot replace direct head-
strengthening activities, and multi-component physical activity to-head comparisons. Furthermore, although we observed only
that emphasizes functional balance and strength training (WHO very little evidence of differences in the effects of different types
2020). Moreover, people improve at what they practice. Thus, of exercise, we cannot rule out the possibility that differences exist
people with PD might be encouraged to select among the between or within the categories we used that might be clinically
diverse landscape of available exercise programs according to relevant for individuals.
their personal preferences, and establish a training routine that
Clinicians and other health professionals informing people with PD
includes a variety of modes and addresses their individual goals,
about the beneficial effects observed in this review may increase
impairments, and activity limitations. Our results are consistent
their motivation to perform physical exercise. Also, given the fact
with the possibility that specific motor symptoms in PD (e.g.
that various types of exercise show positive effects for people with
freezing of gait) may be treated most effectively with PD-specific
PD, it would be helpful to provide regional information on the
programs rather than with 'any kind' of physical exercise. Overall,
availability of specific exercise offers; for example, by self-help
people with PD should be advised to seek professional advice,
groups.
including assessment of motor and non-motor symptoms, in order
to develop a training agenda based on their individual needs.
Implications for research
In this review, we observed up to large beneficial effects of physical Larger, well-conducted studies are needed to increase the
exercise on the severity of motor signs. When expressed as mean confidence in the evidence. In particular, 49% of study results
differences on the motor scale of the Unified Parkinson Disease had a high risk of bias. Most frequently, we had concerns
Rating Scale (UPDRS-M), the point estimates of the beneficial regarding bias due to deviations from the intended interventions,
effects compared to a passive control group ranged between -10.32 as the results reported by trialists frequently lacked data from a
(dance) and -5.49 (Lee Silverman Voice training BIG [LSVT BIG]). substantial proportion of participants who had been randomized.
Comparing these effects to effects of pharmacotherapy in people Therefore, in order to reduce bias and increase the confidence
with PD is difficult, because all participants in our review received in the effects, trialists should report results from intention-to-
pharmacological treatment, and physical exercise is always an treat analyses and include data from all participants randomized.
"add on". Moreover, the interpretability of the effect sizes is limited Furthermore, our confidence in the effects was frequently limited
due to the imprecision of the estimates. However, descriptively, due to large confidence intervals, large prediction intervals, or
the beneficial effects of physical exercise found in our review were both; these primarily affected our assessment of imprecision and
within the range or exceeded the point estimates of the beneficial heterogeneity and, may be, in part, a result of small sample sizes. In
effects of pharmacological agents compared to placebo that were fact, the studies were usually small: on average, only 51 participants
reported in a network meta-analysis on the efficacy and tolerability were randomized per study (range from 10 to 474), and data for the
of the most frequently used drugs in the treatment of people with analyses were provided for only 21 participants per trial arm (range
PD (range between -6.05 for levodopa and -1.60 for cabergoline; from 4 to 115). Among the 156 studies included in our review, only
Zhuo 2017). Notably, comparable to our results, the drug effects 77 studies (49%) described considering test power a priori. Thirty-
were also highly heterogeneous. nine studies considered test power after conducting the trial, and
40 studies did not address this issue. Therefore, in order to increase
In addition to the evidence of the efficacy, no major safety concerns
the confidence in the evidence, more trialists should consider test
were raised for the interventions included in our review. Therefore,
power when designing a trial, and intend to recruit larger samples.
several exercise programs may be selected from when establishing
a training routine, provided that there are no individual safety The samples of most studies included in our review were limited
concerns. Importantly, as the disease progresses, safety concerns to people with mild to moderate PD and without severe cognitive
may increase and the availability of safe exercise options may impairment or dementia. Additional studies on physical exercise
decrease. recruiting people with advanced disease severity and cognitive
impairment might help extend the generalizability of our findings
We observed evidence of beneficial effects in favor of physical
to a broader range of people with PD.
exercise compared with a passive control group, more frequently
when analyzing studies with an intervention lasting for 12 weeks The efficacy outcomes analyzed in this review consisted of
or longer compared to studies with an intervention lasting for two primary outcomes (i.e. the severity of motor signs and
a shorter period. Although these results should be interpreted QoL), for which we performed additional evaluations (i.e.
carefully, longer training periods might have a positive impact on sensitivity analyses and in-depth risk-of-bias assessments), and
the effects of exercise for people with PD. As we only analyzed two secondary outcomes (i.e. freezing of gait and functional
outcomes assessed shortly after the intervention, our review does mobility and balance). The severity of motor signs, usually
not allow us to draw conclusions on the sustainability of the measured using the UPDRS-M, was the most frequently reported
effects of physical exercise. Nevertheless, one might assume that outcome in the included studies. However, as the UPDRS-M
people with PD would benefit from exercising continuously over the was designed to measure changes in motor tone and amplitude
course of disease in order to maintain beneficial effects. Also, while throughout the entire body, it may not highlight other important
eligible studies in this review had to consist of at least five directly aspects, such as gait and balance. Furthermore, in this review, we
supervised sessions, and the impact of remote supervision could did not analyze other well-established tools to measure aspects

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 64
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 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

related to gait and balance, such as the Berg Balance Scale (Berg (i.e. conduct subgroup analyses in studies that include people
1989) or the Falls Efficacy Scale (Tinetti 1990). Depending on with mild cognitive impairment, and in studies that include people
the intervention, effects on specific outcomes may be expected with severe cognitive impairment or dementia). Investigating these
to different degrees: for example, gait training may primarily features may help to better understand the effects of exercise for
affect freezing of gait while other exercise programs may have people with PD and to improve the design of individually-tailored
a more global effect on disease severity. Thus, investigating exercise programs.
the differential effects of exercise more precisely would require
extending our focus beyond global effects. Therefore, our results ACKNOWLEDGEMENTS
may be complemented by future evidence syntheses that address
other specific effects of exercise by analyzing other outcomes and We thank all the people whose support and comments greatly
tools included in core outcome sets. helped to improve this review.

Judgments about the general and comparative safety of different We would like to thank the members of the Central Editorial Service,
types of physical exercise for people with PD based on our review the editorial team of the Cochrane Movement Disorders Group, and
remain very uncertain, as we could not conduct any quantitative members of the Methods Support Unit for their support. We would
analyses due to limited, incomplete, and heterogeneous reporting especially like to thank Gonçalo S Duarte and Kerry Dwan for their
of the occurrence of adverse events. In order to facilitate the helpful comments on the protocol of this review.
conduct of evidence syntheses beyond a narrative report of the
We would like to thank Yuan Chi and Eyelin Ahmadi, who translated
data, trialists should consider reporting the safety of interventions
articles not published in English, for their support.
more consistently and completely for all study arms, including
control groups. This could increase the confidence in the evidence We would like to thank the MATCH-IT team at
of the safety of different physical interventions for people with PD. www.magicevidence.org, especially Per Olav Vandvik, Frankie
Achille, Birk Stokke Hunskaar, Per Olav Løvsletten, Thomas
As we focused on the evaluation of outcomes assessed up to
Agoritsas, Qingyang Shi and Sheyu Li for creating the interactive
six weeks after the intervention, our conclusions are limited to
summary of findings table which was added to the amended
the short-term impact of physical exercise for people with PD.
review.
Therefore, more researchers conducting evidence syntheses in
the future should consider analyzing the medium- and long-term We thank the following people:
effects of physical exercise as well.
• Sign-off Editor (final editorial decision): Robert J Boyle, Imperial
Finally, comparing groups of interventions that represented College London, UK
different exercise types, we investigated the effects of physical
• Managing Editor (selected peer reviewers, collated peer-
exercise using a relatively broad unit of specification. Furthermore,
reviewer comments, provided editorial guidance to authors,
we conducted subgroup analyses only by the length of
edited the article): Colleen Ovelman and Sam Hinsley, Cochrane
intervention, while we could not study the impact of further effect
Central Editorial Service
modifiers specified in the protocol (i.e. age, sex, cognitive stage).
As a result, our review cannot address questions on the impact of • Editorial Assistant (conducted editorial policy checks and
several features that might moderate the effect of physical exercise, supported editorial team): Lisa Wydrzynski, Cochrane Central
such as characteristics of the population (e.g. age, sex, cognitive Editorial Service]
stage, duration and/or severity of disease, phenotype, skills, or • Copy Editor (copy editing and production): Faith Armitage,
personal preferences and joy), parameters of the intervention Copy-edit Support
(e.g. mode, intensity, frequency, complexity, supervision and • Peer-reviewers (provided comments and recommended an
feedback, specificity, personalization, or use of technology), or editorial decision): Natalie Allen, University of Sydney, Sydney,
aspects of the study design (e.g. timing of assessment relative to Australia (clinical/content review), Giselle Petzinger, University
medication status). More nuanced approaches accounting for these of Southern California (clinical/content review), Robert Walton,
features are needed to better understand their role in the effects Cochrane UK (summary sections reviewer), Kerry Dwan,
of exercise for people with PD. First, more investigators could Cochrane Method's Support Unit (methods review), Joanne
study the effects of physical exercise in specific populations (e.g. Abbott, Information Specialist, Cochrane Pain, Palliative and
people with severe cognitive impairment or dementia). Second, Supportive Care (Search methods peer review). One additional
more investigators could conduct studies that directly compare peer reviewer provided clinical/content peer review, but chose
interventions varying in one or more potentially relevant features. not to be publicly acknowledged.
Third, evidence syntheses could study the impact of one or more
of these features by defining more specific research questions, This project was funded by the German Federal Ministry of
selecting other effect modifiers, and/or defining other subgroups Education and Research (grant no 01KG1902).

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 65
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 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

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disease: a randomized controlled trial. Journal of Parkinson's NCT02622737. Study of the effects of three exercise programs in
Disease 2017;7(1):203-10. Parkinson's disease. clinicaltrials.gov/ct2/show/NCT02622737
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Duncan 2012 {published data only}10.1177/1545968311421614
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* Ellis T, De Goede CJ, Feldman RG, Wolters EC, Kwakkel G, Leal LC, Abrahin O, Rodrigues RP, da Silva MC, Araújo AP,
Wagenaar RC. Efficacy of a physical therapy program in patients de Sousa EC, et al. Low-volume resistance training
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Feng 2019 {published data only}10.12659/MSM.916455
Feng H, Li C, Liu J, Wang L, Ma J, Li G, et al. Virtual reality RBR-36cw3y. Strength training for patients with Parkinson's
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de Lima TA, Ferreira-Moraes R, Alves WM, Alves TG, Pimentel CP,
Ferraz 2018 {published data only}10.1016/j.apmr.2017.12.014 Sousa EC, et al. Resistance training reduces depressive
symptoms in elderly people with Parkinson disease: a
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Filho J, Ferraz DD. The effects of functional training and & Science in Sports 2019;29:29.
stationary cycling on respiratory function of elderly with
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the efficacy of a two-week physiotherapy programme with psychological and cognitive features in people with Parkinson's
repetitive exercises of cueing to reduce the severity of disease: a randomized controlled trial. Annals of Physical and
freezing of gait in patients with Parkinson’s disease. Clinical Rehabilitation Medicine 2021;64(1):101407.
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Fisher 2008 {published data only}10.1016/j.apmr.2008.01.013 * Goodwin VA, Richards SH, Henley W, Ewings P, Taylor AH,
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disease. Archives of Physical Medicine and Rehabilitation 2011;82(11):1232-8.
2008;89(7):1221-9.
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Frazzitta 2012 {published data only}10.1177/1545968311416990 function for people with Parkinson's disease (Group Exercise
Trial for Parkinson's disease - GET uP study). isrctn.com/
Frazzitta G, Bertotti G, Riboldazzi G, Turla M, Uccellini D,
ISRCTN50793425 (first received 31 May 2007).
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Neurorehabilitation and Neural Repair 2014;28(2):163-8. Guan 2016 {published data only}10.3969/
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Guan X, Tang X, Liu J. Effect of tai chi training on walking ability
Frazzitta G, Maestri R, Bertotti G, Riboldazzi G, Boveri N,
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Parkinson's disease: a randomized pilot study with a 2-
year follow-up. Neurorehabilitation and Neural Repair Hackney 2007 {published data only}10.1097/
2015;29(2):123-31. NPT.0b013e31815ce78b
Ganesan 2014 {published data only}10.1016/j.pmrj.2013.08.604 Hackney ME, Kantorovich S, Earhart GM. A study on the effects
of Argentine tango as a form of partnered dance for those with
Ganesan M, Pal PK, Gupta A, Sathyaprabha TN. Treadmill gait
Parkinson disease and the healthy elderly. American Journal of
training improves baroreflex sensitivity in Parkinson's disease.
Dance Therapy 2007;29(2):109-27.
Clinical Autonomic Research 2014;24(3):111-8.
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of tango on functional mobility in Parkinson's disease: a
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2007;31(4):173-9.
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Ganesan M, Sathyaprabha TN, Pal PK, Gupta A. Partial body
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alternative forms of exercise in Parkinson disease. Parkinsonism
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only}1d0o.i.1o1rg7/71/00.12167972/01256591218585158282151ISRCTN75458559
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control trial to investigate if people with Parkinson's disease
can exercise at high intensity, and does this improve their * King LA, Salarian A, Mancini M, Priest KC, Nutt J, Serdar A,
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* Harvey M, Weston KL, Gray WK, O'Callaghan A, Oates LL,
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Parkinson's disease: a randomized, controlled feasibility trial. Parkinson's disease. clinicaltrials.gov/show/NCT00982709 (first
Clinical Rehabilitation 2019;33(3):428-38. received 23 September 2009).

ISRCTN75458559. Is a high intensity exercise intervention King 2020 {published data only}10.1177/1545968320909331
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ISRCTN75458559 (first received 10 February 2016). Peterson D, et al. Effects of cognitively challenging agility
exercise program on clinical and objective measures in people
Hass 2012 {published data only}10.1016/j.gaitpost.2011.12.022 with Parkinson’s disease. Movement Disorders 2019;34(Suppl 2):
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anzctr.org.au/ACTRN12613001175763.aspx (first received 21
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in Parkinsonism. clinicaltrials.gov/show/NCT02231073 (first
* Hubble RP, Naughton G, Silburn PA, Cole MH. Trunk exercises received 04 September 2014).
improve gait symmetry in Parkinson disease: a blind phase
II randomised-controlled trial. American Journal of Physical NCT02236286. Frontal cortex and gait freezing in Parkinson's
Medicine and Rehabilitation 2018;97(3):151-9. disease: rehabilitation impact. clinicaltrials.gov/show/
NCT02236286 (first received 10 September 2014).
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2019;43(2):96-105. Hulbert S, Ashburn A, Roberts L, Verheyden G. Dance for
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turning around. Complementary Therapies in Medicine
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Svenningsson P, et al. Feasibility aspects of evaluating
neuroplastic changes after balance training in Parkinson's ISRCTN63088686. PD Dance: dancing with Parkinson's disease
disease: a pilot randomised controlled trial. Movement Disorders (PD). isrctn.com/ISRCTN63088686 (first received 15 February
2018;33:S701-2. 2013).

NCT03213873. Neuroplasticity in Parkinson's disease after * Kunkel D, Fitton C, Roberts L, Pickering RM, Roberts HC,
training. clinicaltrials.gov/show/NCT03213873 (first received 11 Wiles R, et al. A randomized controlled feasibility trial exploring
July 2017). partnered ballroom dancing for people with Parkinson's
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j.apmr.2017.06.009 Kurt 2018 {published data
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ND Jr, Costa LA, et al. Effects of progressive resistance training ISRCTN26292510. To determine whether Ai-chi exercises
on cardiovascular autonomic regulation in patients with (aquatic exercises) can improve balance, functional status and

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 Cochrane Trusted evidence.
Informed decisions.
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quality of life in patients with Parkinson's disease. isrctn.com/ Liao 2015 {published data only}10.1177/1545968314562111
ISRCTN26292510 (first received 15 February 2016). * Liao YY, Yang YR, Cheng SJ, Wu YR, Fuh JL, Wang RY.
Virtual reality-based training to improve obstacle-crossing
* Kurt EE, Büyükturan B, Büyükturan Ö, Erdem HR, Tuncay F.
performance and dynamic balance in patients with
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Liu 2016 {published data only}10.1155/2016/5935782
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walking and balance exercise alleviates motor symptoms
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 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Miyai 2002 {published data only}10.1053/apmr.2002.34603 pain, but not anxiety, in people with Parkinson's disease.
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Volpe 2013 {published data only}10.1186/1471-2318-13-54 performance in Parkinsonian nonfallers: a randomized
Volpe D, Signorini M, Marchetto A, Lynch T, Morris ME. A controlled trial with six-month follow-up. Archives of Physical
comparison of Irish set dancing and exercises for people with Medicine and Rehabilitation 2015;96(12):2103-11.
Parkinson's disease: a phase II feasibility study. BMC Geriatrics
2013;13(54):[6 p.]. Yang 2010 {published data only}10.1097/
PHM.0b013e3181e721c5
Volpe 2014 {published data only}10.1177/0269215514536060 Yang YR, Lee YY, Cheng SJ, Wang RY. Downhill walking training
Volpe D, Giantin MG, Maestri R, Frazzitta G. Comparing the in individuals with Parkinson's disease. American Journal of
effects of hydrotherapy and land-based therapy on balance in Physical Medicine and Rehabilitation 2010;89(9):706-14.
patients with Parkinson's disease: a randomized controlled pilot
study. Clinical Rehabilitation 2014;28(12):1210-7. Yen 2011 {published data only}10.2522/ptj.20100050
NCT01301651. Effects of virtual reality training in patients with
Volpe 2017a {published data only}10.1177/0269215516664122 Parkinson's disease. clinicaltrials.gov/ct2/show/NCT01301651
Volpe D, Giantin MG, Manuela P, Filippetto C, Pelosin E, (first received 23 February 2011).
Abbruzzese G, et al. Water-based vs. non-water-based
physiotherapy for rehabilitation of postural deformities in Yen CY, Lin KH, Hu MH, Wu RM, Lu TW, Lin CH, et al. Effects
Parkinson’s disease: a randomized controlled pilot study. of virtual reality-augmented balance training on sensory
Clinical Rehabilitation 2017;31(8):1107-15. organization and attentional demand for postural control in
people with Parkinson disease: a randomized controlled trial.
Volpe 2017b {published data only}10.1016/ Physical Therapy 2011;91(6):862-78.
j.gaitpost.2016.11.019
Youm 2020 {published data only}10.3390/s20154106KCT0003070
Volpe D, Pavan D, Morris M, Guiotto A, Iansek R, Fortuna S, et
al. Underwater gait analysis in Parkinson's disease. Gait and Youm C, Kim Y, Noh B, Lee M, Kim J, Cheon SM. Impact of trunk
Posture 2017;52:87-94. resistance and stretching exercise on fall-related factors in
patients with Parkinson's disease: a randomized controlled pilot
Wan 2021 {published data only}10.2147/JMDH.S303945 study. Sensors 2020;20(15):4106.
Wan Z, Liu X, Yang H, Li F, Yu L, Li L, et al. Effects of health Qigong
Yuan 2020 {published data only}10.1186/s12984-020-00725-y
exercises on physical function on patients with Parkinson's
disease. Journal of Multidisciplinary Healthcare 2021;14:941-50. Yuan RY, Chen SC, Peng CW, Lin YN, Chang YT, Lai CH. Effects
of interactive video-game-based exercise on balance in older

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 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

adults with mild-to-moderate Parkinson's disease. Journal of Hashimoto 2015 {published data only}10.1016/
Neuroengineering and Rehabilitation 2020;17:91. j.ctim.2015.01.010
Hashimoto H, Takabatake S, Miyaguchi H, Nakanishi H, Naitou Y.
Zhang 2015 {published data only}ChiCTR-TRC-1400470710.1097/
Effects of dance on motor functions, cognitive functions,
PHM.0000000000000351
and mental symptoms of Parkinson's disease: a quasi-
ChiCTR-TRC-14004707. The effect of different patterns of randomized pilot trial. Complementary Therapies in Medicine
rehabilitation training in idiopathic Parkinson's disease. 2015;23(2):210-9.
chictr.org.cn/historyversionpuben.aspx?regno=ChiCTR-
TRC-14004707 (first received 17 April 2014). Israel 2018 {published data only}
Israel V, Yamaguchi MF. Effects of aquatic physical therapy
* Zhang TY, Hu Y, Nie ZY, Jin RX, Chen F, Guan Q, et al. Effects
on Parkinson's disease under a vision of the international
of tai chi and multimodal exercise training on movement
classification of functioning, disability and health (ICF).
and balance function in mild to moderate idiopathic
Movement Disorders 2018;33(Suppl 2):29-40.
Parkinson disease. American Journal of Physical Medicine and
Rehabilitation 2015;94(10 Suppl 1):921-9. Kalyani 2019 {published data
only}ACTRN12618001834246dx.doi.org/10.3233/NRE-192788
Zhu 2011 {published data only}
Kalyani HH, Sullivan KA, Moyle G, Brauer S, Jeffrey ER, Kerr GK.
Zhu Y, Li JX, Li N, Jin HZ, Hua L, Dong Q. Effect of Taijiquan on
Impacts of dance on cognition, psychological symptoms
motion control for Parkinson's disease at early stage. Zhong
and quality of life in Parkinson's disease. Neurorehabilitation
Guo Kang Fu Li Lun Yu Shi Jian [Chinese Journal of Rehabilitation
2019;49:273-83.
Theory and Practice] 2011;17(4):355-8.
Laupheimer 2011 {published data only}
References to studies excluded from this review Laupheimer M, Hartel S, Schmidt S, Bos K. Exercise training
– effects of MOTOmed exercise on typical motor dysfunction
Antunes Marques 2019 {published data only}10.5585/ in Parkinson's disease [Forced Exercise – Auswirkungen
ConsSaude.v18n1.10814 eines MOTOmed-Trainings auf parkinson-typische
Antunes Marques P, Passos Monteiro E, de Oliveira Fagundes A, motorische Dysfunktionen]. Neurologie und Rehabilitation
Rocha da Costa R, Gomes Martinez F, de Souza Pagnussat A, 2011;17(5-6):239-46.
et al. Efeitos da caminhada nórdica no perfil antropométrico
e composição corporal de pessoas com doença de Maciel 2020 {published data only}10.1016/
Parkinson: ensaio clínico randomizado. ConScientiae Saude j.parkreldis.2020.05.037
2019;18(1):105-15. Maciel DP, Mesquita VL, Marinho AR, Ferreira GM, Abdon AP,
Maia FM. Pilates method improves balance control in
Cancela 2020 {published data only}10.1089/rej.2019.2267 Parkinson's disease patients: an open-label clinical trial.
Cancela JM, Mollinedo I, Montalvo S, Vila Suarez ME. Effects of a Parkinsonism & Related Disorders 2020;77:18-9.
high-intensity progressive-cycle program on quality of life and
motor symptomatology in a Parkinson's disease population: Melo 2018 {published data only}
a pilot randomized controlled trial. Rejuvenation Research Melo G, Kleiner AF, Lopes J, Zen GZ, Marson N, Santos T, et al.
2020;23(6):508-15. P100 - Effects of virtual reality training on mobility in individuals
with Parkinson's disease. Gait and Posture 2018;65:394-5.
Capato 2020b {published data only}10.1016/j.jns.2020.117086
Capato TT, Nonnekes J, De Vries NM, IntHout J, Barbosa ER, Moon 2020 {published data only}10.1016/j.ctcp.2020.101169
Bloem BR. Effects of multimodal balance training supported by Moon S, Sarmento CV, Steinbacher M, Smirnova IV, Colgrove Y,
rhythmical auditory stimuli in people with advanced stages of Lai SM et al. Can Qigong improve non-motor symptoms
Parkinson's disease: a pilot randomized clinical trial. Journal of in people with Parkinson's disease? A pilot randomized
the Neurological Sciences 2020;418:117086. controlled trial. Complementary Therapies in Clinical Practice
2020;39:101169.
Combs 2013 {published data only}10.3233/NRE-130828
Combs SA, Diehl MD, Chrzastowski C, Didrick N, McCoin B, Munneke 2010 {published data only}
Mox N, et al. Community-based group exercise for persons Keus SH, Bloem BR, Van Hilten JJ, Ashburn A, Munneke M.
with Parkinson disease: a randomized controlled trial. Effectiveness of physiotherapy in Parkinson's disease: the
Neurorehabilitation 2013;32(1):117-24. feasibility of a randomised controlled trial. Parkinsonism and
Related Disorders 2007;13(2):115-21.
Granziera 2021 {published data only}10.1007/s40520-020-01617-
w * Munneke M, Nijkrake MJ, Keus SH, Kwakkel G, Berendse HW,
Granziera S, Alessandri A, Lazzaro A, Zara D, Scarpa A. Nordic Roos RA, et al. Efficacy of community-based physiotherapy
walking and walking in Parkinson's disease: a randomized networks for patients with Parkinson's disease: a cluster-
single-blind controlled trial. Aging Clinical and Experimental randomised trial. Lancet Neurology 2010;9(1):46-54.
Research 2021;33(4):965-71.

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Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT00330694. Efficiency of physiotherapeutic care in Silva-Batista 2020 {published data only}10.1002/

Parkinson's disease. clinicaltrials.gov/ct2/show/NCT00330694 mds.28128RBR-83vb6bUTN-U1111-1215-9956
(first received 29 May 2006). Silva-Batista C, de Lima-Pardini AC, Nucci MP, Coelho DB,
Batista A, Piemonte ME, et al. A randomized, controlled trial
NCT03637023 {unpublished data only}
of exercise for Parkinsonian individuals with freezing of gait.
NCT03637023. Virtual Reality for Parkinson's disease. Movement Disorders 2020;35(9):1607-17.
clinicaltrials.gov/ct2/show/NCT03637023 (first received 17
August 2018). Soke 2021 {published data only}
Soke F, Guclu-Gunduz A, Kocer B, Fidan I, Keskinoglu P. Task-
NCT04291027 {unpublished data only}
oriented circuit training combined with aerobic training
NCT04291027. Aquatic group exercise for people with Parkinson improves motor performance and balance in people with
disease. clinicaltrials.gov/ct2/show/NCT04291027 (first received Parkinson's disease. Acta Neurologica Belgica 2021;121:535-43.
02 March 2020).
Thaut 1996 {published data only}
Passos-Monteiro 2020 {published data only}
Thaut MH, McIntosh GC, Rice RR, Miller RA, Rathbun J,
Passos-Monteiro E, Schuch FB, Franzoni LT, Carvalho AR, Brault JM. Rhythmic auditory stimulation in gait training
Gomenuka NA, Becker M, et al. Nordic walking and free for Parkinson's disease patients. Movement Disorders
walking improve the quality of life, cognitive function, and 1996;11(2):193-200.
depressive symptoms in individuals with Parkinson's disease:
a randomized clinical trial. Journal of Functional Morphology & Van Wegen 2015 {published data only}
Kinesiology 2020;5:10. Van Wegen EE, Van Den Heuvel M, Daffertshofer A, Beek PJ,
Berendse HW, Kwakkel G. Balance training with augmented
Picelli 2012 {published data only}
visual feedback in Parkinson's disease: a randomized clinical
Picelli A, Melotti C, Origano F, Waldner, Fiaschi A, Santilli V, et al. trial. Journal of the Neurological Sciences 2015;357:e292.
Robot-assisted gait training in patients with Parkinson disease:
a randomized controlled trial. Neurorehabilitation and Neural Wang 2018 {published data only}
Repair 2012;26(4):353-61. Wang F, Liu J, Liu S. Influence of rhythmic auditory attention
stimulation combined with intensive muscle strength training
Rawson 2019 {published data only}10.1097/
on lower limb function and balance function in elderly patients
NPT.0000000000000245
with Parkinson's disease. Huli Yanjiu [Chinese Nursing Research]
Rawson KS, McNeely ME, Duncan RP, Pickett KA, Perlmutter JS, 2018;32(2):229-33.
Earhart GM. Exercise and Parkinson disease: comparing tango,
treadmill, and stretching. Journal of Neurologic Physical Therapy Xiao 2016 {published data only}10.1111/ggi.12571
2019;43(1):26-32. Xiao CM, Zhuang YC. Effect of health Baduanjin Qigong for mild
to moderate Parkinson's disease. Geriatrics and Gerontology
Sage 2009 {published data only}
International 2016;16(8):911-9.
Sage MD, Almeida QJ. Symptom and gait changes after sensory
attention focused exercise versus aerobic training in Parkinson's Yousefi 2009 {published data only}ISRCTN98825027
disease. Movement Disorders 2009;24(8):1132-8. * Yousefi B, Tadibi V, Khoei AF, Montazeri A. Exercise therapy,
quality of life, and activities of daily living in patients with
Sahu 2018 {published data only}10.4103/ijoth.IJOTH_13_18
Parkinson disease: a small scale quasi-randomised trial. Trials
Sahu S, Jali P, Srivastava A. Dual task training, fall, and 2009;10(67):[7 p.].
functional independence in patients with Parkinson's disease:
a longitudinal study. Indian Journal of Occupational Therapy Yu 1998 {published data only}
2018;50(4):134-8. Yu XH, Xu JF, Shao DY, Fa ZG, Chen GZ. Clinical trial of Qigong
for Parkinson's disease. Zhongguo Xing Wei Yi Xue Zazhi [Chinese
Segura 2020 {published data only}ISRCTN13047118
Journal of Behavioral Medical Science] 1998;7(4):303-4.
Segura C, Eraso M, Bonilla J, Mendivil CO, Santiago G, Useche N,
et al. Effect of a high-intensity tandem bicycle exercise program Zhang 2018 {published data only}
on clinical severity, functional magnetic resonance imaging, Zhang J, Yu Y, Jiang R. Influence of rehabilitation exercise
and plasma biomarkers in Parkinson's disease. Frontiers in intervention on limb motor function and self-care ability of
Neurology 2020;11:656. patients with Parkinson's disease. Chinese Nursing Research
2018;32(21):3410-3.
Serrao 2019 {published data only}10.3389/
fneur.2019.00902NCT03346265 Zhu 2020 {published data only}10.23736/S0022-4707.19.10104-1
Serrao M, Pierelli F, Sinibaldi E, Chini G, Castiglia SF, Priori M, Zhu M, Zhang Y, Pan J, Fu C, Wang Y. Effect of simplified Tai
et al. Progressive modular rebalancing system and visual Chi exercise on relieving symptoms of patients with mild to
cueing for gait rehabilitation in Parkinson's disease: a pilot, moderate Parkinson's disease. Journal of Sports Medicine and
randomized, controlled trial with crossover. Frontiers in Physical Fitness 2020;60(2):282-8.
Neurology 2019;10:902.

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 80
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

References to studies awaiting assessment ChiCTR-IOR-16009065 {unpublished data only}ChiCTR-

IOR-16009065
ACTRN12605000566639 {unpublished data
only}ACTRN12605000566639 ChiCTR-IOR-16009065. Exercise programme to enhance
the physical and psychological wellbeing for people with
ACTRN12605000566639. Strength training for people with
Parkinson's disease. chictr.org.cn/showproj.aspx?proj=15362
Parkinson's disease. anzctr.org.au/ACTRN12605000566639.aspx
(first received 19 August 2016).
(first received 30 September 2005).
ChiCTR-IPR-17011875 {unpublished data only}ChiCTR-
ACTRN12609000900213 {unpublished data
IPR-17011875
only}ACTRN12609000900213
ChiCTR-IPR-17011875. Effects of baduanjin combined balance
ACTRN12609000900213. Does aquatic physiotherapy improve
training on gait and posture control of patients with mild and
quality of life, balance and gait in people with early to mid stage
moderate Parkinson's disease. chictr.org.cn/showproj.aspx?
Parkinson's disease? anzctr.org.au/ACTRN12609000900213.aspx
proj=20281 (first received 05 July 2017).
(first received 07 August 2009).
ChiCTR-TRC-14004549 {unpublished data only}ChiCTR-
ACTRN12612001016820 {unpublished data
TRC-14004549
only}ACTRN12612001016820
ChiCTR-TRC-14004549. The effects of tai chi for Parkinson’s
ACTRN12612001016820. Safety, feasibility and efficacy of a
disease: a randomized controlled trial. chictr.org.cn/
dance intervention for people with Parkinson's disease: a pilot
showproj.aspx?proj=5024 (first received 01 March 2014).
study. anzctr.org.au/ACTRN12612001016820.aspx (first received
19 September 2012). CTRI/2017/08/009471 {unpublished data
only}CTRI/2017/08/009471
ACTRN12618000923268p {unpublished data
only}ACTRN12618000923268p CTRI/2017/08/009471. Yoga in Parkinsons disease. ctri.nic.in/
Clinicaltrials/pmaindet2.php?trialid=16632 (first received 23
ACTRN12618000923268. Folk dances from the Basque
August 2017).
Country in Parkinson's community living participants:
sensorimotor and neuropsychological changes. anzctr.org.au/ de Oliveira 2017 {published data only}10.1097/
ACTRN12618000923268.aspx (first received 08 June 2017). PHM.0000000000000612RBR-56brsc
Amara 2020 {published data only}10.1002/mds.28009 RBR-56brsc. Impact of specific physical therapy treatment
on the health of patients with Parkinson's disease.
Amara A, Joop A, Memon R, Pilkington J, Wood K, Bamman M.
ensaiosclinicos.gov.br/rg/RBR-56brsc/ (first received 30 April
The effect of high-intensity exercise on objective sleep
2014).
outcomes in Parkinson’s disease. Neurology 2019;92(15
Suppl):P2.8-022. * de Oliveira RT, Assunção Felippe L, Bucken Gobbi LT,
Barbieri FA, Christofoletti, G. Benefits of exercise on the
* Amara, AW, Wood KH, Joop A, Memon RA, Pilkington J,
executive functions in people with Parkinson disease. American
Tuggle SC, et al. Randomized, controlled trial of exercise on
Journal of Physical Medicine & Rehabilitation 2017;96(5):301-6.
objective and subjective sleep in Parkinson's disease. Movement
Disorders 2020;35(6):947-58. DRKS00008732 {unpublished data only}DRKS00008732
NCT02593955. The effects of a high intensity exercise training DRKS00008732. Neuronal plasticity of network topography in
program in patients with Parkinson's disease. clinicaltrials.gov/ parkinson disease through LSVT-BIG therapy. drks.de/search/
show/NCT02593955 (first received 01 November 2015). de/trial/DRKS00008732 (first received 09 November 2015).

NCT03495193. Impact of exercise in Parkinson's disease. Huang 2020 {published data only}10.1002/mds.28268
clinicaltrials.gov/show/NCT03495193 (first received 11 April Huang X, Chen L, Cai G, Xin J, Yang Y, Ye Q. Improvement
2018). for gait disorders in Parkinson's disease through novel
comprehensive treatment (improve study): a prospective, open-
ChiCTR1800019534 {unpublished data only}ChiCTR1800019534 label, randomized controlled clinical trial. Movement Disorders
ChiCTR1800019534. Application of balance function 2020;35(Suppl 1):S398-9.
rehabilitation of stroke patients and early Parkinson patients
with Pro-Kin balance system. chictr.org.cn/showproj.aspx? IRCT2015040616830N4 {unpublished data
proj=32989 (first received 17 November 2018). only}IRCT2015040616830N4
IRCT2015040616830N4. The effect of balance exercises
ChiCTR-INR-17011340 {unpublished data only}ChiCTR- on balance of patients with Parkinson's disease. en.irct.ir/
INR-17011340 trial/15615 (first received 16 May 2015).
ChiCTR-INR-17011340. Effects of square dance on symptoms
and quality of life in early stage patients with Parkinson's IRCT2016071228885N1 {unpublished data
disease. chictr.org.cn/showproj.aspx?proj=19268 (first received only}IRCT2016071228885N1
09 May 2017). IRCT2016071228885N1. The effect of exercises on motor
symptoms of Parkinson's disease. en.irct.ir/trial/23336 (first
received 04 August 2016).

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 81
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

IRCT20171030037099N1 {unpublished data NCT00167453 {unpublished data only}

only}IRCT20171030037099N1 NCT00167453. Benefits of exercise and education for individuals
IRCT20171030037099N1. Effect of equilibrium exercise with Parkinson's disease (BEEP). clinicaltrials.gov/show/
on physiologic, movement and balance variables among NCT00167453 (first received 14 September 2005).
Parkinson's patients. en.irct.ir/trial/28372 (first received 21
January 2018). NCT00387218 {unpublished data only}
NCT00387218. Exercise study for people with Parkinson's
Kargarfard 2012 {published data only} disease. clinicaltrials.gov/show/NCT00387218 (first received 12
Kargarfard M, Chitsaz A, Azizi S. Effects of an 8-week aquatic October 2006).
exercise training on balance in patients with Parkinson's
disease. Journal of Isfahan Medical School 2012;30(178):141-50. NCT01014663 {unpublished data only}
NCT01014663. Non-contact boxing training and traditional
Khongprasert 2019 {published data only}10.1093/ageing/ therapeutic exercise for persons with Parkinson's disease.
afz164.109 clinicaltrials.gov/show/NCT01014663 (first received 17
Khongprasert S. Thai traditional game-based exercise for gait November 2009).
and balance of people with Parkinson's disease. Age and Ageing
2019;48(2):iv18. NCT01076712 {unpublished data only}
NCT01076712. Effectiveness of physiotherapy interventions
Koli 2018 {published data for patients with Parkinson's disease. clinicaltrials.gov/show/
only}CTRI/2017/04/00834610.1177/1545968318765497 NCT01076712 (first received 26 February 2010).
CTRI/2017/04/008346. Benefits of Indian semi-classical kathak
and bharatnatyam dance movements on quality of life in NCT01246700 {unpublished data only}
Parkinson's disease. ctri.nic.in/Clinicaltrials/pmaindet2.php? NCT01246700. Sensory attention focused exercise in
trialid=17821 (first received 13 April 2017). Parkinson's disease. clinicaltrials.gov/show/NCT01246700 (first
received 23 November 2010).
* Koli J, Karthikbabu S, Mohan D. Indian semi-classical
kathak and bharatnatyam movements for balance confidence NCT01427062 {unpublished data only}
and quality of life in Parkinson's disease: pilot RCT. NCT01427062. Effects of an innovative balance training
Neurorehabilitation and Neural Repair 2018;32(4-5):332. programme in enhancing postural control and reducing falls
in patients with Parkinson's disease. clinicaltrials.gov/show/
Lee 2019 {published data only}
NCT01427062 (first received 01 September 2011).
Lee GH. Effects of virtual reality exercise program using the
Sony Playstation 2 gaming platform on balance, emotion and NCT01439022 {unpublished data only}
quality of life in patients with Parkinson’s disease. Movement NCT01439022. Exercise interventions in Parkinson's disease.
Disorders 2019;34(Suppl 2):[1 p.]. clinicaltrials.gov/show/NCT01439022 (first received 22
September 2011).
Lee G 2018 {published data only}
Lee G. A virtual reality exercise program improves the balance NCT01562496 {unpublished data only}
function and quality of life of patients with Parkinson's disease. NCT01562496. The ParkCycle study: aerobic exercise in PD.
Movement Disorders 2018;33(suppl 2):S114-S115. clinicaltrials.gov/ct2/show/NCT01562496 (first received 23
March 2012).
Mohammadpour 2018 {published data only}
Mohammadpour H, Rahnama N, Alizade MH, Shaighan V. NCT01757509 {unpublished data only}
Effects of a combined aerobic and resistance exercise program NCT01757509. A randomized controlled feasibility trial to
on the quality of life and motor function of elderly men with determine the effectiveness of set dancing for people with
Parkinson's disease. Annals of Tropical Medicine and Public Parkinson's disease. clinicaltrials.gov/show/NCT01757509 (first
Health 2018;12:S725. received 31 December 2012).
NCT00004760 {unpublished data only} NCT01835652 {unpublished data only}
NCT00004760. Study of axial mobility exercises in Parkinson NCT01835652. The effects of exercise in Parkinson's disease.
disease. clinicaltrials.gov/show/NCT00004760 (first received 25 clinicaltrials.gov/show/NCT01835652 (first received 19 April
February 2000). 2013).
NCT00029809 {unpublished data only} NCT01960985 {unpublished data only}
NCT00029809. Chinese exercise modalities in Parkinson's NCT01960985. Balance training in Parkinson's disease using
disease. clinicaltrials.gov/show/NCT00029809 (first received 24 cues. clinicaltrials.gov/show/NCT01960985 (first received 11
January 2002). October 2013).

NCT02017938 {unpublished data only}

NCT02017938. Establishing the central and peripheral fatigue
indexes and VR based anti-fatigue training paradigm for
Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 82
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

individuals with Parkinson disease. clinicaltrials.gov/show/ NCT03406728 {unpublished data only}

NCT02017938 (first received 23 December 2013). NCT03406728. Virtual reality can be used to improve balance
reducing dynamic falls in those with Parkinson's disease.
NCT02267785 {unpublished data only}
clinicaltrials.gov/show/NCT03406728 (first received 23 January
NCT02267785. Exercise targeting cognitive impairment in 2018).
Parkinson's disease. clinicaltrials.gov/show/NCT02267785 (first
received 17 October 2014). NCT03443752 {unpublished data only}
NCT03443752. Comparing the effectiveness of Shotokan-karate
NCT02419768 {unpublished data only}
vs. tai chi on balance and quality of life in Parkinson's disease.
NCT02419768. Effects of exercise on long-range clinicaltrials.gov/show/NCT03443752 (first received 23 February
autocorrelations in Parkinson's disease. clinicaltrials.gov/show/ 2018).
NCT02419768 (first received 17 April 2015).
NCT03568903 {unpublished data only}
NCT02476240 {unpublished data only}
NCT03568903. Changes in functional performance in individuals
NCT02476240. Evaluating the influence of externally vs. with Parkinson's disease following 2-month physiotherapy
internally focused exercise on rehabilitation in Parkinson's intervention. clinicaltrials.gov/show/NCT03568903 (first
disease. clinicaltrials.gov/show/NCT02476240 (first received 19 received 26 June 2018).
June 2015).
NCT03618901 {unpublished data only}
NCT02476266 {unpublished data only}
NCT03618901. Rock steady boxing vs. sensory attention focused
NCT02476266. Two resistance training protocols to reduce exercise. clinicaltrials.gov/show/NCT03618901 (first received 07
the risk of falls in Parkinson's disease. clinicaltrials.gov/show/ August 2018).
NCT02476266 (first received 19 June 2015).
NCT03689764 {unpublished data only}
NCT02615548 {unpublished data only}
NCT03689764. Video game-based exercise for persons with
NCT02615548. Exercise for adults with Parkinson disease. Parkinson's disease. clinicaltrials.gov/show/NCT03689764 (first
clinicaltrials.gov/show/NCT02615548 (first received 26 received 28 September 2018).
November 2015).
NCT04012086 {unpublished data only}
NCT02656355 {unpublished data only}
NCT04012086. Physical therapy and cognitive decline.
NCT02656355. Gait initiation difficulty and anticipatory postural clinicaltrials.gov/show/NCT04012086 (first received 09 July
adjustment (APA) impairment in people with PD - evaluation 2019).
and training. clinicaltrials.gov/show/NCT02656355 (first
received 14 January 2016). Ogundele 2018 {published data only}
Ogundele A, Olaogun M, Komolafe M. Comparison of virtual-
NCT02674724 {unpublished data only}
reality-gaming and activity-based gait and balance training
NCT02674724. The effect of resistance training in Parkinson on gait, balance and quality of life in patients with Parkinson's
disease: a pilot study. clinicaltrials.gov/show/NCT02674724 disease. Movement Disorders 2018;33(Suppl 2):[1 p.].
(first received 04 February 2016).
RBR-34d7jm {unpublished data only}RBR-34d7jm
NCT02745171 {unpublished data only}
RBR-34d7jm. Effects of a dance program in motor and non
NCT02745171. Continuous behavior assessment of the effects motor symptoms of patients with Parkinson's disease.
of a physical therapy program for patients with Parkinson's ensaiosclinicos.gov.br/rg/RBR-34d7jm (first received 17 January
disease. clinicaltrials.gov/show/NCT02745171 (first received 20 2017).
April 2016).
RBR-3vm7bf {unpublished data only}RBR-3vm7bf
NCT02816619 {unpublished data only}
RBR-3vm7bf. Isokinetic exercise in Parkinsonians.
NCT02816619. Evaluation of a personalized physical activity ensaiosclinicos.gov.br/rg/RBR-3vm7bf (first received 26
coaching program in Parkinson's disease. clinicaltrials.gov/ December 2018).
show/NCT02816619 (first received 28 June 2016).
RBR-3z39v3 {unpublished data only}RBR-3z39v3
NCT02999997 {unpublished data only}
RBR-3z39v3. Effects of functional training and mat pilates
NCT02999997. Evaluation of Ronnie Gardiner Method in in elderly patients with Parkinson's disease: a randomized
individuals with Parkinson's disease. clinicaltrials.gov/show/ controlled trial. ensaiosclinicos.gov.br/rg/RBR-3z39v3 (first
NCT02999997 (first received 21 December 2016). received 30 August 2019).
NCT03212014 {unpublished data only} RBR-4m3k2c {unpublished data only}RBR-4m3k2c
NCT03212014. Development and research of an individualized RBR-4m3k2c. Effects of exercise in the treatment of depression,
intelligent platform for rehabilitaion in Parkinson's disease. dementia and Parkinson. ensaiosclinicos.gov.br/rg/
clinicaltrials.gov/show/NCT03212014 (first received 11 July RBR-4m3k2c (first received 10 October 2016).
2017).

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 83
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 Cochrane Trusted evidence.
Informed decisions.
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RBR-6rngmb {unpublished data only}RBR-6rngmb TCTR20180530004 {unpublished data only}TCTR20180530004

RBR-6rngmb. Physiotherapy in the treatment of patients TCTR20180530004. Establish the factors of predicting
with Parkinson's disease through video game therapy. cognitive impairment and the effect of exercise intervention
ensaiosclinicos.gov.br/rg/RBR-6rngmb (first received 02 May on cognitive function in patients with Parkinson's disease.
2019). thaiclinicaltrials.org/show/TCTR20180530004 (first received 30
May 2018).
RBR-7xfkpx {unpublished data only}RBR-7xfkpx
RBR-7xfkpx. Effect of training with instability on a platform in Wroblewska
́ 2019 {published data only}10.1155/2019/3846279
patients with Parkinson's disease. ensaiosclinicos.gov.br/rg/ * Wroblewska
́ A, Gajos A, Smyczynska
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RBR-7xfkpx (first received 22 November 2018). therapeutic effect of Nordic walking on freezing of gait in
Parkinson’s disease: a pilot study. Parkinson's Disease 2019 Dec
Rosenfeldt 2021 {published data only}10.1007/ 27 [Epub ahead of print]. [DOI: 10.1155/2019/3846279]
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Alberts JL, Penko AL, Rosenfeldt A, Zimmerman NM. Results
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NCT01636297. The cyclical lower-extremity exercise for ACTRN12617001057370. The effect of a physiotherapy exercise
Parkinson's trial. clinicaltrials.gov/show/NCT01636297 (first program with a self-management approach vs usual care on
received 10 July 2012). physical activity in people with mild-moderate Parkinson’s
disease: a randomised controlled trial. anzctr.org.au/
Penko AL, Zimmerman NM, Crawford M, Linder SM, Alberts JL. ACTRN12617001057370.aspx (first received 17 July 2017).
Effect of aerobic exercise on cardiopulmonary responses
and predictors of change in individuals with Parkinson's ACTRN12620001135909 {unpublished data
disease. Archives of Physical Medicine and Rehabilitation only}ACTRN12620001135909
2021;102(5):925-31. ACTRN12620001135909. A randomised trial of exercise therapy
for Parkinson’s disease (first received 2020). anzctr.org.au/
* Rosenfeldt AB, Koop MM, Fernandez HH, Alberts JL. High ACTRN12620001135909.aspx (first received 21 August 2020).
intensity aerobic exercise improves information processing and
motor performance in individuals with Parkinson's disease. Bevilacqua 2020 {published data only}https://
Experimental Brain Research 2021;239:777-86. dx.doi.org/10.1186/s12883-020-01759-4
Bevilacqua R, Maranesi E, Di Rosa M, Luzi R, Casoni E, Rinaldi N,
Shen 2014 {published data only}10.1177/1545968313517752
et al. Rehabilitation of older people with Parkinson’s disease: an
* Shen X, Mak MK. Balance and gait training with augmented innovative protocol for RCT study to evaluate the potential of
feedback improves balance confidence in people with robotic-based technologies. BMC Neurology 2020;20:186.
Parkinson's disease: a randomized controlled trial.
Neurorehabilitation and Neural Repair 2014;28(6):524-35. ChiCTR1900022621 {unpublished data only}ChiCTR1900022621
ChiCTR1900022621. The effect of rehabilitation on physical
Shen X, Mak MK. Technology-assisted balance and gait training
function in patients with Parkinson's disease. chictr.org.cn/
reduces falls in patients with Parkinson's disease: a randomized
com/25/showprojen.aspx?proj=34905 (first received 21 April
controlled trial with 12-month follow-up. Neurorehabilitation
2019).
and Neural Repair 2015;29(2):103-11.
ChiCTR2000029025 {unpublished data only}ChiCTR2000029025
Stozek 2017 {published data only}
ChiCTR2000029025. The effect of LSVT BIG treatment on motor
Stozek J, Rudzinska M, Staszczak-Gawelda I, Stenwak A,
and nonmontor symtoms [sic] in patients with Parkinson's
Swiatek K, Podsiadlo S, et al. The effect of dance and Nordic
disease. chictr.org.cn/showproj.aspx?proj=44830 (first received
walking on balance, gait and motor function in Parkinson's
11 January 2020).
disease. Movement Disorders 2017;32:972-3.
ChiCTR2000029135 {unpublished data only}ChiCTR2000029135
Swarnakar 2019 {published data only}
ChiCTR2000029135. Effects of innovative tai chi on motor
Swarnakar R, Wadhwa S, Goyal V, Sreenivas V. Park-ease trial:
symptoms in patients with mild to moderate Parkinson's
a randomized controlled trial to study the efficacy of exercises
disease. chictr.org.cn/showprojen.aspx?proj=48394 (first
in early-stage Parkinson's disease. Movement Disorders
received 15 January 2020).
2019;34:S900.
ChiCTR2000036306 {unpublished data only}ChiCTR2000036306
TCTR20180111003 {unpublished data only}TCTR20180111003
ChiCTR2000036306. A prospective cohort study of exercise
TCTR20180111003. Effects of the square-stepping exercise
rehabilitation in the treatment of Parkinson's disease and its
on corticomotor excitability, balance and cognition in
mechanism. chictr.org.cn/showprojen.aspx?proj=58856 (first
individuals with Parkinson's disease. thaiclinicaltrials.org/
received 22 August 2020).
show/TCTR20180111003 (first received 09 January 2018).

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 84
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 Cochrane Trusted evidence.
Informed decisions.
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ChiCTR2000037178 {unpublished data only}ChiCTR2000037178 Hackney 2020 {published data only}https://doi.org/10.3389/

ChiCTR2000037178. A prospective clinical study of innovative fneur.2020.00943
Wuqinxi exercise intervention in delaying the occurrence Hackney ME, Bay AA, Jackson JM, Nocera JR, Krishnamurthy V,
of freezing of gait in Parkinson's disease. chictr.org.cn/ Crosson B, et al. Rationale and design of the PAIRED Trial:
showprojen.aspx?proj=60001 (first received 27 August 2020). partnered dance aerobic exercise as a neuroprotective, motor,
and cognitive intervention in Parkinson's disease. Frontiers in
ChiCTR2000037305 {unpublished data only}ChiCTR2000037305 Neurology 2020;11:943.
ChiCTR2000037305. A randomized controlled study of
multifactorial interventions to prevent early cognitive decline in Li 2021 {published data only}https://dx.doi.org/10.1186/
elderly people. chictr.org.cn/showprojen.aspx?proj=60460 (first s13063-021-05258-w
received 27 August 2020). Li KP, Zhou ZL, Zhou RZ, Zhu Y, Zhang ZQ. Improvement of
freezing of gait in patients with Parkinson’s disease by music
ChiCTR2000037384 {unpublished data only}ChiCTR2000037384 exercise therapy: a study protocol for a randomized controlled
ChiCTR2000037384. A clinical study of innovative Wuqinxi trial. Trials 2021;22:335.
exercise therapy delaying the occurrence of motor
complications of Parkinson's disease. chictr.org.cn/ Lima 2020 {published data only}http://dx.doi.org/10.1136/
showproj.aspx?proj=60280 (first received 28 August 2020). bmjopen-2020-039941
Lima DP, de Almeida SB, de Carvalho Bonfadini J, Sobreira ES,
CTRI/2018/05/014241 {unpublished data Damasceno PG, Viana Júnior AB, et al. Effects of a power
only}CTRI/2018/05/014241 strength training using elastic resistance exercises on the motor
CTRI/2018/05/014241. A clinical trial to study the effect and non-motor symptoms in patients with Parkinson’s disease
of exercises in early stage Parkinsons disease. ctri.nic.in/ H&Y 1–3: study protocol for a randomised controlled trial (PARK-
Clinicaltrials/pmaindet2.php?trialid=23331 (first received 30 BAND Study). BMJ Open 2020;10(10):e039941.
May 2018).
Mayoral-Moreno 2021 {published data only}https://
CTRI/2019/06/019618 {unpublished data doi.org/10.3390/jpm11050361
only}CTRI/2019/06/019618 Mayoral-Moreno A, Chimpén-López CA, Rodríguez-Santos L,
CTRI/2019/06/019618. Benefits of yoga on daily activities Ramos-Fuentes MI, Vaz-Leal FJ, Moral MA, et al. Falls prevention
and quality of life for individuals with Parkinson's disease. and quality of life improvement by square stepping exercise
trialsearch.who.int/?TrialID=CTRI/2019/06/019618 (first in people with Parkinson’s disease: project report. Journal of
received 2019). Personalized Medicine 2021;11(5):361.

CTRI/2020/06/025794 {unpublished data NCT02457832 {unpublished data only}

only}CTRI/2020/06/025794 NCT02457832. Motor training in PD. clinicaltrials.gov/show/
CTRI/2020/06/025794. Consequence of Pilates on imbalance, NCT02457832 (first received 29 May 2015).
movability and core stability in patients with Parkinson disease.
ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=37645 (first NCT03244813 {unpublished data only}
received 10 June 2020). NCT03244813. Evaluation of the impact of a personalized
program of adapted physical activates [sic] in patients with
DRKS00018841 {unpublished data only}DRKS00018841 Parkinson disease. clinicaltrials.gov/show/NCT03244813 (first
DRKS00018841. Therapeutic influence of treadmill therapy received 10 August 2017).
vs. physiotherapy without treadmill in dual-task-behavior
while walking in Parkinson’s patients [Therapeutischer NCT03343574 {published data only}
Einfluss von Laufbandtherapie vs. Physiotherapie ohne NCT03343574. Cardiovascular effects of exercise in patients with
Laufband auf das Dual-Task-Verhalten während des Gehens bei Parkinson's disease. clinicaltrials.gov/ct2/show/NCT03343574
Parkinsonpatienten]. drks.de/search/de/trial/DRKS000188411 (first received 17 November 2017).
(first received 23 October 2019).
NCT03560089 {unpublished data only}
Gooßes 2020 {published data only}10.3389/ NCT03560089. Serious games rehabilitation programme to
fneur.2020.00790DRKS00017687 treat gait and balance disorders in PD patients (PARKGAME-II).
DRKS00017687. Music-assisted treadmill training in the therapy clinicaltrials.gov/ct2/show/NCT03560089 (first received 18 June
of Parkinson's disease [Musik-unterstütztes Laufbandtraining in 2018).
der Parkinsontherapie]. drks.de/search/de/trial/DRKS00017687
(first received 25 September 2019). NCT03563807 {unpublished data only}
NCT03563807. Golf instruction versus tai chi for people with
Gooßes M, Saliger J, Folkerts AK, Nielsen J, Zierer J, Schmoll P, Parkinson's disease. clinicaltrials.gov/ct2/show/NCT03563807
et al. Feasibility of music-assisted treadmill training in (first received 20 June 2018).
Parkinson's disease patients with and without deep brain
stimulation: insights from an ongoing pilot randomized
controlled trial. Frontiers in Neurology 2020 Sep 4 [Epub ahead
of print]. [DOI: 10.3389/fneur.2020.00790]

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 85
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 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT03582371 {unpublished data only} NCT04046276 {unpublished data only}

NCT03582371. Aqua stand-up paddle balance effect in NCT04046276. Intensity of aerobic training and neuroprotection
Parkinson's disease (AquaSUP PARK). clinicaltrials.gov/ct2/ in Parkinson's disease (AEROPROTECT). clinicaltrials.gov/ct2/
show/NCT03582371 (first received 11 July 2018). show/NCT04046276 (first received 06 August 2019).

NCT03711955 {unpublished data only} NCT04063605 {unpublished data only}

NCT03711955. Comparing the effects of instability resistance NCT04063605. The effect of clinical Pilates training on balance
training versus aerobic training on cognitive and motor and postural control of people with Parkinson's disease.
improvements found in Parkinson's disease participants. clinicaltrials.gov/ct2/show/NCT04063605 (first received 21
clinicaltrials.gov/ct2/show/NCT03711955 (first received 19 August 2019).
October 2018).
NCT04122690 {unpublished data only}
NCT03751371 {unpublished data only} NCT04122690. Partnered dance aerobic exercise as a
NCT03751371. Robotic walking device to improve mobility in neuroprotective, motor and cognitive intervention in
Parkinson's disease. clinicaltrials.gov/ct2/show/NCT03751371 Parkinson's disease (PDAE in PD). clinicaltrials.gov/ct2/show/
(first received 23 November 2018). NCT04122690 (first received 10 October 2019).

NCT03833349 {unpublished data only} NCT04135924 {unpublished data only}

NCT03833349. The impact of three distinct exercise types NCT04135924. Influence of trainning [sic] in Parkinson's disease.
on fatigue, anxiety, and depression in Parkinson's disease. clinicaltrials.gov/ct2/show/NCT04135924 (first received 23
clinicaltrials.gov/show/NCT03833349 (first received 07 February October 2019).
2019).
NCT04194762 {unpublished data only}
NCT03860649 {unpublished data only} NCT04194762. PARK-FIT. Treadmill vs cycling in Parkinson's
NCT03860649. Effects of different physical therapies and dance disease. Definition of the most effective model in gait
in people with Parkinson's disease. clinicaltrials.gov/ct2/show/ reeducation. clinicaltrials.gov/ct2/show/NCT04194762 (first
NCT03860649 (first received 04 March 2019). received 11 December 2019).

NCT03882879 {unpublished data only} NCT04215900 {unpublished data only}

NCT03882879. Kick out Parkinson's disease 2. clinicaltrials.gov/ NCT04215900. High-speed yoga and executive function.
ct2/show/NCT03882879 (first received 20 March 2019). clinicaltrials.gov/ct2/show/NCT04215900 (first received 02
January 2020).
NCT03960931 {unpublished data only}
NCT03960931. Interest of hydrophysiotherapy care in Parkinson NCT04379778 {unpublished data only}
disease's motor and non-motor symptoms (THERMAPARK). NCT04379778. Aerobic exercise and brain health in Parkinson's.
clinicaltrials.gov/ct2/show/NCT03960931 (first received 23 May clinicaltrials.gov/ct2/show/NCT04379778 (first received 07 May
2019). 2020).

NCT03972969 {unpublished data only} NCT04558879 {unpublished data only}

NCT03972969. Highly challenging balance program to reduce NCT04558879. Exercise and sleep in Parkinson's disease.
fall rate in PD. clinicaltrials.gov/ct2/show/NCT03972969 (first clinicaltrials.gov/ct2/show/NCT04558879 (first received 22
received 04 June 2019). September 2020).

NCT03974529 {unpublished data only} NCT04613141 {unpublished data only}

NCT03974529. Intensive running exercise improves Parkinson's NCT04613141. The WalkingTall study: comparing WalkingTall
motor and non-motor symptoms. clinicaltrials.gov/ct2/show/ with Parkinson's disease (WalkingTall-PD) with mobility-
NCT03974529 (first received 05 June 2019). plus to reduce falls and improve mobility (WalkingTall-PD).
clinicaltrials.gov/ct2/show/NCT04613141 (first received 03
NCT03983785 {unpublished data only} November 2020).
NCT03983785. The effect of Pilates and elastic taping on
balance and postural control in early Parkinson's disease. NCT04644367 {unpublished data only}
clinicaltrials.gov/ct2/show/NCT03983785 (first received 12 June NCT04644367. Effects of a biomechanical-based tai chi program
2019). on gait and posture in people with Parkinson's disease.
clinicaltrials.gov/ct2/show/NCT04644367 (first received 25
NCT04000360 {unpublished data only} November 2020).
NCT04000360. Pragmatic cyclical lower extremity exercise
trial for Parkinson's disease. clinicaltrials.gov/ct2/show/ NCT04665869 {unpublished data only}
NCT04000360 (first received 27 June 2019). NCT04665869. Long-term effects of combined balance and brisk
walking in Parkinson's disease. clinicaltrials.gov/ct2/show/
NCT04665869 (first received 14 December 2020).

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 86
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 Cochrane Trusted evidence.
Informed decisions.
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NCT04699617 {unpublished data only} RBR-9v7gj4 {unpublished data only}RBR-9v7gj4

NCT04699617. The feasibility and efficacy of an immersive RBR-9v7gj4. The impact of adapted functional training and the
virtual reality software in Parkinson's disease patients. solo Pilates method on motor and non-motor symptoms of
clinicaltrials.gov/ct2/show/record/NCT04699617 (first received individuals with Parkinson's disease. ensaiosclinicos.gov.br/rg/
07 January 2021). RBR-9v7gj4 (first received 29 September 2020).

NCT04863118 {unpublished data only} TCTR20201009001 {unpublished data only}TCTR20201009001

NCT04863118. Acute effects of strength training and TCTR20201009001. Effects of mindful walking meditation on
high intensity training on functional and biochemical gait, balance and disease severity in patients with Parkinson
measurements of individuals with Parkinson's disease in disease. thaiclinicaltrials.org/show/TCTR20201009001 (first
different environments and depths. clinicaltrials.gov/ct2/show/ received 07 October 2020).
NCT04863118 (first received 28 April 2021).

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* Indicates the major publication for the study

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CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]

Agosti 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/20/NR

Country: Italy

Age (mean in years): 62.9; 63.1

Sex (male/female): 18/2 (90% male)

Duration of disease (mean in years): 6.5; 6

HY (mean): 1.7; 1.8

UPDRS-M (mean): 20

MMSE (mean): ≥ 23.8 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Diagnosis of PD according to the United Kingdom Parkinson’s Disease Society Brain Bank criteria;
MMSE ≥ 23.8; stable dosage of dopaminergic medication in the last 2 months prior to enrollment and
during the study; ability to walk along a 15-meter walkway at least six times without assistance

Exclusion criteria:

Other current neurological, orthopedic, or other medical conditions affecting gait

Interventions Length of intervention: 4 weeks

Intervention 1: Global Postural Reeducation (GPR method is based on the global stretching of anti-
gravity muscle chains, and enhances the contraction of antagonistic muscles) [flexibility training]; 40
minutes, 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes UPDRS-M, three-dimensional motion analysis

Follow-up (maximum time after end of intervention): 8 weeks

Notes Funding sources: "The work was supported by a grant from MIUR (FIRB—MERIT RBNE08LN4P:006)."

Conflicts of interest: All authors disclosed any financial and personal relationships with other people
or organizations that could inappropriately influence (bias) their work.

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 93
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Informed decisions.
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Allen 2010
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 92/48/45

Country: Australia

Age (mean in years): 66.0; 68.0

Sex (male/female): 26/22 (54.2% male)

Duration of disease (mean in years): 7.0; 9.0

HY (mean): NR

UPDRS-M (mean): 29.0; 30.0

MMSE (mean): 29.0; 29.0

Physical capability: Short physical performance battery: 2.10; 2.09; exercise (hr/wk): 2.6; 2.6

Inclusion criteria:

Idiopathic PD diagnosis; independent walking; aged between 30 and 80 years; stable medication in the
last 2 weeks; falls in the last year or at risk of falling (operationalized by a score of 25 cm or less on the
FRT or if they failed to reach criterion one of the balance tests in the QuickScreen Clinical Falls Assess-
ments

Exclusion criteria:

Significant cognitive impairment (MMSE < 24 points); other neurological/musculoskeletal/cardiopul-

monary/metabolic condition that would interfere with the safe conduct of the training or testing proto-
col

Interventions Length of intervention: 6 months

Intervention 1: Lower limb strengthening and balance exercises [gait/balance/functional training]; 40

to 60 minutes, 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapists with experience in neurological rehabilitation

Outcomes PD falls risk score; number of falls; Coordinated Stability Test; yes/no question regarding FoG; FOG-Q;
Swaymeter; Alternate step test component of the BBS; sit to stand time; fast walking speed (m/s); com-
fortable walking speed (m/s); Short Physical Performance Battery; FES; PDQ-39

Follow-up (maximum time after end of intervention): post-intervention

Notes Funding sources: Parkinson’s New South Wales (NSW) Research Grant and a Physiotherapy Research
Foundation National Neurology Group Tagged Grant

Conflicts of interest: "NE Allen received financial assistance from the University of Sydney Faculty of
Health Sciences Postgraduate Research Scholarship, the George Burniston-Cumberland Foundation
Fellowship and the Parkinson’s NSW Research Student Award. C Sherrington and SR Lord receive salary
Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 94
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Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Allen 2010 (Continued)

funding from the National Health and Medical Research Council. SR Lord is a company director of Bal-
ance Systems Inc, which makes equipment items for the PPA (POWMRI FallScreen), which is commer-
cially available through the Prince of Wales Medical Research Institute. All other authors have no finan-
cial disclosures to make."

Almeida 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/42/NR

Country: Canada

Age (mean in years): 63.86; 73.93; 67.43

Sex (male/female): 31/11 (73.8% male)

Duration of disease (mean in years): NR

HY (mean): NR

UPDRS-M (mean): 23.68; 22.07; 24.21

MMSE (mean): NR

Physical capability:

Step length (cm): 63.9; 57.6; 57.7

Velocity (cm/s): 119.2; 108.5; 109.0

Inclusion criteria:

Diagnosed with PD, responsive to anti-Parkinsonian medication, and were in an optimally medicated
or “on” medication state at the time of all training and testing sessions.

Exclusion criteria:

Past history of neurological conditions other than PD or orthopedic or visual disturbances that severe-
ly impaired walking ability. Also, participants were removed if they were unable to independently walk
down an 8-meter GAITRite carpet for a total of 10 trials.

Interventions Length of intervention: 6 weeks

Intervention 1: Treadmill group [gait/balance/functional training]; 30 minutes; 3x/week

Intervention 2: Overground group (walk down equally spaced transverse lines, presented on a 16-me-
ter carpet) [gait/balance/functional training]; 30 minutes; 3x/week

Intervention 3: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): spotters

Outcomes Step length, velocity, TUG, UPDRS-M, 30-second sit to stand test

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Almeida 2012 (Continued)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 6 weeks

Notes Funding sources: supported by a Natural Sciences and Engineering Research Council of Canada
(NSERC) grant, the Canadian Foundation for Innovation, and Sun Life Financial

Conflicts of interest: None

Amano 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/24/24

Country: USA

Age (mean in years): 66; 66

Sex (male/female): 14/10 (58.3% male)

Duration of disease (mean in years): 8; 5

HY (mean): 2.4; 2.4

UPDRS-M (mean): 23.1; 23.1

MMSE (mean): > 26/30 (inclusion criteria)

Physical capability: gait velocity (m/s): 1.01; 1.09

Inclusion criteria:

All participants were diagnosed as having idiopathic PD by a fellowship-trained movement disorders

neurologist using standard criteria.

Exclusion criteria:

Any history or evidence of neurological deficit other than PD; MMSE ≤ 26 points; inability to walk inde-
pendently; previous training in any forms of tai chi or current participation in any structured exercise
program equating to greater than 20 min per week; inability to understand the protocol

Interventions Length of intervention: 16 weeks

Intervention 1: Tai chi [mind-body training]; 60 minutes; 3x/week

Intervention 2: Non-contact control group [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes Experimental gait initiation and gait analysis; UPDRS-M

Severity of motor signs assessed during: on-medication state

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Amano 2013 (Continued)

Follow-up (maximum time after end of intervention): post-intervention

Notes Funding sources: National Institutes of Health

Conflicts of interest: NR

Arfa-Fatollahkhani 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 50/30/20

Country: Iran

Age (mean in years): 60.63; 61.55

Sex (male/female): 15/5 (75% male)

Duration of disease (mean in years): 8.89; 8.50

HY (mean): 2.13; 2.0

UPDRS-M (mean): 18.45; 17.88

MMSE (mean): 27.54; 28.0

Physical capability: Short-form 8 - physical condition score: 37.27; 40.71

Inclusion criteria:

PD according to UK Brain Bank criteria; aged between 30 and 75 years old; UPDRS-M range of 10 to 30;
HY stage between 1.5 and 2.5; and MMSE > 24

Exclusion criteria:

Participants were excluded if they were not in aforementioned stage; had any alterations in dosage
and type of medications; high-risk factors for cardiovascular diseases based on the American College
of Sport Medicine Guideline; visual or auditory disturbances; vertigo; orthopedics problems; dementia;
any other neurologic comorbidities other than PD; were involved in any other exercise or rehabilitation
program.

Interventions Length of intervention: 10 weeks

Intervention 1: Treadmill training [endurance training]; 30 minutes; 2x/week; 10 weeks

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Sports Medicine specialist

Outcomes SF-8; 6-MIN-W; TUG

Follow-up (maximum time after end of intervention): 2 months

Notes Funding sources: NR

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Arfa-Fatollahkhani 2019 (Continued)

Conflicts of interest: NR

Ashburn 2007
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 1107/142/133

Country: UK

Age (mean in years): 72.7; 71.6

Sex (male/female): 86/56 (60.6% male)

Duration of disease (mean in years): 7.7; 9.0

HY (range): 2 to 4

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: No. of falls in previous year: 60; 61

Inclusion criteria:

Confirmed diagnosis of idiopathic PD, independently mobile, living at home in the community, experi-
enced more than one fall in the previous 12 months, and passed a screening test for gross cognitive im-
pairment

Exclusion criteria:

Unable to participate in assessments because of pain, and acute medical condition and in receipt of, or
soon to receive, treatment

Interventions Length of intervention: 6 weeks

Intervention 1: Exercise group (six levels of exercise progression, which comprised muscle strength-
ening (knee and hip extensors, hip abductors), range of movement (ankle, pelvic tilt, trunk, and head),
balance training (static, dynamic, and functional) and walking (inside and outside)) [multi-domain
training]; 60 minutes; 1x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes BBS; self-assessment Parkinson's Disease Disability Scale; QoL thermometer; falls; EQ-5D; muscle
strength

Follow-up (maximum time after end of intervention): 20 weeks

Notes Funding sources: Action Medical Research, John and Lucille Van Geest Foundation

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Ashburn 2007 (Continued)

Conflicts of interest: None

Ashburn 2018
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 541/474/425

Country: UK

Age (mean in years): 71.0; 73.0

Sex (male/female): 266/208 (56.1% male)

Duration of disease (mean in years): 8.0; 8.0

HY (range): 1 to 4

UPDRS-M (mean): NR

MMSE (mean): 28.0; 29.0

Physical capability: PASE: 107.8; 100.1

Inclusion criteria:

Clinically confirmed diagnosis of Parkinson’s disease in accordance with UK Brain Bank criteria; living
in their own home; independently mobile with or without an aid; experienced at least one fall in the
previous 12 months; scored 24 or more on MMSE; cognitive ability to give informed consent; able to un-
derstand and follow commands; considered able to participate in an exercise and strategy programme

Exclusion criteria:

Cognitive impairment

Interventions Length of intervention: 6 months

Intervention 1: PDSAFE (individually tailored, progressive, home-based exercise and strategies to

avoid falls) [gait/balance/functional training]; 60 to 90 minutes; 2x/month

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Registered physiotherapists

Outcomes Fall diaries (number of falls); fractures and rate of near falling; Mini-BESTest; chair stand test; N-FOG-Q;
medication use; Geriatric Depression Scale; FES; PDQ-39; PASE; EQ-5D-3L; deaths/hospitalisation/seri-
ous adverse events

Follow-up (maximum time after end of intervention): 6 months

Notes Funding sources: National Institute for Health Research (NIHR) Health Technology Assessment (HTA)
programme

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Ashburn 2018 (Continued)

Conflicts of interest: During the conduct of the study, LR reports grants from: Newcastle University;
Parkinson’s UK; EU Marie Curie Training Network; the Medical Research Council (MRC); the Engineer-
ing and Physical Sciences Research Council; the Wellcome Trust; the Stroke Association. CB is a mem-
ber of the Primary Care Community and Preventive Interventions HTA group and the associated Meth-
ods group. VG reports grants from the NIHR during the conduct of the study. SEL reports grants from
the NIHR HTA programme during the conduct of the study. SEL was a member of the HTA Additional Ca-
pacity Funding Board, HTA End of life care and add-on studies, HTA Prioritisation Group, and HTA Trau-
ma Board during this study. All other authors declared they have nothing to disclose.

Avenali 2021
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 40/40/34

Country: Italy

Age (mean in years): 72.3

Sex (male/female): 21/13 (61.8% male)

Duration of disease (mean in years): 9.6

HY (mean): 2.4

UPDRS-M (mean): 33.66; 34.15

MMSE (mean): 24.46; 24.36

Physical capability: Tinetti: 14.26; 14.78

Inclusion criteria:

PD according to UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria and HY scale ≤ 3
with PD-MCI (Parkinson's disease - Mild Cognitive Impairment) single- or multiple-domain (level II crite-
ria)

Exclusion criteria:

Pre-existing cognitive impairment (e.g. aphasia, neglect) or PD-dementia and other concomitant psy-
chiatric, neurological, or other clinically relevant health conditions

Interventions Length of intervention: 4 weeks

Intervention 1: Physical therapy [multi-domain training]; 60 minutes, 6x/week

Intervention 2: Control group (no specific intervention) [passive control group]

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes MMSE; MoCA; Corsi's block-tapping; Raven's matrices 1947; Frontal assessment battery; Attentive ma-
trices; TMT; Phonological fluency; UPDRS-M; Tinetti; Hauser

Severity of motor signs assessed during: on-medication state

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Avenali 2021 (Continued)

Follow-up (maximum time after end of intervention): 5 months

Notes Funding sources: This work was supported by a grant of the Italian Ministry of Health (Ricerca Corrente
2017–2019)

Conflicts of interest: None

Bridgewater 1996
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/26/26

Country: Australia

Age (mean in years): 67.3; 66.5

Sex (male/female): 16/10 (61.5% male)

Duration of disease (mean in years): 4

HY (range): 1 to 3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Healthy people with early PD; established stage of disease according to HY scale; diagnosis of idiopath-
ic PD; ability to move to and from a recumbent position

Exclusion criteria:

People with spinal, cardiorespiratory, or neurologic pathology (other than PD) were excluded from the
study

Interventions Length of intervention: 12 weeks

Intervention 1: Aerobic exercise [multi-domain training]; 55 minutes; 2x/week

Intervention 2: Control with interest talk [passive control group]; 1x/3 weeks

Primary setting: Group

Supervision by (if provided): Physiotherapist

Outcomes Webster Rating Scale for Parkinsonian Disabilities, Northwestern University Disability Scale, Human Ac-
tivity Profile; Levine-Pilowsky Depression Questionnaire; Exercise Stress Test; Herz-Echo; Adjusted Ac-
tivity Score

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: The Physiotherapy Research Foundation

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Bridgewater 1996 (Continued)

Conflicts of interest: NR

Burini 2006
Study characteristics

Methods Randomized controlled trial with cross-over after 7 weeks

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/26/22

Country: Italy

Age (mean in years): 65.2

Sex (male/female): 9/17 (34.6% male)

Duration of disease (mean in years): 10.8

HY (range): 2 to 3

UPDRS-M (median): 11;12

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: 6-MIN-W (meters) 419; 405

Inclusion criteria:

Diagnosis of PD; HY stage 2 to 3; stable medication

Exclusion criteria:

Severe cognitive impairment (MMSE < 24); concomitant severe neurologic, cardiopulmonary, or ortho-
pedic disorders; specific contraindication to the execution of a cardiopulmonary test or aerobic train-
ing; recent participation in any physiotherapy or rehabilitation program during the previous 2 months

Interventions Length of intervention: 7 weeks

Intervention 1: Aerobic sessions [endurance training]; 45 minutes; 3x/week

Intervention 2: Qigong [mind-body training]; 50 minutes; 3x/week

Primary setting: Group

Supervision by (if provided): Physical therapist

Outcomes UPDRS; Brown's Disability Scale; 6-Min-W; Borg Scale; BDI; PDQ-39; cardiovascular and respiratory as-
sessments

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

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Cakit 2007
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 62/54/31

Country: Turkey

Age (mean in years): 71.8

Sex (male/female): 16/15 (51.6% male)

Duration of disease (mean in years): 5.58

HY (range): 2 to 3

UPDRS-M (mean): 18.14

MMSE (mean): ≥ 20 (inclusion criteria)

Physical capability: Walking distance on treadmill (m): 266.45; 348.2

Inclusion criteria:

Medically stable; able to walk a 10-meter distance at least three times with or without an assistive de-
vice; able to provide informed consent

Exclusion criteria:

Neurological conditions other than iPD; HY > 3; MMSE < 20; exhibition of postural hypotension, cardio-
vascular disorders, class C or D exercise risk by the American College of Sports Medicine criteria or mus-
culoskeletal disorders; visual disturbance or vestibular dysfunction limiting locomotion or balance

Interventions Length of intervention: 8 weeks

Intervention 1: Stretching, range-of-motion and treadmill training [endurance training]; 30(±5) min-
utes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Physiatrist

Outcomes BBS; Dynamic Gait Index; FES; walking distance on treadmill

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Canning 2012
Study characteristics

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Canning 2012 (Continued)

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 86/20/20

Country: Australia

Age (mean in years): 60.7; 62.9

Sex (male/female): 11/9 (55% male)

Duration of disease (mean in years): 6.1; 5.2

HY (range): 1 to 2

UPDRS-M (mean): 20.9; 17.9

MMSE (mean): 29.9; 29.7

Physical capability: 10-meter walk velocity (m/s): 1.30; 1.17

Inclusion criteria:

Mild Parkinson’s disease (HY 1 to 2); aged between 30 and 80 years; sedentary (< 2 hours per week of
leisure time physical activity in prior three months); had a stable response to levodopa medications.
Participants were accepted into the study if they walked unaided but reported a subjective gait distur-
bance and/or scored one or two on the gait item of the UPDRS.

Exclusion criteria:

Disabling dyskinesias or motor fluctuations; freezing while "on" medication; or significant balance im-
pairment (> 1 on UPDRS postural stability item). People were also excluded if they: scored less than 24
on the MMSE; had fallen more than once in the prior year; experienced severe and frequent dizziness;
experienced any other neurological/musculoskeletal/cardiopulmonary or metabolic conditions that af-
fected walking; or had any other contraindications to moderate intensity, semi-supervised exercise.

Interventions Length of intervention: 6 weeks

Intervention 1: Treadmill walking [endurance training]; 30 to 40 minutes; 4x/week

Intervention 2: Control group (usual care) [passive control group]

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes 6-MIN-W; Exercise heart rate (heart rate end 6-MIN-W – resting heart rate); PDQ-39; 10-meter walk veloc-
ity (comfortable pace); 10-meter walk velocity (multiple task, comfortable pace); Coefficient of varia-
tion (stride time, stride length); UPDRS-M

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 6 weeks

Notes Funding sources: University of Sydney Research and Development Grant to CG Canning

Conflicts of interest: None

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Canning 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 532/231/231

Country: Australia

Age (mean in years): 71

Sex (male/female): 135/96 (58.4% male)

Duration of disease (mean in years): 7.5; 8.3

HY (range): 2 to 4

UPDRS-M (mean): 25.8; 26.7

MMSE (mean): 28.6; 28.7

Physical capability: Number of participants who fell in the past year: 90; 90

Inclusion criteria:

Diagnosis of idiopathic PD (confirmed by a medical practitioner); aged 40 years or older; ability to walk
independently with or without a walking aid; stable anti-Parkinsonian medication for at least 2 weeks;
and one or more falls in the past year or at risk of falls based on physical assessment

Exclusion criteria:

MMSE score of < 24; unstable cardiovascular disease or other uncontrolled chronic conditions that
would interfere with the safety and conduct of the training and testing protocol

Interventions Length of intervention: 6 months

Intervention 1: "PD-WEBB program" (progressive balance and lower limb strengthening exercises and
cueing strategies to reduce freezing of gait for participants reporting freezing) [gait/balance/functional
training]; 40 to 60 minutes; 3x/week

Intervention 2: Control group (usual care) [passive control group]

Primary setting: Individual

Supervision by (if provided): Physical therapist, medical practitioner and community services

Outcomes PD Fall Risk score; mean knee extensor strength of both legs; coordinated stability test; Short Physical
Performance Battery continuous measure; 4-meter fast walk speed; FTSTS; FOG-Q; FES-I; SF-12 physi-
cal; SF-12 mental; SF-6D utility score; exercise; ADL; PDQ-39; positive affect scale

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Australian National Health and Medical Research Council (NHMRC ID: 512326), and
the Harry Secomb Foundation

Conflicts of interest: "C. Canning has received travel expenses and honoraria for lectures and educa-
tional activities not funded by industry; and research support from the Australian Government Nation-
al Health and Medical Research Council, the Harry Secomb Foundation, and Parkinson’s NSW. C. Sher-
rington has received travel expenses and honoraria for lectures and educational activities not funded
by industry; and research support from the Australian Government National Health and Medical Re-
search Council, the Consortium national de formation en santé (Canada), Arthritis New South Wales,
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Canning 2015 (Continued)

NSW Ministry of Health, University of Sydney, Motor Accidents Authority of New South Wales, and The
Trust Company. S. Lord has received travel expenses and honoraria for lectures not funded by indus-
try; a consultancy payment for methodologic advice by Eli Lilly Ltd.; and research support from the
Australian Government National Health and Medical Research Council, The Australian Research Coun-
cil, Multiple Sclerosis Australia, and the NSW Ministry of Health. J. Close has received travel expenses
and honoraria for lectures not funded by industry; and research support from the Australian Govern-
ment National Health and Medical Research Council, Bupa Health Foundation, and the NSW Ministry of
Health. S. Heritier has received funding for 2 Australian Government National Health and Medical Re-
search Council grants unrelated to this study; and royalties from Wiley for his book Robust Methods in
Biostatistics. G. Heller reports no disclosures relevant to the manuscript. K. Howard has received re-
search support from the Australian Government National Health and Medical Research Council and
the Australian Research Council. N. Allen has received research support from Parkinson’s NSW. M. Latt
has received research support from the Australian Government National Health and Medical Research
Council. S. Murray and S. O’Rourke report no disclosures relevant to the manuscript. S. Paul has re-
ceived research support from the Australian Government National Health and Medical Research Coun-
cil and Parkinson’s NSW. J. Song reports no disclosures. V. Fung receives a salary from NSW Health, has
received research grants from the National Health and Medical Research Council of Australia, and is on
advisory boards and/or has received travel grants from Abbott/AbbVie, Allergan, Boehringer-Ingelheim,
Hospira, Ipsen, Lundbeck, Novartis, Parkinson’s KinetiGraph, Solvay, and UCB. Go to Neurology.org for
full disclosures."

Capato 2020a
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 201/154/154

Country: the Netherlands

Age (mean in years): 74.0; 67.0; 73.0

Sex (male/female): 88/66 (57.1% male)

Duration of disease (median in years): 5; 6; 8

HY (range): 1 to 3

UPDRS-M (mean): 15; 17; 19

MMSE (mean): 27; 26; 25

Physical capability: TUG 23.6; 19.4; 22.5

Inclusion criteria:

Diagnosis of PD according to the UK Brain Bank criteria; HY stage 1 to 3; history of falls in the past year;
able to walk 10 minutes continuously; MMSE ≥ 24; able to walk independently indoors without walking
aid; stable medication over the past 3 months; no hearing or visual problems interfering with the tests
or training; and stable deep brain stimulator settings during the past year

Exclusion criteria:

No other physiotherapy interventions or complementary exercises were allowed during the study

Interventions Length of intervention: 5 weeks

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Capato 2020a (Continued)

Intervention 1: Rhythmical auditory stimuli (RAS)-supported Balance Training (gait training with visual
cues combined with rhythmical auditory stimuli, provided by a metronome) [Gait/Balance/Functional];
45 minutes; 2x/week

Intervention 2: Regular Balance Training (gait training with visual cues) [gait/balance/functional train-
ing]; 45 minutes; 2x/week

Intervention 3: Control group (general education program about PD, falls prevention and self-care)
[active control group]; 45 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Physiotherapists

Outcomes Mini-BESTest; UPDRS; TUG; BBS; retropulsion test of the UPDRS; push-and-release test; Rapid Turns
Test; N-FOG-Q; FES-I

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 6 months

Notes Funding sources: University of Sao Paulo General Hospital

Conflicts of interest: NR

Carroll 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 24/21/18

Country: Ireland

Age (mean in years): 71.4

Sex (male/female): 12/6 (66.7% male)

Duration of disease (mean in years): 7; 10.5

HY (range): 1 to 3

UPDRS-M (mean): 17.5; 16.5

MMSE (mean): NR

Physical capability: Step time (seconds): 0.02; 0.02

Inclusion criteria:

Neurologist-confirmed diagnosis of idiopathic PD according to UK Brain Bank criteria; HY I-III; stable

medication status over the past three months. Participants were required to be able to walk 10 meters
three times, without assistance.

Exclusion criteria:

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Carroll 2018 (Continued)

Contraindications to aquatic therapy, including cardiovascular or pulmonary conditions; previous his-
tory of deep brain stimulation or any musculoskeletal condition that affected their ability to participate
in the exercise group

Interventions Length of intervention: 6 weeks

Intervention 1: Aquatic Therapy [aqua-based training]; 45 minutes; 2x/week

Intervention 2: Control group (usual care) [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapist

Outcomes 3D Gait analysis; PDQ-39; UPDRS-M; FOG-Q

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: NR

Conflicts of interest: NR

Carvalho 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 41/22/22

Country: Brazil

Age (mean in years): 64.8; 64.1; 62.1

Sex (male/female): 14/8 (63.6% male)

Duration of disease (mean in years): 6.6; 6.0; 4.3

HY (mean): 2.6; 2.1; 2.3

UPDRS-M (mean): 31.0; 40.4; 34.9

MMSE (mean): 24.6; 25.8; 26.5

Physical capability: 2-Minute Step Test [repetitions]: 50.6; 46.7; 57.9; 10-Meter Walk Test: 9.0; 8.0; 7.2

Inclusion criteria:

Aged between 45 years and 80 years, a diagnosis of PD, and stage 1 to 3 on the HY scale

Exclusion criteria:

Any disease that hindered the application of an evaluation instrument; clinical comorbidities that
made it impossible to use physical effort; individuals of New York Heart Association classes III and IV;
significant physical limitations; and visual or hearing impairment

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Carvalho 2015 (Continued)

Interventions Length of intervention: 12 weeks

Intervention 1: Aerobic Training [endurance training]; 40 minutes, 2x/week

Intervention 2: Strength training [strength/resistance training]; duration not reported, 2x/week

Intervention 3: Physiotherapy [multi-domain training]; 30 to 40 minutes, 2x/week

Primary setting: Individual

Supervision by (if provided): Trained coaches

Outcomes UPDRS-M; Senior Fitness Test; balance; walking speed; electroencephalographic activity (EEG) to exam-
ine possible central nervous system changes

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Chaiwanichsiri 2011
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/30/30

Country: Thailand

Age (mean in years): 67.1; 67.9; 68.6

Sex (male/female): 30/0 (100% male)

Duration of disease (mean in years): 3.7; 7.4; 4.4

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: 6-MIN-W (meters): 426.6; 426.8; 449.3

Inclusion criteria:

Male PD patients aged 60 to 80 years diagnosed by neurologists as idiopathic PD, HY stage 2 to 3, with
good cognitive function on Thai Mental State Examination score > 23, stable symptoms with unmodi-
fied anti-Parkinsonian medication throughout the study, independent walking without using any gait
aids. Good vision and hearing were required to ensure that the participants could follow the program.

Exclusion criteria:

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Chaiwanichsiri 2011 (Continued)

"Patients should have no other medical conditions that could interfere with the training program and
[should not have participated] in any training program during the previous two months"

Interventions Length of intervention: 8 weeks

Intervention 1: Treadmill with music and home walking [gait/balance/functional training]; 30 minutes;
3x/week and 3x/week at home

Intervention 2: Treadmill and home walking [gait/balance/functional training]; 30 minutes; 3x/week

and 3x/week at home

Intervention 3: Home walking [active control group]; 30 minutes; 6x/week

Primary setting: Group and individual

Supervision by (if provided): NR

Outcomes Step length, Stride length, Cadence, 6-meter walk time, Speed, 6-MIN-W, TUG

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University

Conflicts of interest: None

Cheng 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 46/36/36

Country: Taiwan

Age (mean in years): 66.4; 65.8; 67.3

Sex (male/female): 25/11 (69.4% male)

Duration of disease (mean in years): 6.5; 6.1; 8.1

HY (mean): 1.6; 1.8; 2.0

UPDRS-M (mean): NR; 19.7; 19.5

MMSE (mean): 28.1; 27.7; 28.1

Physical capability: Curved-walking: speed (cm/s): NR; 58.3; 60.6, step length (cm): NR; 38.3; 38.0,
Straight-walking: speed (cm/s): NR; 83.2; 84.6, step length (cm): NR; 46.3; 46.6

Inclusion criteria:

Participants with idiopathic PD diagnosed by a neurologist, presence of at least two of four features
(resting tremor, bradykinesia, rigidity, and asymmetric onset), and one of which had to be resting
tremor or bradykinesia, HY stages 1 to 3, independent walking, and a score of ≥ 24 on the MMSE

Exclusion criteria:

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Cheng 2017 (Continued)

Unstable medical condition, motor fluctuations, or severe dyskinesia which might interfere with the
training, and any history of other diseases known to interfere with participation in the study

Interventions Length of intervention: 4 to 6 weeks

Intervention 1: Specific exercise group (balance exercises and muscle strengthening) [gait/bal-
ance/functional training]; 30 minutes; 2 to 3x/week

Intervention 2: Turning-based training group (turning training on a rotational treadmill) [gait/bal-

ance/functional training]; 30 minutes; 2 to 3x/week

Intervention 3: Control group (trunk exercises combining upper limb movements in the sitting posi-
tion that minimally challenged their standing balance and lower extremity muscle strength) [multi-do-
main training]; 40 minutes; 2 to 3x/week

Primary setting: Group and individual

Supervision by (if provided): Physical therapist

Outcomes Curved-walking performance (Speed, Cadence, Step length), FOG-Q, straight-walking performance
(Speed, Cadence, Step length), TUG, functional gait assessment, UPDRS-M, PDQ-39

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 month

Notes Funding sources: This work was supported by grants from the Ministry of Science and Technology.

Conflicts of interest: None

Cherup 2021
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 53/46/33

Country: USA

Age (mean in years): 70.6

Sex (male/female): 21/12 (63.6% male)

Duration of disease (mean in years): NR

HY (range): 1 to 3

UPDRS-M (mean): 26.3; 30.8

MMSE (mean): NR

Physical capability: TUG: 8.2; 9.7

Inclusion criteria:

40 to 90 years old; diagnosed with mild to moderate PD (HY stages 1 to 3); free from uncontrolled car-
diovascular, musculoskeletal, or nerve disease; cleared for exercise by their physician; and not current-
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Cherup 2021 (Continued)

ly involved in any formal training program that targeted lower body strength, balance, or propriocep-
tion

Exclusion criteria:

NR

Interventions Length of intervention: 12 weeks

Intervention 1: Yoga meditation [mind-body training]; 90 minutes; 2x/week

Intervention 2: Proprioception training [gait/balance/functional training]; 45 minutes; 2x/week

Primary setting: Group and individual

Supervision by (if provided): Certified yoga instructors; instructor

Outcomes FES; Balance Error Scoring System; Tinetti balance assessment tool; TUG; Joint position sense; Joint
kinesthesia

Follow-up (maximum time after end of intervention): within 2 weeks

Notes Funding sources: None

Conflicts of interest: None

Cheung 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 52/20/20

Country: USA

Age (mean in years): 63.0

Sex (male/female): NR/NR

Duration of disease (mean in years): 4.8

HY (range): 1 to 3

UPDRS-M (mean): 25.6; 24.4

MMSE (mean): NR

Physical capability: Longitudinal Aging Study Amsterdam (LASA) Physical Activity Questionnaire level
(min) 5745; 7344

Inclusion criteria:

Individuals diagnosed with mild to moderate idiopathic PD (HY stages 1 to 3), aged 45 to 75 years, on
stable dopaminergic therapy for 4 weeks prior to enrollment if taking medication, and able to ambu-
late 6 m with/without assistive device

Exclusion criteria:

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Cheung 2018 (Continued)

Atypical parkinsonism or other significant brain conditions such as a stroke; had any medical condition
that prohibited safe exercise as assessed by the Exercise Assessment and Screening for You Question-
naire; had significant cognitive impairment as indicated by scoring less than 26 in the MoCA; had a de-
cline in immune function such as pneumonia or systemic infection; had spinal fusion or other orthope-
dic surgery in the past 6 months; had a significant psychiatric disease; needed greater than minimal as-
sistance for gait and transfers; were already practicing yoga regularly; or were unable to commit to at-
tend scheduled yoga sessions

Interventions Length of intervention: 12 weeks

Intervention 1: Yoga [mind-body training]; 60 minutes; 2x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Group

Supervision by (if provided): Yoga instructor

Outcomes UPDRS; MoCA; BDI; blood oxidative stress markers; Parkinson’s Disease Quality of Life Scale; Longitudi-
nal Aging Study Amsterdam Physical Activity Questionnaire; Parkinson’s Disease Sleep Scale

Follow-up (maximum time after end of intervention): 6 months

Notes Funding sources: University of Minnesota Grant-in-Aid of Research; University of Minnesota Founda-
tion, Artistry and Scholarship Program; and Midwest Nursing Research Society Sally Lusk Grant for the
conduct of the research. Research reported in this publication was supported by the National Center
for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114.

Conflicts of interest: None

Choi 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 30/22/20

Country: Korea

Age (mean in years): 60.81; 65.54

Sex (male/female): NR/NR

Duration of disease (mean in years): 5.2; 5.2

HY (range): 1 to 2

UPDRS-M (mean): 22.36; 17.67

MMSE (mean): NR

Physical capability: 6-MIN-W: 442.6; 369.9

Inclusion criteria:

HY 1 to 2; stable drug regimen

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Choi 2013 (Continued)

Exclusion criteria:

Severe cognitive impairment; concomitant severe neurologic, cardiopulmonary, or orthopedic disor-

ders; specific contraindications to exercise; had recently participated in any physiotherapy or rehabili-
tation program

Interventions Length of intervention: 12 weeks

Intervention 1: Tai chi [mind-body training]; 60 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes UPDRS, light stimulus test, one-legged stance test

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Cholewa 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/70/NR

Country: Poland

Age (mean in years): 70.2; 70.2

Sex (male/female): 46/28 (62.2% male)

Duration of disease (mean in years): 8.0; 7.3

HY (mean): 3.0

UPDRS-M (mean): 21.6; 22.0

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Idiopathic PD; only people in stage 3 according to the HY scale were included

Exclusion criteria:

People with cognitive dysfunction as well as with depression

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Cholewa 2013 (Continued)

Interventions Length of intervention: 12 weeks

Intervention 1: Rehabilitation exercises (frequent movement repetitions, coupling movements with

acoustic movement initiator (step), repeating movements with different frequencies, introducing free
movements stimulated by different visual, audio or sensual signals, visualizing movement prior to exe-
cution, provoking equivalent movements, realizing improper postures and correcting them) [multi-do-
main training]; 60 minutes; 2x/week

Intervention 2: Control [passive control group]

Primary setting: Group

Supervision by (if provided): Therapist

Outcomes UPDRS-I; UPDRS-II; UPDRS-M; Schwab and England scale; PDQ-39

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Claesson 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 33/28/22

Country: Sweden

Age (mean in years): 69.0

Sex (male/female): 11/17 (39.3% male)

Duration of disease (mean in years): 6.8

HY (mean): 1.8

UPDRS-M (median): 23.0

MMSE (mean): > 22 (inclusion criteria)

Physical capability: 10-meter walk (s) 8.05 (at comfortable speed, starting stationary)

Inclusion criteria:

Community-dwelling people with a diagnosis of idiopathic PD; early stage of Parkinson’s disease de-
fined as HY < 3 and under a stable Parkinson’s disease drug therapy. Furthermore, they should have an
MMSE result of > 22 and a normal bedside sensory status.

Exclusion criteria:

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Claesson 2018 (Continued)

No other disease apart from Parkinson’s disease affecting motor performance; attendance to exercise
was less than 50% (eight out of 16 sessions) or if their Parkinson’s disease medication was modified
during the study period

Interventions Length of intervention: 8 weeks

Intervention 1: Balance Training [gait/balance/functional training]; 45 minutes; 2x/week

Intervention 2: Control group (delayed start) [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapist

Outcomes BBS; Bäckstrand Dahlberg Liljenäs Balance Scale; TUG; UPDRS-M; 10-meter walk test

Follow-up (maximum time after end of intervention): 6 months (intervention group only)

Notes Funding sources: The study was supported by grants from the National Doctor School of Health Care
and Sciences at Karolinska Institutet, the Stockholm City Council, the Swedish Association for People
with Neurological Disabilities and the Norrbacka-Eugenia Foundation.

Conflicts of interest: None

Colgrove 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 18/13/13

Country: USA

Age (mean in years): 62.8; 73.4

Sex (male/female): 6/7 (46.2% male)

Duration of disease (mean in years): 3 years 2.75 months; 3 years 8.4 months

HY (range): 1 to 2

UPDRS-M (mean): 19.12; 16.2

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: gait velocity (m/s): 0.92; 0.95

Inclusion criteria:

Patients with HY 1 to 2 who could ambulate with or without an assistive device for at least 50 feet and
were able to get up and down from the floor with minimal assist or less, and score 24 or above on the
Folstein MMSE

Exclusion criteria:

HY ≥ 3, decline in immune function such as pneumonia or systemic infection, progressive degenera-

tive disease besides PD, spinal fusion or other orthopedic surgery in the past six months, mental dis-
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Colgrove 2012 (Continued)

ease/psychosis such as dementia, greater than minimal assistance required for gait and transfers, in-
ability to make regular time commitments to the scheduled yoga sessions, or experience with regular
practice of yoga within the past year

Interventions Length of intervention: 12 weeks

Intervention 1: Yoga [mind-body training]; 60 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Certified master yoga instructor

Outcomes UPDRS-M, BBS, measures of range of motion, strength, posture, standing postural sway, gait initiation,
biomechanical measures

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: University of Kansas Medical Center’s School of Allied Health Research Committee;
National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH)

Conflicts of interest: NR

Conradsson 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 146/100/91

Country: Sweden

Age (mean in years): 72.9; 73.6

Sex (male/female): 51/41 (55.4% male)

Duration of disease (mean in years): 6.0; 5.6

HY (range): 2 to 3

UPDRS-M (mean): 36; 37

MMSE (mean): 28; 28 (reported for follow-up sample)

Physical capability: norm velocity (m/s): 1.19; 1.16 (normal walking conditions); recurrent fallers (%):
53; 55

Inclusion criteria:

Community-dwelling individuals with idiopathic PD with impaired balance; HY: 2/3; age ≥ 60; ability to
independently ambulate indoors without a walking aid; ≥ 3 weeks of stable anti-Parkinsonian medica-
tion

Exclusion criteria:
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MMSE < 24; other medical conditions influencing balance performance or participation

Interventions Length of intervention: 10 weeks

Intervention 1: HiBalance training (motor-learning principles, dual task exercises combining cognitive
tasks with motor tasks, balance components (sensory integration, anticipatory postural adjustments,
motor agility, stability limits)) [gait/balance/functional training]; 60 minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Physical therapists

Outcomes Mini-BESTest, gait velocity, step length, cadence (each as normal condition, and while performing cog-
nitive task), average steps/day, FES-I, UPDRS-II, modified-figure-of-eight test; adverse events

Follow-up (maximum time after end of intervention): 12 months

Notes Funding sources: Swedish Research Council, Swedish Parkinson Foundation, Karolinska Institutet,
Loo and Hans Ostermans Foundation, Gun and Bertil Stohnes Foundation, Swedish NEURO Founda-
tion, Norrbacka Eugenia Foundation, regional agreement on medical training and clinical research
(ALF) between Stockholm County Council and Karolinska Institutet

Conflicts of interest: None

Corcos 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 70/48/38

Country: USA

Age (mean in years): 58.6; 59.0

Sex (male/female): 28/20 (58.3% male)

Duration of disease (mean in years): 6.5; 6.5

HY (mean): 2.3; 2.2

UPDRS-M (mean): 20.9; 21.6

MMSE (mean): 29.1; 29.3

Physical capability: 6-MIN-W: 507.5; 548.3, Modified Physical Performance Test: 31.1; 30.7, walk speed:
1.7; 1.6 (m/s)

Inclusion criteria:

People with idiopathic PD with moderate disease severity, between 50 and 67 years old, on stable med-
ication, able to walk for 6 minutes

Exclusion criteria:

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Neurological history other than PD, significant arthritis, failed Physical Activity Readiness Question-
naire, had cognitive impairment (MMSE < 23); were already exercising; or had undergone surgery for
Parkinson’s disease

Interventions Length of intervention: 24 months

Intervention 1: Modified Fitness Counts (stretches, balance exercises, breathing, and non progressive
strengthening) [multi-domain training]; 60 to 90 minutes; 1x/week

Intervention 2: Progressive Resistance Exercise (strengthening exercises) [strength/resistance train-

ing]; 60 to 90 minutes; 1x/week

Primary setting: Individual

Supervision by (if provided): Certified personal trainer

Outcomes UPDRS-M, elbow flexor muscle strength and movement speed, modified Physical Performance Test,
PDQ-39, TUG, BBS, 6-MIN-W, walk speed (50-feet); sit to stand test, FRT, stride length, cadence, double
support time, ankle strength (on/off; comfortable/fast speed), cognition

Severity of motor signs assessed during: on- and off-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: National Institute of Neurological Disorders and Stroke

Conflicts of interest: DMC received grant support from the National Institutes of Health (NIH) and
Michael J. Fox, and receives lecture and reviewer fees from NIH. JAR, FJD, and CP received grant sup-
port from NIH. SEL was a statistical consultant for this project through the University of Illinios at Chica-
go. DEV received grant support from NIH, Michael J. Fox, and consults for projects at UT Southwestern
Medical Center and Great Lakes NeuroTechnologies. MRR had scholarship support from the Foundation
for Physical Therapy and received grant support from NIH. WMK received grant support from NIH and
DoD and consulting fees from NIH. CLC received research support from Allergan Inc., Merz Pharmaceu-
ticals, Ipsen Limited, NIH, and Parkinson Disease Foundation, and consulting fees from Neupathe, Al-
lergan Inc., Merz Pharmaceuticals, Ipsen Limited, and Medtronic Corporation.

Cugusi 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 20/20/20

Country: Italy

Age (mean in years): 67.3

Sex (male/female): 16/4 (80% male)

Duration of disease (mean in years): 7

HY (mean): 2.4; 2.3

UPDRS-M (mean): 25.3; 25.0

MMSE (mean): ≥ 24 (inclusion criteria)

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Cugusi 2015 (Continued)

Physical capability: TUG: 8.8; 9.2, 6-MIN-W: 330.9; 328.1

Inclusion criteria:

Diagnosis of probable PD, performed by a neurologist (PS) with expertise in PD and other movement
disorders; disease severity ranging between stage 1 to 3 on the HY staging; age between 40 to 80 years;
stable medication use

Exclusion criteria:

MMSE score lower than 24 (Folstein F, Folstein, SE & McHugh, 1975); debilitating conditions or vision
impairment that would impede full participation in the study; any disorder interfering with the correct
assessment of clinical aspects of the disease; unavailability during the study period.

Interventions Length of intervention: 12 weeks

Intervention 1: Nordic walking [endurance training]; 60 minutes; 2x/week

Intervention 2: Control group (Conventional care) [passive control group]

Primary setting: Group

Supervision by (if provided): Adapted physical activity professionals

Outcomes UPDRS-M; HY; resting heart rate; systolic blood pressure at rest; diastolic blood pressure at rest; 6-MIN-
W; FTSTS; hand-grip test; BBS; TUG; sit and reach test; back scratch test; Parkinson's Fatigue Scale; BDI-
II; Starkstein Apathy Scale; non-motor Symptoms Scale

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

da Silva Rocha Paz 2019

Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 27/27/24

Country: Brazil

Age (mean in years): 61.8; 67.4

Sex (male/female): 18/6 (75% male)

Duration of disease (mean in years): 4.9; 6.4

HY (mean): 1.9; 2.0

UPDRS-M (mean): 23.5; 24.2

MMSE (mean): NR

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da Silva Rocha Paz 2019 (Continued)

Physical capability: 6-MIN-W (m): 500.7; 420.6, Gait speed (m/s): 1.16; 1.13

Inclusion criteria:

Both genders, aged between 55 and 75 years old, diagnosed with PD according to the Brain Bank of the
United Kingdom standards, and classified in stages from 1 to 3 on HY scale

Exclusion criteria:

People without an adequate drug regimen for at least three months; had undergone physiotherapy
within three months before the protocol; inability to perform physical exercises; presence of other neu-
rological disorders and/or severe impairment of the cardiorespiratory and/or musculoskeletal system.
'In cases in which patients had changes in the drug regimen during the study or missed sessions, they
were disregarded [understood to mean excluded].'

Interventions Length of intervention: 14 weeks

Intervention 1: Treadmill training and kinesiotherapy [endurance training]; 50 minutes; 2x/week

Intervention 2: Conventional physiotherapy [multi-domain training]; 50 minutes; 2x/week

Primary setting: Group/Individual/Group and individual

Supervision by (if provided): Physical therapists

Outcomes TUG, 6-MIN-W, gait speed, UPDRS-total, UPDRS-II, UPDRS-M, upstairs-test and downstairs-test

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Daneshvar 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/20/20

Country: Iran

Age (mean in years): 55.8; 57.0

Sex (male/female): NR

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

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Daneshvar 2019 (Continued)

Inclusion criteria:

A known case of PD in stages 2 or 3 according to Hoehn and Yahr scale; aged 20 to 50 years old; being at
the onset stage of the disease (response to drugs); being at the moderate stage of the disease accord-
ing to the UPDRS; and voluntary agreement of the individual to participate in the research

Exclusion criteria:

People with any history of spinal or lower limb severe injury or surgery during last year, those with any
skeletal deformity who were not able to do the exercises, those who were absent in more than 30% of
sessions, and those who did not agree to participate in the study were excluded.

Interventions Length of intervention: 8 weeks

Intervention 1: Rebound exercise (trampolining training) [gait/balance/functional training]; 20 to 45

minutes; 3x/week

Intervention 2: Treadmill training [endurance training]; 20 to 45 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): Researcher

Outcomes PDQ-39; Proprioception (Biodex Isokinetic testing machine), Range of motion (metal goniometer)

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: University of Isfahan

Conflicts of interest: None

Dashtipour 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/11/11

Country: USA

Age (mean in years): 63.4

Sex (male/female): 5/6 (45.5% male)

Duration of disease (mean in years): 3.8

HY (mean): 1.8; 1.3

UPDRS-M (mean): 17.2; 18.4

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

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Dashtipour 2015 (Continued)

30 to 90 years old; stable dose of PD medications for the last 28 days; clinical condition at time of study
enrollment did not require any changes of medication for the next four months; being clinically stable
to attend either the outpatient physical therapy for LSVT BIG therapy or a general exercise program at
the Loma Linda University Research Laboratory for sixteen 1-hour sessions over four weeks

Exclusion criteria:

Atypical PD; participation in an ongoing exercise program; history of repeated strokes with stepwise
progression of Parkinsonian features; evidence of severe depression or other significant behavioral
disorders; significant or unstable medical or surgical condition that may preclude safe and complete
study participation

Interventions Length of intervention: 4 weeks

Intervention 1: LSVT BIG Therapy [LSVT BIG]; 60 minutes; 4x/week

Intervention 2: General exercise (treadmill exercise and seated upper extremity exercise) [multi-do-
main training]; 60 minutes; 4x/week

Primary setting: Individual

Supervision by (if provided): LSVT BIG certified physical therapist; research investigator

Outcomes UPDRS (total); UPDRS-M; Beck Anxiety Inventory; Modified Fatigue Impact Scale

Follow-up (maximum time after end of intervention): 6 months

Notes Funding sources: NR

Conflicts of interest: None

De Assis 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/20/17

Country: Brazil

Age (mean in years): 65.0; 66.4

Sex (male/female): 13/4 (76.5% male)

Duration of disease (mean in years): 12.3; 10.8

HY (mean): 3.0; 3.0

UPDRS-M (mean): 16; 17

MoCA (mean): 21.1; 20.4

Physical capability: NR

Inclusion criteria:

Medical permission to exercise; diagnosis of PD; HY 2 to 3

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De Assis 2018 (Continued)

Exclusion criteria:

Inability to walk independently; lack of completion of at least 85% of the exercise program

Interventions Length of intervention: 4 weeks

Intervention 1: Water-walking program [aqua-based training]; 40 minutes, frequency not reported

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided):

Outcomes UPDRS; Senior Fitness test battery

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

De Moraes Filho 2020

Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 75/62/40

Country: Brazil

Age (mean in years): 64.7; 64.4

Sex (male/female): 30/10 (75% male)

Duration of disease (mean in years): 5.7; 7.2

HY (range): 1 to 3

UPDRS-M (mean): NR

MMSE (mean): > 24 [> 19] (inclusion criteria)

Physical capability: TUG: 9.2; 9.3

Inclusion criteria:

Diagnosed with PD, HY stage 1 to 3, between 50 and 80 years old, no cognitive impairment as assessed
by the MMSE, where the cut-off points for inclusion were > 24 points for literate individuals and > 19 for
non-literate individuals, and attested to participate in the resistance training (RT) program

Exclusion criteria:

Diagnosed with any other neurological disease, with cardiovascular disease, hematologic or orthope-
dic disorders; with motor fluctuations or severe dyskinesia that could affect their ability to perform the

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De Moraes Filho 2020 (Continued)

experimental protocol. Moreover, participants who did not reach the minimum frequency of 75% or
missed 3 consecutive training sessions were excluded from analyses.

Interventions Length of intervention: 9 weeks

Intervention 1: Resistance training program [strength/resistance training]; 50 to 60 minutes; 2x/week

Intervention 2: Control group (lectures) [passive control group]

Primary setting: Individual

Supervision by (if provided): Proficient professionals

Outcomes 30-second sit to stand test; TUG; 10MWT; peak torques; bradykinesia subscale of the UPDRS-M

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Dipasquale 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 297/40/31

Country: Italy

Age (mean in years): 67

Sex (male/female): 26/14 (65% male)

Duration of disease (mean in years): 2.25; 2.33

HY (mean): 2 (inclusion criteria)

UPDRS-M (median): 11; 8.5

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG (median): 10.3;8.5

Inclusion criteria:

Idiopathic Parkinson’s disease; time from diagnosis ≥ 24 months; HY 2; medical therapy unchanged for
at least one month; ability to follow the study protocol

Exclusion criteria:

Contraindications for physical activity at study's intensity level; > 85 years; MMSE < 24; > 3 in one or
more Cumulative Illness Rating Scale categories; physiotherapy treatment or supervised physical activ-
ity in the past six months

Interventions Length of intervention: 4 months

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Dipasquale 2017 (Continued)

Intervention 1: Physiotherapy program (transfers, body posture, reaching and grasping, balance and
gait) [gait/balance/functional training]; 60 minutes; 2x/week

Intervention 2: General exercise program (upper limbs, lower limbs, spine, balance, and breathing)
[multi-domain training]; 60 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Physiotherapist; expert in physical education

Outcomes UPDRS, UPDRS-M; Hamilton Rating Scale - Depression; Functional Independence Measure; TUG

Follow-up (maximum time after end of intervention): 118 to 190 days

Notes Funding sources: NR

Conflicts of interest: None

Duncan 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 123/62/3

Country: USA

Age (mean in years): 69.3; 69.0

Sex (male/female): 30/22 (57.7% male)

Duration of disease (mean in years): 5.8; 7.0

HY (mean): 2.6; 2.5

UPDRS-M (mean): 44.5; 48.0

MMSE (mean): NR

Physical capability: Physical Activity Scale for the Elderly: 124.2; 115.4

Inclusion criteria:

Diagnosed with idiopathic PD, HY stages I to IV, and experienced clear motor benefit from levodopa.
Participants had to be able to walk independently for 3 meters with or without an assistive device

Exclusion criteria:

Serious medical condition, evidence of abnormality other than PD-related changes on brain imaging,
history or evidence of neurological deficit other than PD, history or evidence of musculoskeletal prob-
lem

Interventions Length of intervention: 12 months

Intervention 1: Tango [dance]; 60 minutes; 2x/week

Intervention 2: Control [passive control group]

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Duncan 2012 (Continued)

Primary setting: Group

Supervision by (if provided): Experienced dance instructor

Outcomes MDS-UPDRS-M, UPDRS-I, UPDRS-II, MiniBESTest balance test; FOG-Q; 6-MIN-W; gait velocity, Nine-Hole
Peg Test; BDI-II; Activity Card Sort

Severity of motor signs assessed during: off-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Parkinson’s Disease Foundation

Conflicts of interest: None

Ebersbach 2010
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/60/58

Country: Germany

Age (mean in years): 67.1; 65.5; 69.3

Sex (male/female): 22/36 (37.9% male)

Duration of disease (mean in years): 6.1; 7.8; 7.4

HY (mean): 2.8; 2.6; 2.5

UPDRS-M (mean): 21.1; 18.5; 19.1

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: 10MWT (sec): 7.7; 7.9; 7.9

Inclusion criteria:

Idiopathic PD, HY 1 to 3, outpatient treatment, stable medication 4 weeks prior to inclusion

Exclusion criteria:

MMSE < 25, severe depression, disabling dyskinesia, and comorbidity affecting mobility or ability to ex-
ercise

Interventions Length of intervention: 4/8 weeks

Intervention 1: LSVT BIG [LSVT BIG]; 60 minutes; 4x/week, 4 weeks

Intervention 2: Nordic walking [endurance training]; 60 minutes; 2x/week, 8 weeks

Intervention 3: Control (received 1-hour instruction of domestic training with practical demonstration
and training) [passive control group]; 4 weeks

Primary setting: Group and individual

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Ebersbach 2010 (Continued)

Supervision by (if provided): LSVT BIG and Nordic-walking-certified physiotherapist

Outcomes UPDRS-M, PDQ-39, TUG, Timed 10 m (sec); Test battery for Attentional Performance subtest for alert-
ness

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 8/12 weeks (overall 16 weeks after baseline)

Notes Funding sources: Deutsche Parkinson Gesellschaft

Conflicts of interest: Georg Ebersbach: honoraries for presentations from Boehringer Ingelheim Phar-
ma, Cephalon, Desitin Pharma, GlaxoSmithKline, Valeant, Novartis, Orion, and Schwarz Pharma (UCB).
Honoraries for consultancy and advisory board activities from Axxonis Pharma, Boehringer Ingelheim
Pharma, Cephalon, Desitin Pharma, Valeant, Orion. Grants from Deutsche Parkinson Gesellschaft (DPV)
and Deutsche Forschungs-Gesellschaft (DFG). Jörg Wissel: honoraries for presentations and adviso-
ry board activities from Allergan, Eisai, Ipsen Medtronic, and Merz. Andreas Kupsch: honoraries for
presentations from Allergan, Boehringer Ingelheim Pharma, Desitin Pharma, GlaxoSmithKline, Ipsen,
Lundbeck, Merz Pharma, Medtronic, Novartis, Orion, and Schwarz Pharma (UCB). Honoraries for advi-
sory board activities and consultancy from Novartis and Medtronic. Grants from Deutsche Forschungs-
Gesellschaft (DFG) and Fresenius-Körner-Foundation.

Ellis 2005
Study characteristics

Methods Randomized controlled trial with cross-over after 6 weeks

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/68/65

Country: USA, Netherlands

Age (mean in years): 64

Sex (male/female): 51/17 (75% male)

Duration of disease (mean in years): NR

HY (mean): 2.4

UPDRS-M (mean): 30.2

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: comfortable walking speed (m/s): 0.77; 0.83

Inclusion criteria:

Patients with idiopathic PD (early-middle stages); stable medication usage; HY: 2/3; at least 1 score of
2 or more for at least 1 limb for either the tremor, rigidity, or bradykinesia item of the UPDRS; ability to
walk independently; aged 35 to 75 years; no severe cognitive impairments (MMSE ≥ 24); not having par-
ticipated in a physical therapy or rehabilitation program in the previous 2 months

Exclusion criteria:

Other severe neurologic, cardiopulmonary, or orthopedic disorders; participation in physiotherapy or

rehabilitation program in previous 2 months

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Ellis 2005 (Continued)

Interventions Length of intervention: 6 weeks

Intervention 1: Physical therapy, rehabilitation program, and medication [multi-domain training]; 90

minutes; 2x/week

Intervention 2: Medication only [passive control group]

Primary setting: Group

Supervision by (if provided): Licensed physical therapist

Outcomes Sickness Impact Profile, the mobility portion of the Sickness Impact Profile-68, UPDRS, comfortable
walking speed, UPDRS-M

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-cross-over)

Notes Funding sources: NR

Conflicts of interest: NR

Feng 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 31/28/28

Country: China

Age (mean in years): 67.5; 66.9

Sex (male/female): 17/13 (56.7% male)

Duration of disease (mean in years): 7.1; 6.6

HY (mean): 3.0; 3.0

UPDRS-M (mean): 25.1; 24.7

MMSE (mean): 27.1; 26.3

Physical capability: TUG 34.2; 37.9, Functional Gait Assessment 14.7; 16.2

Inclusion criteria:

Diagnosis of PD; improved HY classification grade 2.5 to 4, in which there is balance dysfunction but in-
dependent walking; aged 50 to 70 years old; signed informed consent

Exclusion criteria:

Other causes of tremor, such as hereditary ataxia and cerebellar or vestibular lesions; bone and joint
diseases or serious diseases affecting organ function; visual or hearing disorders; unable to cooperate
with the study

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Feng 2019 (Continued)

Interventions Length of intervention: 12 weeks

Intervention 1: Virtual reality training [gait/balance/functional training]; 45 minutes; 5x/week

Intervention 2: Conventional physical therapy [multi-domain training]; 45 minutes; 5x/week

Primary setting: Individual

Supervision by (if provided): Therapist

Outcomes BBS; TUG; UPDRS-M; Functional Gait Assessment

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Heilongjiang Health and Family Planning Commission

Conflicts of interest: NR

Ferraz 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 76/72/62

Country: Brazil

Age (mean in years): 69

Sex (male/female): 37/25 (59.7% male)

Duration of disease (mean in years): 6

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): 27.00; 27.00; 27.00

Physical capability: 6-MIN-W (m): 354.9; 405.2; 365.4; 10MWT (s):1.3; 1.3; 1.2

Inclusion criteria:

≥ 60 years; idiopathic PD; regular use of medication; MHY 2, 2.5, or 3; no walking devices

Exclusion criteria:

Visual or hearing impairment; parkinsonian syndromes other than PD; bone, joint, or muscle diseases
that limit the practice of physical activity; chronic uncontrolled diseases (hypertension, diabetes mel-
litus, chronic pain); unstable cardiovascular disease (acute heart failure, recent myocardial infarction,
unstable angina, and arrhythmias uncontrolled); current alcohol and other toxic substance use; con-
traindications for performing physical exercise; practicing any physical exercise program in the past 6
months, participating in regular resistance training in the previous 12 months

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Ferraz 2018 (Continued)

Interventions Length of intervention: 8 weeks

Intervention 1: Functional group [gait/balance/functional training]; 50 minutes; 3x/week

Intervention 2: Bike training group [endurance training]; 50 minutes; 3x/week

Intervention 3: Exergaming Group [gaming]; 50 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes 6-MIN-W, 10MWT, PDQ-39, World Health Organization Disability Assessment Schedule 2.0, sit to stand
test, EQ-5D, 15-item Geriatric Depression Scale

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: NR

Conflicts of interest: None

Ferrazzoli 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 250/250/234

Country: Italy

Age (mean in years): 66.5; 66.9

Sex (male/female): 136/98 (58.1% male)

Duration of disease (mean in years): 9.0; 7.4

HY (mean): 2.6; 2.6

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: TUG (s): 13.3; NR

Inclusion criteria:

Diagnosis of idiopathic PD according to the UK Brain Bank criteria, HY stages 2 to 4 and stable pharma-
cological treatment in the last 6 weeks

Exclusion criteria:

Any focal brain lesion detected with brain imaging studies, psychosis (evaluated with Neuropsychiatric
Inventory), auditory, visual and/or vestibular dysfunctions, and chronic diseases other than PD with a
known impact on QoL

Interventions Length of intervention: 4 weeks

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Ferrazzoli 2018 (Continued)

Intervention 1: "MIRT Group" (multidisciplinary, aerobic, motor-cognitive, intensive and goal-based
rehabilitation) [multi-domain training]; 60 minutes per session; 5x/week 4 sessions and 1x/week physi-
cal exercise

Intervention 2: Control group [passive control group]

Primary setting: Group and individual

Supervision by (if provided): Therapist; neuropsychologists

Outcomes PDQ-39, UPDRS, Parkinson's Disease Disability Scale, TUG, BBS

Follow-up (maximum time after end of intervention): 3 months

Notes Funding sources: NR

Conflicts of interest: None

Ferreira 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 70/35/35

Country: Brazil

Age (mean in years): 67.6; 64.1

Sex (male/female): NR

Duration of disease (mean in years): 4.5; 6.4

HY (range): 1 to 3

UPDRS-M (median): 30; 29

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Diagnosis of PD; age ≥ 60 years; HY 1 to 3; stable use of medication; not have participated in any exer-
cise protocol in the previous three months

Exclusion criteria:

MMSE < 24; unstable cardiovascular disease; other uncontrolled chronic conditions that would inter-
fere with participants' safety, or our conducting of the training and testing protocol and interpretation
of the results; ability to walk independently; other neurological, cardiopulmonary, or orthopedic dis-
ease

Interventions Length of intervention: 6 months

Intervention 1: Resistance training group [strength/resistance training]; 30 to 40 minutes; 2x/week

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Ferreira 2018 (Continued)

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Exercise specialist; neurologist

Outcomes Beck’s Anxiety Inventory, PDQ-39, UPDRS-M, TUG

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Fietzek 2014
Study characteristics

Methods Randomized controlled trial with cross-over after 2 weeks

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 53/23/21

Country: Germany

Age (mean in years): 69.8; 64.2

Sex (male/female): 16/6 (72.7% male)

Duration of disease (mean in years): 12.1; 13.3

HY (mean): 3; 3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosis of PD, a gait disorder with freezing while other motor symptoms (e.g. bradykinesia, rigidity,
tremor) convincingly responded to dopaminergic medication, a HY score of less than four and the abili-
ty to walk independently outside the house

Exclusion criteria:

NR

Interventions Length of intervention: 2 weeks

Intervention 1: Cueing [gait/balance/functional training]; 30 minutes; 3x/week

Intervention 2: Control [passive control group]

Primary setting: Individual

Supervision by (if provided): Physiotherapists

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Fietzek 2014 (Continued)

Outcomes Freezing score; freezing questionnaire; MDS-UPDRS question 11; PDQ-39 mobility; falls

Follow-up (maximum time after end of intervention): 4 weeks (8 weeks after baseline)

Notes Funding sources: German Parkinson Association; German Foundation Neurology

Conflicts of interest: None

Fil-Balkan 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 34/30/24

Country: Turkey

Age (mean in years): 72.75; 71.83

Sex (male/female): 13/11 (54,2% male)

Duration of disease (mean in years): 6.91; 6.83

HY (range): 2.5 to 3

UPDRS-M (mean): 21.66; 20.41

MMSE (mean): 29.25; 28.92

Physical capability: TUG: 16.75; 16.59

Inclusion criteria:

Idiopathic PD diagnosis by a neurologist; HY 2 to 3; at least 26 points in the MMST; age 50+; no other
neurologic disease; no changes in PD medications or dosages during the course of treatment

Exclusion criteria:

Severe mental and psychological disorders; participation in a physiotherapy program within the last 6
months

Interventions Length of intervention: 6 weeks

Intervention 1: Classic physiotherapy program (flexibility, strengthening, posture, breathing balance,

walking exercises, and other functional activities) [multi-domain training]; 60 minutes; 2x/week

Intervention 2: Classic physiotherapy program + sensorimotor integration training [gait/balance/func-

tional training]; 90 minutes; 2x/week

Primary setting: Individual

Supervision by (if provided): NR

Outcomes UPDRS-M; UPDRS-II; TUG; FRT; BBS; postural control evaluated with Computerized Dynamic Posturog-
raphy

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Fil-Balkan 2018 (Continued)

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 6 weeks

Notes Funding sources: None

Conflicts of interest: None

Fisher 2008
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/30/30

Country: USA

Age (mean in years): 64.0; 61.5; 63.1

Sex (male/female): 19/11 (63.3% male)

Duration of disease (mean in month): 14.7; 8.8; 17.7

HY (range): 1 to 2

UPDRS-M (mean): 27.6; 30.5; 27.6

MMSE (mean): 28.9; 29.3; 29.6

Physical capability: Walking velocity (m/s): 1.46; 1.40; 1.39

Inclusion criteria:

PD diagnosis within 3 years of study participation; HY 1 to 2; 18 years of age or older; medical clearance
from the primary care physician to participate in an exercise program; ability to walk

Exclusion criteria:

Medical or physical screening examination showed a score of less than 24 on the MMSE; physician-de-
termined major medical problems such as cardiac dysfunction that would interfere with participation;
musculoskeletal impairments or excessive pain in any joint that could limit participation in an exercise
program; insufficient endurance and stamina to participate in exercise 3 times a week for a 1-hour ses-
sion

Interventions Length of intervention: 8 weeks

Intervention 1: High-intensity group (treadmill) [endurance training]; 45 minutes; 3x/week

Intervention 2: Low-intensity group (general or traditional physical therapy) [multi-domain training];

45 minutes; 3x/week

Intervention 3: Zero-intensity group (education classes) [active control group]; 60 minutes; 6x/8 weeks

Primary setting: Individual

Supervision by (if provided): Physical therapist

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Fisher 2008 (Continued)

Outcomes UPDRS; HY; biomechanic analysis of self-selected and fast walking and sit to stand tasks; corticomotor
excitability using transcranial magnetic stimulation

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Supported by the Kinetics Foundation and National Institute of Neurological Disor-
ders and Stroke

Conflicts of interest: None

Frazzitta 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 68/50/50

Country: Italy

Age (mean in years): 72;70

Sex (male/female): 24/26 (48% male)

Duration of disease (mean in years): 8;9

HY (mean): 3

UPDRS-M (mean): 21; 22

MMSE (mean): ≥ 26 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Diagnosis of “clinically probable” idiopathic PD, HY stage 3, ability to walk without physical assistance,
no cognitive impairment (MMSE ≥ 26), no comorbidity, no vestibular/visual dysfunction limiting loco-
motion or balance, and anti-Parkinsonian medications stable for > 4 weeks.

Exclusion criteria:

NR

Interventions Length of intervention: 2x4 weeks

Intervention 1: Intensive rehabilitation treatment (physiotherapy) [multi-domain training]; 60 min-

utes; 3x/day, 5x/week

Intervention 2: Control group (pharmacological treatment only) [passive control group]

Primary setting: Individual

Supervision by (if provided): NR

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Frazzitta 2012 (Continued)

Outcomes UPDRS-II, UPDRS-M; UPDRS-total, levodopa equivalent daily dosage

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: "The author(s) received no financial support for the research, authorship, and/or
publication of this article."

Conflicts of interest: None

Frazzitta 2014
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 27/25/24

Country: Italy

Age (mean in years): 67; 65

Sex (male/female): NR

Duration of disease (mean in months): 8; 8

HY (range): 1 to 1.5

UPDRS-M (mean): 16.4; 15.6

MMSE (mean): ≥ 26 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

A diagnosis of “clinically probable” idiopathic PD, HY stage 1 to 1.5, no other neurological condition,
rasagiline monotherapy for at least 8 weeks, MMSE score greater than 26, visual and hearing function
sufficient to perceive cues, and ability to walk without any physical assistance. "We chose to evaluate
patients who were all treated with the same drug (rasagiline) in order to avoid possible influences of
different pharmacological classes on both motor performance and BDNF levels"

Exclusion criteria:

Postural hypotension, cardiovascular disorders, musculoskeletal disorders, vestibular dysfunctions

limiting locomotion or balance, and depression (Hamilton Depression Rating Scale > 8)

Interventions Length of intervention: 28 days

Intervention 1: Intensive rehabilitation treatment (physiotherapy) [multi-domain training]; 60 min-

utes; 3x/day, 5x/week

Intervention 2: Control [passive control group]

Primary setting: Individual

Supervision by (if provided): NR

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Frazzitta 2014 (Continued)

Outcomes Serum brain-derived neurotrophic factor concentration; UPDRS-M, UPDRS-II, BBS, 6-MIN-W

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: "The author(s) received no financial support for the research, authorship, and/or
publication of this article."

Conflicts of interest: None

Frazzitta 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 47/40/31

Country: Italy

Age (mean in years): 69; 68

Sex (male/female): NR

Duration of disease (mean in years): NR

HY (range): 1 to 1.5

UPDRS-M (mean): 15.8; 11.3

MMSE (mean): ≥ 26 (inclusion criteria)

Physical capability: 6-MIN-W (m): 371; 408

Inclusion criteria:

Diagnosis of “clinically probable” idiopathic PD, HY stage 1 to 1.5, ability to walk without physical assis-
tance, MMSE score ≥ 26, no serious comorbidity, and no vestibular/visual dysfunction limiting locomo-
tion or balance

Exclusion criteria:

NR

Interventions Length of intervention: 2x4 weeks

Intervention 1: Multidisciplinary intensive rehabilitation treatment [multi-domain training]; 60 min-

utes; 3x/day, 5x/week

Intervention 2: Control group (drug only) [passive control group]

Primary setting: Individual

Supervision by (if provided): Neurologists, physiatrists, psychologists, nurses, physiotherapists, occu-

pational therapists

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Outcomes UPDRS-II; UPDRS-M; 6-MIN-W; TUG; self-assessment Parkinson's Disease Disability Scale; levodopa
equivalent daily dosage; number of participants in monotherapy with rasagaline

Follow-up (maximum time after end of intervention): 24 months (post-baseline)

Notes Funding sources: "The author(s) received no financial support for the research, authorship, and/or
publication of this article."

Conflicts of interest: None

Ganesan 2014
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 94/60/60

Country: India

Age (mean in years): 59.1; 57.7; 57.6

Sex (male/female): 46/14 (76.7% male)

Duration of disease (mean in years): 5.5; 4.9; 5.7

HY (range): 2 to 2.5

UPDRS-M (mean): 30.15; 30.70; 31.95

MMSE (mean): 28.7; 28.8; 29.3

Physical capability: Tinetti Performance-Oriented Mobility Assessment: 13.0; 13.5; 12.9

Inclusion criteria:

Diagnosis of PD confirmed by a movement disorders specialist as per the United Kingdom Brain Bank
Criteria

Exclusion criteria:

People with cognitive deficits (MMSE ≤ 24), moderate to severe depression (BDI ≥ 17), severe dyskinesia
(Goetz score > 3), advanced PD (HY stage > 3), unpredictable motor fluctuations, and orthopedic prob-
lems affecting gait training, as well as people who had undergone previous formal gait training or bal-
ance training, were excluded from the study.

Interventions Length of intervention: 4 weeks

Intervention 1: Control group [Passive control]

Intervention 2: Conventional gait training [gait/balance/functional training]; 30 minutes; 4x/week

Intervention 3: Partial weight supported treadmill gait training [gait/balance/functional training]; 30

minutes; 4x/week

Primary setting: Group/individual

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Supervision by (if provided): NR

Outcomes UPDRS-total and UPDRS-M as well as further UPDRS-M subscores; dynamic posturography; BBS; Tinet-
ti Performance-Oriented Mobility Assessment; blood pressure including mean systolic blood pressure
(SBP), mean diastolic blood pressure, co-variation of SBP, low frequency component of SBP and spon-
taneous baroflex sensitivity; 10MWT; 2-MIN-W

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Gao 2014
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 80/80/76

Country: China

Age (mean in years): 69.5; 68.3

Sex (male/female): 50/26 (65.8% male)

Duration of disease (mean in years): 9.2; 8.4

HY (range): 1 to 3

UPDRS-M (mean): 31.86; 30.62

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: TUG 10.89; 11.58

Inclusion criteria:

Diagnosis as idiopathic PD; over 40 years old; could walk independently and fell at least one time dur-
ing the past 12 months

Exclusion criteria:

MMSE < 24; had a serious medical problem such as heart failure and severe hypertension (equal to or
greater than a systolic 180 or diastolic of 110) and could not endure moderate exercise for 60 minutes
due to any reason

Interventions Length of intervention: 12 weeks

Intervention 1: Tai chi [mind-body training]; 60 minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

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Supervision by (if provided): Tai chi instructor

Outcomes BBS, UPDRS, TUG, falls

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 6 months

Notes Funding sources: "This research received no specific grant from any funding agency in the public,
commercial, or not-for-profit sectors."

Conflicts of interest: None

Gobbi 2021
Study characteristics

Methods Randomized controlled trial with cross-over after 32 weeks of intervention and 4 months detraining pe-
riod

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/152/107

Country: Brazil

Age (mean in years): 69.6; 67.8; 69.5

Sex (male/female): 78/74 (51.3% male)

Duration of disease (mean in years): 8.0; 5.0; 5.9

HY (mean): 1.9; 1.8; 1.7

UPDRS-M (mean): 23.7; 22.8; 22.6

MMSE (mean): 28.2; 28.0; 27.7

Physical capability: NR

Inclusion criteria:

Initially, participants from a support group (Program of Physical Activity for People with Parkinson’s
disease [PROPARKI]) volunteered to participate in the study. People with idiopathic PD according to the
United Kingdom PD Brain Bank criteria, who walked unassisted and without ambulation aids during
the intervention, did not have any other neurological (self-reported) or cognitive impairment (assessed
by the MMSE) and were > 40 years old were eligible for the study. The protocol was approved by the Hu-
man Studies Ethics Committee at Sao Paulo State University (n. 1058), and all participants gave their
signed informed consent. Participants who attended at least 70% of the sessions without 5 consecutive
absences were included in the final analysis.

Exclusion criteria:

NR

Interventions Length of intervention: 32 weeks

Intervention 1: Multimodal (aerobic resistance; general flexibility; lower/upper limbs and trunk
strength; motor coordination; balance) [gait/balance/functional training]; 60 minutes; 2x/week

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Gobbi 2021 (Continued)

Intervention 2: Functional mobility [gait/balance/functional training]; 60 minutes; 2x/week

Intervention 3: Mental/leisure [active control group]; 60 minutes; 2x/week

Primary setting: Individual

Supervision by (if provided): NR

Outcomes Hospital Anxiety and Depression scale; PDQ-39; Lipp's Stress Symptoms Inventory for Adults; MMSE;
clock drawing test; verbal fluency; Wechsler Memory Scale; Wechsler Adult Intelligence Scale; Wiscon-
sin Card Sort Test

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: supported in part by de Cordenacao de Aperfeicoamento de Pessoal de Nıvel Superi-
or, Brasil (CAPES), and by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Conflicts of interest: None

Goodwin 2011
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 204/130/124

Country: Great Britain

Age (mean in years): 72.0; 70.1

Sex (male/female): 74/56 (56.9% male)

Duration of disease (mean in years): 9.1; 8.2

HY (mean): 2.6; 2.4

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: Median "Phone-FITT" household physical activity levels: 16.0; 19.0

Inclusion criteria:

Diagnosis of idiopathic PD as confirmed by a PD specialist (geriatrician or neurologist) using UK Brain

Bank criteria, a self-reported history of recurrent falls (two or more) in the preceding year, the ability
to mobilise independently indoors, with or without a walking aid, and being resident in Devon or regis-
tered with a Devon general practitioner

Exclusion criteria:

Potential participants were excluded if they needed supervision or assistance to mobilise indoors, had
a significant comorbidity or symptoms that affected ability or safety to exercise (e.g. unstable angina,
significant postural hypotension, severe pain) or were unable to follow written or verbal instructions in
English

Interventions Length of intervention: 10 weeks

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Goodwin 2011 (Continued)

Intervention 1: Exercise group (physiotherapy-led, group-delivered strength and balance training pro-
gram with supplementary home exercises) [multi-domain training]; 60 minutes; 1x/week + 2x/week
home exercise

Intervention 2: Usual care [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapists

Outcomes Number of falls during the 10-week group intervention period and the 10-week follow-up period (self-
reported and collected via weekly diaries); FES-I, EQ-5D, "Phone-FITT", BBS, TUG

Follow-up (maximum time after end of intervention): 10 weeks

Notes Funding sources: NIHR Researcher Development Award

Conflicts of interest: PCMD (VG, WH) and University of Exeter (AT) received funding from NIHR to un-
dertake this research.

Gu 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 49/38/35

Country: China

Age (mean in years): 67.4; 69.5

Sex (male/female): 25/10 (71.4% male)

Duration of disease (mean in years): 5.8; 6.2

HY (range): 1 to 3

UPDRS-M (mean): 30.5; 31.0

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Early and intermediate PD (HY 1 to 3); participants were required to have had Parkinson's medication
for at least 2 weeks and be effective on Parkinson's medication

Exclusion criteria:

Parkinson's syndrome and Parkinson's superimposed syndrome from various causes; people who had
undergone rehabilitation training in the 4 months prior to inclusion in this study; comorbid severe cog-
nitive impairment MMSE score of less than 24; people with comorbid depression who were unable to
actively participate in rehabilitation training; people with comorbid schizophrenia or other severe psy-
chiatric disorders; people with comorbid severe heart, liver, kidney, lung disease, etc. People with or-
ganic lesions of the organs that affected activity or life.

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Gu 2013 (Continued)

Interventions Length of intervention: 8 weeks

Intervention 1: PD WEBB (weight-bearing exercise for better balance) [gait/balance/functional train-

ing]; 40 to 60 minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: NR

Supervision by (if provided): Physicians

Outcomes FES; UPDRS; Mini-BESTest

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Science and Technology Plan Fund of Hunan Province, China

Conflicts of interest: NR

Language: Chinese

Guan 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/62/62

Country: China

Age (mean in years): 70.2; 69.7

Sex (male/female): 33/29 (53.2% male)

Duration of disease (mean in years): 4.4; 4.3

HY (mean): 2.05; 2.07

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: 10-meter gait speed (m/min): 55.3; 54.4

Inclusion criteria:

Diagnosis of PD; HY stage 1 to [upper limit understood to be 3]; clear consciousness, no obvious cogni-
tive impairment, able to learn tai chi movements; informed consent to this study and willing to cooper-
ate

Exclusion criteria:

People with organic diseases such as psychosis, severe heart, liver, spleen, kidney, etc.; secondary
Parkinson's syndrome and Parkinson's superimposed syndrome by various causes; people who have to

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Guan 2016 (Continued)

withdraw halfway through study; people who cannot stand or walk independently due to fractures or
other reasons; participation in other rehabilitation training

Interventions Length of intervention: 12 weeks

Intervention 1: Tai chi [mind-body training]; 60 minutes; 4x/week

Intervention 2: Control group [passive control group]

Primary setting: NR

Supervision by (if provided): Professional Taijiquan coaches

Outcomes TUG; BBS; ABC; gait parameters

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Language: Chinese

Hackney 2007
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/19/19

Country: USA

Age (mean in years): 72.6; 69.6

Sex (male/female): 12/7 (63.2% male)

Duration of disease (mean in years): 6.2; 3.3

HY (mean): 2.3; 2.2

UPDRS-M (mean): 30.6; 28.2

MMSE (mean): NR

Physical capability: walking velocity (m/s): 0.86; 0.89

Inclusion criteria:

Diagnosed with idiopathic PD; demonstrated clear benefit from PD medications

Exclusion criteria:

"Subjects in both groups were not engaged in any other dancing or group exercise activities during the
course of the study"

Interventions Length of intervention: 13 weeks

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Hackney 2007 (Continued)

Intervention 1: Tango [dance]; 60 minutes; 2x/week

Intervention 2: Exercise classes (breathing, stretching, resistance, dexterity, core strengthening) [mul-
ti-domain training]; 60 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Instructor (both a professional ballroom dancer and American Council
on Exercise-certified personal trainer)

Outcomes UPDRS; BBS; FOG-Q; TUG; velocity of Walking and dual-task walking

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: Marian Chace Foundation; American Parkinson Disease Association

Conflicts of interest: NR

Hackney 2009
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/75/61

Country: USA

Age (mean in years): 68.2; 66.8; 64.9; 66.5

Sex (male/female): 45/16 (73.8% male)

Duration of disease (mean in years): 6.9; 9.2; 8.7; 5.9

HY (range): 1 to 3

UPDRS-M (mean): 27.6; 26.9; 26.3; 27.4

MMSE (mean): NR

Physical capability: Gait velocity (m/s) 1.11; 1.11; NR; 1.07; 6-MIN-W 364.2; 358.1; NR; 368.4

Inclusion criteria:

"Idiopathic PD using diagnostic criteria for clinically defined “definite PD”; at least 40 years of age,
could stand for at least 30 minutes, and walk independently 3 or more meters with or without an assis-
tive device. Individuals with HY stages of I to III participated. Individuals had been previously screened
for dementia by their neurologists and none were diagnosed with dementia. As another measure of
cognitive function and a separate part of the study not reported here, all participants were required to
perform a subtraction task while simultaneously walking. All participants understood the directions
and were able to complete the task with at least 85 percent accuracy, and as such we considered them
to be cognitively intact for the purposes of this study."

Exclusion criteria:

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Hackney 2009 (Continued)

History of neurological deficit other than PD

Interventions Length of intervention: 13 weeks

Intervention 1: Tango [dance]; 60 minutes; 2x/week

Intervention 2: Waltz/foxtrott [dance]; 60 minutes; 2x/week

Intervention 3: Tai chi [mind-body training]; 60 minutes; 2x/week

Intervention 4: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Experienced instructor (both a professional ballroom dancer and an
American Council on Exercise-certified personal trainer)

Outcomes PDQ-39; BBS; 6-MIN-W; UPDRS; TUG; FOG; stride length; velocity

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: American Parkinson Disease Association

Conflicts of interest: NR

Harvey 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 32/20/18

Country: United Kingdom

Age (mean in years): 68.5

Sex (male/female): 12/8 (60% male)

Duration of disease (mean in years): NR

HY (range): 1 to 3

UPDRS-M (mean): NR

MoCA (mean): 24.5; 25.5

Physical capability: NR

Inclusion criteria:

Diagnosis of idiopathic PD; HY 1 to 3; had not participated in an exercise study in the past 12 months;
did not have a pacemaker or a history of a serious cardiac event or cardiac or cardiorespiratory dys-
function; had sufficient cognitive ability to follow an exercise protocol (based on physician assessment)
and provided informed consent

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Harvey 2019 (Continued)

Exclusion criteria:

"All participants underwent a medical assessment by a doctor (RWW, RD) prior to cardiopulmonary ex-
ercise tests to assess their suitability for high-intensity interval training. Some of those recruited were
subsequently excluded on medical grounds"

Interventions Length of intervention: 12 weeks

Intervention 1: High-intensity interval training [strength/resistance training]; 45 minutes; 3x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapist; exercise scientist

Outcomes Maximal heart rates, recruitment rate, attendance, dropout, change in peak oxygen consumption, car-
diac output, cognitive function and QoL; 6-MIN-W; MoCA; PDQ-39

Follow-up (maximum time after end of intervention): 6 weeks

Notes Funding sources: Graham Wylie Foundation; Speedflex Europe Ltd

Conflicts of interest: KLW was employed by Speedflex Europe Ltd as an exercise physiologist from July
2013 to January 2014, but had no involvement with the company at the time of the study

Hass 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/18/18

Country: USA

Age (mean in years): 64; 67

Sex (male/female): 14/4 (77.8% male)

Duration of disease (mean in years): 11.1; 6.4

HY (mean): 2.3; 2.3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosed with idiopathic PD; MHY stage 1 to 3 and the ability to ambulate without assistance. All par-
ticipants were on stable doses of anti-Parkinsonian medications which remained consistent through-
out the testing and intervention protocol

Exclusion criteria:

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Hass 2012 (Continued)

History of significant cardiovascular, musculoskeletal, vestibular or other neurological disorder, use of
an assisted device while ambulating, and recent participation in a balance or resistance-training pro-
gram

Interventions Length of intervention: 10 weeks

Intervention 1: Resistance training [strength/resistance training]; duration not reported; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Certified health fitness instructor; personal trainer; certified athletic
trainer

Outcomes Displacement of the center-of-pressure during gait initiation; initial stride length and velocity

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Hirsch 2003
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/15/NR

Country: USA

Age (mean in years): 75.7; 70.8

Sex (male/female): NR

Duration of disease (mean in years): 8.3; 5.5

HY (mean): 1.9;1.8

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Had been diagnosed with iPD by their neurologist and not participated in any organized balance or
muscle strengthening activities before being pre-tested. All participants were ambulatory, were not
acutely ill, were able to follow simple commands, and were not suffering from unstable cardiovascular
disease or other uncontrolled chronic conditions that would interfere with the safety and conduct of
the training and testing protocol

Exclusion criteria:

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Hirsch 2003 (Continued)

NR

Interventions Length of intervention: 10 weeks

Intervention 1: Balance group [gait/balance/functional training]; 30 minutes; 3x/week

Intervention 2: Combined group (balance and resistance training) [multi-domain training]; 45 min-
utes; 3x/week

Primary setting: Individual

Supervision by (if provided): Therapist

Outcomes Sensory Orientation Test; latency to fall; percentage of trials resulting in falls; muscle strength

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: NR

Conflicts of interest: None

Hubble 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 34/24/22

Country: Australia

Age (mean in years): 65.4

Sex (male/female): 15/7 (68.2% male)

Duration of disease (mean in years): 6.7

HY (mean): 1.9

UPDRS-M (mean): 19.4

MMSE (mean): NR

Physical capability: Walking speed (m/s): 1.33; 1.31

Inclusion criteria:

Idiopathic PD

Exclusion criteria:

An inability to walk independently; uncontrolled hypertension; a prescription for psychotropic med-

ications; significant limitations due to osteoporosis; orthopedic surgery within the previous year; seri-
ous neck, shoulder, or back injuries (including spinal fusions); received deep brain stimulation surgery
for symptom management; a neurological condition other than PD; or no history of falls or near misses
within the past year

Interventions Length of intervention: 12 weeks

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Hubble 2018 (Continued)

Intervention 1: Exercise group (trunk mobility and endurance plus education) [gait/balance/functional
training]; 90 minutes; 1x/week

Intervention 2: Education group (multidisciplinary educational brochure) [passive control group]

Primary setting: Group

Supervision by (if provided): Exercise scientist

Outcomes Addenbrooke Cognitive Examination; Bailey-Lovie high-contrast visual acuity test; TUG; ABC; PDQ-39;
UPDRS-M; HY score; Schwab & England ADL Scale; gait parameters (head and trunk accelerations, bilat-
eral activation of the thoracic and lumbar erector spinae), FoG score

Follow-up (maximum time after end of intervention): 12 weeks

Notes Funding sources: Australian Catholic University

Conflicts of interest: None

Johansson 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 16/13/12

Country: Sweden

Age (mean in years): 69.7

Sex (male/female): 9/4 (69.2% male)

Duration of disease (median in years): 10.0; 7.0

HY (range): 2 to 3

UPDRS-M (median): 35.0; 32.5

MoCA (median): 27.0; 26.6

Physical capability: Falls in last year: 0; 0

Inclusion criteria:

Diagnosis of Idiopathic PD, ≥ 60 years of age, HY stage 2 to 3, and scored ≥ 21 on MoCA

Exclusion criteria:

Magnetic resonance imaging (MRI)-incompatible implants or claustrophobia or any other neuromuscu-

lar disorder that impacted gait and balance function

Interventions Length of intervention: 10 weeks

Intervention 1: HiBalance (highly challenging balance exercises) [gait/balance/functional training]; 60

minutes; 2x/week plus 1x/week home exercise

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Johansson 2018 (Continued)

Intervention 2: HiCommunication control (training program for speech and communication) [active
control group]; 60 minutes; 2x/week plus 1x/week home exercise

Primary setting: Group

Supervision by (if provided): Physical therapists; speech and language pathologist

Outcomes Mini-BESTest; ABC; gait speed; EQ-5D; PDQ-39; Hospital Anxiety and Depression Scale; MDS-UPDRS-I,
MDS-UPDRS-II; structural and functional magnetic resonance imaging, blood sampling, neuropsycho-
logical assessment, and speech/voice assessment

Follow-up (maximum time after end of intervention): within 3 weeks

Notes Funding sources: Swedish Research Council

Conflicts of interest: None

Kanegusuku 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 44/30/27

Country: Brazil

Age (mean in years): 67; 63

Sex (male/female): 22/5 (81.5% male)

Duration of disease (mean in years): 8.5; 9.0

Modified HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosis of PD; age ≥ 50 years; MHY stages between 2 and 3

Exclusion criteria:

Presence of other neurologic disorders, hypertension, or any other diagnosed cardiovascular disease;
use of medications that could affect the cardiovascular system except for those used for the treatment
of PD; presence of musculoskeletal problems that preclude resistance training; presence of cardiovas-
cular abnormalities at rest or on exercise electrocardiograms; change in medication during participa-
tion in the study; and practicing any regular physical activity except for physical therapy for PD

Interventions Length of intervention: 12 weeks

Intervention 1: Resistance training [strength/resistance training]; duration not reported; 2x/week

Intervention 2: Control group [passive control group]

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Kanegusuku 2017 (Continued)

Intervention 3: Healthy control

Primary setting: Individual

Supervision by (if provided): Exercise specialist

Outcomes Spectral analysis of heart rate variability and cardiovascular responses to autonomic stress tests (deep
breathing, Valsalva maneuver, orthostatic stress)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Supported by the Brazilian Council for the Scientific and Technological Development
(CNPQ) and the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES)
and Program with Academic Excellence (PROEX)

Conflicts of interest: None

King 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 94/51/39

Country: USA

Age (mean in years): 65.7; 65.1

Sex (male/female): 25/14 (64.1% male)

Duration of disease (mean in years): NR

HY (mean): 2.5; 2.4

UPDRS-M (mean): 33.4; 32.3

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosis of idiopathic PD by a movement disorders neurologist, treatments with levodopa, between

the ages of 45 and 85, and willing and able to come to the clinic 4 times per week for 4 weeks

Exclusion criteria:

Unable to ambulate unassisted, had other neurologic, cardiovascular, or orthopedic problems which
could impact mobility, or had cognitive impairments that would limit participation in the intervention

Interventions Length of intervention: 4 weeks

Intervention 1: Agility boot camp [multi-domain training]; 75 minutes; 4x/week

Intervention 2: Treadmill training [gait/balance/functional training]; 75 minutes; 4x/week

Primary setting: Individual

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King 2013 (Continued)

Supervision by (if provided): Specially trained physical therapists

Outcomes PDQ-39; ABC; UPDRS-II; Mini-BESTest; BBS; UPDRS-M; turn duration; stride velocity; peak arm speed;
ROM trunk horizontal; sway range

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Kinetics Foundation, Foundation for Physical Therapy, and Oregon Clinical Transla-
tional Institute

Conflicts of interest: NR

King 2020
Study characteristics

Methods Randomized controlled trial with cross-over after 6 weeks

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 108/46/42

Country: USA

Age (mean in years): 68.0

Sex (male/female): NR

Duration of disease (mean in years): 7.3; 9.7

HY (mean): 2.4; 2.6

MDS-UPDRS-M (mean): 44.9; 50.0

MoCA (mean): 26.6; 24.3

Physical capability: NR

Inclusion criteria:

Mild to moderate severity of idiopathic PD (HY Levels 2 to 3 and FoG, defined as > 0 on the N-FOG-Q);
50 to 90 years old, without major musculoskeletal or peripheral or central nervous system disorders
(other than PD) that could significantly affect their balance and gait, without recent changes in medica-
tion, excessive use of alcohol or recreational drugs, without history of structural brain disease, active
epilepsy, stroke, or dementia that would interfere with ability to follow intervention and testing proce-
dures, able to stand or walk for 2 min without an assistive device, without a medical condition that pre-
cludes exercise, without claustrophobia, severe tremor, or any health history (i.e. implanted devices,
deep brain stimulation) that would put the participant at risk near the magnetic resonance imaging
(MRI) scanner

Exclusion criteria:

NR

Interventions Length of intervention: 6 weeks

Intervention 1: Agility boot camp-Cognition [multi-domain training]; 80 minutes; 3x/week

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King 2020 (Continued)

Intervention 2: Education group [active control group]; 80 minutes; 1x/week and 30 minutes 5x/week
at home

Primary setting: Group

Supervision by (if provided): Trained and experienced exercise trainer with oversight from a licensed
physical therapist

Outcomes FOG ratio; N-FOG-Q; dual task cost gait speed; balance; executive function; functional magnetic reso-
nance imaging: right supplementary motor cortex-pedunculopontine nucleus connectivity, MDS-UP-
DRS-M, PDQ-39

Severity of motor signs assessed during: off-medication state

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: Department of Veterans Affairs grant; National Institutes of Health (NIH): NIA grant
Collins Trust grant; Oregon Clinical and Translational Research Institute (OCTRI), NIH grant

Conflicts of interest: Dr. Horak has an equity interest in APDM, a company that may have a commer-
cial interest in the results of this study. This potential conflict of interest has been reviewed and man-
aged by the Research & Development Committee at the VA Portland Health Care System and Oregon
Health & Science University. They have put in place a plan to help ensure that this research study is not
affected by the financial interest.

Kunkel 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 103/51/45

Country: UK

Age (mean in years): 71.3; 69.7

Sex (male/female): 25/26 (49% male)

Duration of disease (mean in years): 4.7; 7.0

HY (range): 1 to 3

UPDRS-M (mean): 12.9; 10.6

MoCA (mean): 25.1; 26.0

Physical capability: 6-MIN-W: 347.3; 394.5

Inclusion criteria:

Diagnosis of Parkinson’s disease, HY 1 to 3 indicating mild to moderate disease severity, lived at home,
could understand and follow commands, had previous falls recorded

Exclusion criteria:

Lacked sufficient stability to dance with another person

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Kunkel 2017 (Continued)

Interventions Length of intervention: 10 weeks

Intervention 1: Partnered ballroom dancing [dance]; 60 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Professional dance teachers

Outcomes BBS, PDQ-39, TUG, 6-MIN-W, ABC, standing-start 180° turn test

Follow-up (maximum time after end of intervention): 3.5 months

Notes Funding sources: National Institute for Health Research (NIHR) Research for Patient Benefit (RfPB) pro-
gramme

Conflicts of interest: None

Kurt 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 64/40/40

Country: Turkey

Age (mean in years): 62.41; 63.61

Sex (male/female): 24/16 (60% male)

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (mean): 30.09; 28.06

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG: 19.2;14.0

Inclusion criteria:

Idiopathic PD; ability to follow a stable medication regimen; HY 2 to 3; lack of dementia (MMSE ≥ 24)

Exclusion criteria:

Physical therapy in the previous 6 months; fear of water; allergy to chlorine; inability to walk indepen-
dently; having undergone surgical treatment for PD; history or evidence of neurological deficit oth-
er than PD (stroke, neuromuscular disease, etc.); uncontrolled hypertension; diabetes; incontinence;
open wounds; osteoarthritis; osteoporosis at a level that impaired walking and balance

Interventions Length of intervention: 5 weeks

Intervention 1: Ai Chi [aqua-based training]; 60 minutes; 5x/week

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Kurt 2018 (Continued)

Intervention 2: Land-based exercise control (stretching of spine and limbs, articular mobilization, gait
exercises) [multi-domain training]; 60 minutes; 5x/week

Primary setting: Group

Supervision by (if provided): Physiotherapist experienced in both neurologic rehabilitation and Ai Chi

Outcomes BBS; TUG; PDQ-39; UPDRS-M; dynamic balance measures

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Ahi Evran University Medical Faculty Educational and Research Hospital

Conflicts of interest: None

Kurtais 2008
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 30/27/24

Country: Turkey

Age (mean in years): 63.8; 65.7

Sex (male/female): 12/12 (50% male)

Duration of disease (mean in years): 5.3; 5.4

HY (mean): 2.5; 2.2

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: 20-meter walking time (s): 20.2; 18.9, Timed U-turn task (s): 14.2; 13.9

Inclusion criteria:

On stable anti-Parkinsonian medication, ability to walk independently, and not having participated in a
rehabilitation program in the previous 3 months

Exclusion criteria:

Severe cognitive impairments and other disorders that might interfere with or contraindicate the exer-
cise program

Interventions Length of intervention: 6 weeks

Intervention 1: Treadmill [gait/balance/functional training]; 40 minutes; 3x/week

Intervention 2: Control group [passive control group]; minutes; x/week

Primary setting: Individual

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Kurtais 2008 (Continued)

Supervision by (if provided): Supervisor

Outcomes 20-meter walking time; timed U-turn task; turning around a chair; climbing up and down a flight of
stairs; arising from an armless chair; standing on one foot (right and left); ergospirometric exercise test
(exercise duration, peak oxygen consumption (VO2), metabolic equivalents, maximal heart rate, sys-
tolic and diastolic blood pressure)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Kwok 2019
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 187/138/138

Country: China/Hong Kong

Age (mean in years): 63.6

Sex (male/female): 65/73 (47.1% male)

Duration of disease (mean in years): NR

HY (range): 1 to 3

MDS-UPDRS-M (mean): 34.9; 31.64

MMSE (mean): NR

Physical capability: TUG (mean): 17.54; 14.05

Inclusion criteria:

Clinical diagnosis of idiopathic PD; HY 1 to 3; age above 18 years old; ability to stand unaided and walk
with or without an assistive device; participants who can give written consent

Exclusion criteria:

Currently receiving treatment for mental disorders or with uncontrolled mood disorders; current par-
ticipation in any other behavioral or pharmacological trial or instructor–led exercise program; cogni-
tive impairment as indicated by the "Abbreviated mental test" lower than 6; other debilitating condi-
tions except PD, e.g. hearing or vision impairment, that can impede full participation in the study

Interventions Length of intervention: 8 weeks

Intervention 1: Mindfulness yoga for PD [mind-body training]; 90 minutes; 1x/week

Intervention 2: Stretching and resistance training exercises [multi-domain training]; 60 minutes; 1x/
week

Primary setting: Group

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Kwok 2019 (Continued)

Supervision by (if provided): Yoga instructor with mindfulness-based stress reduction teacher qualifi-
cations

Outcomes Hospital Anxiety and Depression scale; MDS-UPDRS-M; TUG; holistic well-being scale; PDQ-8; adverse
events

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 3 months

Notes Funding sources: Professional Development Fund, Association of Hong Kong Nursing Staff

Conflicts of interest: None

Landers 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 96/49/44

Country: USA

Age (mean in years): 72.2; 70.2; 70.1; 74.3

Sex (male/female): 25/16 (61% male)

Duration of disease (mean in years): NR

HY (range): 1.5 to 4

UPDRS-M (mean): NR

MMSE (mean): 27.6; 26.6; 29.6; 28.5

Physical capability: Self-Selected Gait Velocity (m/s): 1.22; 1.26; 1.26; 1.18

Inclusion criteria:

Idiopathic PD

Exclusion criteria:

Non-ambulatory or if significant comorbidities were present (e.g. stroke, total hip/knee replacement);
history of surgical intervention for Parkinson’s disease.

Interventions Length of intervention: 4 weeks

Intervention 1: Balance training external focus instructions [gait/balance/functional training]; 45 min-

utes; 3x/week

Intervention 2: Balance training internal focus instructions [gait/balance/functional training]; 45 min-

utes; 3x/week

Intervention 3: Balance training no focus [gait/balance/functional training]; 45 minutes; 3x/week

Intervention 4: Control [passive control group]

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Primary setting: Individual

Supervision by (if provided): Research assistants

Outcomes BBS; Sensory Organization Test, Self-Selected Gait Velocity, Dynamic Gait Index, ABC, and obstacle
course completion time

Follow-up (maximum time after end of intervention): 8 weeks

Notes Funding sources: American Parkinson’s Disease Association Research Grant

Conflicts of interest: None

Lee HJ 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 35/32/26

Country: Korea

Age (mean in years): 65.7

Sex (male/female): 17/24 (41.5% male)

Duration of disease (mean in years): NR

HY (range): 1 to 3

UPDRS-M (mean): 14.8; 11.9

MMSE (mean): 26.2; 26.1 (Korean MMSE)

Physical capability: NR

Inclusion criteria:

PD, aged between 50 and 80 years, stage 1 to 3 on the HY scale, no other neurological, or cognitive im-
pairments (Korean-MMSE > 20), and not having received any exercise therapy within the 3 months prior
to the study

Exclusion criteria:

NR

Interventions Length of intervention: 8 weeks

Intervention 1: Turo PD program [mind-body training]; 60 minutes; 2x/week

Intervention 2: Waiting list [passive control group]

Primary setting: Group

Supervision by (if provided): Qigong instructor

Outcomes UPDRS, PDQ-L, BDI, BBS

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Lee HJ 2018 (Continued)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: This research was supported by grants from the National Research Foundation of
Korea funded by the Korean government (Grant nos. NRF-2005–0049404 and NRF- 2017R1A2B4009963)

Conflicts of interest: NR

Lehman 2005
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/11/11

Country: USA

Age (mean in years): 77.6; 74.3

Sex (male/female): 8/3 (72.7% male)

Duration of disease (mean in years): 6.5

HY (range): 2 to 2.5

UPDRS-M (mean): NR (subscale scores reported for each participant)

MMSE (mean): 28

Physical capability: NR

Inclusion criteria:

Gait impairments due to Parkinson Disease

Exclusion criteria:

Persons with other neurological and/or orthopadic impairments that could not walk the distances re-
quired of the training program were excluded

Interventions Length of intervention: 2 weeks

Intervention 1: Treatment group (walking 1800 feet per day) [gait/balance/functional training]; dura-
tion not reported; 5x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Instructor

Outcomes Step length of left extremity

Follow-up (maximum time after end of intervention): 1 month

Notes Funding sources: NR

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Lehman 2005 (Continued)

Conflicts of interest: NR

Li 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 309/195/195

Country: USA

Age (mean in years): 68; 69; 69

Sex (male/female): 122/73 (62.6% male)

Duration of disease (mean in years): 8; 8; 6

HY (range): 1 to 4

UPDRS-M (mean): 15.28; 15.32; 15.06

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: gait velocity (cm/s) on 4.3-meter (15 ft) walkway ("GAITrite"): 110.1; 109.2; 110.9

Inclusion criteria:

Clinical diagnosis of Parkinson’s disease, HY 1 to 4; 40 to 85 years of age; at least one score of 2 or more
for at least one limb for the tremor, rigidity, postural stability, or bradykinesia items in the motor sec-
tion of the UPDRS-M; stable medication use; ability to stand unaided and walk with or without an assis-
tive device; medical clearance for participation; and willingness to be assigned to any of the three inter-
ventions

Exclusion criteria:

Current participation in any other behavioral or pharmacologic study or instructor-led exercise pro-
gram; MMSE < 24 (indicating some degree of cognitive impairment); debilitating conditions or vision
impairment that would impede full participation in the study; unavailability during the study period

Interventions Length of intervention: 24 weeks

Intervention 1: Tai chi [mind-body training]; 60 minutes; 2x/week

Intervention 2: Resistance training [strength/resistance training]; 60 minutes; 2x/week

Intervention 3: Stretching control [flexibility training]; 60 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Trained and certified tai chi instructors; certified exercise instructors

Outcomes Postural stability (measured by computerized dynamic posturography); maximum excursion; direc-
tional control; movement accuracy; gait (stride length, walking velocity); strength of bilateral knee ex-
tensors and flexors; FRT; TUG; UPDRS-M; falls (fall calendars); adverse events; PDQ-8, Vitality plus scale

Severity of motor signs assessed during: on-medication state

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Li 2012 (Continued)
Follow-up (maximum time after end of intervention): 3 months

Notes Funding sources: National Institute of Neurological Disorders and Stroke

Conflicts of interest: None

Liao 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/36/36

Country: Taiwan

Age (mean in years): 67.3; 65.1; 64.6

Sex (male/female): 17/19 (47.2% male)

Duration of disease (mean in years): 7.9; 6.9; 6.4

HY (range): 1 to 3

UPDRS-M (mean): NR

MMSE (mean): 29.5; 29.8; 29.7

Physical capability: obstacle crossing velocity (cm/s): 75.2; 77.5; 80.4

Inclusion criteria:

Idiopathic PD; at least 2 of the 4 features (resting tremor, bradykinesia, rigidity, and asymmetric onset)
in which the resting tremor or bradykinesia must be present; HY 1 to 3; ability to walk independently
without any walking aids; stable medication usage; with or without deep brain stimulation; MMSE score
≥ 24

Exclusion criteria:

Unstable medical condition; history of other neurological, cardiopulmonary, or orthopedic diseases

known to interfere with participation in the study; past history of seizure; use of cardiac pacemaker; vi-
sion deficits

Interventions Length of intervention: 6 weeks

Intervention 1: Virtual-reality-based WiiFit exercise and treadmill training [multi-domain training]; 60

minutes; 2x/week

Intervention 2: Traditional exercise and treadmill training [multi-domain training]; 60 minutes; 2x/
week

Intervention 3: Control [passive control group]

Primary setting: Group

Supervision by (if provided): Physical therapist

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Liao 2015 (Continued)

Outcomes Obstacle crossing performance (crossing stride length, crossing stride velocity, vertical toe-obstacle
clearance); dynamic balance performance (limits of stability, movement velocity, maximum excursion,
directional control); sensory organization test (sensory integration ability); PDQ-39; FES-I; TUG; muscle
strength

Follow-up (maximum time after end of intervention): 30 days

Notes Funding sources: National Science Council and Aim for the Top University Plan of the Ministry of Edu-
cation of the Republic of China

Conflicts of interest: None

Liu 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/54/41

Country: China

Age (mean in years): 65.8; 62.5

Sex (male/female): 25/29 (46.3% male)

Duration of disease (mean in years): NR

HY (mean): NR

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: TUG 10.19

Inclusion criteria:

Mild or moderate PD, ability to walk independently, normal state of mental health, ability to follow in-
structions, absence of other complications, and ability to participate in physical exercise

Exclusion criteria:

Any previous practical experience with Health Qigong, a recent or planned change in medication, and
signs of a central nervous system disease other than PD, such as aphasia or dementia (as defined by
the MMSE)

Interventions Length of intervention: 10 weeks

Intervention 1: Health Qigong [mind-body training]; 60 minutes; 5x/week

Intervention 2: Control [passive control group]

Primary setting: Group

Supervision by (if provided): NR

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Liu 2016 (Continued)

Outcomes TUG; hand-eye coordination (turn-over-jars) test; physical stability (9-holed instrument) test; one-
legged blind balance test

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Mak 2008
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/60/52

Country: China

Age (mean in years): 63.0; 66.1; 62.9

Sex (male/female): NR

Duration of disease (mean in years): 5.9; 6.1; 5.9

HY (mean): NR

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

PD diagnosis; stable on anti-Parkinsonian medications and with no dyskinesia, orthopaedic, arthritic,

and heart problems; aged 50 to 75 years; can stand up from a chair independently

Exclusion criteria:

NR

Interventions Length of intervention: 4 weeks

Intervention 1: Audio-visual group [gait/balance/functional training]; 20 minutes; 3x/week

Intervention 2: Exercise group [multi-domain training]; 45 minutes; 2x/week

Intervention 3: Control [passive control group]

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes Three-dimensional kinematics data; vertical, antero-posterior, and medio-lateral components of

ground reaction force

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Mak 2008 (Continued)

Follow-up (maximum time after end of intervention): 2 weeks

Notes Funding sources: NR

Conflicts of interest: NR

Mak 2021
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 154/70/64

Country: Hong Kong

Age (mean in years): 61.9; 62.7

Sex (male/female): 20/44 (31.3% male)

Duration of disease (mean in years): 5.8; 5.0

MHY (mean): 2.4; 2.5

MDS-UPDRS-M (mean): 29.7; 28.7

MoCA (mean): 27.5; 27.5

Physical capability: TUG: 10.9; 10.1

Inclusion criteria:

Aged 30 years or over, diagnosed with idiopathic PD, stable on anti-Parkinsonian medications, and able
to walk independently for 30 meters without aid

Exclusion criteria:

Significant cardiopulmonary, neurological (other than PD) or musculoskeletal conditions, had received
neurosurgery, had cognitive impairment with a MoCA score < 25, or had joined a structured exercise
program in past three months

Interventions Length of intervention: 6 months

Intervention 1: Brisk walking [endurance training]; 90 minutes; 1x/week of supervised practice and 2x/
week self-practice in the first 6 weeks, then 1x/month supervised session and 2 to 3x/week self-practice
(monitored by smartwatch)

Intervention 2: Upper limb training [active control group]; 90 minutes; 1x/week of supervised practice
and 2x/week self-practice

Primary setting: Group

Supervision by (if provided): Physiotherapist and an assistant

Outcomes MDS-UPDRS-M; 6-MIN-W; Mini-BESTest; fast gait speed; TUG

Severity of motor signs assessed during: on-medication state

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Mak 2021 (Continued)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Shun Hing Education and Charity Fund

Conflicts of interest: None

Martin 2015
Study characteristics

Methods Randomized controlled trial with cross-over after 6 months

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 29/21/16

Country: New Zealand

Age (mean in years): 72

Sex (male/female): 13/8 (61.9% male)

Duration of disease (mean in years): 11

HY (mean): 2.8

UPDRS-M (mean): NR

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

PD diagnosis confirmed by a movement disorder specialist neurologist; aged over 65 years, presence of
FOG as indicated by answering “yes” to question 1 on N-FOG-Q, independently mobile with or without
walking aid, stable PD medication regimen at the time of recruitment

Exclusion criteria:

Significant cognitive impairment (MMSE of < 24), had comorbidities that would prohibit safe participa-
tion in exercise, were unable to press metronome buttons, or hear a metronome adequately

Interventions Length of intervention: 6 months

Intervention 1: Cued Up! program (home-based exercise and education program designed to address
FOG and falls that may result from FOG) [gait/balance/functional training]; 30 to 60 minutes; 6 home
visits within the first 4 weeks, followed by weekly phone calls and independent completion of the exer-
cises

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Physical therapist with experience in PD and FOG and the use of cues

Outcomes Feasibility questionnaire, N-FOG-Q; falls diary

Follow-up (maximum time after end of intervention): 6 months

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Martin 2015 (Continued)

Notes Funding sources: Physiotherapy New Zealand’s Older Adult and Neurology Special Interest Groups;
Hope Foundation for Research on Ageing

Conflicts of interest: None

Medijainen 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 50/24/24

Country: Estonia

Age (mean in years): 71.1; 69.9

Sex (male/female): 10/14 (41.7% male)

Duration of disease (mean in years): 8.0; 7.7

HY (mean): 2.2; 2.3

UPDRS-M (mean): 39.1; 36.4

MMSE (mean): 28.0; 27.2

Physical capability: Short Physical Performance Battery (SPPB) - total score: 10.8; 10.6; standing to
walking transition gait speed calculated based on SPPB gait test performance (m/s): 1.0; 0.9

Inclusion criteria:

Diagnosis of mild to moderate idiopathic PD according to the HY scale; aged over 60 and under 81 years
old; able to walk without an assistive device in their home setting (usage of assistive device for commu-
nity-based ambulation was not an exclusion criteria); no other untreated medical conditions that might
affect gait or postural stability; no participation in physiotherapy during the previous year; MMSE score
above 24

Exclusion criteria:

NR

Interventions Length of intervention: 8 weeks

Intervention 1: Physical therapy (physical capacity, transfers, manual activities, balance, gait) [mul-
ti-domain training]; 60 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Specialist in neurological physiotherapy

Outcomes FOG, Short Physical Performance Battery; dominant side hip flexion range of motion; dominant side
hip abduction range

Follow-up (maximum time after end of intervention): 1 week

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Medijainen 2019 (Continued)

Notes Funding sources: Estonian Research Council

Conflicts of interest: None

Michels 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 14/13/13

Country: USA

Age (mean in years): 69.2

Sex (male/female): 6/7 (46.2% male)

Duration of disease (mean in years): NR

HY (mean): 2.11; 2.50

UPDRS-M (mean): 31.6

MoCA (mean): 27.0; 25.25

Physical capability: TUG: 8.41; 14.43

Inclusion criteria:

Diagnosis of idiopathic PD, any HY stage or disease severity, stable PD medication regimen for at least
one month prior to the study and continue that regimen without any changes throughout the course of
the study

Exclusion criteria:

Therapeutic dance intervention within three months before the start of the study or initiated any new
PD treatments or involvement in other PD-focused interventions throughout the course of the study;
cognitive impairment MoCA < 24; < 18 years of age

Interventions Length of intervention: 10 weeks

Intervention 1: Dance therapy [dance]; 60 minutes; 1x/week

Intervention 2: Control (group discussions) [active control group]; duration not reported; 1x/week

Primary setting: Group

Supervision by (if provided): Board-certified dance therapists and licensed clinical counselors

Outcomes MDS-UPDRS, MDS-UPDRS-M, MoCA, TUG, BBS, PDQ-39, visual analogue fatigue scale, fatigue severity
scale, BDI, HY

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 to 2 weeks

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Michels 2018 (Continued)

Notes Funding sources: NR

Conflicts of interest: Kristi Michels has no financial disclosures. Ornella Dubaz MD has no financial dis-
closures. Danny Bega MD MSCI has received royalties from the British Medical Journal. He has served as
a contractor for Medscape, LLC. He is on the speaker’s bureau for Neurocrine, Adamas, and Teva Phar-
maceuticals.

Miyai 2000
Study characteristics

Methods Randomized controlled trial with cross-over after 4 weeks

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/10/10

Country: Japan

Age (mean in years): 67.6

Sex (male/female): 5/5 (50% male)

Duration of disease (mean in years): 4.2

HY (range): 2.5 to 3

UPDRS-M (mean): 18.2; 17.0

MMSE (mean): 28.5

Physical capability: Walking endurance (m): 381.2; 372.5; Gait speed (sec/10 m): 10.0; 9.5; Steps
(steps/10 m): 22.3; 21.5

Inclusion criteria:

PD patients with HY between 2.5 and 3; not demented (MMSE > 27)

Exclusion criteria:

NR

Interventions Length of intervention: 4 weeks

Intervention 1: Body weight–supported treadmill training (BWSTT) [gait/balance/functional training];

45 minutes; 3x/week

Intervention 2: Physical therapy [multi-domain training]; 45 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): NR

Outcomes UPDRS-M, UPDRS-I, UPDRS-II, UPDRS-complications, UPDRS-total; overground ambulation endurance,

gait speed; number of steps taken for 10-meter walk

Follow-up (maximum time after end of intervention): 0 (post-intervention)

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Miyai 2000 (Continued)

Notes Funding sources: Fund for Comprehensive Research on Aging and Health from the Ministry of Health
and Welfare, Japan

Conflicts of interest: None

Miyai 2002
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 24/24/20

Country: Japan

Age (mean in years): 69.5; 69.8

Sex (male/female): 10/10 (50% male)

Duration of disease (mean in years): 4.1; 4.5

HY (range): 2.5 to 3

UPDRS-M (mean): 18.5; 18.6

MMSE (mean): 28.3; 28.7

Physical capability: Gait speed (sec/10 m): 10.8; 11.5; Steps (steps/10 m): 23.4; 22.8

Inclusion criteria:

PD patients with HY between 2.5 and 3; PD diagnosis based on the presence of rest tremor, bradykine-
sia, rigidity, positive response to levodopa, and no evidence of vascular lesions on magnetic resonance
imaging; not demented (MMSE > 27)

Exclusion criteria:

NR

Interventions Length of intervention: 1 month

Intervention 1: Body weight–supported treadmill training (BWSTT) [gait/balance/functional training];

45 minutes; 3x/week

Intervention 2: Physical therapy [multi-domain training]; 45 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): NR

Outcomes UPDRS-M, UPDRS-I, UPDRS-II, UPDRS-complications, UPDRS-total; gait speed; number of steps taken
for 10-meter walk

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

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Miyai 2002 (Continued)

Notes Funding sources: Fund for Comprehensive Research on Aging and Health from the Ministry of Health
and Welfare, Japan

Conflicts of interest: None

Morris 2009
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 124/28/28

Country: Australia

Age (mean in years): 66; 68

Sex (male/female): NR

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): > 23 (inclusion criteria)

Physical capability: 10MWT(s): 7.7; 8.4; 2-MIN-W (m): 150.7; 139.1

Inclusion criteria:

21 to 80 years of age and medically stable, with a diagnosis of idiopathic PD confirmed by a neurologist;
more than 23 out of 30 on the MMSE with a minimum of two of three on the recall question. Needed to
have disease severity of HY stage 2 or 3 and be able to walk 10 m three times without assistance

Exclusion criteria:

Unsafe to participate in the therapy programs, other neurological conditions in addition to PD, muscu-
loskeletal, visual, or cardiopulmonary conditions that affected mobility, cognitive impairment, not in
hospital for 2 weeks or unable or unwilling to consent to participate in the study

Interventions Length of intervention: 2 weeks

Intervention 1: Musculoskeletal exercises [multi-domain training]; up to 45 minutes; 7x/week

Intervention 2: Movement strategy training [gait/balance/functional training]; up to 45 minutes; 7x/

week

Primary setting: Individual

Supervision by (if provided): Physiotherapist; occupational therapist

Outcomes UPDRS (only motor and ADL components combined); PDQ-39; TUG; 10MWT, 2-MIN-W; Balance pull test

Follow-up (maximum time after end of intervention): 3 months

Notes Funding sources: NR

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Morris 2009 (Continued)

Conflicts of interest: None

Morris 2015
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 245/210/195

Country: Australia

Age (mean in years): 67.9

Sex (male/female): 140/70 (66.7% male)

Duration of disease (mean in years): 6.7

HY (range): 0 to 4

UPDRS-M (mean): 14.6; 14.9; 16.2

MMSE (mean): 28.2

Physical capability: Walking speed (m/s): 1.18; 1.23; 1.13

Inclusion criteria:

Diagnosis of PD; MMSE ≥ 24; HY < 5, medically able and safe to perform the interventions

Exclusion criteria:

People who received deep brain stimulation

Interventions Length of intervention: 8 weeks

Intervention 1: Progressive resistance strength training [strength/resistance training]; 120 minutes;

1x/week + 1x/week home exercise program

Intervention 2: Movement strategy training (walking, turning, reaching in standing, sit to stand, trans-
fer from chair to chair, getting up from bed, protective stepping in standing, complex walking tasks)
[gait/balance/functional training]; 120 minutes; 1x/week + 1x/week home exercise program

Intervention 3: Control group (social activities, practical advice, information sessions and group dis-
cussions but not any content related to falls or mobility; brochures, DVDs, booklets, audiotapes) [active
control group]; 120 minutes; 1x/week + 1x/week home exercise program

Primary setting: Group

Supervision by (if provided): Occupational therapists, physical therapists, speech pathologists, social
workers

Outcomes Falls, fallers, UPDRS-M, UPDRS-II, walking speed, PDQ-39, EQ-5D visual analogue scale, TUG

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 12 months

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Morris 2015 (Continued)

Notes Funding sources: Michael J. Fox Foundation (US) Clinical Discovery Grant. HBM is a National Health
and Medical Research Council Senior Research Fellow

Conflicts of interest: None

Morris 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 143/133/120

Country: Australia

Age (mean in years): 71

Sex (male/female): 80/53 (60.2% male)

Duration of disease (mean in years): NR

HY (range): 1 to 4

UPDRS-M (mean): 35.0; 36.0

MMSE (mean): 28.3

Physical capability: Fallen in last year (n): 38;35

Inclusion criteria:

Idiopathic PD; modified HY stage ≤ 4, MMSE ≥ 24, and community dwelling

Exclusion criteria:

Other health conditions that preclude safe participation in the exercise program, insufficient English to
follow instructions, and unwillingness to be assessed and treated at home

Interventions Length of intervention: 6 weeks

Intervention 1: Exercise group (progressive resistance strength training, movement strategy train-
ing, and education about methods with which to prevent falls) [multi-domain training]; 60 minutes; 1x/
week + 1x/week at home

Intervention 2: Control group (guided education and discussion sessions on topics of interest that
were selected by participants from a predefined syllabus) [active control group]; 60 minutes; 1x/week +
1x/week at home

Primary setting: Individual

Supervision by (if provided): Physiotherapist or trained clinician; trained allied health professionals,
including occupational therapists, physiotherapists, and speech pathologists

Outcomes Rate of falls; disability and health-related QoL; MDS-UPDRS; EQ-5D; PDQ-39

Severity of motor signs assessed during: on-medication state

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Morris 2017 (Continued)

Follow-up (maximum time after end of intervention): 12 months

Notes Funding sources: National Health and Medical Research Council

Conflicts of interest: None

Muller 1997
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/29/NR

Country: Germany

Age (mean in years): 62.7; 61.5

Sex (male/female): 20/9 (69% male)

Duration of disease (mean in years): 7.7; 9.0

HY (mean): 2.13; 2.07

UPDRS-M (mean): 1.37; 1.24

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosis of idiopathic PD; all participants were prescribed a combination of levodopa with either a
dopamine agonist and/or a monoamine oxidase inhibitor. There was no change in medication at least 4
weeks prior to treatment. Average levodopa doses were 300 mg/day in both groups

Exclusion criteria:

People suffering from depression, dementia, or other psychiatric disorders according to the Diagnostic
and Statistical Manual of Mental Disorders (DSM-Ill-R); none of the participants had a history of alcohol
or drug abuse nor any other significant physical illness

Interventions Length of intervention: 10 weeks

Intervention 1: Behavioral group (walking, standing in an upright position, getting up from a chair,
turning in bed, and handwriting) [gait/balance/functional training]; 90 minutes; 2x/week

Intervention 2: Control group (nonspecific treatment; information about the disease; breathing exer-
cise; physical exercises discussion of disease-related problems) [active control group]; 90 minutes; 2x/
week

Primary setting: Individual

Supervision by (if provided): NR

Outcomes Posture and gait initiation by using an optoelectronic motion analyzer; UPDRS; HY; BDI

Severity of motor signs assessed during: on-medication state

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Muller 1997 (Continued)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Robert Bosch Foundation

Conflicts of interest: NR

Please note that the values in UPDRS-M are relatively small. It is unclear whether they represent total
scores or, potentially, average scores per item.

Mulligan 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/41/41

Country: New Zealand

Age (mean in years): 69.4; 69.8

Sex (male/female): 26/15 (63.4% male)

Duration of disease (mean in years): 7.9; NR

HY (mean): NR

UPDRS-M (mean): 32.5; 28.4

MMSE (mean): NR

Physical capability: 6-MIN-W (m): 304.6; 293.6

Inclusion criteria:

Diagnosed with idiopathic PD; adults (> 60 years of age); without any other atypical movement disor-
ders; Conversion to Dementia score of > 5%, meaning they were at risk of developing dementia in the
next four years, but were not yet classified as having mild cognitive impairment

Exclusion criteria:

Current involvement in any longitudinal studies on cognitive changes in Parkinson’s; involved in other
studies that included pharmacological intervention; were currently using any medications that could
impact cognition; had any other current or past neurological or psychiatric conditions; had a poor com-
prehension of the English language; history of major illness in the past year, alcohol or substance abuse
or learning disability

Interventions Length of intervention: 8 months

Intervention 1: Intervention group (aerobic, progressive resistance, and balance exercises) [multi-do-
main training]; 60 minutes; 1x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapists

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Mulligan 2018 (Continued)

Outcomes Individual or group interviews; 6-MIN-W; Mini-BESTest

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: None

Myers 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/28/26

Country: USA

Age (mean in years): 70.5; 65.0

Sex (male/female): 15/11 (57.7% male)

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (median): 24; 29

MMSE (median): 29; 29

Physical capability: NR

Inclusion criteria:

Clinical diagnosis of Parkinson’s disease, able to stand for at least 30 minutes, normal peripheral ner-
vous system function, no history of vestibular disease, and MMSE score > 24.

Exclusion criteria:

Diagnosis of any other major medical condition, having deep brain stimulation or neural implants, di-
agnosis of peripheral neuropathy, use of neuroleptic or dopamine-blocking medications, and has a cur-
rent, regular yoga practice.

Interventions Length of intervention: 12 weeks

Intervention 1: Yoga [mind-body training]; 60 minutes; 2x/week

Intervention 2: Control (usual routines) [passive control group]

Primary setting: Group

Supervision by (if provided): Yoga instructor

Outcomes BESTest, Beck Anxiety Inventory, and Revised Oswestry Disability Index

Follow-up (maximum time after end of intervention): within 2 weeks

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Myers 2020 (Continued)

Notes Funding sources: US National Institutes of Health

Conflicts of interest: None

Nadeau 2014
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 297/93/34

Country: Canada

Age (mean in years): 64.0; 60.1; 64.3

Sex (male/female): 27/7 (79.4% male)

Duration of disease (mean in years): NR

HY (mean): 1.92; 1.95; 1.86

UPDRS-M (mean): 29.1; 21.9; 17.9

MMSE (mean): 27.8; 28.7; 28.6

Physical capability: 6-MIN-W: 422.9; 520.2; 497.6; Gait speed (cm/s): 102.5;122.7; 125.8

Inclusion criteria:

Diagnosis of idiopathic PD; ≤ 2 HY; aged 40 to 80; no musculoskeletal impairments or excessive pain in
any joints that could limit participation in an exercise program; no signs of dementia (MMSE > 24); living
up to 45 min away from the university

Exclusion criteria:

Major health problem (cancer, heart/lung problem, etc.)

Interventions Length of intervention: 24 weeks

Intervention 1: Speed treadmill training [endurance training]; 60 minutes; 3x/week

Intervention 2: Mixed treadmill training [endurance training]; 60 minutes; 3x/week

Intervention 3: Control (Viactive program; low intensity exercises with elements of tai chi, Latin dance,
resistance band exercises and coordination movements) [multi-domain training]; 60 minutes; 2x/week
+ 1x/week at home

Primary setting: Group and individual

Supervision by (if provided): Exercise trainer

Outcomes MDS-UPDRS; MMSE; BDI-II; PDQ-39; gait parameters; 6-MIN-W

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 1 week

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Nadeau 2014 (Continued)

Notes Funding sources: Clinique Ste-Anne ‘‘Me´moire et Mouvement’’; Natural Sciences and Engineering Re-
search Council (NSERC)

Conflicts of interest: None

Ni 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 64/41/37

Country: USA

Age (mean in years): 72.2

Sex (male/female): 24/13 (64.9% male)

Duration of disease (mean in years): 6.6; 6.9; 5.9

HY (mean): 2.2; 2.2; 2.1

UPDRS-M (mean): 32.9; 28.2; 27.6

MMSE (mean): 29.1; NR; 29.4

Physical capability: 10-meter maximal walking speed (m/s): 1.52; 1.49; 1.41 and 10-meter usual walk-
ing speed (m/s): 1.03; 1.06; 1.04

Inclusion criteria:

Diagnosis of idiopathic PD with mild to moderate impairment (HY stages 1 to 3), aged 60 to 90 years,
capable of ambulation for at least 50 feet with or without an assistive device, able to get up and down
from the floor with minimal assistance, and with no cognitive impairment (MMSE < 24)

Exclusion criteria:

Unstable cardiovascular disease or other uncontrolled chronic conditions which would affect either
their safety, the conduct of testing, or the interpretation of the results. Additionally, they may not have
regularly practiced (1 to 2 times weekly) high-intensity resistance training within the past year.

Interventions Length of intervention: 12 weeks

Intervention 1: Power-based resistance training [strength/resistance training]; duration not reported;

2x/week

Intervention 2: Yoga [mind-body training]; 60 minutes; 2x/week

Intervention 3: Control [passive control group]

Primary setting: Group and individual

Supervision by (if provided): NR

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Ni 2016 (Continued)

Outcomes UPDRS-M; BBS; Mini-BESTest; TUG; PDQ-39; bradykinesia scores; 1 repetition maximum & peak power;
10-meter usual and maximal walking speed tests, 1 repetition maximum and peak power for leg press;
postural sway test

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 2 weeks

Notes Funding sources: No financial support

Conflicts of interest: None

Nieuwboer 2007
Study characteristics

Methods Randomized controlled trial with cross-over after 3 weeks

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 289/153/153

Country: Belgium

Age (median in years): 67.5; 69.0

Sex (male/female): 88/65 (57.5% male)

Duration of disease (median in years): 7; 8

HY (range): 2 to 4

UPDRS-M (median): 31.0; 34.0

MMSE (median): 28.5; 29.0

Physical capability: Walking speed (m/s); Median: 0.86; 0.83

Inclusion criteria:

Showing mild to severe gait disturbance with score 0.1 on the UPDRS (item 29); diagnosis of idiopathic
Parkinson’s disease; stable drug usage; HY stage 2 to 4; and aged 18 to 80 years

Exclusion criteria:

Had undergone deep brain stimulation or other stereotactic neurosurgery; had cognitive impairment
(MMSE < 24); had disorders interfering with participation in cueing training, including neurological
(stroke, multiple sclerosis, tumour), cardiopulmonary (chronic obstructive disorders, angina pectoris)
and orthopaedic (osteoarthritis, rheumatoid arthritis, and back pain) conditions; had unpredictable
and long-lasting off periods (score 1 on item 37 and score 0.2 on item 39 of the UPDRS) and had partici-
pated in a physiotherapy program 2 months before starting the trial

Interventions Length of intervention: 3 weeks

Intervention 1: Cueing ("RESCUE"; with rhythmical cueing modalities) [gait/balance/functional train-

ing]; 30 minutes; 3x/week

Intervention 2: Control group [passive control group]

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Nieuwboer 2007 (Continued)

Primary setting: Individual

Supervision by (if provided): Therapist

Outcomes PDQ-39; posture and gait scores; Carer Strain Index; TUG; gait analysis; FES; FOG-Q; Nottingham Ex-
tended ADL Index

Follow-up (maximum time after end of intervention): 6 weeks

Notes Funding sources: European Commission Framework V funding

Conflicts of interest: "The proceeds of the sale of the CD-Rom will be used to fund completion of
analysis of the full RESCUE dataset. We may be involved in this further work."

Ortiz-Rubio 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 50/46/46

Country: Spain

Age (mean in years): 74.2; 75.4

Sex (male/female): 33/13 (71.7% male)

Duration of disease (mean in years): 4.00; 4.27

HY (range): 2 to 3

MDS-UPDRS-M (mean): 24.1; 26.4

MMSE (mean): 26.7; 26.7

Physical capability: NR

Inclusion criteria:

Clinical diagnosis of PD according to UK Brain Bank Criteria in the 2 to 3 HY stages; age 65+; stable med-
ication usage; ability to walk 10 m without assistance from another person or a walking frame

Exclusion criteria:

Cognitive impairment (MMSE lower than 24); comprehension deficits that prevented them from follow-
ing verbal commands; visual or acoustic limitations; diagnosis of a neurological condition other than
PD; clinically significant comorbidities likely to affect gait

Interventions Length of intervention: 8 weeks

Intervention 1: Resistance training program [strength/resistance training]; 60 minutes; 2x/week

Intervention 2: Control group (low-intensity exercise program) [active control group]; duration and
frequency not reported

Primary setting: Group

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Ortiz-Rubio 2018 (Continued)

Supervision by (if provided): NR

Outcomes Mini-BESTest; Revised Paper Fatigue Scale

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: None

Conflicts of interest: None

Palmer 1986
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/14/14

Country: USA

Age (mean in years): 63.9; 65.9

Sex (male/female): 12/2 (85.7% male)

Duration of disease (mean in years): NR

HY (mean): NR

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Idiopathic PD; stabilization on a regimen of pharmacologic therapy; ability to attend the scheduled
evaluation and exercise sessions

Exclusion criteria:

Physical problems that might cause them to risk injury during the exercises

Interventions Length of intervention: 12 weeks

Intervention 1: United Parkinson Foundation exercise program (slow stretching exercises) [flexibility
training]; 60 minutes; 3x/week

Intervention 2: Karate training program [mind-body training]; 60 minutes; 3x/week

Primary setting: Group

Supervision by (if provided): Corrective therapist; rehabilitation nursing student who had a black belt
in karate

Outcomes Parkinson's Disease Motor Battery (Walk index, Arm tremor, Activated rigidity, Resting rigidity, Pursuit
score, Pronation-supination rate); ADL (grip strength, 9-hole coordination test, placing and turning test,
arm swing test, rapid arm movement, button board, putting shirt on and off, putting shoes and socks
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Palmer 1986 (Continued)

on and off, getting up from chair); Arm acceleration; long-latency stretch response; Patient question-
naire (asking their impressions of the benefits of the exercise program for specific Parkinson symp-
toms)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Park 2014
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/31/31

Country: USA

Age (mean in years): 59.9

Sex (male/female): 20/11 (64.5% male)

Duration of disease (mean in years): 0-10

HY (range): 1 to 2

UPDRS-M (mean): 14.00; 16.60

MMSE (mean): NR

Physical capability: Timed walk (s): 6.04; 6.26

Inclusion criteria:

Aged 40 to 70 years diagnosed with PD within three years of symptom onset with a HY stage 1 or 2; met
the UK Parkinson’s Disease Brain Bank criteria; could be on either no anti-Parkinsonian medications, or
could be taking amantadine, monoamine oxidase B inhibitors, and/or dopamine agonists; adequate vi-
sion and English sufficient for compliance with testing and surveys

Exclusion criteria:

HY stage 3 or higher; atypical or secondary parkinsonism; any other condition (other than the primary
indications) which in the opinion of the investigators might contribute to gait or balance impairments
or complicate its assessment; have been or are on any formulation of levodopa

Interventions Length of intervention: 24 weeks

Intervention 1: Early start group exercise (cardiovascular, core strength and joint integrity plan) [mul-
ti-domain training]; 60 minutes; 3x/week; 24 weeks

Intervention 2: Delayed start group [passive control group]

Primary setting: Group

Supervision by (if provided): Personal trainer

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Park 2014 (Continued)

Outcomes UPDRS, TUG, Tinetti Mobility Test, PDQ-39, BDI

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Madden Center Development Fund. OSU Parkinson’s Disease Our Goal is a Cure
Fund. Columbus branch of the National Parkinson’s Foundation. OSU Center for Clinical and Transla-
tional Science

Conflicts of interest: NR

Participants in intervention 2 received same intervention as the intervention group, beginning after 24
weeks

Paul 2014
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 72/40/36

Country: Australia

Age (mean in years): 68.1; 64.5

Sex (male/female): 25/15 (62.5% male)

Duration of disease (mean in years): 7.8

HY (mean): 2.0; 1.9

MDS-UPDRS-M (mean): 37.1; 35.7

MMSE (mean): 29.1; 28.9

Physical capability: Preferred walking speed (m/s): 1.27; 1.17 Fast walking speed (m/s): 1.77; 1.67

Inclusion criteria:

Idiopathic PD; aged over 40 years and were able to walk independently with or without an aid

Exclusion criteria:

Significant cognitive impairment (MMSE < 24) or suffered from any unstable cardiovascular, or-
thopaedic, or neurological conditions that would interfere with the safety of assessment and/or inter-
pretation of results

Interventions Length of intervention: 12 weeks

Intervention 1: Muscle power training [strength/resistance training]; 45 minutes; 2x/week

Intervention 2: Low intensity control group (exercises at home) [passive control group]

Primary setting: Group

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Paul 2014 (Continued)

Supervision by (if provided): Physiotherapist

Outcomes Peak power of four leg muscle groups; muscle strength, mobility, balance and falls; fast and preferred
walking pace; TUG; one-legged stance test; tests of stepping; maximum balance range; N-FOG-Q; num-
ber of falls

Follow-up (maximum time after end of intervention): 0 to 1 week

Notes Funding sources: Parkinson’s NSW Unity Walk Research Grant and a University of Sydney Bridging
Support Grant

Conflicts of interest: SS Paul received financial assistance from a National Health and Medical Re-
search Council (NHMRC) of Australia postgraduate scholarship. C Sherrington receives salary funding
from the NHMRC. VSC Fung is on advisory boards and/or has received travel grants from Abbott, Aller-
gan, Boehringer-Ingelheim, Hospira, Lundbeck and Novartis. CG Canning and J Song declare no com-
peting interests.

Pazzaglia 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/51/NR

Country: Italy

Age (mean in years): 71

Sex (male/female): 35/16 (68.6% male)

Duration of disease (mean in months): 73.2

HY (mean): NR

UPDRS-M (mean): 23; 25

MMSE (mean): > 25 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Diagnosis of PD; ability to perform the rehabilitation programme with a low risk of falling; ability to
perform motor rehabilitation independently; absence of cognitive impairment (MMSE > 25); and no
changes in drug therapy for PD during the rehabilitation programme

Exclusion criteria:

People with secondary Parkinsonism or Parkinson’s plus; severe hearing loss and/or visual deficit; and
serious comorbidities making it impossible to perform rehabilitation (e.g. postural hypotension, heart
disease, stroke, severe shoulder–hip disease)

Interventions Length of intervention: 6 weeks

Intervention 1: Virtual reality [gaming]; 40 minutes; 3x/week

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Pazzaglia 2020 (Continued)

Intervention 2: Conventional rehabilitation programme [gait/balance/functional training]; 40 minutes;
3x/week

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes BBS; Dynamic Gait Index; Disabilities of the Arm, Shoulder and Hand scale to measure performance of
the upper limb; SF-36

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: BTS Spa

Conflicts of interest: None

Pedreira 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 71/44/32

Country: Brazil

Age (mean in years): 61.1; 66.2

Sex (male/female): 22/9 (71% male)

Duration of disease (mean in years): 8.6; 7.3

HY (mean): 2.5; 2.4

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Clinical diagnosis of PD; any sex; aged between 45 and 80 years; HY 1 to 3

Exclusion criteria:

Cognitive impairment (dementia); poorly controlled arterial hypertension; poorly controlled cardiopa-
thy; psychiatric disorders, and illnesses that prevented exercise understanding and performance

Interventions Length of intervention: 4 weeks

Intervention 1: Nintendo Wii [gaming]; 50 minutes; 3x/week

Intervention 2: Traditional physical therapy [multi-domain training]; 12 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): NR

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Pedreira 2013 (Continued)

Outcomes PDQ-39; UPDRS

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: Federal University of Bahia

Conflicts of interest: NR

Peloggia Cursino 2018

Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 93/26/21

Country: Brazil

Age (mean in years): 63.29; 70; 72

Sex (male/female): 12/9 (57.1% male)

Duration of disease (mean in years): 2.86; 4.14; 6.29

HY (mean): 2; 1.71; 2.29

UPDRS-M (mean): NR

MMSE (mean): 27.29; 27.86; 25.57

Physical capability: Step length (cm): 65.83; 66.69; 59.20; Gait speed (m/s): 1.20; 1.16; 0.99

Inclusion criteria:

Idiopathic PD; ability to walk without the use of aid devices; no participation in a pharmacological
adaptation phase; carry out the evaluations and interventions during on-medication state

Exclusion criteria:

Pain, fracture, serious injury to soft tissue in the six months before the study, severe osteoporosis, his-
tory of cognitive and other neurological impairments, or uncontrolled cardiovascular or respiratory
changes or other chronic uncontrolled conditions that may interfere with the safety and performance
of the training protocol and testing

Interventions Length of intervention: 6 weeks

Intervention 1: Group with partial body weight support [gait/balance/functional training]; 30 minutes;
3x/week

Intervention 2: Group with auditory stimulus [gait/balance/functional training]; 30 minutes; 3x/week

Intervention 3: Treadmill group [endurance training]; 30 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): NR

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Peloggia Cursino 2018 (Continued)

Outcomes PDQ-39; step length; step length variability; step width; step width variability; gait speed

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: None

Conflicts of interest: None

Picelli 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 45/17/17

Country: Italy

Age (mean in years): 70.0

Sex (male/female): 12/5 (70.6% male)

Duration of disease (mean in years): 9.9

HY (mean): 3 (inclusion criteria)

UPDRS-M (mean): NR

MoCA (median): 24.0; 23.0

Physical capability: 6-MIN-W (m): 310.2; 298.8

Inclusion criteria:

Confirmed diagnosis of idiopathic PD; HY stage 3, determined in the “on” phase; and a MMSE score
greater than 24

Exclusion criteria:

Severe dyskinesias or “on-off” fluctuations; important modifications of PD medication during the study
(i.e. drug changes); deficits of somatic sensation involving the lower limbs; vestibular disorders or
paroxysmal vertigo; other neurological or orthopedic conditions involving the lower limbs (muscu-
loskeletal diseases, severe osteoarthritis, peripheral neuropathy, joint replacement); and cardiovascu-
lar comorbidity (recent myocardial infarction, heart failure, uncontrolled hypertension, orthostatic hy-
potension)

Interventions Length of intervention: 4 weeks

Intervention 1: Treadmill training [gait/balance/functional training]; 45 minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): NR

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Picelli 2016 (Continued)

Outcomes UPDRS; Frontal Assessment Battery-Italian version; 6-MIN-W; MoCA; TMT; memory with interference
test; BDI; 10MWT (fastest speed)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Pohl 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 193/18/16

Country: Sweden

Age (mean in years): 68.2

Sex (male/female): 8/10 (44.4% male)

Duration of disease (mean in years): 8.8

HY (mean): 2.4

UPDRS-M (mean): 19.0; 17.5

MMSE (mean): NR

Physical capability: TUG: 10.5; 10.0

Inclusion criteria:

Diagnosis of PD; any duration of PD; any PD therapy or treatment, but stable; able to get down in a
squatting position and to walk at least 10 meters without support; correctable auditory and visual ca-
pability and able to access transportation to and from research sessions

Exclusion criteria:

Secondary or atypical PD; colour blindness; severe depression; participating in any other ongoing study
or having ≥ 3 points per question in UPDRS-I, in question numbers 13 to 15 in UPDRS-II and in question
numbers 24 to 30 in UPDRS-M

Interventions Length of intervention: 6 weeks

Intervention 1: Ronnie Gardiner Rhythm and Music Method (RGRM) [dance]; 60 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): RGRM practitioner

Outcomes Posturo-Locomotion-Manual-test; TUG; UPDRS-M; Text recall test; Symbol Digit Modalities Test; Clox
and Cube; Naming 30 items; Stroop test; Parallel Serial Mental Operations; PDQ-39

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Pohl 2013 (Continued)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Ostergotland County Council and Department of Neurology

Conflicts of interest: None

Pohl 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 59/51/46

Country: Sweden

Age (mean in years): 69.7; 70.4

Sex (male/female): 32/14 (69.6% male)

Duration of disease (mean in years): 6.0; 6.8

HY (range): 1 to 3

UPDRS-M (mean): 34.0; 28.6

MoCA (mean): 25.5; 25.0

Physical capability: TUG: 18.5; 19.9

Inclusion criteria:

Community-dwelling individuals from 18 years of age with a diagnosis of Parkinson’s disease and HY up
to stage 3, stable medication for 4 months, and capacity to walk 10 meters without gait assistance. To
enhance the generalizability of the findings, any medical treatment, even surgical, was accepted

Exclusion criteria:

Other neurological deficits or serious health conditions that would compromise participation; signifi-
cant visual or hearing impairments that would make participation impossible; or severe motor fluctua-
tions

Interventions Length of intervention: 12 weeks

Intervention 1: Ronnie Gardiner Method [dance]; 60 minutes; 2x/week

Intervention 2: Control [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapists (certified Ronnie Gardiner practitioners)

Outcomes TUG, subtracting serial-7s measuring the effect of cognitive demands on functional mobility (mo-
tor-cognitive dual-tasking); MoCA; three parts of the Cognitive Assessment Battery; Stroop test; Symbol
Digit Modalities Test; Mini-BESTest; FES-I; FOG-Q; PDQ-39

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Pohl 2020 (Continued)

Follow-up (maximum time after end of intervention): 3 month

Notes Funding sources: Region Östergötland, the Henry and Ella Margareta Ståhls Foundation, the Tornspi-
ran Foundation, Neuro Sweden, Swedish Parkinson’s foundation, and Linköping University Hospital
Research Fund

Conflicts of interest: PP is a non-practicing certified practitioner of the Ronnie Gardiner Method. She
was blind to the results of the outcome evaluations of all participants and did not take part in the inter-
views. EW, FL, PE and ND report no conflicts of interest.

Poier 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/29/21

Country: Germany

Age (mean in years): 68.5; 68.9

Sex (male/female): 12/17 (41.4% male)

Duration of disease (range in years): 0 to 10

HY (mean): NR

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosed with PD; aged between 50 and 90 years and with signed informed consent

Exclusion criteria:

People with significant cognitive impairments (no independent completing of questionnaires) and/or
who are permanently bound to a wheelchair/walker were not included

Interventions Length of intervention: 10 weeks

Intervention 1: Tango Argentino [dance]; 60 minutes; 1x/week

Intervention 2: Tai chi [mind-body training]; 60 minutes; 1x/week

Primary setting: Group

Supervision by (if provided): Professional teacher

Outcomes PDQ-39; Brief Multidimensional Life Satisfaction Scale; Inner Correspondence and feelings of Peaceful
Relief; perceived impairment in everyday life via Numeric Rating Scale

Follow-up (maximum time after end of intervention): 10 weeks

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Poier 2019 (Continued)

Notes Funding sources: Stiftung Helixor

Conflicts of interest: None

Poliakoff 2013
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 56/32/21

Country: UK

Age (mean in years): 66.6; 63.7

Sex (male/female): 21/11 (65.6% male)

Duration of disease (mean in years): 7.39; 4.68

HY (mean): NR

UPDRS-M (mean): 18.5; 15.2

MMSE (mean): NR

Physical capability: 6-foot walk (s): 11.0; 10.9

Inclusion criteria:

People with PD

Exclusion criteria:

Diagnosed or suspected dementia, attendance of a group exercise class for PD or other neurodegenera-
tive disease and > 2 weeks holiday booked during the study period

Interventions Length of intervention: 10 weeks

Intervention 1: Gym training (cardiovascular activity, including treadmill, recumbent bikes, bikes,
cross trainers and rowers) [multi-domain training]; 60 minutes; 2x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Group

Supervision by (if provided): Gym staff with previous experience working with PD patients

Outcomes PDQ-39; reaction times, UPDRS-M; Brief Illness Perception Questionnaire; 6-foot walk; chair stand test;
Timed hand (10x pronation-supination); Timed leg (10x heel taps)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 10 weeks

Notes Funding sources: Parkinson’s UK

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Poliakoff 2013 (Continued)

Conflicts of interest: NR

Protas 2005
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/18/18

Country: USA

Age (mean in years): 71.3; 73.7

Sex (male/female): 18/0 (100% male)

Duration of disease (mean in years): 7.1; 8.1

HY (mean): 2.8; 2.9

UPDRS-M (mean): 28.3; 30.4

MMSE (mean): NR

Physical capability: Gait speed (m/s): 1.28; 1.26

Inclusion criteria:

Postural instability-gait difficulty predominant PD; experiences with freezing episodes, and/or a histo-
ry of falls; stable regimen of anti-Parkinsonian medications; ability to stand and walk with or without
assistance; stage 2 or 3 of the HY staging; scores of moderate or higher on all scales of the Neurobehav-
ioral Cognitive Status Examination (Cognistat)

Exclusion criteria:

NR

Interventions Length of intervention: 8 weeks

Intervention 1: Training group (treadmill; gait, step training) [gait/balance/functional training]; 60

minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Physical therapist

Outcomes Gait speed, cadence, stride length right and left, step test, provocative test for freezing and motor
blocks

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

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Pérez de la Cruz 2017

Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 38/30/30

Country: Spain

Age (mean in years): 66.80; 67.53

Sex (male/female): 13/16 (44.8% male)

Duration of disease (mean in years): 6.2; 6.7

HY (mean): 2.82; 2.66

UPDRS-M (mean): 15.23

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG: 11.6;11.5

Inclusion criteria:

Diagnosed with PD, HY 1 to 3; > 40 years of age; during off-medication state and with a score greater,
or equal to, 24 on the MMSE; in addition, there were no medical contradictions, and all participants ac-
cepted the study norms (regular assistance and active participation); "we decided to perform the as-
sessment 12 h after withdrawing medication, therefore we eliminated the probability of motor fluctua-
tions appearing that were dependent on the medication"

Exclusion criteria:

Individuals who did not comply with the above mentioned criteria or who had articular and/or muscu-
lar lesions in the lower limbs affecting their independent gait

Interventions Length of intervention: 10 weeks

Intervention 1: Aquatic Ai Chi [aqua-based training]; 45 minutes; 2x/week

Intervention 2: Dry land therapy (strength training and aerobic exercises) [multi-domain training]; 45
minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Expert physiotherapist trained in clinical Ai Chi

Outcomes Visual analogue scale; BBS; Tinetti scale; FTSTS; TUG; UPDRS; PDQ-39; Short-Form Health Survey; Geri-
atric depression scale

Severity of motor signs assessed during: off-medication state

Follow-up (maximum time after end of intervention): 1 month

Notes Funding sources: This research received no specific grant from any funding agency in the public, com-
mercial, or not-for-profit sectors.

Conflicts of interest: None

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Qutubuddin 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/33/19

Country: USA

Age (mean in years): 68.2

Sex (male/female): NR

Duration of disease (mean in years): 7.2

HY (mean): NR

UPDRS-M (mean): 15.7; 16.9

MMSE (mean): ≥ 23 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Three-year confirmed PD diagnosis with good response to standard Parkinson’s medications and a UP-
DRS-M score of > 30

Exclusion criteria:

Nonambulating; demented; already enrolled in an ongoing PD drug research study; uncontrolled di-
abetes or hypertension; chronic obstructive pulmonary disease; history of coronary artery disease or
congestive heart failure

Interventions Length of intervention: 8 weeks

Intervention 1: Exercise group (cycling program) [endurance training]; 30 minutes (+ warm up and
cool down, duration not specified); 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): NR

Outcomes BBS; UPDRS-M; PDQ-39; finger tapping test

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 4 months

Notes Funding sources: NR

Conflicts of interest: None

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Reuter 2011
Study characteristics

Methods Randomized controlled trial

Unclear if single center or multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): NR/90/90

Country: Germany

Age (mean in years): 62; 63; 62.1

Sex (male/female): 45/45 (50% male)

Duration of disease (mean in years): 64.1; 71.9; 62.33 (in months)

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): > 24

Physical capability: 12-meter Webster Walking Test: 8.4; 8.0; 8.6

Inclusion criteria:

PD patients, both sexes, HY stage 2 and 3

Exclusion criteria:

Severe concomitant diseases, which limit physical performances; a second neurological disease

Interventions Length of intervention: 6 months

Intervention 1: Nordic walking training [endurance training]; 70 minutes; 3x/week

Intervention 2: Walking training [endurance training]; 70 minutes; 3x/week

Intervention 3: Flexibility exercises and relaxation training [flexibility training]; 70 minutes; 3x/week

Primary setting: Group

Supervision by (if provided): Physiotherapists

Outcomes UPDRS; PDQ-39; pain (visual analogue scale for several body regions); BBS; walking (12-/24-meter Web-
ster Walking Test); gait parameters assessment on a treadmill including stride time, stride length; maxi-
mal exercise test on a treadmill; telephone interview on current activity level

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 6 months (telephone interview on current ac-
tivity level)

Notes Funding sources: NR

Conflicts of interest: NR

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Ribas 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 30/20/20

Country: Brazil

Age (mean in years): 61.7; 60.2

Sex (male/female): 8/12 (40% male)

Duration of disease (mean in years): 6.5; 7.0

HY (mean): 1.5

UPDRS-M (median): 22.5; 20.5

MMSE (median): 27.5; 27.5

Physical capability: 6-MIN-W (m): 352; 384

Inclusion criteria:

Clinical diagnosis of PD according to the UK Parkinson's Disease Society Brain Bank criteria for idio-
pathic Parkinson's disease confirmed by a neurologist; aged 40 to 80 years; disease stage 1, 2, or 3
based on the modified HY scale; low risk of falls (Berg score > 45); and being recruited from the Paraná
State Parkinson's Disease Association between August 2013 and December 2013

Exclusion criteria:

Any type of dementia or cognitive deficit (assessed by the MMSE using a cutoff of 24); acute pain or co-
morbid conditions (e.g. orthopedic disease, severe or unstable heart disease and other neurologic dis-
eases); visual impairment; use of any assistive device that could prevent performing the exercises cor-
rectly; having attended any other rehabilitation program (physical or occupation therapy) in the last
three months; and having used a Wii balance board at any time in the past

Interventions Length of intervention: 12 weeks

Intervention 1: Exergames group (seven Wii Fit games) [gait/balance/functional training]; 30 minutes;
2x/week

Intervention 2: Conventional exercise group (warming, stretching, active exercises, resistance exercis-
es for the limbs, diagonal exercises for the trunk, neck, and limbs) [multi-domain training]; 30 minutes;
2x/week

Primary setting: Group and individual

Supervision by (if provided): Physiotherapists

Outcomes PDQ-39; BBS; 6-MIN-W, Fatigue Severity Scale

Follow-up (maximum time after end of intervention): 60 days

Notes Funding sources: NR

Conflicts of interest: NR

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Ridgel 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 88/16/16

Country: USA

Age (mean in years): 69.9; 70.0

Sex (male/female): 9/7 (56.3% male)

Duration of disease (mean in years): 4.5; 6.38

HY (mean): 1.4; 1.9

UPDRS-M (mean): 14.13; 14.38

MMSE (mean): NR

Physical capability: Physical activity (steps/day): 4096.18; 4207.26

Inclusion criteria:

Diagnosis of idiopathic PD; HY 1 to 3; 50 to 79 years of age; no contraindications to exercise including

untreated cardiovascular disease or stroke

Exclusion criteria:

High risk for a cardiovascular event; unpredictable motor fluctuations

Interventions Length of intervention: 15 days

Intervention 1: High-cadence cycling [endurance training]; 40 minutes; 3x/week

Intervention 2: Stretching [flexibility training]; 40 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): NR

Outcomes UPDRS-M; bradykinesia and gait assessment ("Kinesia ONE"; speed and amplitude); TUG

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 2 days

Notes Funding sources: NR

Conflicts of interest: Angela Ridgel is a co-inventor on two patents which are related to the device
used in this study: “Bike System for Use in Rehabilitation of a Patient,” US 10,058,736 and US 9,802,081.
No royalties have been distributed from this patent.

Rios Romenets 2015

Study characteristics

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Rios Romenets 2015 (Continued)

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 40/33/33

Country: Canada

Age (mean in years): 63.2; 64.3

Sex (male/female): 19/14 (57.6% male)

Duration of disease (mean in years): 5.5; 7.7

HY (mean): 1.7; 2.0

MDS-UPDRS-M (mean): 20.7; 27.5

MoCA (mean): 27.0; 26.7

Physical capability: NR

Inclusion criteria:

Idiopathic PD with HY 1 to 3; all participants spoke either English or French sufficiently to fill out ques-
tionnaires and understand the instructions for dance classes

Exclusion criteria:

People who could not stand for at least 30 min or walk for ≥3 m without an assistive device; dementia
(defined according to MDS dementia criteria); severe hearing and vision problems; change in dopamin-
ergic therapy over the preceding three months; serious medical conditions which precluded dancing or
could be worsened by exercise; more than 3 falls in the 12 preceding months (to ensure safety of inter-
vention); other medical conditions which could affect study participation (e.g. drug abuse/alcoholism)

Interventions Length of intervention: 12 weeks

Intervention 1: Tango [dance]; 60 minutes; 2x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Group

Supervision by (if provided): Professional tango instructors without expertise in PD

Outcomes MDS-UPDRS-M; off fluctuations and dyskinesia; Mini-BESTest; TUG; falls questionnaire; FOG-Q; Pur-
due pegboard test for assessment of upper extremity function; MoCA; BDI; apathy scale; Krupp Fatigue
severity scale; PDQ-39; clinical global impression of change; exit questionnaire; adverse events and side
effects (cramps, fatigue, falls)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Parkinson Society of Canada; Fonds de recherché santé Québec

Conflicts of interest: Dr. Ronald B. Postuma received personal compensation for travel and speak-
er fees from Novartis Canada and Teva Neurosciences, and is funded by grants from the Fonds de la
Recherche en Santé du Québec, the Parkinson Society of Canada, the Webster Foundation, and by the
Canadian Institutes of Health Research

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Santos 2017a
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 41/28/28

Country: Spain

Age (mean in years): 73.38; 73.8

Sex (male/female): 15/13 (53.6% male)

Duration of disease (mean in years): 10.84; 10.46

HY (mean): 1.92; 1.86

MDS-UPDRS-M (mean): 7.61; 8.8

MMSE (mean): 28.69; 29

Physical capability: speed (mm/s): 3.95; 3.97; 10MWT (m/s, preferred rhythm): 0.87; 0.98; 10MWT (m/s,
fast rhythm): 1.20; 1.24

Inclusion criteria:

Diagnosis with akinesia and rigidity subtype PD; HY 1 to 2; no type of dementia as assessed by MMSE;
able to stand for 2 min without assistance; able to walk 10 meters without assistance

Exclusion criteria:

Neurological disease other than PD or if they did not meet the eligibility criteria

Interventions Length of intervention: 8 weeks

Intervention 1: Progressive resistance exercise [strength/resistance training]; 60 to 70 minutes; 2x/

week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Conditioning coaches

Outcomes Static posturography; 10MWT; FOG-Q; MDS-UPDRS; PDQ-39; 6-20 Borg scale (perceived exertion); ad-
verse events

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: University of Oviedo

Conflicts of interest: None

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Santos 2017b
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 62/40/40

Country: Brazil

Age (mean in years): 67.0; 68.5

Sex (male/female): 18/8 (69.2% male)

Duration of disease (mean in years): 5.6; 5.4

HY (mean): 2.3; 2.3

UPDRS-M (mean): 21.7; 21.3

MMSE (mean): 27.8; 27.2

Physical capability: NR

Inclusion criteria:

Idiopathic PD, HY 1.5 to 3, aged 50 years old or older, able to walk independently, and not enrolled in
any other therapeutic program besides medication

Exclusion criteria:

Neurological or musculoskeletal diseases, associated or cognitive disorders that would potentially in-
terfere in the assessment

Interventions Length of intervention: 8 weeks

Intervention 1: Resistance training [strength/resistance training]; 60 minutes; 2x/week

Intervention 2: Balance training/neurofunctional training [gait/balance/functional training]; 60 min-

utes; 2x/week

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes Center of pressure sway measures in different balance conditions on a force platform, BESTest; UP-
DRS-M; PDQ-39

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Universidade Estadual de Londrina

Conflicts of interest: None

Santos 2017c
Study characteristics

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Santos 2017c (Continued)

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/22/20

Country: Spain

Age (mean in years): 73.09; 78.09

Sex (male/female): 11/11 (50% male)

Duration of disease (mean in years): 10.72; 10.90

HY (mean): 2.18; 1.9

MDS-UPDRS-M (mean): 9.72; 9.18

MMSE (mean): > 27

Physical capability: NR

Inclusion criteria:

Idiopathic PD diagnosis; HY 1 to 3; absence of dementia (MMSE); ability to stand on two feet for ≥ 2 min;
ability to walk ≥ 10 meters without assistance

Exclusion criteria:

Previous history of neurological disease; severe dyskinesias or on-off phenomenon; any alteration in
the Parkinson’s medication regimen

Interventions Length of intervention: 6 weeks

Intervention 1: Slackline training program [gait/balance/functional training]; 23 minutes; 2x/week

Intervention 2: Control [passive control group]

Primary setting: Individual

Supervision by (if provided): Therapist

Outcomes Center of pressure; FOG-Q; FES; rate perceived exertion (Borg’s 6–20 scale); local muscle perceived ex-
ertion

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: NR

Conflicts of interest: None

Santos 2019
Study characteristics

Methods Randomized controlled trial

Single center

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Santos 2019 (Continued)

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 66/45/41

Country: Brasil

Age (mean in years): 64.3

Sex (male/female): 31/10 (75.6% male)

Duration of disease (mean in years): 7.1

HY (mean): 1.4; 1.3; 1.5

UPDRS-M (mean): NR

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG: 11.5; 10.7; 13.9

Inclusion criteria:

Participants with PD certified by a neurologist according to the United Kingdom Brain Bank Criteria
with moderate motor impairment (stages 1 to 3 on HY scale); between 40 and 80 years of age; ability to
walk independently; absence of visual or auditory deficits that impede the performance of activities, as
reported by the individual

Exclusion criteria:

Cognitive impairment (< 24 MMSE); other associated neurological dysfunctions; uncontrolled orthope-
dic or chronic injuries that make it impossible to carry out the proposed activities; participation in oth-
er physical interventions

Interventions Length of intervention: 8 weeks

Intervention 1: Nintendo Wii [gaming]; 50 minutes; 2x/week

Intervention 2: Conventional exercises [multi-domain training]; 50 minutes; 2x/week

Intervention 3: Nintendo Wii & conventional Exercises; minutes; 50 minutes; 2x/week

Primary setting: Individual

Supervision by (if provided): Physiotherapists

Outcomes BBS; Dynamic Gait Index; TUG; PDQ-39

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Federal University of Bahia

Conflicts of interest: None

Schaible 2021
Study characteristics

Methods Randomized controlled trial

Single center

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Schaible 2021 (Continued)

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 60/44/39

Country: Germany

Age (mean in years): 63.29; 66.20

Sex (male/female): 13/16 (44.8% male)

Duration of disease (mean in years): 5.4; 5.3

HY (mean): 2.0; 1.7

UPDRS-M (mean): 26.8; 22.6

MMSE (mean): 29.1; 28.9

Physical capability: Walking velocity (m/s): 1.44; 1.43

Inclusion criteria:

HY stages 1 to 3, aged between 35 and 80 years, no walking aids, stable medication 4 weeks prior to and
during the study

Exclusion criteria:

Dementia (PANDA (Parkinson’s Neuropsychometric Dementia Assessment) < 14), depression (BDI > 28),
antidepressive or antipsychotic medication, participation in an LSVT BIG therapy in the past year, dis-
abling bradykinesia to ensure participants are able to participate in the intensive physiotherapy (based
on clinical impression and in accordance to UPDRS-M Item 14) and prior history of cardiovascular, neu-
rological or musculoskeletal disorders known to interfere with testing PD features

Interventions Length of intervention: 4/8 weeks

Intervention 1: LSVT BIG [LSVT BIG]; 60 minutes; 4x/week, 4 weeks

Intervention 2: Intense physiotherapy [multi-domain training]; 60 minutes; 4x/week, 4 weeks

Intervention 3: Normal physiotherapy; 60 minutes; 2x/week, 8 weeks

Primary setting: Individual

Supervision by (if provided): Qualified LSVT BIG therapist; physiotherapists

Outcomes Non-motor symptom assessment scale for Parkinson’s disease; UPDRS-M; chair stand test; force-mea-
suring gangway; PDQ-39; BDI-II; Apathy Evaluation Scale, Parkinson Neuropsychometric Dementia As-
sessment, MMSE

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: None

Conflicts of interest: TVE received grants from the German Research Foundation and honoraria from
Lilly Germany. LT received payments as a consultant for Medtronic Inc., Boston Scientific Inc. LT re-
ceived honoraria as a speaker on symposia sponsored by Bial Inc., Zambon Pharma Inc., UCB Pharma
Inc., Desitin Pharma, Medtronic Inc., Boston Scientific Inc., Abbott Inc. CE received payments as a con-
sultant for Abbvie Inc. CE received honoraria as a speaker from Abbvie Inc., Daiichi Sankyo Inc., Bayer
Vital Inc. CE received payments as a consultant for Abbvie Inc. and Philyra Inc.

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Schenkman 1998
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 147/51/46

Country: USA

Age (mean in years): 70.6; 71.2

Sex (male/female): 34/12 (73.9% male)

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): ≥ 23 (inclusion criteria)

Physical capability: 6-MIN-W (ft): 1426; 1295, 10MWT (comfortable pace, sec): 9.7; 10.1

Inclusion criteria:

PD diagnosis from a neurologist; HY 2 to 3; FAR-p (functional axial rotation-physical) ≤ 120 to either side

Exclusion criteria:

Hospitalization within the past 3 months; changes in PD medications within the past month; other neu-
rological disorders; MMSE < 23

Interventions Length of intervention: 10 to 13 weeks

Intervention 1: Exercise group (moving in a relaxed manner, with the participation of appropriate
muscle groups only) [multi-domain training]; 45 to 60 minutes; 3x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Individual

Supervision by (if provided): Physical therapist

Outcomes Functional axial rotation; Functional Reach; Supine to stand (sec); Stand to supine (sec); 360° turn test;
6-MIN-W; 10MWT; cervical range of motion; lumbar range of motion; spine configuration; extremity
range of motion; turning while standing

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: National Institutes of Aging, National Center for Research Resources

Conflicts of interest: NR

Schenkman 2012
Study characteristics

Methods Randomized controlled trial

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Schenkman 2012 (Continued)

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 162/121/96

Country: USA

Age (mean in years): 64.5; 63.4; 66.3

Sex (male/female): 76/45 (62.8% male)

Duration of disease (mean in years): 4.9; 3.9; 4.5

HY (range): 1.5 to 3

UPDRS-M (mean): 23.7

MMSE (mean): 28.8; 28.3; 28.8

Physical capability: Continuous Scale–Physical Functional Performance Test: 48.8

Inclusion criteria:

PD diagnosis by a movement disorders specialist (UK Brain Bank criteria); HY 1 to 3; living in the com-
munity; ambulating independently

Exclusion criteria:

Uncontrolled hypertension; on-state freezing or exercise limitations from other disorders; MMSE < 24

Interventions Length of intervention: 16 months

Intervention 1: Flexibility/balance/function exercise [multi-domain training]; duration not reported;

3x/week

Intervention 2: Supervised aerobic exercise [endurance training]; 40 to 50 minutes; 3x/week

Intervention 3: Control (exercises in the home setting); duration not reported; 5x to 7x/week at home;
1x/month supervised

Primary setting: Group and individual

Supervision by (if provided): Physical therapist

Outcomes UPDRS total, UPDRS-M; UPDRS-II; Continuous Scale-Physical Functional Performance score; FRT; oxy-
gen uptake; PDQ-39

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: National Institutes of Health, Parkinson's Disease Foundation

Conflicts of interest: NR

Schenkman 2018
Study characteristics

Methods Randomized controlled trial

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Schenkman 2018 (Continued)

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 384/128/128

Country: USA

Age (mean in years): 64

Sex (male/female): 73/55 (57% male)

Duration of disease (median in years): 0.3; 0.3; 0.4 (since PD diagnosis) and 1.5; 1.5; 1.4 (duration of
symptoms)

HY (range): 1 to 2

UPDRS-M (mean): 17; 16; 17

MoCA (mean): 28; 28; 28

Physical capability: NR

Inclusion criteria:

Idiopathic PD; aged 40 to 80 years; HY 1 to 2; within 5 years of diagnosis; not exercising at moderate in-
tensity more than 3 times per week, and were not expected to need dopaminergic medication within 6
months

Exclusion criteria:

NR

Interventions Length of intervention: 26 weeks

Intervention 1: High-intensity exercise (treadmill) [endurance training]; 50 minutes; 4x/week

Intervention 2: Moderate-intensity exercise (treadmill) [endurance training]; 50 minutes; 4x/week

Intervention 3: Usual care [passive control group]

Primary setting: Individual

Supervision by (if provided): NR

Outcomes UPDRS; UPDRS-M; adherence to prescribed heart rate and exercise frequency of 3 days per week and
safety; maximal aerobic power

Severity of motor signs assessed during: off-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: National Institute of Neurologic Disease and Stroke (Drs Schenkman and Corcos)
and received additional support from the University of Pittsburgh Clinical and Translational Science In-
stitute (Dr Delitto), the University of Colorado Clinical and Translational Science Award program (Drs
Kohrt and Melanson), the Nutrition and Obesity Research Center (Drs Kohrt and Melanson), the Nation-
al Institutes of Health (Dr Christiansen), and the Parkinson’s Disease Foundation (Drs Hall and Comel-
la).

Conflicts of interest: None

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Schilling 2010
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/18/15

Country: USA

Age (mean in years): 61.3; 57.0

Sex (male/female): 9/6 (60% male)

Duration of disease (mean in years): NR

HY (range): 1.5 to 2.5

UPDRS-M (mean): NR

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: 6-MIN-W (m): 537.7; 468.8

Inclusion criteria:

Mild to moderate PD; have the ability to walk a 20-foot path, turn, and return to the start without use of
an assistive device; not participating in a structured exercise program; primary PD with a HY stage of 1
to 2.5 when in an on-medication state; none were receiving deep-brain stimulation

Exclusion criteria:

Orthostatic hypotension, dementia (MMSE Scores < 24), or other significant comorbidities (i.e. stroke,
musculoskeletal problems in the lower extremity)

Interventions Length of intervention: 8 weeks

Intervention 1: Training group (leg press, seated leg curl, and calf press) [strength/resistance training];
duration not reported; 2x/week

Intervention 2: Control group [passive control group]; minutes

Primary setting: Individual

Supervision by (if provided): Certified strength and conditioning specialist

Outcomes Leg press strength relative to body mass; TUG; 6-MIN-W; ABC

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Life Fitness, Inc.

Conflicts of interest: NR

Schlenstedt 2015
Study characteristics

Methods Randomized controlled trial

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Schlenstedt 2015 (Continued)

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 172/40/32

Country: Germany

Age (mean in years): 75.7; 75.7

Sex (male/female): 21/11 (65.6% male)

Duration of disease (mean in years): 10.1; 9.3

HY (mean): 2.8; 2.7

UPDRS-M (mean): 23.6; 22.3

MMSE (mean): 27.3; 27.7

Physical capability: Gait velocity (cm/sec): 104.4; 106.9

Inclusion criteria:

Diagnosed with idiopathic PD; postural instability (Fullerton Advanced Balance scale ≤ 25 points);
able to follow exercise instructions (assessed during a pre-examination during which the Fullerton Ad-
vanced Balance scale was performed).

Exclusion criteria:

Deep brain stimulation; other diseases that could influence stance and gait performance; participa-
tion in a specific resistance training or balance training program (beside usual physical therapy) dur-
ing the last 6 months; participation in any other medical, behavioral or exercise treatment (additional
to the usual received therapeutic treatment) during the study period; unstable medication; cardiopul-
monary/metabolic diseases that could interfere with the safe conduct of the study protocol. Cognitive
impairments (assessed with MMSE) were not defined as exclusion criteria so that a representative sam-
ple of affected participants could be included.

Interventions Length of intervention: 7 weeks

Intervention 1: Resistance training [strength/resistance training]; 60 minutes; 2x/week

Intervention 2: Balance training [gait/balance/functional training]; 60 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Sport scientist

Outcomes Fullerton Advanced Balance scale; TUG; UPDRS; Clinical Global Impression; gait analysis; maximal iso-
metric leg strength, PDQ-39, BDI, center of mass analysis during surface perturbations

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 5 weeks

Notes Funding sources: Coppenrath-Stiftung, Geeste/Groß-Hesepe, Niedersachsen, Germany; Krumme-

Stiftung, Eckernförde, Schleswig-Holstein, Germany

Conflicts of interest: None

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Schmitz-Hubsch 2006
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 96/56/52

Country: Germany

Age (mean in years): 63.8

Sex (male/female): 43/13 (76.8% male)

Duration of disease (mean in years): 5.8

HY (range): 1 to 4

UPDRS-M (mean): 15.45; 16.9

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

PD diagnosis (UK brain bank criteria); HY: all stages; with or without motor complications

Exclusion criteria:

Previous practical experience with Qigong; recent (≤ 1 month) or planned change of medication; signs
of central nervous system disease other than PD; MMSE < 24

Interventions Length of intervention: 16 (2 x 8 weeks - pause in between)

Intervention 1: Qigong [mind-body training]; 60 minutes; 1x/week (except during 8 weeks' break)

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Experienced teacher

Outcomes UPDRS-M; PDQ-39; Montgomery-Asberg Depression Rating Scale; structured interview for assessment
of depressive symptoms in PD patients; structured interview to assess the presence of non-motor
symptoms (sleep disturbance, daytime sleepiness, dizziness, urinary dysfunction, sexual dysfunction,
constipation, loss of appetite, or nausea and pain)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 24 weeks

Notes Funding sources: German Parkinson’s patients’ organization (dPV)

Conflicts of interest: NR

Sedaghati 2016
Study characteristics

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Sedaghati 2016 (Continued)

Methods Randomized controlled trial

Unclear if single center or multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 47/44/41

Country: Iran

Age (mean in years): 59.13; 58.77; 57.22

Sex (male/female): 30/14 (68.2% male)

Duration of disease (mean in years): 4.9; 5.2; 4.9

HY (mean): 2.53; 2.57; 2.6

UPDRS-M (mean): NR

MMSE (mean): 27.0; 26.7; 26.4

Physical capability: TUG: 13.53; 14.23; 13.26

Inclusion criteria:

Diagnosis of idiopathic PD for three years; being able to walk independently; aged between 50 and 70
years; consumed the same anti-Parkinsonian medication for past 2 weeks; history of falling in the past
year

Exclusion criteria:

Significant cognitive impairment (MMSE < 24); other neurological/musculoskeletal/ cardiopul-

monary/metabolic conditions that would interfere with safe conduction of training or exercise program

Interventions Length of intervention: 10 weeks

Intervention 1: Exercise group with balance pad [gait/balance/functional training]; 60 minutes; 3x/
week

Intervention 2: Exercise group without balance pad [gait/balance/functional training]; 60 minutes; 3x/
week

Intervention 3: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes Number of falls; FES-I; BBS; TUG

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Shahmohammadi 2017
Study characteristics

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Shahmohammadi 2017 (Continued)

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 27/22/20

Country: Iran

Age (mean in years): 60.5; 63.2

Sex (male/female): 22/0 (100% male)

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (mean): 22.5

MMSE (mean): > 24 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Males with PD; stage 2 or 3 according to HY; no signs of dementia (MMSE > 24)

Exclusion criteria:

History of fracture or have had orthopedic surgery within the last year

Interventions Length of intervention: 8 weeks

Intervention 1: Aquatic exercise [aqua-based training]; 60 minutes; 3x/week

Intervention 2: Land exercise [gait/balance/functional training]; 60 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): Expert physical trainer

Outcomes Postural sway (force plate); PDQ-L

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: None

Conflicts of interest: None

Shanahan 2017
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 99/90/41

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Country: Republic of Ireland

Age (mean in years): 69; 69

Sex (male/female): 26/15 (63.4% male)

Duration of disease (mean in years): 5.5; 6

HY (mean): 1.25; 2.0

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Diagnosis of idiopathic PD, stages 1 to 2.5 on the MHY scale. They were able to walk 3 meters unaided
and had a DVD player to enable participation in the home dance program.

Exclusion criteria:

Serious cardiovascular/pulmonary condition, neurological deficit other than PD, evidence of a muscu-
loskeletal problem, issues contraindicating participation in exercise, or a cognitive or hearing problem
which affected their ability to follow instructions or hear music; attendance of regular dance classes in
the six months prior to the trial

Interventions Length of intervention: 10 weeks

Intervention 1: Irish set dancing [dance]; 90 minutes; 1x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Dancing teachers who were also clinicians or experienced teaching clini-
cal populations

Outcomes UPDRS-M, 6-MIN-W, Mini-BESTest, PDQ-39; feasibility

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: John and Pauline Ryan Postgraduate Scholarship; and the Mid-Western Branch of
the Irish Society of Chartered Physiotherapists Research Bursary

Conflicts of interest: NR

Shen 2021
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 121/32/30

Country: China

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Shen 2021 (Continued)

Age (mean in years): 68.67; 66.93

Sex (male/female): 20/10 (66.7% male)

Duration of disease (mean in years): 6.27; 7.0

HY (mean): 1.86; 2.2

UPDRS-M (mean): 26.67; 18.0

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG: 12.52; 12.80

Inclusion criteria:

Clinical diagnosis of PD, aged between 55 and 80 years, and with a disease severity from mild to moder-
ate level (rating from 1 to 3 out 5) according to the HY scale; drug treatment is stable; can walk indepen-
dently or with the aid of walkers

Exclusion criteria:

Currently involved in any behavioural or pharmacological intervention study or instructor-led exercise

training program; serious organic diseases (heart disease, hypertension, tuberculosis, nephritis, etc.)
in the past two years; history of alcoholism, smoking, and visual or hearing impairment; an MMSE score
lower than 24 and deep brain stimulation surgery

Interventions Length of intervention: 12 weeks

Intervention 1: Wuqinxi Exercise (coordination of body movements, breathing and mind, loosening
the limbs, and relaxing the spirit) [mind-body training]; 90 minutes; 2x/week

Intervention 2: Stretching [flexibility training]; 90 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Professional trainer; coach

Outcomes Frontal assessment battery; Stroop test; MoCA; UPDRS-M; TUG

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Outstanding Clinical Discipline Project of Shanghai Pudong and Shanghai Science
Popularization Project

Conflicts of interest: None

Shulman 2013
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 945/80/67

Country: USA
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Shulman 2013 (Continued)

Age (mean in years): 65.8

Sex (male/female): 50/17 (74.6% male)

Duration of disease (mean in years): 6.2

HY (mean): 2.2

UPDRS-M (mean): 32.1

MMSE (mean): 27.4

Physical capability: 6-MIN-W (ft): 1374.2; 1446.7; 1395.5

Inclusion criteria:

PD diagnosis (asymmetrical onset of at least 2 of 3 cardinal signs (resting tremor, bradykinesia, or rigid-
ity); no atypical signs or exposure to dopamine-blocking drugs; HY 1 to 3 (on-medication state for mo-
tor fluctuators); mild to moderate gait or balance impairment (UPDRS-gait/UPDRS-postural stability = 1
to 2; ≥ 40 years; MMSE ≥ 23

Exclusion criteria:

Unstable medical/psychiatric comorbidities; orthopedic conditions restricting exercise; performance of

> 20 minutes of aerobic exercise > 3x/week (to avoid prior training effect)

Interventions Length of intervention: 3 months

Intervention 1: Higher-intensity treadmill training [gait/balance/functional training]; 15 to 30 minutes;

3x/week

Intervention 2: Lower-intensity treadmill training [gait/balance/functional training]; 15 to 50 minutes;

3x/week

Intervention 3: Stretching and resistance training [multi-domain training]; duration not reported; 3x/
week

Primary setting: Group

Supervision by (if provided): Exercise physiologists

Outcomes UPDRS-total; UPDRS-M; TUG; BDI; PD Fatigue Scale; PDQ-39-Summary Index; FES; Schwab and England
ADL scale; number of steps per day; 6-MIN-W; 10MWT (comfortable pace, fast pace); 50-foot walk (fast
pace); peak oxygen consumption per unit time; muscle strength (1-repetition maximum strength)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Michael J. Fox Foundation for Parkinson's Research

Conflicts of interest: Dr Shulman serves as Editor-in-Chief of the American Academy of Neurolo-

gy's Neurology Now Patient Book Series, receives royalties from Johns Hopkins University Press, and
receives research support from the National Institutes of Health (NIH; grant U01AR057967-01), the
Michael J. Fox Foundation, Teva Pharmaceuticals, and the Rosalyn Newman Foundation. Dr Katzel
serves as site visitor for the Association for the Accreditation of Human Research Protection Programs
and receives research support from NIH grants P30 AG028747-01, K30HL04518, 1R01HL095136-01, RO1
AG034161, and RO1 DK090401-01A1, the Department of Veterans Affairs (VA), and the Michael J Fox
Foundation. Dr Ivey receives government research support through VA Rehabilitation Research and De-
velopment on 2 VA Merit Awards. Dr Sorkin receives research support from the Baltimore VA Medical
Center Geriatric Research Educational and Clinical Center, the Claude D. Pepper Older Americans Inde-
pendence Center (grant 5T32AG000219-18), and the Michael J. Fox Foundation. Dr Anderson receives
research support from the Department of VA (merit grant E7158R) and the Michael J. Fox Foundation
and is a consultant for Guidepoint Global, HD Drug-works, the Huntington's Disease Society of Ameri-

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Shulman 2013 (Continued)

ca, Neurosearch Sweden, Lundbeck Pharmaceuticals, and the CHDI Foundation. She received speaking
fees from the University of Illinois at Chicago. She served as a consultant for Bradley vs CSX, Gilmore vs
Charlotte Hall, and Rosenberry vs Patel and serves as a section editor for Current Treatment Options in
Neurology. Dr Smith received research support from the Michael J. Fox Foundation. Dr Reich receives
research support from Chiltern and the National Institute of Neurological Disorders and Stroke and re-
ceives royalties from Informa. Dr Weiner receives research support from EMD Serono, Abbott Labora-
tories, and the NIH. He receives royalties from Lippincott, Elsevier, and Demos. He served on advisory
boards for Santhera, Rexahn, and Shiongi Pharma. Dr Macko receives research support from the Balti-
more VA Medical Center, Geriatric Research Educational and Clinical Center, the Claude D. Pepper Old-
er Americans Independence Center, and the Michael J. Fox Foundation.

Silva 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 36/28/25

Country: Brazil

Age (mean in years): 63.12; 64.23

Sex (male/female): 11/14 (44% male)

Duration of disease (mean in years): NR

HY (mean): 3; 3

UPDRS-M (mean): 17.53; 16.45

MMSE (mean): NR

Physical capability: TUG: 15.69; 14.33

Inclusion criteria:

Clinical diagnosis of idiopathic PD, stages 1 to 4 in the HY scale and had a medical certificate to perform
aquatic exercises and to use a heated swimming pool

Exclusion criteria:

Did not present independent gait (whether or not this was related to PD); diagnosed with another dis-
ease that could interfere in the physical assessments (for example, people with body balance alter-
ations of vestibular origin); visual or auditory impairment; unable to follow verbal and visual instruc-
tions (determined by MMSE); contraindications to use a heated swimming pool, such as fever, incon-
tinence, severe blood pressure change, and open wounds; presented alterations in the parameters of
medication intake, based on levodopa, during the study period; or did not agree with the informed con-
sent terms

Interventions Length of intervention: 10 weeks

Intervention 1: Dual task aquatic exercises [aqua-based training]; 60 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

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Supervision by (if provided): NR

Outcomes TUG; FTSTS; balance; BBS; Dynamic Gait Index

Follow-up (maximum time after end of intervention): 3 months

Notes Funding sources: Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES).
The authors would like to thank the Pontificia Universidad Catolica for yielding the heated swimming
pool and the Academic Publishing Advisory Center (Centro de Assessoria de Publicação Acadêmica, CA-
PA - www.capa.ufpr.br) of the Federal University of Paraná for assistance with English language editing.

Conflicts of interest: None

Silva-Batista 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 91/39/39

Country: Brazil

Age (mean in years): 64.1; 64.2; 64.2

Sex (male/female): 29/10 (74.4% male)

Duration of disease (mean in years): 9.6; 10.5; 10.7

HY (mean): 2.5; 2.5; 2.5

UPDRS-M (mean): 43.7; 45.1; 43.4

MMSE (mean): 28.5; 28.8; 28.5

Physical capability: TUG (s) 9.4; 9.5; 9.2

Inclusion criteria:

Diagnosis of idiopathic PD, HY 2 to 3, stable use of medication, 50 to 80 years of age, not participating
in structured physical training in the last 3 years, not presenting neurological disorders other than PD,
significant arthritis, and cardiovascular disease, and not having a MMSE score < 23

Exclusion criteria:

NR

Interventions Length of intervention: 12 weeks

Intervention 1: Resistance training [strength/resistance training]; 50 minutes; 2x/week

Intervention 2: Resistance training instability (with increase in load/resistance and degree of instabili-
ty of the exercises) [strength/resistance training]; 50 minutes; 2x/week

Intervention 3: Control group [passive control group]

Primary setting: Individual

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Silva-Batista 2018 (Continued)

Supervision by (if provided): Investigators

Outcomes BESTest; MoCA; overall stability index; FES-I; neuromuscular outcomes: quadriceps muscle cross-sec-
tional area, root mean square and mean spike frequency of electromyographic signal, peak torque, rate
of torque development, and half relaxation time of the knee extensors and plantarflexors during max-
imum ballistic voluntary isometric contractions; Total Training Volume calculated for lower limb exer-
cises

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Associacao Brasil Parkinson (ABP), Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo (FAPESP), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ), Premio Pemberton Coca-Cola, Diagnos-
ticos das Americas S/A (DASA), and Center for Psychobiology and Exercise Studies.

Conflicts of interest: None

Silveira 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 311/76/58

Country: Canada

Age (mean in years): 70.63; 69.76; 67.60

Sex (male/female): 41/16 (71.9% male)

Duration of disease (mean in years): 5.95; 6.09; 5.60

HY (mean): NR

UPDRS-M (mean): 25.38; 27.64; 21.76

MoCA (mean): 25.22; 24.57; 25.80

Physical capability: NR

Inclusion criteria:

Confirmed diagnosis of idiopathic PD by a neurologist

Exclusion criteria:

History of neurological diseases other than PD; uncontrolled diabetes; uncontrolled hypertension; his-
tory of cardiovascular disease; history of chronic obstructive pulmonary disease; uncorrected visual
impairments

Interventions Length of intervention: 12 weeks

Intervention 1: Aerobic training [endurance training]; 60 minutes; 3x/week

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Silveira 2018 (Continued)

Intervention 2: Goal-based training (walking exercises coordinating upper and lower limbs, non-pro-
gressive muscle-toning exercises, whole body stretching exercises) [multi-domain training]; 60 min-
utes; 3x/week

Intervention 3: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes Digit Span (forward and backward), Corsi Block test; executive functions: TMT, Stroop test; Short-form
of the California Verbal Learning Test, Rey-Osterrieth Complex Figure Test (immediate recall, and de-
layed recall); verbal fluency tasks (phonemic and semantic), Short-form of the Boston Naming Test; In-
tersecting Pentagons, Benton Line Orientation Test; oxygen uptake peak at test termination

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: National Council for Scientific and Technological Development CNPq/Brazil; Canada
Foundation for Innovation; Natural Sciences and Engineering Research Council of Canada

Conflicts of interest: None

Smania 2010
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 130/64/55

Country: Italy

Age (mean in years): 67.6; 67.3

Sex (male/female): 29/26 (52.7% male)

Duration of disease (mean in years): 10.4; 8.6

HY (mean): 3.0; 3.1

UPDRS-M (mean): NR

MMSE (mean): > 23 (inclusion criteria)

Physical capability: Number of falls within one month: 4.6; 46.1

Inclusion criteria:

Idiopathic PD and postural instability; HY stage 3 to 4; all participants were outpatients, did not require
assistance to rise from chairs or beds, not affected by unstable cardiovascular disease or other chronic
conditions that could interfere with their safety during testing or training procedures; no other neuro-
logical conditions or mental deterioration (MMSE > 23); no severe dyskinesias or on-off phases

Exclusion criteria:

NR

Interventions Length of intervention: 7 weeks

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Smania 2010 (Continued)

Intervention 1: Balance training [gait/balance/functional training]; 50 minutes; 3x/week

Intervention 2: Control training (active joint mobilization, muscle stretching, and motor coordination
exercises) [multi-domain training]; 50 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes BBS; ABC; postural transfer test, self-destabilization of the center of foot pressure test, number of falls,
UPDRS, modified HY; Geriatric Depression Scale

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 month

Notes Funding sources: None

Conflicts of interest: None

Solla 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 36/20/19

Country: Italy

Age (mean in years): 67.4

Sex (male/female): 13/7 (65% male)

Duration of disease (mean in years): 4.4; 5.0

HY (mean): 2.1; 2.3

UPDRS-M (mean): 13.0; 14.7

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: 6-MIN-W (m): 330.7; 333.3

Inclusion criteria:

Clinical diagnosis of PD; a score ≤ 3 on the HY scale, ability to walk without walking aids, stable medica-
tion regimen in the 4 weeks before the study, and a score ≥ 24 on the MMSE

Exclusion criteria:

HY stage > 3, diagnosis of dementia according to Diagnostic and Statistical Manual of Mental Disorders
5 criteria, atypical parkinsonism, pharmacologic treatment with drugs not approved for PD, the pres-
ence of any complementary disability or autonomic problems that precluded the training program, or
any specific health condition for which exercise was contraindicated. A history of falls in the previous 3-
month period, as well as the presence of dyskinesias, freezing, and static–dynamic postural instability,
was also verified before enrollment.

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Solla 2019 (Continued)

Interventions Length of intervention: 12 weeks

Intervention 1: Sardinian folk dance [dance]; 90 minutes; 2x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Physiotherapist assisted by two APA specialists; Sardinian folk dance
teacher

Outcomes UPDRS-M; 6-MIN-W; BBS; TUG; FTSTS; Back Scratch Test; sit and reach test; instrumented gait analysis;
Parkinson’s Disease Fatigue Scale; BDI; Starkstein Apathy Scale; MoCA

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Fondazione Banco di Sardegna

Conflicts of interest: None

Sparrow 2016
Study characteristics

Methods Randomized controlled trial with cross-over after 3 months

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 58/23/16

Country: USA

Age (mean in years): 66.7

Sex (male/female): 10/6 (62.5% male)

Duration of disease (mean in years): 4.3

HY (range): 2 to 3

MDS-UPDRS-M (mean): 36.0

MMSE (mean): > 25 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

Diagnosis of idiopathic PD; HY 2 to 3 in the on-medication state; on a stable dose of PD medications for
2 weeks prior to enrollment; experienced 1 fall in the past 3 months and 2 falls in the past year; were
able to walk without physical assistance or an assistive device for at least 5 continuous minutes

Exclusion criteria:

Diagnosis of atypical Parkinsonism; MMSE < 26; previous surgical management of PD, or serious comor-
bidities that may interfere with ability to participate in the exercise program

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Sparrow 2016 (Continued)

Interventions Length of intervention: 3 months

Intervention 1: Balance group [gait/balance/functional training]; 90 minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Physical therapists with expertise in PD

Outcomes Falls; Mini-BESTest; FES-I; ABC; 6-MIN-W; FOG; UPDRS; PDQ-39; Beck Anxiety Inventory; Penn State Wor-
ry Questionnaire; Anxiety Sensitivity Index; changes in Social Phobia Inventory; changes in Social Inter-
action Anxiety Scale

Follow-up (maximum time after end of intervention): 12 weeks

Notes Funding sources: Boston University Charles River Campus

Conflicts of interest: None

Stack 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 47/47/35

Country: UK

Age (median in years): 74.0

Sex (male/female): 35/12 (74.5% male)

Duration of disease (median in years): 7.0

HY (range): 1 to 4

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: 12-month fall history: 6; 6 (single fall)/14; 10 (repeated falls)

Inclusion criteria:

Diagnosis of PD, stages 1 to 4: stage 1 indicating mild unilateral symptoms; stage 2, bilateral symptoms
without balance impairment; stage 3, postural instability but independently mobile; stage 4, severe
PD although able to stand and walk with assistance; fulfilling the UKPDS Brain Bank diagnostic crite-
ria; self-reported chair transfers as being excessively slow and/or requiring much effort, assistance, or
repeated attempts and/or associated with a previous fall; scored at least 8/12 on the Middlesex Elder-
ly Assessment of Mental State; were willing and able to undertake all aspects of the intervention; were
willing and able to complete the outcome measures (albeit with help from another person in complet-
ing questionnaires, if handwriting was problematic

Exclusion criteria:

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NR

Interventions Length of intervention: 4 weeks

Intervention 1: Home-based physiotherapy [gait/balance/functional training]; up to 60 minutes; 3x/

week

Intervention 2: Control group [passive control group]

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes Sit to stand test; Parkinson’s Activity Scale chair transfer; UPDRS posture; 15D instrument of health-re-
lated quality of life; Standing-start 180 degree turn test; PD Self-Assessed Disability Scale

Follow-up (maximum time after end of intervention): 8 weeks

Notes Funding sources: Parkinson’s UK

Conflicts of interest: NR

Stozek 2016
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/64/61

Country: Poland

Age (mean in years): 64.0; 67.0

Sex (male/female): 29/32 (47.5% male)

Duration of disease (mean in years): 4.6; 4.3

HY (mean): 2.3; 2.3

UPDRS-M (mean): 19.7; 23.2

MMSE (mean): NR

Physical capability: 10-meter walk test (at normal preferred speed): 10.52; 13.11

Inclusion criteria:

PD diagnosis (UK PD Society Brain Bank criteria); HY 1.5 to 3.0; unchanged pharmacological treatment
for ≥ 3 months preceding study

Exclusion criteria:

Severe gait disability with inability to walk unassisted; neurological, vascular or systemic disorders that
may have caused permanent or intermittent weakness or instability; severe hepatic or renal insufficien-
cy, cancer, a history of orthopedic hip or knee surgery which led to gait difficulties; other chronic disor-

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Stozek 2016 (Continued)

ders of the musculoskeletal system leading to restricted mobility; all other contraindications to exer-
cise

Interventions Length of intervention: 4 weeks

Intervention 1: Rehabilitation group [gait/balance/functional training]; 120 minutes; 11x/week (first

two weeks); 3x/week (last two weeks)

Intervention 2: Control [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes Pastor test (shoulder tug); Tandem stance; 10-meter walk at preferred speed; 360° turn; Physical Per-
formance Test; timed motor activities; range of spinal rotation

Follow-up (maximum time after end of intervention): 1 month

Notes Funding sources: NR

Conflicts of interest: None

Sujatha 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 12/10/10

Country: India

Age (mean in years): NR

Sex (male/female): NR

Duration of disease (mean in years): NR

HY (mean): NR

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

NR

Exclusion criteria:

Cardiovascular diseases and other orthopedic conditions

Interventions Length of intervention: 12 weeks

Intervention 1: Endurance exercise [endurance training]; 20 to 45 minutes; 3x/week

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Sujatha 2019 (Continued)

Intervention 2: Stretch-balance training [multi-domain training]; 20 to 45 minutes; 3x/week

Primary setting: Group

Supervision by (if provided): NR

Outcomes "HADS-D"; Digit-Symbol-Task

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Szefler-Derela 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 40/40/40

Country: Poland

Age (median in years): 64

Sex (male/female): 20/20 (50% male)

Duration of disease (median in years): 6.0

HY (range): 2 to 3

UPDRS-M (median): 21.0; 24.0

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG median: 7.09; 7.49

Inclusion criteria:

Idiopathic PD (typical clinical presentation, good response to levodopa, and a full differential diagno-
sis, also involving neuroimaging techniques, diagnosed according to the UK Parkinson’s Disease Soci-
ety Brain Bank clinical diagnostic criteria and HY disease stages 2 to 3, selected from an outpatients’
database in our center

Exclusion criteria:

People with dementia (MMSE < 24), severe motor fluctuations, freezing, orthostatic hypotension, dis-
abling dyskinesia, severe depression, or other medical conditions significantly affecting mobility or
ability to exercise were excluded

Interventions Length of intervention: 6 weeks

Intervention 1: Nordic walking [endurance training]; 90 minutes; 2x/week

Intervention 2: Standard rehabilitation [multi-domain training]; 45 minutes; 2x/week

Primary setting: Group and individual

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Szefler-Derela 2020 (Continued)

Supervision by (if provided): Physiotherapist with qualification in Nordic walking; physiotherapist

Outcomes UPDRS-M; Dynamic Gait Index; TUG; PDQ-39

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: None

Conflicts of interest: MA is an employee of Novartis

Szymura 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/NR/29

Country: Poland

Age (mean in years): 65.69

Sex (male/female): 19/10 (65.5% male)

Duration of disease (mean in years): NR

HY (range): 2 to 3

UPDRS-M (mean): NR

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: NR

Inclusion criteria:

The inclusion criteria for participants with PD were age ≥ 60 years, diagnosis of idiopathic PD (HY stage
between 2 and 3), no changes regarding the applied pharmacotherapy in the month preceding the test,
no orthopaedic conditions limiting physical exercise or deep brain stimulation surgery, independent
gait, and physical fitness enabling participation in the training program. Inclusion criteria for healthy
older people were age ≥ 60 years, no medication affecting the functioning of central nervous system
(e.g. neuroleptics, antidepressants), no neurological or orthopedic disorders limiting physical exercise,
independent gait and physical fitness allowing participation in the training program

Exclusion criteria:

Exclusion criteria were lack of informed consent to participate in the study, musculoskeletal injuries
(e.g. fractures and prostheses), diabetes, diagnosed dementia (MMSE < 25), previous stroke or severe
traumatic brain injury, other CNS diseases and participation in regular physical exercises

Interventions Length of intervention: 12 weeks

Intervention 1: PD balance training [gait/balance/functional training]; 30 to 60 minutes; 3x/week

Intervention 2: Non-training PD group [passive control group]

Intervention 3: Healthy people balance training; 30 to 60 minutes; 3x/week

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Szymura 2020 (Continued)

Intervention 4: Healthy non-training group

Primary setting: Individual

Supervision by (if provided): Physiotherapist

Outcomes Performance-Oriented Mobility Assessment (Tinetti Performance-Oriented Mobility Assessment); con-

centration of selected cytokines, neutrophic factors and CD200 proteins as well as fractalkine

Follow-up (maximum time after end of intervention): 2 days

Notes Funding sources: National Science Centre, Poland

Conflicts of interest: None

Taheri 2011
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/24/24

Country: Iran

Age (mean in years): 62.5

Sex (male/female): 12/12 (50% male)

Duration of disease (mean in years): NR

HY (mean): 3 (inclusion criteria)

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Idiopathic PD; HY stage 3; perform daily tasks independently; avoidance of secondary complications
such as cardiovascular disease, osteoarthritis, or cognitive impairment; participants did not engage in
exercise or physical therapy at the time of the study

Exclusion criteria:

If a person did not participate in training programs on a regular basis, he or she would be excluded
from the study

Interventions Length of intervention: 10 weeks

Intervention 1: Stretching group [flexibility training]; 60 minutes; 4x/week

Intervention 2: Control group [passive control group]

Primary setting: NR

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Taheri 2011 (Continued)

Supervision by (if provided): NR

Outcomes BBS; Tinetti scale; Gait balance scale

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Language: Persian

Terrens 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 208/59/30

Country: Australia

Age (mean in years): 72.0

Sex (male/female): 24/6 (80% male)

Duration of disease (mean in years): 5.5

HY (median): 3

UPDRS-M (median): 50.5

MMSE (mean): 27.5

Physical capability: Number of falls in past 12 months: 0; 3; 1 (single fall)/ 6; 2; 4 (≥ 2 falls)

Inclusion criteria:

Participants were required to have a diagnosis of idiopathic PD confirmed by a neurologist, transfer

and walk without assistance with or without gait aid (as participants are required to independently
transfer in and out of the pool via steps), and have a MMSE score of 24 or above so that they can follow
instructions

Exclusion criteria:

Those with unstable medical conditions or a self-reported history of any musculoskeletal, cardiotho-
racic, other neurological or psychological condition that might potentially affect participation were ex-
cluded.

Interventions Length of intervention: 12 weeks

Intervention 1: Halliwick Aquatic exercises (core-specific exercises and exercises from the Halliwick
concept) [aqua-based training]; 60 minutes; 1x/week

Intervention 2: Traditional aquatic exercise [aqua-based training]; 60 minutes; 1x/week

Intervention 3: Land-based exercise [multi-domain training]; 60 minutes; 1x/week

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Terrens 2020 (Continued)

Primary setting: Group

Supervision by (if provided): Physiotherapist and allied health assistant experienced in treating peo-
ple with PD

Outcomes Falls; adverse events; UPDRS-M; BBS; Mini-BESTest; fear of falling measured by FES

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: Lee Silverman Voice Treatment (LSVT)

Conflicts of interest: NR

Tollar 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 88/74/74

Country: Hungary

Age (mean in years): 70; 70.6; 67.5

Sex (male/female): 36/38 (48.6% male)

Duration of disease (mean in years): 7.5; 7.5; 7.3

HY (mean): 2.3; 2.4; 2.4

UPDRS-M (mean): 18.2; 18.9; 19.0

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: 6-MIN-W (m): 204.6; 222.4; 270.2

Inclusion criteria:

PD diagnosis (UK Brain Bank criteria); HY 2 to 3; neurologically and pharmacologically stable condition
for ≥ 6 months; presence of mobility, balance, and postural problems

Exclusion criteria:

MMSE < 24; BDI score > 40; severe cardiac disease; uncontrolled diabetes; a history of stroke; traumat-
ic brain injury; a seizure disorder; deep brain stimulator; ongoing orthopedic surgeries; pacemaker; he-
mophilia; clinically significant motor fluctuations; LD-induced dyskinesia; current participation in a
self-directed or formal group exercise program

Interventions Length of intervention: 5 weeks

Intervention 1: Agility exergaming [gait/balance/functional training]; 60 minutes; 5x/week

Intervention 2: Stationary cycling [endurance training]; 60 minutes; 5x/week

Intervention 3: Wait-list control [passive control group]

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Tollar 2018 (Continued)

Primary setting: Group

Supervision by (if provided): Physical therapists

Outcomes UPDRS-II; PDQ-39; BDI; Schwab and England ADL scale; EQ-5D; BBS; BESTest; Tinetti Assessment Tool;
Dynamic Gait Index; 6-MIN-W; standing posturography

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Department of Neurology, Somogy County Kaposi Mór Teaching Hospital

Conflicts of interest: None

Tollar 2019
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 72/55/46

Country: Hungary

Age (mean in years): 67.6

Sex (male/female): 29/26 (52.7% male)

Duration of disease (mean in years): 6.8

HY (mean): 2.4

UPDRS-M (mean): NR

MMSE (mean): ≥ 24 (inclusion criteria)

Physical capability: TUG (s): 17.00

Inclusion criteria:

PD patients; HY 2 to 3; mobility difficulty and postural instability based on a qualitative assessment of

gait and postural stability, turns, rigidity, interjoint coordination, trunk posture, and equilibrium while
participants walked forward, backwards, and sideways

Exclusion criteria:

Brain abnormalities based on a diagnostic MRI, MMSE < 24, a BDI score > 40, severe cardiac disease, un-
controlled diabetes, a history of stroke, traumatic brain injury, seizure disorder, past or current deep
brain stimulation, or current participation in a self-directed or formal group exercise program

Interventions Length of intervention: 3 weeks/2 years

Intervention 1: Exercise group (sensorimotor and visuomotor agility training, X-box virtual reality ex-
ergame) [multi-domain training]; 60 minutes; 5x/week; 3 weeks

Intervention 2: Exercise and maintenance group (same exercises as intervention 1 with longer dura-
tion) [multi-domain training]; 60 minutes; 3x/week; 2 years

Intervention 3: Control group [passive control group]

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Tollar 2019 (Continued)

Primary setting: Group

Supervision by (if provided): Therapists

Outcomes MDS-UPDRS-M, MDS-UPDRS-II; Schwab and England ADL; EQ-5D; PDQ-39; BDI; TUG; postural stability
by the magnitude of sway measured on a force platform

Follow-up (maximum time after end of intervention): 24 months

Notes Funding sources: Somogy Megyei Kaposi Mór Teaching Hospital

Conflicts of interest: None

Toole 2000
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 11/11/7

Country: USA

Age (mean in years): 71.7

Sex (male/female): 4/3 (57.1% male)

Duration of disease (mean in years): NR

HY (range): 1 to 3

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Parkinsonism, stage 1 to 4 (later stage 4 was eliminated for group-stage consistency; so only stages 1 to
3 were included)

Exclusion criteria:

Medical problems (radiation treatment for melanoma, depression, and eye surgery)

Interventions Length of intervention: 10 weeks

Intervention 1: Treatment group (resistance and balance exercises) [multi-domain training]; 60 min-
utes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): NR

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Toole 2000 (Continued)

Outcomes Computerized dynamic posturography; Biodex (peak torque, ankle inversion, knee extension, knee
flexion)

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: This project was supported, in part, by a grant to Tonya Toole, PhD and Charles G.
Maitland, MD from the Neuroscience Center of the Tallahassee Memorial Regional Medical Center, Tal-
lahassee, FL.

Conflicts of interest: NR

Van Puymbroeck 2018

Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 111/30/27

Country: USA

Age (mean in years): 67.7

Sex (male/female): 17/10 (63% male)

Duration of disease (mean in years): NR

MHY (range): 1.5 to 3

UPDRS-M (mean): 28.27; 31.58

Short MMSE (mean): ≥ 4 (inclusion criteria)

Physical capability: Functional Gait Assessment: 14.93; 15.83

Inclusion criteria:

Diagnosis of PD; 1.5 to 3 on the MHY Scale of Parkinson’s Disease Progression; endorse a fear of falling;
be able to stand and walk 10 meters with or without an assistive device; be ≥ 18 years old; be able to
speak English; score ≥ 4 out of 6 on the short MMSE; and be able and willing to attend twice weekly ses-
sions for 8 weeks

Exclusion criteria:

Self-reported life expectancy < 12 months; identified an inability to attend sessions due to transporta-
tion issues; were currently receiving physical therapy or enrolled in an intervention study; or were un-
able or refused to provide informed consent

Interventions Length of intervention: 8 weeks

Intervention 1: Yoga [mind-body training]; duration not reported; 2x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Group

Supervision by (if provided): Certified yoga therapist

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Van Puymbroeck 2018 (Continued)

Outcomes Functional Gait Assessment; FOG-Q; Mini-BESTest; MHY; MDS-UPDRS-M

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: College of Health, Education, and Human Development at Clemson University

Conflicts of interest: None

Vergara-Diaz 2018
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 98/32/27

Country: USA

Age (mean in years): 63.8

Sex (male/female): 16/16 (50% male)

Duration of disease (mean in years): 2.9

HY (range): 2 to 2.5

UPDRS-M (mean): 23.5

MMSE (mean): NR

Physical capability: TUG: 9.69; 9.72

Inclusion criteria:

Diagnosed with idiopathic PD (< 10 years) and had limited disease progression (MHY stages 1 to 2.5); 40
to 75 years of age; and willing to undergo baseline and follow-up testing while off PD-related medica-
tion for 12 hours

Exclusion criteria:

Diagnosis of atypical parkinsonism; history of major neurological or psychiatric disease, orthopedic im-
pairment, or other disease that could likely contribute to a gait disturbance; any severe, chronic condi-
tion or acute medical event for which participation in exercise programs was contraindicated; history
of deep brain stimulation or other brain surgery; or significant tai chi experience (> 6 months training in
past 2 years).

Interventions Length of intervention: 6 months

Intervention 1: Tai chi [mind-body training]; 60 minutes; 2x/week + 1x/week at home

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Instructors

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Vergara-Diaz 2018 (Continued)

Outcomes UPDRS; PDQ-39; TUG; TMT; ABC; feasibility (recruitment rate, adherence, and compliance); change in
dual-task gait stride-time variability

Severity of motor signs assessed during: off-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Harvard University Faculty of Medicine

Conflicts of interest: PMW is the founder and sole owner of the Tree of Life Tai Chi Center. PMW’s inter-
ests were reviewed and managed by the Brigham and Women’s Hospital and Partner’s HealthCare in
accordance with their conflict of interest policies. The other authors have no conflicts of interest to de-
clare.

Vivas 2011
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 15/12/11

Country: Spain

Age (mean in years): 67.0

Sex (male/female): 7/5 (58.3% male)

Duration of disease (mean in years): 4.2; 7.8

HY (mean): 2.7; 2.4

UPDRS-M (mean): NR

MMSE (mean): 27.8; 27.5

Physical capability: NR

Inclusion criteria:

Idiopathic PD; ability to follow a stable medication schedule; to be in PD stages 2 or 3 according to the
HY Scale while in the off-medication state; and lack of dementia (MMSE ≥ 24)

Exclusion criteria:

Unable to walk independently or had undergone surgical treatment for PD

Interventions Length of intervention: 4 weeks

Intervention 1: Water-based therapy (trunk mobility exercises, postural stability, transferring oneself
and changing body position) [aqua-based training]; 45 minutes; 2x/week

Intervention 2: Land-based therapy (trunk mobility exercises, postural stability, transferring oneself
and changing body position) [multi-domain training]; 45 minutes; 2x/week

Primary setting: Individual

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Vivas 2011 (Continued)

Supervision by (if provided): Physiotherapist

Outcomes UPDRS (total); TUG; BBS; FRT; Gait analysis

Follow-up (maximum time after end of intervention): 17 days

Notes Funding sources: Programme Alban, the European Union Programme of High Level Scholarships for
Latin America, Consellería de Educación, and Conselleria de Industria Xunta de Galicia

Conflicts of interest: None

Volpe 2013
Study characteristics

Methods Randomized controlled trial

Single-center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/24/NR

Country: Italy

Age (mean in years): 61.6; 65.0

Sex (male/female): 13/11 (54.2% male)

Duration of disease (mean in years): 9.0; 8.9

HY (mean): 2.2; 2.2

UPDRS-M (mean): 24.58; 23.92

MMSE (mean): 26.5; 26.3

Physical capability: NR

Inclusion criteria:

Idiopathic Parkinson’s disease as diagnosed by a medical practitioner and were rated level 0 to 2.5 on
the MHY scale; mild to moderately severe PD for safety reasons as people at stage 3 or more on the HY
scale have a high risk of falls

Exclusion criteria:

Did not speak Italian; had comorbidities that prevented dancing, mobility, or safe exercise; deep brain
stimulation surgery; unable to travel to the dancing or physiotherapy venues

Interventions Length of intervention: 6 months

Intervention 1: Irish set dancing group [dance]; 90 minutes (dance class); 60 minutes (at home); 1x/
week (dance class); 2x/week (at home)

Intervention 2: Standard physiotherapy [multi-domain training]; 90 minutes (physiotherapy); 60 min-

utes (at home); 1x/week (physiotherapy); 1x/week (at home)

Primary setting: Group and individual

Supervision by (if provided): Dancing teachers

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Volpe 2013 (Continued)

Outcomes UPDRS-M, BBS, FOG-Q, PDQ-39, TUG

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 3 weeks

Notes Funding sources: NR

Conflicts of interest: None

Volpe 2014
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 40/34/34

Country: Italy

Age (mean in years): 68; 66

Sex (male/female): NR

Duration of disease (mean in years): 7.5; 7.6

HY (mean): 2.82; 2.65

UPDRS-M (mean): 41.9; 39.2

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: TUG (s): 13.1; 12.8

Inclusion criteria:

Diagnosis of ‘clinically probable’ idiopathic Parkinson’s disease; HY stage 2.5 and 3; ability to walk with-
out any assistance; at least two falls in the last year; MMSE ≥ 25; no relevant comorbidity or vestibu-
lar/visual dysfunctions, limiting locomotion or balance; stable dopaminergic therapy in the last four
weeks

Exclusion criteria:

History of deep brain stimulation surgery and other conditions limiting hydrotherapy (for example, car-
diopulmonary disease)

Interventions Length of intervention: 2 months

Intervention 1: Hydrotherapy [aqua-based training]; 60 minutes; 5x/week

Intervention 2: Land-based rehabilitation (balance exercises) [gait/balance/functional training]; 60

minutes; 5x/week

Primary setting: NR

Supervision by (if provided): NR

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Volpe 2014 (Continued)

Outcomes Centre of pressure sway area; in the antero-posterior and medio-lateral directions with open/closed
eyes; UPDRS-II; UPDRS-M; BBS; TUG; ABC; falls; FES; PDQ-39

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 1 week

Notes Funding sources: None

Conflicts of interest: None

Volpe 2017a
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 41/30/24

Country: Italy

Age (mean in years): 70.6; 70.0

Sex (male/female): 19/11 (63.3% male)

Duration of disease (mean in years): 9.4; 9.0

HY (mean): 2.6; 2.7

UPDRS-M (mean): 41.1; 45.2

MMSE (mean): 26.5; 26.6

Physical capability: TUG (s): 12.9; 14.8

Inclusion criteria:

Diagnosis of idiopathic Parkinson’s disease (according to the United Kingdom Parkinson’s Disease So-
ciety Brain Bank criteria); HY stage ≤ 3; MMSE > 2; flexion (in the sagittal plane) of the thoraco-lumbar
spine with an almost complete resolution in the supine position, and/or lateral flexion (in the coronal
plane) that could be almost completely alleviated by passive mobilization or supine positioning, ability
to attend physiotherapy

Exclusion criteria:

Fixed postural deformities (ankylosing spondylitis, vertebral fractures, idiopathic or degenerative sco-
liosis), in the presence of major depression (diagnosed by means of Diagnostic and Statistical Manual
of Mental Disorders criteria), if they were implanted for deep brain stimulation, in case of severe comor-
bidities (cardiac, pulmonary or orthopedic diseases) or urinary incontinence

Interventions Length of intervention: 8 weeks

Intervention 1: Water-based physiotherapy [aqua-based training]; 60 minutes; 5x/week

Intervention 2: Non-water-based physiotherapy [multi-domain training]; 60 minutes; 5x/week

Primary setting: NR

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Volpe 2017a (Continued)

Supervision by (if provided): Physiotherapists

Outcomes Body Analysis Kapture; shoulder symmetry; pelvic symmetry; UPDRS-M; BBS; ABC; TUG; FES; PDQ-39;
Likert pain scale

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 8 weeks

Notes Funding sources: None

Conflicts of interest: None

Volpe 2017b
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 40/22/22

Country: Italy

Age (mean in years): 69.1; 78.4

Sex (male/female): 13/9 (59.1% male)

Duration of disease (mean in years): NR

HY (mean): 2.5; 2.4

UPDRS-M (mean): 25.6; 26.5

MMSE (mean): NR

Physical capability: 6-MIN-W (m): 315.8; 310.7

Inclusion criteria:

Participants were eligible for inclusion if they consented to participation, had PD diagnosed according
to the current criteria; HY stage 3 on levodopa, and no history of falls in the past

Exclusion criteria:

Presence of important freezing of gait affecting gait analysis recording, dyskinesias and peripheral neu-
ropathy, presence of co-morbidities preventing mobility (orthopedic diseases) or safe exercise (includ-
ing major medical conditions such as malignancies), history of deep brain stimulation surgery or other
conditions affecting stability (e.g. poor visual acuity or vestibular dysfunction), HY ≥4 on levodopa, and
inability to travel to the physiotherapy venues

Interventions Length of intervention: 3 weeks

Intervention 1: Hydrotherapy ("PDS2-UW") [aqua-based training]; 40 minutes; 7x/week

Intervention 2: Land-based walking ("PDS1-LBW") [gait/balance/functional training]; 40 minutes; 7x/

week

Intervention 3: Hydrotherapy ("PDS1-UW"); 40 minutes; 7x/week

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Volpe 2017b (Continued)

Intervention 4: Control group hydrotherapy ("CS1"); 40 minutes; 7x/week

Intervention 5: Control group land-based walking ("CS2-LBW"); 40 minutes; 7x/week

Primary setting: NR

Supervision by (if provided): Physiotherapists with license of lifeguard

Outcomes UPDRS-M; 6-MIN-W; TUG; BBS; PDQ-39

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Wan 2021
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 52/52/40

Country: China

Age (mean in years): 64.95; 67.03

Sex (male/female): 19/21 (47.5% male)

Duration of disease (mean in years): 3.63; 3.25

HY (range): 1 to 4

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: TUG: 11.47; 11.77

Inclusion criteria:

No obvious cognitive or mobility impairment, and no auxiliary equipment required for activities; aged
40 to 85 years; HY scale score 1 to 4; UPDRS-M: at least one limb score of tremor, stiffness, posture sta-
bility, or slow movement items ≥ 2 points; stable medication doses; and medical clearance to partici-
pate in the experiment

Exclusion criteria:

History of non-Parkinson’s neurological impairments; currently participation in other behavioral or

pharmacological studies or coach-guided exercise programs; mental status score of fewer than 24
points; physical weakness, impaired vision, or inability to understand the test content

Interventions Length of intervention: 12 weeks

Intervention 1: Health Qigong [mind-body training]; 60 minutes; 4x/week

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Wan 2021 (Continued)

Intervention 2: Control group [passive control group]

Primary setting: Group

Supervision by (if provided): Professional Health Qigong coach

Outcomes Reaction time; one-legged blind balance test; TUG; normal speed-walking; fast speed-walking; sit and
reach test; knee flexion; hip flexion; hip extension; shoulder joint

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Beijing Sport University International cooperation topics

Conflicts of interest: Dr Zhirong Wan reports grants from Beijing Sport University, during the conduct
of the study. Dr Xiaolei Liu reports grants from Beijing Sport University, during the conduct of the study.
Professor Hui Yang reports grants from Beijing Sport University, during the conduct of the study. Miss
Fang Li reports grants from Beijing Sport University, during the conduct of the study. Miss Lei Li reports
grants from Beijing Sport University, during the conduct of the study. Professor Yulin Wang reports
grants from Beijing Sport University, during the conduct of the study. Dr Hao Jiang reports grants from
Beijing Sport University, during the conduct of the study. Prof. Dr. Jichen Du reports grants from Beijing
Sport University, during the conduct of the study. The authors report no other conflicts of interest in
this work.

Wang 2017
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/40/40

Country: China

Age (mean in years): 63.4; 64.45

Sex (male/female): 26/14 (65% male)

Duration of disease (mean in years): 3.8; 4.3

HY (mean): 1.93; 2.00

UPDRS-M (mean): 26.75; 29.95

MMSE (mean): 27.85; 28.05

Physical capability: 6-MIN-W (m): 178.35; 183.55

Inclusion criteria:

The diagnostic criteria were developed by the Parkinson's Disease and Movement Disorders Section of
the Chinese Medical Association Neurological Society in 2006; HY grade 1 to 3; aged 55 to 75 years; dis-
ease duration ≥ 1 year; educational level of junior high school and above; MMSE score ≥ 24; no cognitive
impairment; possess regular rehabilitation training and water exercise training conditions, i.e. stable
vital signs, good blood pressure control, able to walk with support

Exclusion criteria:

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Wang 2017 (Continued)

Non-primary Parkinson's disease, such as trauma, poisoning, and vascular disease as causes of Parkin-
son's syndrome; presence of contraindications to aquatic exercise training, such as cardiac and renal
dysfunction, tumors, extreme physical disability, and bleeding tendencies; presence of other neurolog-
ical diseases

Interventions Length of intervention: 8 weeks

Intervention 1: Aquatic exercise training [aqua-based training]; 50 minutes; 5x/week

Intervention 2: Regular land-based rehabilitation training (walking, mat training, Bobath ball training,
balance board training, land platform training) [gait/balance/functional training]; 50 minutes; 5x/week

Primary setting: NR

Supervision by (if provided): Rehabilitation therapist

Outcomes UPDRS-M; BBS; TUG; 6-MIN-W, 10MWT

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Language: Chinese

Winward 2012
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/39/39

Country: UK

Age (mean in years): 64.1

Sex (male/female): 31/8 (79.5% male)

Duration of disease (mean in years): 5.79

HY (range): 0 to 4

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: 2-MIN-W (m): 134.1

Inclusion criteria:

PD diagnosis; ≥ 18 years; ability to use an exercise facility or gym; walk 10 meters; HY 0 to 4; participate
for the duration of the study

Exclusion criteria:

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Winward 2012 (Continued)

Unable to meet the study criteria; any contraindications to exercise

Interventions Length of intervention: 12 weeks

Intervention 1: Gym-based exercise group (aerobic, cardiovascular fitness, strength, flexibility) [mul-
ti-domain training]; 30 to 45 minutes; 5x/week

Intervention 2: Wait-list control [passive control group]

Primary setting: Group

Supervision by (if provided): NR

Outcomes PASE; Parkinson's Disease Questionnaire Summary Index; 2-MIN-W; Fatigue Severity Scale

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Long-term Neurological Conditions, Department of Health, UK; Thames Valley Pri-
mary Care Trust; National Institute for Health Research; Parkinson's Disease Society; and the University
of Birmingham, UK

Conflicts of interest: None

Wong-Yu 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 144/84/80

Country: China

Age (mean in years): 59.4; 62.6

Sex (male/female): 46/34 (57.5% male)

Duration of disease (mean in years): 7.1; 5.6

HY (mean): 2.5; 2.4

MDS-UPDRS-M (mean): 26.9; 31.3

MMSE (mean): ≥ 25 (inclusion criteria)

Physical capability: PASE score: 102.4; 97.7, gait speed(m/s): 1.19; 1.17

Inclusion criteria:

Diagnosed with PD, aged 30 years or over, had no falls or only one fall in the past six months, were sta-
ble on anti-Parkinsonian medications and could walk independently for 30 meters with or without an
assistive device

Exclusion criteria:

Neurological conditions other than PD, any history of neurosurgery, significant musculoskeletal or car-
diopulmonary diseases, disorders that might affect balance or locomotion, communication or cogni-

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Wong-Yu 2015 (Continued)

tive deficits with MMSE < 24, or had joined any structured exercise programme in the previous three
months

Interventions Length of intervention: 8 weeks

Intervention 1: Balance group [gait/balance/functional training]; 120 minutes; 1x/week + 3x/week at

home

Intervention 2: Control group (upper limb training) [active control group]; 120 minutes; 1x/week + 3x/
week at home

Primary setting: Group

Supervision by (if provided): Physiotherapist and an assistant who had attended a trainers' program

Outcomes BESTest; gait speed; TUG; dual-task TUG; ABC; fall-related outcomes

Follow-up (maximum time after end of intervention): 12 months

Notes Funding sources: Hong Kong Parkinson's Disease Foundation

Conflicts of interest: None

Yang 2010
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 64/33/30

Country: Taiwan

Age (mean in years): 68.07; 66.27

Sex (male/female): 16/14 (53.3% male)

Duration of disease (mean in years): 4.77; 5.27

HY (mean): 2.23; 2.17

UPDRS-M (mean): NR

MMSE (mean): NR

Physical capability: Walking speed (cm/sec): 88.75; 79.81

Inclusion criteria:

Idiopathic PD (as defined by the UK Brain Bank criteria) diagnosed by a neurologist; HY 1 to 3; ability
to walk independently; stable medication usage; freedom from any other problems that might affect
training; ability to understand instructions and follow commands

Exclusion criteria:

NR

Interventions Length of intervention: 4 weeks

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Yang 2010 (Continued)

Intervention 1: Downhill walking [gait/balance/functional training]; 30 minutes; 3x/week

Intervention 2: Conventional therapy (flexibility exercises, strengthening exercises, proprioceptive

neuromuscular facilitation, coordinating training, balance training, overground walking training) [mul-
ti-domain training]; 30 minutes; 3x/week

Primary setting: Individual

Supervision by (if provided): Physical therapist

Outcomes Gait parameters measured with the "GAITRite" system, including walking speed, cadence, stride
length; thoracic kyphosis measured with an electronic goniometer; muscle strength evaluated using a
hand-held dynamometer

Follow-up (maximum time after end of intervention): 1 month

Notes Funding sources: Mackay Memorial Hospital

Conflicts of interest: None

Yen 2011
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 67/42/38

Country: Taiwan

Age (mean in years): 70.4; 70.1; 71.6

Sex (male/female): 33/9 (78.6% male)

Duration of disease (mean in years): 6.0; 6.1; 7.8

HY (mean): 2.6; 2.4; 2.6

UPDRS-M (mean): 15.1; 15.9; 16.8

MMSE (mean): 28.5; 28.5; 28.1

Physical capability: NR

Inclusion criteria:

Idiopathic PD, intact cognition (MMSE score > 24), HY 2 to 3, previous lack of participation in balance or
gait training, and able to follow simple commands and having no uncontrolled chronic diseases

Exclusion criteria:

History of other neurological, cardiovascular, or orthopedic diseases affecting postural stability and
on-off motor fluctuation and dyskinesia above grade 3 on the UPDRS

Interventions Length of intervention: 6 weeks

Intervention 1: Virtual reality balance training (VR balance board) [gait/balance/functional training];
30 minutes; 2x/week
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Yen 2011 (Continued)

Intervention 2: Conventional balance training [gait/balance/functional training]; 30 minutes; 2x/week

Intervention 3: Control [passive control group]

Primary setting: Individual

Supervision by (if provided): Physical therapist

Outcomes Equilibrium scores, sensory ratios, and verbal reaction times

Follow-up (maximum time after end of intervention): 4 weeks

Notes Funding sources: National Taiwan University Hospital

Conflicts of interest: NR

Youm 2020
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: Yes

Participants Number of participants (recruited/randomized/evaluated): 23/23/17

Country: Korea

Age (mean in years): 68.0; 72.1

Sex (male/female): 10/7 (58.8% male)

Duration of disease (mean in years): 6.4; 8.0

HY (mean): 2.40; 2.29

UPDRS-M (mean): 40.35; 44.43

MMSE (mean): 26.60; 27.60

Physical capability: 30-second sit to stand test (repetitions): 15.3; 13.9

Inclusion criteria:

Diagnosis of idiopathic PD, a HY stage of 1 through 3, treatment with dopaminergic medications, and a
MMSE score of greater than 24 points

Exclusion criteria:

History of orthopedic, neurosurgical, or neurological issues within the preceding six months

Interventions Length of intervention: 12 weeks

Intervention 1: Exercise group (progressive trunk resistance and stretching exercise program) [mul-
ti-domain training]; 60 to 90 minutes; 3x/week

Intervention 2: Control group [passive control group]

Primary setting: Group

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Youm 2020 (Continued)

Supervision by (if provided): not specified ("with guidance")

Outcomes MMSE; UPDRS-total; UPDRS-M; HY; 30-second sit to to stand test; "2 min step"; 2.44 m TUG; arm curl;
chair sit and reach test; back scratch; trunk mobility scale; First and Second Step Phase for Sit-to-Walk-
Test (step time, step length, step speed, toe clearance height)

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Dong-A University research funds

Conflicts of interest: None

Yuan 2020
Study characteristics

Methods Randomized controlled trial with cross-over after 6 weeks of intervention and 6 weeks wash-out

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/24/24

Country: Taiwan

Age (mean in years): 67.8; 66.5

Sex (male/female): 11/13 (45.8% male)

Duration of disease (mean in years): NR

HY (range): 1 to 3

UPDRS-M (mean): NR

MMSE (mean): 28.5; 26.0

Physical capability: Number of falls in the past year: 0; 4

Inclusion criteria:

Aged 60 to 80 years; clinical diagnosis of idiopathic mild to moderate PD of HY stage 1 to 3; independent

community-living ambulatory individuals; and cognitive level as assessed by the MMSE score > 23

Exclusion criteria:

History of dementia, previous stroke, arthritis, vision impairment, diabetes, or uremia; previous en-
gagement in any exergaming training program or commercial exergaming system within 6 months; and
inability to walk without assistance or the presence of cardiovascular disease that impaired walking

Interventions Length of intervention: 6 weeks

Intervention 1: Interactive video-game-based training [gait/balance/functional training]; 30 minutes;

3x/week

Intervention 2: Control group [passive control group]

Primary setting: Individual

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Yuan 2020 (Continued)

Supervision by (if provided): Certified physical therapist

Outcomes BBS; SF-36; Modified FES; Multi-Directional Reach Test, and Maximum Step Length test

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: Ministry of Science and Technology and the Higher Education Sprout Project by the
Ministry of Education in Taiwan

Conflicts of interest: None

Zhang 2015
Study characteristics

Methods Randomized controlled trial

Single center

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): 109/40/40

Country: China

Age (mean in years): 66.0; 64.4

Sex (male/female): 24/16 (60% male)

Duration of disease (mean in years): 6.8; 4.9

HY (range): 1 to 3

UPDRS-M (mean): 18.5; 15.2

MMSE (mean): 27.4; 26.4

Physical capability: Gait velocity (cm/s): 106.0; 119.9

Inclusion criteria:

Idiopathic PD, HY 1 to 4, complete the 10-meter walking test and TUG with or without an assistive de-
vice; stable medication use; UPDRS-M ≥ 2; willing to be assigned to any of the two interventions

Exclusion criteria:

Participating in any other behavioral or pharmacologic study; MMSE < 24, MMSE < 17 for people who
had not gone to school; MMSE < 20 for people who had informal literacy training or elementary educa-
tion; other neurologic/musculoskeletal/cardiopulmonary/metabolic conditions that would impede full
participation in the study

Interventions Length of intervention: 12 weeks

Intervention 1: Tai chi [mind-body training]; 60 minutes; 2x/week

Intervention 2: Multimodal exercise training (core muscle training, crossing obstacle training, standing
on ankle joint correcting board, cycle ergometer) [multi-domain training]; 60 minutes; 2x/week

Primary setting: Group

Supervision by (if provided): Rehabilitation trainer

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Zhang 2015 (Continued)

Outcomes BBS; UPDRS-M; TUG; stride length; gait velocity

Severity of motor signs assessed during: on-medication state

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: National Major Scientific and Technological Special Project for BSignificant New
Drugs Development; National Natural Science Foundation of China; Shanghai Education Development
Foundation and Shanghai Municipal Education Commission BShuguang Program and the Shanghai
Science and Technology Commission

Conflicts of interest: None

Zhu 2011
Study characteristics

Methods Randomized controlled trial

Multicenter

A priori consideration of test power: No

Participants Number of participants (recruited/randomized/evaluated): NR/40/38

Country: China

Age (mean in years): 63.35; 64.83

Sex (male/female): 23/17 (57.5% male)

Duration of disease (mean in years): 2.72; 2.78

HY (range): 1 to 2

UPDRS-M (mean): 17.74; 17.79

MMSE (mean): NR

Physical capability: NR

Inclusion criteria:

Primary Parkinson's disease; 40 to 85 years old; course of disease is less than 3 years, and the revised
HY stage is 1 to 2; voluntary cooperation in treatment

Exclusion criteria:

Various secondary Parkinson's syndrome and Parkinson's superposition syndrome; concurrent schizo-
phrenia or other severe psychosis; serious organic damage to heart, liver, kidney and other organs; ac-
companied by other serious central system diseases; mid-term interruption of treatment for reasons
other than curative effect; forced termination of treatment due to adverse reactions; delayed follow-up
visit or lost to follow-up, unable to judge the curative effect or incomplete data affecting the curative
effect; do not follow the design scheme; the dosage of drugs taken during the treatment exceeds 10%;
the total number of training sessions is less than 70%, or the time and intensity of each training session
is less than 70% of the training requirements.

Interventions Length of intervention: 4 weeks

Intervention 1: Tai chi practice [mind-body training]; 30 to 45 minutes; 2x/day; 5x/week

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Zhu 2011 (Continued)

Intervention 2: Walk exercise [gait/balance/functional training]; at least 40 minutes; 2x/day; 5x/week

Primary setting: NR

Supervision by (if provided): Coach Hua Liang, a national Wuying level athlete & Dong Qing, a nation-
al Taijiquan first-level athlete; Li Jianxing and Li Ning provided home training for some participants

Outcomes UPDRS-M; BBS

Severity of motor signs assessed during: NR

Follow-up (maximum time after end of intervention): 0 (post-intervention)

Notes Funding sources: NR

Conflicts of interest: NR

Language: Chinese

We display the categories used for inclusion in the analysis in square brackets. Labels in square brackets are not displayed for arms that
we did not include in the analysis.
ABC: Activities-specific Balance Confidence; ADL: activities of daily living; BBS: Berg Balance Scale; BDI: Beck Depression Inventory;
BESTest: Balance Evaluation Systems Test; CNS: central nervous system; CT: computed tomography; EQ-5D: EuroQol 5 Dimensions; FES:
Falls Efficacy Scale; FES-I: Falls Efficacy Scale International; FTSTS: Five-Times-Sit-To-Stand; FoG: freezing of gait; FOG-Q: Freezing of
Gait Questionnaire; FRT: Functional Reach Test; HY: Hoehn and Yahr scale; iPD: idiopathic Parkinson's disease; MDS: Movement Disorder
Society; MDS-UPDRS-I: Movement Disorder Society Unified Parkinson's Disease Rating Scale/Part 1 (mentation, behavior and mood);
MDS-UPDRS-II: Movement Disorder Society Unified Parkinson's Disease Rating Scale/Part 2 (activities of daily living); MDS-UPDRS-M:
Movement Disorder Society Unified Parkinson Disease Rating Scale/Motor Score; MHY: Modified Hoehn and Yahr scale; min: minute;Mini-
BESTest: Mini-Balance Evaluation Systems Test; MMSE: Mini Mental State Examination; MoCA: Montreal Cognitive Assessment; MRI:
magnetic resonance imaging; N-FOG-Q: New Freezing of Gait Questionnaire; NR: not reported; QoL: quality of life; PASE: Physical Activity
Scale for the Elderly; PDQ-8: Parkinson's Disease Questionnaire 8; PDQ-39: Parkinson's Disease Questionnaire 39; PDQ-L: Parkinson’s
Disease Quality of Life Questionnaire; ROM: range of motion; SF-8/SF-12: Short-Form Health Survey - 8-item/12-item questionnaire; SF-36:
Short-Form Health Survey - 36-item questionnaire; 2-MIN-W: 2-minute walk test; 6-MIN-W: 6-minute walk test; 10MWT: 10-meter walk
test; TMT: Trail Making Test; TUG: Timed up and go; UPDRS-I: Unified Parkinson's Disease Rating Scale/Part 1 (mentation, behavior and
mood); UPDRS-II: Unified Parkinson's Disease Rating Scale/Part 2 (activities of daily living); UPDRS-M: Unified Parkinson's Disease Rating
Scale/Motor Score

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Antunes Marques 2019 Similar interventions

Cancela 2020 Similar interventions

Capato 2020b Similar interventions

Combs 2013 Similar interventions

Granziera 2021 Similar interventions

Hashimoto 2015 Not an RCT

Israel 2018 Not an RCT

Kalyani 2019 Not an RCT

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Study Reason for exclusion

Laupheimer 2011 No supervision (participants were provided with cycling system at home and training
sessions were unsupervised)

Maciel 2020 Not an RCT

Melo 2018 Similar interventions

Moon 2020 Similar interventions

Munneke 2010 Cluster-RCT

NCT03637023 Terminated

NCT04291027 Terminated

Passos-Monteiro 2020 Similar interventions

Picelli 2012 Similar interventions

Rawson 2019 Not an RCT

Sage 2009 Not an RCT

Sahu 2018 Similar interventions

Segura 2020 Not an RCT

Serrao 2019 Similar interventions

Silva-Batista 2020 Similar interventions

Soke 2021 Similar interventions

Thaut 1996 No supervision

Van Wegen 2015 Similar interventions

Wang 2018 Similar interventions

Xiao 2016 Fewer than five supervised sessions (only four training sessions followed by unsuper-
vised training at home)

Yousefi 2009 Not an RCT

Yu 1998 Not an RCT

Zhang 2018 Not an RCT

Zhu 2020 Similar interventions

RCT: randomized controlled trial

Characteristics of studies awaiting classification [ordered by study ID]

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ACTRN12605000566639
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 18 to 80 years old

• Gender: both
• Diagnosis of Parkinson's disease confirmed using the United Kingdom Brain Bank Parkinson's dis-
ease criteria
• Rated between Grade 1 and 4 on the Hoehn & Yahr staging of Parkinson's disease
• Able to walk without physical assistance for at least 14 meters

Sample size (planned): 28

Sample size (actual): NR

Interventions Community-based progressive strength training vs. active control group

Outcomes Muscle strength, maximum weight, footstep patterns, walking endurance, upper extremity func-
tion, measure of participation, adverse events

Notes Study start: 2005

Study completion: NR
Recruitment status: not yet recruiting

ACTRN12609000900213
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: no limit
• Gender: both
• Diagnosis of Parkinson's disease

Sample size (planned): 84

Sample size (actual): NR

Interventions Water-based exercises vs. active control group

Outcomes Severity of disease, gait quality & function (TUG), functional mobility & balance

Notes Study start: 2007

Study completion: NR
Recruitment status: recruiting

ACTRN12612001016820
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 18 to 75 years old

• Diagnosed with idiopathic Parkinson's disease by a neurologist
• Between Hoehn and Yahr stages 1 to 3
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ACTRN12612001016820 (Continued)
• Be medically safe to participate in an active exercise program, as assessed by participants' neu-
rologist, GP or other medical practitioner

Sample size (planned): 20

Sample size (actual): NR

Interventions Weekly dance classes vs. usual care

Outcomes Adherence, feasibility, functional mobility (TUG), gait speed, quality of life (PDQ-39), balance

Notes Study start: 2012

Study completion: NR
Recruitment status: not yet recruiting

ACTRN12618000923268p
Methods Randomized controlled trial

Participants Inclusion criteria

• Community-living men and women

• Independence to walk continuously for 6 minutes without walking aids and able to cover 300 m
• Walk 8-meter test over or equal to 0.8 m per second velocity
• Score between 1 and 2 on Hoehn and Yahr scale
• Less than 4 risk factors determined by the Quick screen (copyright)
• Score 6 or more in the Short Physical Performance Battery
• Minimum age: 50 years
• Maximum age: 75 years
• Gender: males and females

Sample size (planned): 30

Sample size (actual): NR

Interventions Folk dance lessons plus education on physical activity vs. education on physical activity

Outcomes Step time, balance, cognitive function, functional performance, mental health, neurological symp-
toms (UPDRS), HY, motivation for physical activity, satisfaction, adherence

Notes Study start: 2019

Study completion: NR
Recruitment status: not yet recruiting

Amara 2020
Methods Randomized controlled trial

Participants Inclusion criteria:

• Inclusion required age ≥ 45 years

• Clinical diagnosis of idiopathic PD
• Hoehn and Yahr stages 2 to 3
• Stable medication regimen for at least 4 weeks prior to study entry without anticipation of med-
ication change during the study

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Amara 2020 (Continued)

Sample size (planned): 75

Sample size (actual): 71

Interventions Supervised exercise training vs. improved sleep hygiene vs. healthy control

Outcomes TUG (according to trial record); polysonography (sleep architecture: including sleep efficiency, to-
tal sleep time, wake after sleep onset (amount of time spent awake after sleep onset); latency to
sleep onset, time and percentage of each sleep stage, latency to first REM period, arousal index, pe-
riodic limb movement index, apnea hypopnea index, and REM sleep without atonia); MDS-UPDRS;
Pittsburgh Sleep Quality Index (PSQI); Epworth Sleepiness Scale (ESS); Fatique Severity Scale (FSS);
Psychomotor vigilance test (PVT)

Notes Study start: 2015

Study completion: 2020
Recruitment status: completed

ChiCTR-INR-17011340
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of idiopathic Parkinson's disease

• Must speak either English or French sufficiently to fill out questionnaires and understand the in-
structions for dance classes

Sample size (planned): 120

Sample size (actual): NR

Interventions Square dance vs. usual care

Outcomes UPDRS-M, HY, PDQ-39, TUG, Berg Balance Scale, modified Frozen Questionnaire

Notes Study start: 2017

Study completion: 2017
Recruitment status: not yet recruiting

ChiCTR-IOR-16009065
Methods Randomized controlled trial

Participants Inclusion criteria:

• A clinical diagnosis of Parkinson's disease, with a disease severity rating of stage 1 to 3 on the
Hoehn and Yahr scale
• Aged above 18 years old
• Ability to stand unaided or walk with or without an assistive device

Sample size (planned): 160

Sample size (actual): NR

Interventions Yoga vs. usual care

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ChiCTR-IOR-16009065 (Continued)

Outcomes Psychological distress, heart rate, UPDRS II, TUG, well-being, PDQ-8

Notes Study start: 2016

Study completion: NR
Recruitment status: completed, no results posted

ChiCTR-IPR-17011875
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of primary Parkinson's disease (meet the 2013 Criteria of Guidelines for the diagnosis
of Parkinson's disease of European Neurological Union)
◦ Reduced capacity of movement
◦ Meets at least one of the following clinical manifestations, including muscle rigidity; resting
tremor; posture instability
◦ Unilateral disease; resting tremor; progressive disorder; after the onset of persistent asymmet-
ric involvement; levodopa treatment at first effective
• Hoehn and Yahr grades 1 to 3, able to walk independently
• No change to participant drug regime in the week prior to enrolment in the trial, medication during
treatment unchanged
• Auditory, visual, and cognitive ability is normal

Sample size (planned): 90

Sample size (actual): NR

Interventions Baduajin aerobic exercises vs. balance function training vs. usual care

Outcomes Gait, UPDRS, blood composition

Notes Study start: 2017

Study completion: 2019
Recruitment status: not yet recruiting

ChiCTR-TRC-14004549
Methods Randomized controlled trial

Participants Inclusion criteria:

• Adults diagnosed with idiopathic Parkinson's disease with a disease severity rating of stage 1 to
4 on the Hoehn and Yahr scale
• Prescribed one or more anti-parkinsonian medications by a consultant neurologist or consultant
physician with specialist knowledge of movement disorders
• Not demented or significantly cognitively impaired

Sample size (planned): 142

Sample size (actual): NR

Interventions Tai chi vs. rehabilitation training + medication

Outcomes Balance, gait, quality of life

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ChiCTR-TRC-14004549 (Continued)

Notes Study start: 2014

Study completion: 2017
Recruitment status: not yet recruiting

ChiCTR1800019534
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 80 years
• No history of leg injuries or other diseases associated with balance impairments
• Berg Balance Scale (BBS < 56)
• MMSE > 22
• Individuals were referred if they were within 3 weeks of their stroke, could stand unassisted for
1 minute, and were in need of balance training according to the judgment of the senior physical
therapist

Sample size (planned): 80

Sample size (actual): NR

Interventions Balance training vs. active control

Outcomes Balance

Notes Study start: 2018

Study completion: NR
Recruitment status: not yet recruiting

CTRI/2017/08/009471
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: from 18 to 70 years

• Gender: both male and female
• Patient group: diagnosis of PD according the UKPDS Brain Bank criteria by a movement disorder
specialist (Hoehn Yahr stage 4 or less)
• Healthy volunteers: non-practitioner of yoga
• No known medical co-morbidities that will interfere with doing yoga or transcranial magnetic
stimulation

Sample size (planned): 245

Sample size (actual): NR

Interventions Yoga vs. aerobic exercise

Outcomes UPDRS, PDQ-39, motor & non-motor symptoms, fatigue

Notes Study start: 2016

Study completion: 2019
Recruitment status: open to recruitment

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de Oliveira 2017
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 60 to 90 years old

• Community-dwelling individuals with idiopathic PD
• All sedentary (not performing any physical activity superior to 3 METs [metabolic equivalent of
task])
• HY stage: 1 to 3

Sample size (planned): 30

Sample size (actual): 24

Interventions Individualized exercises vs. group exercises vs. monitoring

Outcomes Wisconsin card sorting test; Raven colored matrices (both cognition), according to trial record; cog-
nitive functions; functionality; quality of life

Notes Study start: 2014

Study completion: 2017
Recruitment status: completed

DRKS00008732
Methods Randomized controlled trial

Participants Sample size (planned): 60

Sample size (actual): NR

Interventions LSVT BIG therapy vs. intensive physiotherapy vs. regular physiotherapy

Outcomes Non-motor function (NMS score), severity of motor signs (UPDRS-M), psychometric function (BDI-II,
adverse events, Parkinson’s Neuropsychometric Dementia Assessment- (PANDA), MMSE, quality of
life (PDQ-39)

Notes Study start: 2015

Study completion: NR
Recruitment status: recruiting

Huang 2020
Methods Randomized controlled trial

Participants Inclusion criteria

• Diagnosed with postural instability and gait disorder Parkinson's Disease

Sample size (planned): NR

Sample size (actual): 80

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Huang 2020 (Continued)

Interventions Drug-only vs. drug-combined virtual reality training vs. drug-combined audiovisual training vs.
drug-combined repetitive transcranial magnetic stimulation

Outcomes Rating scales (BBS, FOG-Q, TUG, MDS-UPDRS)

Notes Study start: NR

Study completion: NR
Recruitment status: NR

IRCT2015040616830N4
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 55 to 65 years old

• Parkinson's disease according to neurologist diagnosis
• Level 1 to 3 according to Hoehn and Yahr scale
• Having an acceptable level of cognitive function, i.e. score of more than 21 on the Mini Mental
State Examination (MMSE)
• Able to walk independently and without assistive device at least 10 meters
• No other neurological diseases or any orthopedic problems

Sample size (planned): 40

Sample size (actual): NR

Interventions Sensory reweighting excercises vs. usual care

Outcomes Postural control, functional balance, functional mobility

Notes Study start: 2015

Study completion: NR
Recruitment status: completed, no results posted

IRCT2016071228885N1
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: from 50 to 70 years

• Gender: both male and female
• Diagnosis of Parkinson's disease at moderate levels (levels 2 and 3)
• Passage of at least 3 years after the disease diagnosis
• Lack of other neurological diseases or any acute and chronic physical or mental disorder
• The ability to stand and walk independently

Sample size (planned): 48

Sample size (actual): NR

Interventions Pilates exercises vs. balance exercise vs. walking

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IRCT2016071228885N1 (Continued)

Outcomes Gait, functional balance, falling risk

Notes Study start: 2016

Study completion: NR
Recruitment status: completed, no results posted

IRCT20171030037099N1
Methods Randomized controlled trial

Participants Inclusion criteria:

• No age limit
• Gender: both
• Moderate Parkinson's disease; lack of chronic cardiac disease
• No regular physical activity or physiotherapy intervention during the study time
• Not having open surgery in the past 6 months to one year

Sample size (planned): 30

Sample size (actual): 30

Interventions Balance exercises vs. usual care (medication)

Outcomes Balance, muscle strength, walking time (TUG)

Notes Study start: 2017

Study completion: NR
Recruitment status: completed, no results posted

Kargarfard 2012
Methods Randomized controlled trial

Participants Inclusion criteria

• Gender: only female

• Parkinson's disease patients who had been referred to neurologists in Isfahan

Sample size (planned): NR

Sample size (actual): 20

Interventions Aquatic exercise therapy vs. medications

Outcomes BBS

Notes Study start: NR

Study completion: NR
Recruitment status: NR

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Khongprasert 2019
Methods Randomized controlled trial

Participants Inclusion criteria

• Diagnosed with Parkinson's disease (mild to moderate severity)

Sample size (planned): NR

Sample size (actual): 22

Interventions Thai traditional game-based exercise for gait and balance

Outcomes BBS, balance platform, TUG, the GaitRite walkway

Notes Study start: NR

Study completion: NR
Recruitment status: NR

Koli 2018
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 80 years old

• H&Y stage 1.5 to 3
• Ability to follow simple commands
• Capacity to walk independently

Sample size (planned): 34

Sample size (actual): 25

Interventions Indian classical dance therapy vs. physiotherapy

Outcomes UPDRS-I, Activities-specific Balance Confidence Scale (ABC scale), PDQ-39

Notes Study start: 2017

Study completion: 2018
Recruitment status: NR

Lee 2019
Methods Randomized controlled trial

Participants Inclusion criteria:

• Participants with idiopathic PD

Sample size (planned): NR

Sample size (actual): 30

Interventions Gaming vs. normal activity

Outcomes BBS, Static posturography and Sensory Organization Test (SOT) of Computerized Dynamic Postur-
ography (CDP)

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Lee 2019 (Continued)

Notes Study start: NR

Study completion: NR
Recruitment status: NR

Lee G 2018
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: between 50 and 80 years

• Stage 1 to 3 on the Hoehn and Yahr scale
• No other neurological, or cognitive impairments
• Not having received any exercise therapy within the 3 months prior to the study

Sample size (planned): NR

Sample size (actual): 50

Interventions Wii balance-training vs. standard physiotherapy

Outcomes "Verbal analogue scale", activities-specific balancing confidence scale (ABC), PDQ-39, fall index,
Sensory Organization Test (SOT) of Computerized Dynamic Posturography (CDP)

Notes Study start: NR

Study completion: NR
Recruitment status: NR

Mohammadpour 2018
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of Parkinson's idsease

• Lack of chronic cardiovascular diseases or cognitive disorders approved by a specialist physician

Sample size (planned): NR

Sample size (actual): 30

Interventions Combined aerobic and resistance exercise program vs. no regular physical activity (only drugs)

Outcomes PDQOL, UPDRS-M

Notes Study start: NR

Study completion: NR
Recruitment status: NR

NCT00004760
Methods Randomized controlled trial

Participants Inclusion criteria:

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NCT00004760 (Continued)
• Age: 50 to 90 years
• Stage 2 or 3 Parkinson's disease (Hoehn and Yahr scale)
• Able to ambulate independently
• Able to function independently in home
• Moderate rigidity
• No moderate or severe tremor
• No unstable angina
• No psychiatric or medical contraindication to exercise, e.g. dementia, hip fracture
• No other neurologic disorder, e.g. stroke, multiple sclerosis
• Resides within 30 miles of Duke University

Sample size (planned): NR

Sample size (actual): 80

Interventions Axial exercise program vs. standard care

Outcomes NR

Notes Study start: 1995

Study completion: 1997
Recruitment status: completed, no results posted

NCT00029809
Methods Randomized controlled trial

Participants Inclusion Criteria:

• Age: 40 to 85 years old

• Ambulatory patients with Parkinson's Disease, defined as a clinical state in which at least two of
these four cardinal features are present
◦ slowness of movement
◦ tremor at rest
◦ muscular rigidity
◦ gait disturbance or posture imbalance.
• Not exercising regularly more than 2x per week

Sample size (planned): 40

Sample size (actual): NR

Interventions Chinese exercise modalities vs. NR

Outcomes Motor control, motor disability

Notes Study start: NR

Study completion: NR
Recruitment status: completed, no results posted

NCT00167453
Methods Randomized controlled trial

Participants Inclusion criteria:

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NCT00167453 (Continued)
• Age: 40 to 80 years old
• Clinical diagnosis of Parkinson's disease or Parkinson Syndrome
• Stages 1 to 3 of disease progression

Sample size (planned): 45

Sample size (actual): NR

Interventions Exercise vs. education + exercise vs. no intervention

Outcomes Self-efficacy, activity-specific balance (ABC), TUG, PDQ-8, social & physical activities, Schwab &
England ADL scale, Northwestern University Disability scale

Notes Study start: 2005

Study completion: 2007
Recruitment status: completed, no results posted

NCT00387218
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: older than 30 years old

• Community-dwelling, independently ambulatory adults with mild to moderate Parkinson's dis-
ease (Stages 2, 2.5, and 3 on the modified Hoehn and Yahr scale)
• A diagnosis of PD made by their attending neurologist using criteria from the UK Brain Bank, e.g. at
least two of the cardinal signs of PD (i.e., bradykinesia, resting tremor, rigidity, postural instability)
• Without PD medication other known or suspected causes of parkinsonism
• Must be on a stable regimen for at least one month prior to enrollment

Sample size (planned): 170

Sample size (actual): NR

Interventions Usual care vs. aerobic training vs. targeted flexibility vs. functional training

Outcomes Balance, oxygen consumption, functional capacity, UPDRS, UPDRS-ADL, PDQ-39, spinal range of
motion

Notes Study start: 2002

Study completion: 2009
Recruitment status: unknown (was recruiting, but no verification since 2008)

NCT01014663
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of Parkinson's disease

• Currently not receiving physical therapy services
• Medically stable with a physician release stating approval to enter an exercise program
• Independently ambulatory in the home setting with or without the use of an assistive device

Sample size (planned): NR

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NCT01014663 (Continued)
Sample size (actual): 31

Interventions Non-contact boxing training vs. traditional therapeutic exercise

Outcomes Mobility (TUG, Four-Square Step Test, 6-Minute Walk Test, Berg Balance Scale, Functional Reach
Test)

Notes Study start: 2009

Study completion: 2011
Recruitment status: completed, no results posted

NCT01076712
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 35 to 75 years old

• Stable medication usage
• Hoehn and Yahr stage 2 to 4
• At least 1 score of 2 or more for at least 1 limb of either the tremor, rigidity, or bradykinesia item
of the Unified Parkinson's Disease Rating Scale (UPDRS)
• Able to walk independently
• No severe cognitive impairments (Mini Mental State Examination - Chinese Cantonese version)
score greater than 24

Sample size (planned): 112

Sample size (actual): NR

Interventions Physiotherapy vs. education classes

Outcomes MDS-UPDRS-M, levodopa equivalent daily dosage, TUG, activities-specific balance confidence
scale, PDQ-39, number of injurious falls

Notes Study start: 2010

Study completion: 2012
Recruitment status: unknown (was recruiting, but no verification since 2010)

NCT01246700
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of Parkinson's disease by a clinician/neurologist

• Absence of mentation
• Established medication schedule and dosage

Sample size (planned): NR

Sample size (actual): 76

Interventions Sensory attention focused exercise (SAFEx) then no treatment vs. no treatment then SAFEx

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NCT01246700 (Continued)

Outcomes Disease severity (UPDRS), TUG, 30-second chair stand, grooved pegboard, step length, velocity,
step to step length variability

Notes Study start: 2008

Study completion: 2010
Recruitment status: unknown (was active, but no verification since 2010)

NCT01427062
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 45 years or older

• Diagnosed as having Parkinson's disease
• Stable on anti-parkinsonian medications for at least 6 weeks prior to entry into the study
• Able to walk a 10-meter distance at least 3 times with or without walking aids independently
• At stage 2 or 3 of the Hoehn and Yahr staging

Sample size (planned): 52

Sample size (actual): NR

Interventions Anticipatory & compensatory postural control training vs. strength-focused training

Outcomes Reaction time of limits of stability test, one-leg-stance time, pull test, fall rate, movement velocity &
end point excursion of limits of stability test, gait velocity, stride length, cadence

Notes Study start: 2009

Study completion: 2012
Recruitment status: unknown (was recruiting, but no verification since 2011)

NCT01439022
Methods Randomized controlled trial

Participants Inclusion criteria:

• Parkinson's disease diagnosed by neurological examination; idiopathic PD defined by the UK

Parkinson's Disease Society Brain Bank Criteria
• Able to walk ≥ 100m
• Maintained a stable medical regime for 12 weeks prior to initiation of the study, and anticipated
to maintain a stable regime for the course of study (as determined by the referring clinician)

Sample size (planned): NR

Sample size (actual): 105

Interventions Exercise programme vs. handwriting programme

Outcomes Change in 2 minute walk, TUG, nine-hole peg test, health status (SF-36), quality of life (EQ-5D),
blood pressure, BMI, aerobic fitness, leg power, grip strength, disease status (UPDRS), non-motor
symptoms, process evaluation, adherence

Notes Study start: 2011

Study completion: 2014
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NCT01439022 (Continued)
Recruitment status: completed, no results posted

NCT01562496
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: between 30 and 75 years

• Diagnosis of idiopathic Parkinson's disease according to the UK Queen Square Brain Bank Criteria
• Hoehn & Yahr disease stages 1 to 2
• Having insufficient physical activity according to the American College of Sports Medicine (ACSM)
guideline for adults, 50 to 64 years old with a chronic condition
• Untreated with anti-parkinsonian medication or receiving medication, for less than two years,
medication-responsive without fluctuations

Sample size (planned): NR

Sample size (actual): 35

Interventions Aerobic exercise vs. no intervention

Outcomes Trails A & B track, UPDRS, cognitive function (MMSE, Scales for Outcomes in Parkinson's Disease
(SCOPA)), kinetics (TUG, finger-tap test, pegboard test), quality of life (PDQ-39), maximal exercise,
feasibility, neuroplasticity

Notes Study start: 2012

Study completion: 2014
Recruitment status: completed, no results posted

NCT01757509
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: over 18 years old

• Diagnosis of idiopathic Parkinson's disease, stage 1 to 2.5 on the Hoehn and Yahr scale
• Showing a clear benefit from anti-parkinson medication
• Able to walk three meters with or without an assistive device
• Not pregnant

Sample size (planned): NR

Sample size (actual): 24

Interventions Set dancing intervention + usual care vs. usual care

Outcomes Balance (Berg Balance Scale), UPDRS-M, quality of life (PDQ-39), functional exercise tolerance (6-
minute walk test), caregiver burden (Zarit Care Giver Burden Interview (ZCBI))

Notes Study start: 2012

Study completion: 2013
Recruitment status: completed, no results posted

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NCT01835652
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 70 years old

• Gender: both
• Idiopathic Parkinson's disease according to UK Brain Bank criteria (modified to permit inclusion
of participants with a family history)
• Mild to moderate Parkinsonism (Hoehn & Yahr stages 1 to 3)

Sample size (planned): NR

Sample size (actual): 13

Interventions Active aerobic exercise training vs. passive exercise (stretching, balance-based)

Outcomes Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), motor func-
tion (MDS-UPDRS-M, finger tapping, Purdue pegboard), cognitive function (Montreal Cognitive
Assessment, Wisconsin Card-Sorting Task, Trail-Making B Test, computerized reaction time test),
mood & apathy (Beck Depression inventory, Starkstein apathy scale)

Notes Study start: 2013

Study completion: 2015
Recruitment status: completed, no results posted

NCT01960985
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 65 to 85 years old

• Definitive idiopathic Parkinson's disease as diagnosed by a neurologist
• Hoehn and Yahr Stage 1 to 3
• Able to ambulate without an assistive device
• On stable doses of Parkinson's medications prior to study onset

Sample size (planned): NR

Sample size (actual): 42

Interventions Motor training (external cues) vs. motor training vs. no treatment

Outcomes UPDRS, balance (BBS), gait (dynamic gait index), retropulsion test, TUG, balance (BESTest)

Notes Study start: 2006

Study completion: 2012
Recruitment status: completed, no results posted

NCT02017938
Methods Randomized controlled trial

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NCT02017938 (Continued)

Participants Inclusion criteria:

• Age: 20 years and older

• Gender: both
• Clinical diagnosis of Parkinson disease
• Hoehn and Yahr ≤ 3

Sample size (planned): 90

Sample size (actual): NR

Interventions Virtual reality anti-fatigue ergo cycling training vs. control (NR)

Outcomes Muscle twitch force, muscle voluntary activity level, heart rate, heart rate variability, Borg's rate of
perceived exertion

Notes Study start: 2013

Study completion: 2016
Recruitment status: unknown (was recruiting, but no verification since 2013)

NCT02267785
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 30 to 85 years old

• Confirmed diagnosis of idiopathic Parkinson's disease based on the United Kingdom Brain Bank
criteria
• Mild cognitive impairment (Level II criteria Movement Disorder Task Force)
• Medically eligible for MRI imaging
• Able to provide a written medical clearance from their primary physician to participate in exercise
• Stable PD medications for 3 months

Sample size (planned): NR

Sample size (actual): 25

Interventions Skill-based exercise vs. aerobic exercise vs. social contact

Outcomes Context-dependent motor learning, dual task performance (during fMRI), verbal fluency, Tower of
London test, Wisconsin Card Sorting test, quality of life (PDQ-39), motor symptoms (MDS-UPDRS,
physical performance test, TUG), activity-specific balance (ABC), control beliefs, self-efficacy, car-
diovascular fitness, BMI, mental health (geriatric depression/anxiety scales, daily activities, cogni-
tive function

Notes Study start: 2014

Study completion: 2019
Recruitment status: unknown (was active, but no verification since 2019)

NCT02419768
Methods Randomized controlled trial

Participants Inclusion criteria:

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NCT02419768 (Continued)
• Diagnosis idiopathic Parkinson according to the Brain Bank criteria of the United Kingdom Parkin-
son's Disease Society
• Disease severity according to modified Hoehn & Yahr stages 1 to 4
• Absence of dementia Minimal Mini Mental State Examination score of 24 or higher
• Stable drug usage in the last 4 weeks

Sample size (planned): 50

Sample size (actual): NR

Interventions Physical exercise vs. no intervention

Outcomes Balance (BESTest), MDS-UPDRS-M, 6-minute walking test, 10-meter walking test, longe-range au-
tocorrelations, instrumented gait analysis, Impact on Participation and Autonomy Questionnaire
(IPAQ), activities based balance (ABC)

Notes Study start: 2014

Study completion: 2016 (estimated)
Recruitment status: unknown (was recruiting, but no verification since 2016)

NCT02476240
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosed with idiopathic Parkinson's disease by a neurologist

• Able to stand 2 minutes, unassisted
• Able to walk 10 meters, unassisted
• Able to understand English instructions

Sample size (planned): NR

Sample size (actual): 65

Interventions Internally focused PD-SAFEx (sensory attention focused exercise) vs. externally focused PD-SAFEx
vs. control group

Outcomes UPDRS-M, single & dual task walking, anxiety (Parkinson anxiety scale), cognitive status (MoCA
test), quality of life (PDQ-39), physical activity (Community Health Activities Model Program for Se-
niors questionnaire (CHAMPS))

Notes Study start: 2015

Study completion: 2016
Recruitment status: completed, no results posted

NCT02476266
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosed with idiopathic Parkinson's disease by a neurologist

• Able to stand two minutes, unassisted
• Able to understand English instructions
• Signed Physical Activity Readiness Medical Examination (PARmed-X) by physician
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NCT02476266 (Continued)
Sample size (planned): NR
Sample size (actual): 53

Interventions Power training vs. strength training vs. no intervention

Outcomes Muscle activity (Lean-and-Release perturbation technique), severity of motor signs (UPDRS-M),
gait, balance, muscle strength, TUG, thirty-second sit to stand, quality of life (PDQ-39), physical ac-
tivity (Community Health Activities Model Program for Seniors questionnaire (CHAMPS))

Notes Study start: 2015

Study completion: 2016
Recruitment status: completed, no results posted

NCT02615548
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 45 to 80 years
• Gender: both
• Idiopathic Parkinson's disease
• Hoehn & Yahr stages 1 to 3
• Willing and able to participate in 60 minutes of physical activity, 3x/week for 12 weeks, then 2x/
week for 36 weeks

Sample size (planned): NR

Sample size (actual): 30

Interventions Community exercise class vs. self-directed exercise acitivity

Outcomes Gait (functional gait assessment FGA), physical endurance (6-Minute Walk Test), attitude towards
intervention

Notes Study start: 2016

Study completion: 2017
Recruitment status: submitted, not posted on ClinicalTrials.gov

NCT02656355
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 20 years and older

• Gender: both
• Clinical diagnosis of Parkinson disease

Sample size (planned): 90

Sample size (actual): NR

Interventions Weight shift training + anticipatory postural adjustment (APA) feedback vs. weight shift training vs.
usual care

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NCT02656355 (Continued)

Outcomes Gait, balance

Notes Study start: 2015

Study completion: 2017
Recruitment status: unknown (was recruiting, but no verification since 2016)

NCT02674724
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 75 years
• Hoehn and Yahr stages 2 to 3
• Idiopathic Parkinson's disease diagnosed according to the United Kingdom Parkinson's Disease
Society Brain Research Centre Criteria
• Ability to walk independently without walking devices aid
• Absence of orthopedic injuries or pain in joints that could interfere with training program
• Stable medication regimen for PD treatment at recruitment stage
• Mini Mental State Examination Scale (MMSE) ≥ to 27 for literate patients and schooling ≥ of 4 years
of formal education
• No cardiovascular instability, no pacemaker, decompensated metabolic disease, vestibular dys-
function, and stroke

Sample size (planned): 63

Sample size (actual): NR

Interventions Gym group vs. free weights vs. stretching

Outcomes Postural sway, balance (BBS, Mini-BESTest, TUG, Dynamic Posturography), quality of life (PDQ-39)

Notes Study start: 2016

Study completion: 2018
Recruitment status: completed, no results posted

NCT02745171
Methods Randomized controlled trial

Participants Inclusion criteria:

• People diagnosed with idiopathic Parkinson's disease

• Gender: both
• People in stages 1 to 3 of modified version of the Hoehn and Yahr scale

Sample size (planned): 20

Sample size (actual): NR

Interventions Physical therapy vs. no intervention

Outcomes Quality of life (PDQ-39)

Notes Study start: 2016

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NCT02745171 (Continued)
Study completion: 2016
Recruitment status: unknown (was recruiting, but no verification since 2016)

NCT02816619
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: from 18 to 80
• Gender: both
• Clinical criteria for Parkinson's disease
• Social security coverage
• Ability to provide informed consent

Sample size (planned): 50

Sample size (actual): NR

Interventions Personalised physical activitiy program vs. free practice of physical activitiy

Outcomes UPDRS-M, PDQ-39, ADL, activity, balancing abilities (stabilometry), muscular strength (isometric
test), cardiorespiratory function, 6-MIN-W, body mass, dropout rates

Notes Study start: 2016

Study completion: 2018
Recruitment status: unknown (was recruiting, but no verification since 2016)

NCT02999997
Methods Randomized controlled trial

Participants Sample size (planned): NR

Sample size (actual): 51

Interventions Exercise with Ronnie Gardiner Method vs. no exercise

Outcomes TUG cognitive & manual, Mini-BESTest, Four Step Square Test, BBS, Chair Stand 30s, MoCA, audi-
tory memory test, symbol digit modalities test, Victoria Stroop test, grooved pegboard, Trail Mak-
ing Test, Rey complex figures, WHO Disability Assessment Schedule (WHODAS) 2.0, FOG-Q, PDQ-39,
FES-I, actigraphy

Notes Study start: 2017

Study completion: 2018
Recruitment status: completed, no results posted

NCT03212014
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 85 years old

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NCT03212014 (Continued)
• Parkinson's disease diagnosis, Hoehn-Yahr level 1 to 3
• Stable medicine intake for 2 weeks at least
• Able to walk independently for 15 meters

Sample size (planned): 75

Sample size (actual): NR

Interventions LSVT-BIG vs. power Rehabilitation vs. traditional rehabilitation

Outcomes Balance (Mini-BESTest), UPDRS, muscle power of lower extremity, quality of life (PDQ-39)

Notes Study start: 2017

Study completion: 2017
Recruitment status: unknown (was recruiting, but no verification since 2017)

NCT03406728
Methods Randomized controlled trial

Participants Inclusion criteria:

• Gender: both
• Confirmed diagnosis of Parkinson's disease by a registered movement disorders specialist
• Currently taking dopaminergic medication
• Able to walk 15 m, unassisted
• Able to stand for 2 minutes unassisted
• Able to understand English Instructions

Sample size (planned): 36

Sample size (actual): NR

Interventions Parkinson's Disease Sensory Attention Focused Exercise (PDSAFEx) vs. usual daily activities vs. vir-
tual reality intervention

Outcomes UPDRS, sensory organisation (SOT), number of falls, TUG, balance (ABC), falls efficacy (FES), quality
of life (PDQ-39)

Notes Study start: 2018

Study completion: 2018
Recruitment status: unknown (was not recruiting, no verification since 2018)

NCT03443752
Methods Randomized controlled trial

Participants Inclusion criteria:

• A clinical diagnosis of Parkinson's disease

• Stable medication use
• Ability to comprehend English,
• Ability to stand without aid and walk with or without assisted aids

Sample size (planned): 60

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NCT03443752 (Continued)
Sample size (actual): NR

Interventions Shotokan karate vs. tai chi

Outcomes UPDRS-II, PDQ-39, TUG, gait

Notes Study start: 2018

Study completion: 2018
Recruitment status: unknown (was not recruiting, no verification since 2018)

NCT03568903
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 60 to 81 years old

• Diagnosis of idiopathic Parkinson's disease
• No other untreated medical conditions that might affect gait or postural stability
• Able to walk without assistive device
• Score of Mini Mental State Examination above 24
• No other neurological conditions in medical anamnesis

Sample size (planned): 44

Sample size (actual): NR

Interventions Comprehensive physical therapy vs. no intervention

Outcomes Gait speed (TUG), body composition, Tinetti test, range of motion, handwriting, quality of life
(PDQ-39), pain, patient satisfaction, activities of daily living

Notes Study start: 2013

Study completion: 2017
Recruitment status: completed, no results posted

NCT03618901
Methods Randomized controlled trial

Participants Inclusion criteria:

• Gender: both
• Able to understand verbal instructions in English
• Diagnosed with idiopathic Parkinson's disease by a neurologist

Sample size (planned): 60

Sample size (actual): NR

Interventions Rock steady boxing vs. PD SAFEx

Outcomes Motor symptom improvements (UPDRS), quality of life (PDQ-39), balance (biodex balance system,
Mini-BESTest, ABC), gait (TUG), strength, cognitive abilities (Scale of Outcomes of Parkinson Dis-

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NCT03618901 (Continued)
ease (SCOPA), Montreal Cognitive Assessment, MMSE), physical activity (Community Health Activi-
ties Model Program for Seniors questionnaire (CHAMPS))

Notes Study start: 2018

Study completion: 2019
Recruitment status: unknown (was recruiting, but no verification since 2019)

NCT03689764
Methods Randomized controlled trial

Participants Sample size (planned): NR

Sample size (actual): 24

Interventions Interactive video-game exercise then no intervention vs. no intervention then interactive video-
game exercise

Outcomes Balance (BBS), SF-36, falls efficacy (MFES), multidirectional reach (MDRT), maximum step length

Notes Study start: 2014

Study completion: 2019
Recruitment status: completed, no results posted

NCT04012086
Methods Randomized controlled trial

Participants Sample size (planned): NR

Sample size (actual): 40

Interventions Physical therapy vs. no physical therapy

Outcomes Cognitive function (MoCA), motor performance (MDS-UPDRS-M)

Notes Study start: 2015

Study completion: 2018
Recruitment status: completed, results not posted

Ogundele 2018
Methods Randomized controlled trial

Participants Inclusion criteria: people with Parkinson's disease

Sample size (planned): NR

Sample size (actual): 43

Interventions Virtual reality gaming vs. activity-based gait and balance training

Outcomes Gait analysis (assessing balance, step length, gait velocity, cadence), PDQ-39

Notes Study start: NR

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Ogundele 2018 (Continued)

Study completion: NR
Recruitment status: NR

RBR-34d7jm
Methods Randomized controlled trial

Participants Inclusion criteria:

• Participants between stages 1 to 3 of the Hoehn & Yahr scale

• Regular use of specific medication for Parkinson's disease

Sample size (planned): 100

Sample size (actual): NR

Interventions Dance & rhythmic activities vs. socializing activities

Outcomes Cognitive function (executive function, memory, attention), gait (velocity, step length), postural
control, disease severity (HY, UPDRS), global cognitive function (MMSE), visuospatial ability, quali-
ty of life (PDQ-39), anxiety, depression, stress, coordination of upper & lower limbs, functional bal-
ance (BBS), functional mobility (TUG), fear of falls

Notes Study start: 2015

Study completion: NR
Recruitment status: completed, results not posted

RBR-3vm7bf
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 72 years old

• Idiopathic Parkinson's disease diagnosed by a neurologist physician according to the CBCL
• Stage II and / or III, according to the Hoehn and Yahr scale
• Individuals who do not present with dementia verified by the Addenbrooke's Cognitive Examina-
tion Revised (ACE-R) scale
• Ability to wander and stand independently and safely.

Sample size (planned): 30

Sample size (actual): NR

Interventions Isokinetic training vs. standard exercise

Outcomes Muscle performance, functional capacity, neurodegeneration

Notes Study start: 206

Study completion: NR
Recruitment status: completed, results not posted

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RBR-3z39v3
Methods Randomized controlled trial

Participants Inclusion criteria:

• Individuals with Parkinson's disease

• Age: between 60 and 80 years old
• Members of an extension project
• Classified in stages I and II according to the Hoehn and Yahr Scale
• Without cognitive alterations
• Medical release for physical activity

Sample size (planned): 30

Sample size (actual): NR

Interventions Pilates vs. functional training

Outcomes Gait performance determined by Kinematic gait analysis, American Alliance for Health, Physical Ed-
ucation and Recreation and Dance (AAHPERD score)

Notes Study start: 2019

Study completion: NR
Recruitment status: recruiting

RBR-4m3k2c
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: over 60 years

• Gender: both sexes
• Diagnosed with major depression
• Alzheimer's disease
• Parkinson's disease

Sample size (planned): 180

Sample size (actual): NR

Interventions Physical training & exercise vs. no physical exercise

Outcomes Depressive symptoms (geriatric depression scale), overall cognitive state performance (MMSE), UP-
DRS

Notes Study start: 2014

Study completion: 2019
Recruitment status: recruiting

RBR-6rngmb
Methods Randomized controlled trial

Participants Inclusion criteria:

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RBR-6rngmb (Continued)
• Participants with clinical diagnosis of Parkinson's disease (International Classification of Diseases
(ICD) 10: G20)
• Both sexes
• Age range between 50 and 75 years
• Signature of the "TCLE"
• Have performed a physiotherapeutic review that freed the individual for therapy

Sample size (planned): 20

Sample size (actual): NR

Interventions Game therapy through virtual reality vs. conventional physiotherapy

Outcomes BBS, baropodometry

Notes Study start: 2019

Study completion: NR
Recruitment status: recruiting

RBR-7xfkpx
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of Parkinson's disease obtained by a neurologist

• Presenting with gait blocking symptom, with scores greater than or equal to 4 by the New Freezing
of Gait Questionnaire scale
• Stages 3 or 4 of the disease by the Hoehn and Yahr modified scale
• Score equal to or greater than 23 in the MMSE
• Not presenting neurological or physical dysfunctions

Sample size (planned): 30

Sample size (actual): NR

Interventions Postural pertubation training (moving platform) vs. strength training

Outcomes Reactive postural response, dynamic & global balance, mobility (TUG), freezing, motor status (UP-
DRS II, III), events of daily life, fear of falls, anxiety (HADS)

Notes Study start: 2018

Study completion: 2019
Recruitment status: recruiting

Rosenfeldt 2021
Methods Randomized controlled trial

Participants Inclusion criteria

• Clinical diagnosis of idiopathic PD

• Age: between 30 and 75 years
• Not currently engaged in formal exercise intervention or clinical study
• Hoehn and Yahr stage 2 to 3 in an on-medication state
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Rosenfeldt 2021 (Continued)

Sample size (planned): NR
Sample size (actual): 50

Interventions Forced exercise on a stationary cycle that was controlled by a motor, to augment voluntary cycling
rate by 35% vs. voluntary exercise on a stationary cycle without motor assistance

Outcomes MDS-UPDRS-M, Trail Making Test, number of participants with increased motor cortex and thala-
mus connectivity (using functional magnetic resonance imaging)

Notes Study start: 2012

Study completion: 2018
Recruitment status: completed

Shen 2014
Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of idiopathic PD according to the United Kingdom PD Society Brain Bank Criteria
• Be stable on anti-Parkinsonian medications
• Be able to walk independently for 10 m
• Be able to follow instructions—that is, MMSE score > 23.19
• No other neurological conditions, uncompensated cardiovascular disease, visual disturbance, or
recent musculoskeletal disorders in the back or lower limbs that would interfere with balance and
locomotion

Sample size (planned): NR

Sample size (actual): 51

Interventions Balance and gait training vs. active control

Outcomes Self-perceived balance confidence level, measured by the validated Activities-Specific Balance
Confidence (ABC) Scale; limit of stability (LOS) test, single-leg-stance (SLS) test

Notes Study start: NR

Study completion: NR
Recruitment status: completed

Stozek 2017
Methods Randomized controlled trial

Participants Inclusion criteria:

• PD patients
• HY stage: 1.5 to 3.0

Sample size (planned): NR

Sample size (actual): 30

Interventions Dance vs. Nordic walking vs. passive control

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Stozek 2017 (Continued)

Outcomes UPDRS, Functional Reach Test, BBS, Retropulsion test (Pastor), TUG, 10-meter walk test, timed 360°
turn, Physical Performance Test

Notes Study start: NR

Study completion: NR
Recruitment status: NR

Swarnakar 2019
Methods Randomized controlled trial

Participants Inclusion criteria:

• Individuals with newly diagnosed Parkinson’s disease

• Stable dose of PD medications
• Hoehn and Yahr stage ≤ 2

Sample size (planned): NR

Sample size (actual): 22

Interventions Strengthening, stretching, aerobic, agility, trunk exercises vs. stretching exercise

Outcomes UPDRS I-VI

Notes Study start: NR

Study completion: NR
Recruitment status: NR

TCTR20180111003
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 85 years old

• Gender: both
• Diagnosed idiopathic Parkinson's Disease according to the United Kingdom Brain Bank Criteria
with Hoehn and Yahr stages 1 to 3
• Stable on anti-PD medications
• Could walk 10 m with or without any walking assist

Sample size (planned): 40

Sample size (actual): NR

Interventions Square stepping exercise group vs. trunk and upper limb training

Outcomes Cortical excitability, balance (Mini-BESTest), cognition (MoCA, Trail Making Test, Digit Span Task),
quality of life (PDQ-39)

Notes Study start: 2018

Study completion: 2019
Recruitment status: recruiting

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TCTR20180530004
Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 20 to 85 years old

• Gender: both
• Clinical diagnosis of idiopathic Parkinson's disease by a neurologist
• Hoehn and Yahr stage 1 to 3
• Independent walking
• No cognitive impairment

Sample size (planned): 60

Sample size (actual): NR

Interventions Multicomponent exercise vs. dual-task training vs. control exercise

Outcomes Quantitative electroencephalogram (EEG), neuropsychological tests, gait performance, disease

severity and clinical characteristics (UPDRS), quality of life (PDQ-8)

Notes Study start: 2018

Study completion: 2019
Recruitment status: not yet recruiting

Wroblewska
́ 2019
Methods Randomized controlled trial*

Participants Inclusion criteria:

• Outpatients with PD who suffered from freezing of gait episodes during the "on"-state
• HY 2 to 3
• Stable pharmacotherapy
• Sufficient general health condition for the training intervention
• No previous experience with Nordic walking

Sample size (planned): NR

Sample size (actual): 40

Interventions Nordic walking vs. no intervention

Outcomes FOG-Q, TUG, provocative test for freezing and motor blocks

Notes Study start: NR

Study completion: NR
Recruitment status: completed

*Please note that it was unclear whether an appropriate method of randomization was applied.

ADL: activities of daily living; BBS: Berg Balance Scale; BDI: Beck Depression Inventory; BMI: body mass indexBESTest: Balance Evaluation
Systems Test; EQ-5D: EuroQoL 5 Dimensions; FES: Falls Efficacy Scale; FOG-Q: Freezing of Gait Questionnaire; HADS: Hospital Anxiety
and Depression Scale; HY: Hoehn and Yahr scale; LSVT BIG: Lee Silverman Voice training BIG; MDS-UPDRS-M: Movement Disorder
Society Unified Parkinson Disease Rating Scale/Motor Score; MHY: Modified Hoehn and Yahr scale; Mini-BESTest: Mini-Balance Evaluation

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Systems Test; MMSE: Mini Mental State Examination; MoCA: Montreal Cognitive Assessment; N-FOG-Q: New Freezing of Gait Questionnaire;
PDQ-39: Parkinson's Disease Questionnaire 39; PDQ-8: Parkinson's Disease Questionnaire 8; PDQ-L: Parkinson's disease quality of life;
SAFEx: Sensory Attention Focused Exercise; SF-36: Short-Form Health Survey-36 item questionnaire; 6-MIN-W: 6-minute walk test; TUG:
Timed up and go; UPDRS-M: Unified Parkinson's Disease Rating Scale/Motor Score

Characteristics of ongoing studies [ordered by study ID]

ACTRN12617001057370
Study name The effect of a physiotherapy exercise program with a self-management approach versus usual
care on physical activity in people with mild-moderate Parkinson’s disease: a randomised con-
trolled trial

Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of idiopathic PD confirmed by a neurologist

• Modified Hoehn and Yahr stage 1 to 3
• Living in the community
• Able to attend assessment and treatment sessions
• Montreal Cognitive Assessment Scale (MoCA) score of > 23/30
• Provide consent
• Minimum age: 18 years
• Maximum age: no limit
• Gender: both males and females

Sample size (planned): 92

Sample size (actual): 44

Interventions Group exercise, chronic disease self-management, usual care vs. usual care

Outcomes Physical activity, step length, gait speed and endurance, PDQ-39, outcome expectations, self-effica-
cy

Starting date Study start: 2017

Study completion: 2021 (anticipated)

Recruitment status: recruiting

Contact information [email protected]

Notes anzctr.org.au/ACTRN12617001057370.aspx

ACTRN12620001135909
Study name A randomised trial of exercise therapy for Parkinson’s disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Parkinson’s disease
• Modified Hoehn & Yahr stage 3 or less
• Age 30 to 75 years

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ACTRN12620001135909 (Continued)
• Sedentary lifestyle (low levels of aerobic physical activity, defined by the American College of
Sports Medicine recommendation for older adults as any level below recommended weekly
amount of aerobic exercise)
• Receiving a stable dopaminergic medication dose

Sample size (planned): 16

Sample size (actual): NR

Interventions Strength training and aerobic exercises vs. stretching, flexibility or relaxation exercises

Outcomes MDS-UPDRS, 6-meter walk test, 6-minute walk test, PDQ-39, reported falls

Starting date Study start: 2020

Study completion: 2021

Recruitment status: recruiting

Contact information [email protected]

Notes anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620001135909

Bevilacqua 2020
Study name Rehabilitation of older people with Parkinson’s disease: an innovative protocol for RCT study to
evaluate the potential of robotic-based technologies

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 65 and older

• Hoehn and Yahr scale: 1 to 3
• "FAC ≤ 2"
• Ranking scale score ≤ 3
• Stability of drug treatment for at least 1 month
• Geriatric Depression Scale 5-items: negative

Sample size (planned): 195

Sample size (actual): NR

Interventions Virtual reality games vs. robotic treadmill vs. traditional physical rehabilitation therapy

Outcomes Tinetti performance-oriented mobility assessment (POMA), walking speed through instrumental
Gait Analysis, Falls Efficacy Scale - International short form (FES-I Short form)

Starting date Study start: 2019

Study completion: 2022

Recruitment status: recruiting

Contact information [email protected]

Notes bmcneurol.biomedcentral.com/articles/10.1186/s12883-020-01759-4

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ChiCTR1900022621
Study name The effect of rehabilitation on physical function in patients with Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: < 75 years

• People diagnosed with Parkinson's Syndrome in accordance with the 2015 International Diagnos-
tic Association (MDS) Diagnostic Criteria and the Chinese Parkinson's Disease Diagnostic Criteria

Sample size (planned): 80

Sample size (actual): NR

Interventions Rehabilitation vs. usual care

Outcomes Motor function

Starting date Study start: 2019

Study completion: 2021

Recruitment status: not yet recruiting

Contact information [email protected]

[email protected]

Notes www.chictr.org.cn/showproj.aspx?proj=34905

ChiCTR2000029025
Study name The effect of LSVT BIG treatment on motor and nonmontor symtoms [sic] in patients with Parkin-
son's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 30 to 85 years old

• Diagnosed with primary Parkinson's disease: Hoehn and Yahr stages 1 to 3
• Stable anti-parkinsonism medication at 1 month before study initiation and at the end of fol-
low-up

Sample size (planned): 30

Sample size (actual): NR

Interventions LSVT BIG treatment vs. non-rehabilitation

Outcomes UPDRS-M, PDQ-8, Non-Motor Symptoms Scale (NMSS), TUG, Box and Block-Test (BBT), BDI-II,

Starting date Study start: 2020

Study completion: NR

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ChiCTR2000029025 (Continued)
Recruitment status: recruiting

Contact information [email protected]

Notes www.chictr.org.cn/showproj.aspx?proj=44830

ChiCTR2000029135
Study name Effects of innovative tai chi on motor symptoms in patients with mild to moderate Parkinson's dis-
ease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 70 years
• Primary Parkinson's disease diagnostic standards that meet the 2016 Chinese PD Diagnostic Stan-
dards
• Meet the improved Hoehn and Yahr clinical grading standard grades 1 to 2.5
• Those who take the base dose of medopa have a stable effect

Sample size (planned): 40

Sample size (actual): NR

Interventions Innovative tai chi exercise vs. stretching training

Outcomes UPDRS-M, BBS, TUG, functional reach test, PDQ-39, height, weight, pressure, heart rate, stability
limit

Starting date Study start: 2020

Study completion: NR

Recruitment status: data analysis completed

Contact information [email protected]

Notes www.chictr.org.cn/showproj.aspx?proj=48394

ChiCTR2000036306
Study name A prospective cohort study of exercise rehabilitation in the treatment of Parkinson's disease and its
mechanism

Methods Randomized controlled trial

Participants Inclusion criteria:

• People with primary Parkinson's disease who meet the clinical diagnostic criteria of MDS
• People with early Parkinson's disease with HY stage 1 to 2.5
• Aged 50 to 70 years old
• Primary school grade 6 and above with educational attainment
• Sedentary lifestyle, no regular or regular exercise history in the past 2 years

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ChiCTR2000036306 (Continued)
• The drug treatment regimen remains stable for at least 3 months, and the treatment regimen
remains unchanged during the follow-up period
• Can walk or live independently
• MMSE score is greater than or equal to 24

Sample size (planned): 90

Sample size (actual): NR

Interventions Tai chi training vs. brisk walking training vs. no intervention

Outcomes UPDRS, TUG, BBS, Parkinson's Disease Cognitive Rating Scale (PD-CRS), plasma metabonomics,
brain magnetic resonance imaging

Starting date Study start: 2020

Study completion: 2023

Recruitment status: recruiting

Contact information [email protected]

Notes www.chictr.org.cn/showproj.aspx?proj=58856

ChiCTR2000037178
Study name A prospective clinical study of innovative Wuqinxi exercise intervention in delaying the occurrence
of freezing of gait in Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• People who were diagnosed with PD according to the 2015 international MDS PD criteria
• No history of FOG (N-FOG-Q score = 0)
• PD patients at high risk of developing FOG (the risk value was accounted according to our estab-
lished predicting model for FOG)
• Having received a stable anti PD medication therapy for at least 2 months
• Aged ranging from 45 to 85 years old.

Sample size (planned): 100

Sample size (actual): NR

Interventions Innovative Wuqinxi vs. low intensity stretching exercise

Outcomes Incidence of freezing of gait, MDS-UPDRS-M, Frontal Assessment Battery (FAB), Clinical Global Im-
pression Scale (CGI-Skala), PDQ-39, Bold signal of activated brain areas, Apathy scale score, Hamil-
ton Anxiety Rating Scale (HAM-A), Hamilton Depression Scale

Starting date Study start: 2020

Study completion: NR

Recruitment status: recruiting

Contact information [email protected]

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ChiCTR2000037178 (Continued)

Notes www.chictr.org.cn/showproj.aspx?proj=60001

ChiCTR2000037305
Study name A randomized controlled study of multifactorial interventions to prevent early cognitive decline in
elderly people

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 60 years old or older

• One or more of the following diseases: family history of dementia, diabetes, hypertension, hyper-
lipidemia, ischemic heart disease, atrial fibrillation, smoking, drinking, obesity, weight loss, after
65-year-old history of Parkinson's disease, cerebrovascular disease, depression, chronic kidney
disease (CKD), low level of education, the lack of physical and mental activity and low social sup-
port, etc.
• Existing mild cognitive impairment (namely MMSE score: illiteracy 18 to 27)

Sample size (planned): 290

Sample size (actual): NR

Interventions Comprehensive intervention vs. health education

Outcomes MMSE, Mini Nutritional Assessment, Cooper Healthy Lifestyle Questionnaire, Pittsburgh sleep qual-
ity index, atherosclerotic cardiovascular disease (ASCVD) 10-year risk forecasting model, Patient
Health Questionnaire-9, 6-MIN-W

Starting date Study start: 2020

Study completion: NR

Recruitment status: recruiting

Contact information [email protected]

Notes www.chictr.org.cn/showprojen.aspx?proj=60460

ChiCTR2000037384
Study name A clinical study of innovative Wuqinxi exercise therapy delaying the occurrence of motor complica-
tions of Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 75 years old

• People who has been clinically diagnosed with Parkinson's disease according to the 2015 inter-
national MDS PD criteria
• People at HY grades 1 and 2
• Have been treated with stable anti-Parkinson medications
• Could walk independently

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ChiCTR2000037384 (Continued)
Sample size (planned): 60

Sample size (actual): NR

Interventions Innovative “Wuqinxi” exercise therapy in combination with routine anti-PD medication treatment
vs. routine exercise in combination with routine anti-PD medication treatment

Outcomes The time point of motor complication (wearing-off phenomenon), MDS-UPDRS-M, Non-Motor
Symptoms Questionnaire (PD-NMSQ30), gait parameters, activated brain areas and network,
PDQ-8, Clinical Global Impressions Scale (CGI)

Starting date Study start: 2020

Study completion: NR

Recruitment status: recruiting

Contact information [email protected]

Notes www.chictr.org.cn/showproj.aspx?proj=60280

CTRI/2018/05/014241
Study name A clinical trial to study the effect of exercises in early stage Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: From 18 to 99 years

• Gender: both male and female
• Newly diagnosed Parkinson's disease, Hoehn and Yahr stage 1 or 2
• On stable pharmacological regimes during the study and for 6 months before entry into the study

Sample size (planned): 30

Sample size (actual): 40

Interventions Active strengthening exercises vs. passive strengthening exercises

Outcomes UPDRS I, II, III, VI, quality of life (PDQ-39)

Starting date Study start: 2018

Study completion: 2019

Recruitment status: completed, no results posted

Contact information [email protected]

Notes www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=23331

CTRI/2019/06/019618
Study name Benefits of yoga on daily activities and quality of life for individuals with Parkinson's disease

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CTRI/2019/06/019618 (Continued)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Hoehn and Yahr scale: 1 to 3

• Able to follow simple commands
• Pull test < 3

Sample size (planned): 34

Sample size (actual): NR

Interventions Yoga vs. standard physical therapy

Outcomes UPDRS, Adenbrook Cognitive Examination - Revised, BESTest, PDQ-39, BDI

Starting date Study start: 2019

Study completion: 2022

Recruitment status: not yet recruiting

Contact information [email protected]

Notes trialsearch.who.int/?TrialID=CTRI/2019/06/019618

CTRI/2020/06/025794
Study name Consequence of Pilates on imbalance, movability and core stability in patients with Parkinson dis-
ease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 80 years old

• People with Parkinson's disease
• Balance instability
• Core instability
• Decreased mobility
• Exertion

Sample size (planned): 17

Sample size (actual): NR

Interventions Pilates vs. simple walking

Outcomes Mini-BESTest Scale, Lindop Parkinson Rating Scale

Starting date Study start: 2020

Study completion: NR

Recruitment status: not yet recruiting

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CTRI/2020/06/025794 (Continued)

Contact information [email protected]

Notes www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=37645

DRKS00018841
Study name Therapeutischer Einfluss von Laufbandtherapie vs. Physiotherapie ohne Laufband auf das Dual-
Task-Verhalten während des Gehens bei Parkinsonpatienten

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 20 to 80 years old

• Idiopathic Parkinson's disease
• Hoehn and Yahr Stages 1 to 3
• Free walking on a treadmill for a period of 25 minutes
• Must be cognitively able to perform the required tasks

Sample size (planned): 100

Sample size (actual): 100

Interventions Treadmill therapy vs. physiotherapy

Outcomes Gait analysis, MDS-UPDRS-M, BBS

Starting date Study start: 2019

Study completion: 2021

Recruitment status: completed

Contact information W.Jost at parkinson-klinik.de

Notes www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018841

Gooßes 2020
Study name Feasibility of music-assisted treadmill training in Parkinson's disease patients with and without
deep brain stimulation: insights from an ongoing pilot randomized controlled trial

Methods Randomized controlled trial

Participants Inclusion criteria:

• Clinical diagnosis of idiopathic PD (according to UK Brain Bank Criteria) and confirmed by a neu-
rologist
• Non-demented (score ≥ 17 in the MoCA)
• No clinically relevant depression (score ≤ 10 on the Geriatric Depression Scale—GDS), or other
concurrent neurologic or psychiatric illness
• No orthopedic or cardiac contraindication to performing the training

Sample size (planned): NR

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Sample size (actual): 32

Interventions Music-assisted treadmill training (MATT) vs. ergometer training

Outcomes Adverse events (e.g. abortions of single training sessions, cardiovascular incidences, falls or almost
falls during/after MATT; extreme fatigue that caused the cancellation of other training sessions af-
ter the MATT session or ergometer training); participants’ subjective training perception, including
mood, motivation, exhaustion, and fun (four-point Likert scale, e.g. “very happy,” “rather happy,”
“rather unhappy,” and “very unhappy”; “not exhausted at all,” “hardly exhausted,” “little exhaust-
ed,” and “very exhausted”)

Starting date Study start: 2019

Study completion: NR

Recruitment status: NR

Contact information [email protected]

Notes www.frontiersin.org/articles/10.3389/fneur.2020.00790/full#h3

Hackney 2020
Study name Rationale and design of the PAIRED Trial: partnered dance aerobic exercise as a neuroprotective,
motor, and cognitive intervention in Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 years and older

• Diagnosis of Parkinson's disease
• Hoehn and Yahr stage 1 to 3
• ≥1 on UPDRS-IV item 4.3
• PD diagnosis based on established criteria and determined by a board-certified neurologist with
training in movement disorders
• At least 3 of the cardinal signs (rigidity, bradykinesia, tremor, postural instability)
• Show clear symptomatic benefit from antiparkinsonian medications

Sample size (planned): 102

Sample size (actual): NR

Interventions Partnered dance aerobic exercise vs. walking aerobic exercise

Outcomes BDI II, the Composite Physical Function index, Physical Activity Scale for the Elderly, PDQ-39, SF-12,
five-item Satisfaction with Life Scale, Multidimensional Scale of Perceived Social Support (MSPSS),
MDS-UPDRS parts I–IV, spatial function (reverse Corsi blocks), Brooks spatial memory, Benton's
judgment of line orientation, executive function (Trail Making Test, Tower of London), 6-MIN-W,
spatiotemporal parameters (6-meter computerized GAITRite walkway), Mini-BESTest, dynamic gait
index, TUG, four-square step test, VO2 max and initial fitness level (Young Men's Christian Associ-
ation's [YMCA] submaximal test), Neuromelanin-sensitive MRI (NM-MRI), T2*-weighted blood-oxy-
gen-level-dependent (BOLD), Magnetization Prepared Rapid Gradient-Echo (MPRAGE)

Starting date Study start: NR

Study completion: NR
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Hackney 2020 (Continued)

Recruitment status: NR

Contact information [email protected]

Notes www.frontiersin.org/articles/10.3389/fneur.2020.00943/full#h13

Li 2021
Study name Improvement of freezing of gait in patients with Parkinson’s disease by music exercise therapy: a
study protocol for a randomized controlled trial

Methods Randomized controlled trial

Participants Inclusion criteria:

• Complying with the diagnostic criteria

• Aged 40 to 85 years
• The participant's vital signs are stable, conscious and can cooperate well with the evaluation-level
treatment
• Slow onset
• Static tremor, stiffness and motor decline in at least two of the three items
• Levodopa treatment is effective, and symptoms fluctuate and motor disorders occur after many
years of application

Sample size (planned): 60

Sample size (actual): NR

Interventions Stretch training combined with music and exercise therapy vs. routine rehabilitation therapy

Outcomes Parkinson Comprehensive Score Scale, 6-MIN-W, ADL

Starting date Study start: 2019

Study completion: 2021

Recruitment status: not yet recruiting

Contact information [email protected]

Notes www.chictr.org.cn/showproj.aspx?proj=43563

Lima 2020
Study name Effects of a power strength training using elastic resistance exercises on the motor and non-mo-
tor symptoms in patients with Parkinson’s disease H&Y 1–3: study protocol for a randomised con-
trolled trial (PARK-BAND Study)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of Parkinson’s disease according to the UK PD Brain Bank Diagnostic Criteria

• Stages 1 to 3 according to the modified Hoehn and Yarh scale

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• Stable anti-parkinsonian medication regime for at least 4 weeks before the intervention
• Independent in basic daily living activities according to Schwab and England score greater or
equal to 80%
• Age of 40 years or more

Sample size (planned): 50

Sample size (actual): NR

Interventions Power training with elastic bands and resistance tubes vs. health education

Outcomes UPDRS, Short Physical Performance Battery (SPPB), PDQ-39, Pittsburgh Sleep Quality Index (IQSP),
Epworth Sleepiness Scale (ESE), Parkinson's Disease Sleep Rating Scale (PDSS), REM sleep disor-
ders screening questionnaire - Brazilian version (QRDCSR-BR), sleep latency, total sleep time, fre-
quency of awakening, sit and stand test five times (TSL5x), 4-meter walk test, Fall Effectiveness
Scale - International (FES-I), assessing knee extensor and flexor strength, number of falls, new
freezing of gait questionnaire (N-FOG-Q)

Starting date Study start: 2020

Study completion: 2022

Recruitment status: not yet recruiting

Contact information

Notes ensaiosclinicos.gov.br/rg/RBR-5w2sqt

Mayoral-Moreno 2021
Study name Falls prevention and quality of life improvement by square stepping exercise in people with Parkin-
son’s disease: project report

Methods Randomized controlled trial

Participants Inclusion criteria:

• ≥18 years old

• Diagnosed with Parkinson's disease, in stages 1 to 3, according to HY scale
• No pathology that contraindicates the physical exercise program
• The Physical Activity Fitness Questionnaire (PAR-Q) will be administered to find out if they are
living with diseases that prevent physical load
• Not be suffering from moderate and severe cognitive impairment, determined by Mini Mental
State Examination scores

Sample size (planned): 60

Sample size (actual): NR

Interventions Square Stepping Exercise training program vs. usual care

Outcomes Applicability (percentage of participants who are able to perform the set exercise), safety (doc-
umentation of difficulties/injuries), balance (L-Test, TUG), number of falls, fear of falling (FES-I),
physical condition (2-minute walking test), lower extremity strength (stand up and sit on a chair
for 30 s), speed (Brisk Walking Test), Functional Reach Test, Short Physical Performance Battery
(SPPB), International Fitness Scale (International Fitness Scale-IFIS), Brief International Cognitive

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Mayoral-Moreno 2021 (Continued)

Assessment (BICAMS), PDQ-8, BDI-II, Perceived Functional Social Support (Duke-UNC), Anticipatory
Cognitions Questionnaire (ACQ)

Starting date Study start: NR

Study completion: NR

Recruitment status: NR

Contact information [email protected]

Notes www.mdpi.com/2075-4426/11/5/361

NCT02457832
Study name Motor training in PD

Methods Randomized controlled trial

Participants Inclusion Criteria:

• Age: 40 to 70 years
• Able to walk with or without an assistive device 10 feet
• Best corrected/aided acuity better than 20/70 in the better eye
• Absence of dementia or vascular cognitive impairment
• Absence of primary memory deficits

Samples size (planned): 99

Sample size (actual): NR

Interventions Internally guided exercise vs. externally guided exercise vs. behavioural control vs. normal control

Outcomes Percent signal change, connectivity strength

Starting date Study start: 2014

Study completion: 2023
Recruitment status: active, not recruiting

Contact information Madeleine E. Hackney, Atlanta VA Medical and Rehab Center, Decatur

Notes clinicaltrials.gov/ct2/show/record/NCT02457832

NCT03244813
Study name Evaluation of the impact of a personalized program of adapted physical activates [sic] in patients
with Parkinson disease (ACTIPARK)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 80 years old

• The participant has experienced symptoms of Parkinson's disease for at least 5 years and is in a
stable state (no medical event or change of treatment in at least 1 month)

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NCT03244813 (Continued)
• The functional impact and duration of fluctuations is ≥ 3 (MDS UPDRS)
• The participant can walk autonomously, including using a technical aid

Sample size (planned): NR

Sample size (actual) :19

Interventions Adapted physical activity vs. usual care

Outcomes Weekly activity, quality of life (PDQ-39), risk of fall (TUG, Tinneti Falls Efficacy Scale, 0 to 10 scale),
endurance (6-minute walk test), activity of care giver, burden of care giver, grip strength (pinch
test), patient dependence (activities of daily living), dementia

Starting date Study start: 2018

Study completion: 2019
Recruitment status: completed, no results posted

Contact information

Notes clinicaltrials.gov/ct2/show/record/NCT03244813

NCT03343574
Study name Cardiovascular effects of exercise in patients with Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 90 years old

• Gender: both
• Clinical diagnosis of Parkinson's Disease
• Between stages 2 and 4 of Hoehn and Yahr classification of Parkinson's disease

Sample size (planned): 300

Sample size (actual): NR

Interventions Abdominal strengthening exercise vs. usual care

Outcomes Blood pressure, heart rate, composite autonomic severity score, Middle Cerebral Artery flow veloc-
ity, oxy-/deoxy-haemoglobin ratio, Composite Autonomic Symptom Scale (COMPASS), orthostatic
hypotension, dizziness

Starting date Study start: 2017

Study completion: 2020

Recruitment status: active, not recruiting

Contact information Mandar Jog, Western University, London

Notes clinicaltrials.gov/ct2/show/record/NCT03343574

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NCT03560089
Study name Serious games rehabilitation programme to treat gait and balance disorders in PD patients
(PARKGAME-II)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 18 to 75 years old

• Gender: both
• Parkinson's disease
• Gait and balance disorders resistant to dopaminergic medication

Sample size (planned): 50

Sample size (actual): NR

Interventions Serious game vs. placebo serious game

Outcomes TUG, step length, step velocity, MDS-UPDRS, gait, PD-QoL, cognitive function (Montreal Cognitive
Assessment)

Starting date Study start: 2018

Study completion: 2021

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT03560089

NCT03563807
Study name Golf instruction versus tai chi for people with Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: > 18
• Gender: both male and female
• A diagnosis of Parkinson's disease by a movement disorders specialist, HY stage 2 to 3 in the "on"
state treated with Parkinson's disease medications
• Participants must be capable of providing informed consent and complying with trial procedures
including transportation to and from classes
• Participants who are engaged in physical therapy or other exercise programs must be at a stable
regimen for 60 days prior to the start of the study and must be willing to maintain their current
regimen for the duration of the study

Sample size (planned): 35

Sample size (actual): NR

Interventions Golf vs. tai chi

Outcomes Tolerability, safety, balance (Mini-BESTest), activity-specific balance confidence

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NCT03563807 (Continued)

Starting date Study start: 2018

Study completion: 2020

Recruitment status: completed, no results posted

Contact information

Notes clinicaltrials.gov/ct2/show/record/NCT03563807

NCT03582371
Study name Aqua stand-up paddle balance effect in Parkinson's disease (AquaSUP PARK)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 18 to 80 years old

• Idiopathic Parkinson's disease according to the criteria of the UK Parkinson's Disease Society
Brain Bank Clinical Diagnostic
• Presence of balance disorder: Hoehn and Yahr stage 2.5 to 4
• Motor level stable, without change of treatment in last 6 weeks
• Participants affiliated to a social security scheme or beneficiary of an equivalent scheme

Sample size (planned): 96

Sample size (actual): NR

Interventions Stand-up paddle rehabilitation vs. physiotherapy rehabilitation

Outcomes Balance (BBS), MDS-UPDRS-M, cognitive function, TUG, functional capacity, 2-minute walking test,
PDQ-39, mental health (Beck Depression Inventory)

Starting date Study start: 2018

Study completion: 2022

Recruitment status: recruiting

Contact information FLABEAU Olivier, Centre Hospitalier de la côte Basque

Notes clinicaltrials.gov/ct2/show/record/NCT03582371

NCT03711955
Study name Comparing the effects of instability resistance training versus aerobic training on cognitive and
motor improvements found in Parkinson's disease participants

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 80 years old

• Idiopathic Parkinson's disease
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NCT03711955 (Continued)
• On stable medication (dopaminergic medication)
• Hoehn and Yahr stage between 2 and 3
• No other neurological disorder
• No significant arthritis, cardiovascular disease, and cognitive impairment by Mini Mental State
Examination (score < 23)

Sample size (planned): 30

Sample size (actual): NR

Interventions Aerobic training vs. instability training

Outcomes Executive function (MoCA), gait variability (TUG), motor/non-motor symptoms (UPDRS)

Starting date Study start: 2019

Study completion: 2020

Recruitment status: recruiting

Contact information Alisha Mistry, Movement Disorder Research and Rehabilitation Center

Notes clinicaltrials.gov/ct2/show/record/NCT03711955

NCT03751371
Study name Robotic walking device to improve mobility in Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of idiopathic Parkinson's disease

• Age: from 50 to 80 years
• Able to ambulate without assistance (Hoehn and Yahr stages 1 to 3)
• On stable doses of Parkinson's medications for at least 4 weeks prior to the study

Sample size (planned): 46

Sample size (actual): NR

Interventions Training with Honda Walking Assist (HWA) device vs. usual care

Outcomes Gait velocity, 6-minute walk test, stride length, double support time, swing time, perceived ease of
walking, self-efficacy, number of steps, time spent walking, number of falls, adverse events, freez-
ing of gait

Starting date Study start: 2019

Study completion: 2021 (estimated)

Contact information Anne Kloos, Ohio State University

Notes clinicaltrials.gov/ct2/show/record/NCT03751371

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NCT03833349
Study name The impact of three distinct exercise types on fatigue, anxiety, and depression in Parkinson's dis-
ease (PDExercise)

Methods Randomized controlled trial

Participants Inclusion criteria:

• People diagnosed with idiopathic Parkinson's disease

• Age: 18 to 75 years
• Hoehn and Yahr stage less than or equal to 3
• Mini Mental State Exam (MMSE) score of over 23 at screening
• If participants are taking any medications for depression, fatigue, or anxiety, regimen must be
stable for 8 weeks prior to baseline visit
• Participants willing and able to give informed consent

Sample size (planned): 24

Sample size (actual): NR

Interventions Spinning class vs. yoga class vs. dance class

Outcomes Fatigue (FSS), anxiety (Zung's self-reported anxiety scale), depressive symptoms (Beck Depression
Inventory II)

Starting date Study start: 2019

Study completion: 2019

Recruitment status: completed, no results posted

Contact information Mary Feldman

Notes clinicaltrials.gov/ct2/show/study/NCT03833349

NCT03860649
Study name Effects of different physical therapies and dance in people with Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: over 40 years

• Gender: both sexes
• Clinical diagnosis of idiopathic Parkinson's disease, staging between 1 and 4 in Hoehn and Yahr
scale

Sample size (planned): NR

Sample size (actual): 100

Interventions Nordic walking vs. jogging vs. dance vs. Pilates training

Outcomes TUG, Locomotor Rehabilitation Index (LRI), walking speed (self-selected, optimal), quality of life
(PDQ-39), cognitive function (MoCA, MMSE, GDS), FOG-Q, UPDRS

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NCT03860649 (Continued)

Starting date Study start: 2018

Study completion: 2022

Recruitment status: active, not recruiting

Contact information Leonardo A. Peyré-Tartaruga, Federal University of Rio Grande do Sul

Notes clinicaltrials.gov/ct2/show/record/NCT03860649

NCT03882879
Study name Kick out Parkinson's Disease 2

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 30 to 90 years old

• Gender: both
• Diagnosed with Parkinson's disease by a treating healthcare provider

Sample size (planned): NR

Sample size (actual): 52

Interventions Karate classes vs. usual exercise routine then karate classes

Outcomes Mobility (TUG), well-being (Patient Global Impression of Change Scale), depression and anxiety,
quality of life (PDQ-39), cognitive abilities, "Instrumented" TUG (i-TUG), "Instrumented-WALK (i-
WALK)", "Instrumented-SWAY (i-SWAY)"

Starting date Study start: 2019

Study completion: 2020

Recruitment status: completed

Contact information Jori Fleisher, Rush University Medical Center

Notes clinicaltrials.gov/ct2/show/record/NCT03882879

NCT03960931
Study name Interest of hydrophysiotherapy care in Parkinson disease's motor and non-motor symptoms
(THERMAPARK)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 18 to 75 years old

• Suffering from Parkinson's disease (stage 2 or 3 of Hoehn and Yahr)
• Motor fluctuation lower than 25% of awaked time
• Dyskinesia lower than 25% of awake time (according to MDS-UPDRS scale)
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NCT03960931 (Continued)
• Stable pharmacological treatment during the 30 days before study
• Already benefiting from physiotherapy

Sample size (planned): 126

Sample size (actual): NR

Interventions Aquatic rehabilitation vs. land-based physical activities vs. conventional rehabilitation

Outcomes PDQ-39, anxiety (PAS), pain (visual analogue scale 0 to 10), TUG, walking distance and velocity, step
height/length/width

Starting date Study start: 2019

Study completion: 2021

Recruitment status: not yet recruiting

Contact information

Notes clinicaltrials.gov/ct2/show/record/NCT03960931

NCT03972969
Study name Highly challenging balance program to reduce fall rate in PD

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 89 years old

• Physician diagnosis of idiopathic Parkinson's disease
• At least 2 of the 3 cardinal signs of PD (resting tremor, rigidity, bradykinesia)
• Response to dopaminergic medication

Sample size (planned): 162

Sample size (actual): NR

Interventions Facility-based exercise vs. remote exercise vs. health education

Outcomes Falls

Starting date Study start: 2019

Study completion: 2023

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT03972969

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NCT03974529
Study name Intensive running exercise improves Parkinson's motor and non-motor symptoms

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 60 years old

• Participants with idiopathic Parkinson's disease
• Participants who are able to walk independently without walking aids for a distance of 30 meters

Sample size (planned): 30

Sample size (actual): NR

Interventions Intensive running vs. physiotherapy

Outcomes UPDRS, PDQ-39, endurance, gait, Mini-BESTest, mood

Starting date Study start: 2018

Study completion: 2020

Recruitment status: recruiting

Contact information Danny TM Chan, Chinese University of Hong Kong

Notes clinicaltrials.gov/ct2/show/record/NCT03974529

NCT03983785
Study name The effect of Pilates and elastic taping on balance and postural control in early Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Diagnosis of idiopathic Parkinson's disease

• Mini Mental Test Score ≥ 24
• Modified Hoehn and Yahr Score ≤ 2
• Ability to stand 1 minute independently
• Ability to walk 10 meters

Sample size (planned): 31

Sample size (actual): NR

Interventions Pilates vs. elastic taping vs. no intervention

Outcomes Balance, postural control

Starting date Study start: 2017

Study completion: 2020

Recruitment status: completed, no results posted

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NCT03983785 (Continued)

Contact information Evrim Goz, Dokuz Eylul University

Notes clinicaltrials.gov/ct2/show/record/NCT03983785

NCT04000360
Study name Pragmatic cyclical lower extremity exercise trial for Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Adults with a diagnosis of idiopathic Parkinson's disease by a physician or physician extender

• Hoehn and Yahr stage 1 to 3
• Demonstrate the ability to safely mount and dismount the Peloton stationary cycle

Sample size (planned): 250

Sample size (actual): NR

Interventions High-intensity aerobic exercise vs. usual care

Outcomes MDS-UPDRS-M, nine-hole peg test, processing speed

Starting date Study start: 2019

Study completion: 2024

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04000360

NCT04046276
Study name Intensity of aerobic training and neuroprotection in Parkinson's disease (AEROPROTECT)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: > 18 years old

• Diagnosis of Parkinson's disease according to the UKPDSBB criteria
• Previous MRI available, to further help distinguish idiopathic PD from atypical parkinsonism
Hoehn and Yahr stage 1 to 3 in 'off' state

Sample size (planned): 69

Sample size (actual): NR

Interventions Conventional therapy vs. medium-intensity aerobic exercise vs. high-intensity aerobic exercise

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NCT04046276 (Continued)

Outcomes MDS-UPDRS-M, mobility (2-minute walking test, 20-meter up and go test, Global Mobility Task
(GMT)), upper limb performance, aerobic capacity, MoCA, digit span task, trail making test

Starting date Study start: 2019

Study completion: 2021

Recruitment status: not yet recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04046276

NCT04063605
Study name The effect of clinical Pilates training on balance and postural control of people with Parkinson's
disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 45 to 70 years old

• Stage 2 to 3 of Modified Hoehn and Yahr Scale
• 26 or > 26 points on the Mini Mental test
• Having had Parkinson's disease at least 2 years

Sample size (planned): 38

Sample size (actual): 40

Interventions Clinical Pilates vs. classic physiotherapy

Outcomes One-leg stance test, tandem stance test, Functional reach test, Sit-to-stand test, TUG, BBS

Starting date Study start: 2019

Study completion: 2022

Recruitment status: completed

Contact information Beliz Belgen Kaygisiz, European University of Lefke

Notes clinicaltrials.gov/ct2/show/record/NCT04063605

NCT04122690
Study name Partnered dance aerobic exercise as a neuroprotective, motor and cognitive intervention in Parkin-
son's disease (PDAE in PD)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: older than 40 years

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NCT04122690 (Continued)
• Montreal Cognitive Assessment (MoCA) score > 17
• Able to walk with or without an assistive device at least 10 feet
• Best corrected/aided acuity better than 20/70 in the better eye
• Willingness to be randomized to either group
• HY stages 1 to 3
• Report 'off' times (reporting > 0 on item 4.3 of the UPDRS-IV)

Sample size (planned): 150

Sample size (actual): NR

Interventions Partnered dance aerobic exercise vs. walking aerobic exercise

Outcomes MDS-UPDRS-M, visuospatial working memory (Corsi blocks), endurance (6-minute walk test),
change in iron accumulation, cardiovascular output, spatial cognition, change in loss of neurome-
lanin, executive function, orientation, gait, attention, spatial imagery, Mini-BESTest, 4 square step
test, dynamic gait index, PDQ-39, self-reported daily activities, satisfaction, Multidimensional Scale
of Perceived Social Support (MSPSS)

Starting date Study start: 2020

Study completion: 2024

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04122690

NCT04135924
Study name Influence of trainning [sic] in Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 55 to 75 years old

• No cognitive impairment
• Mini Mental State Examination with scores above 23
• Clinical diagnosis of Parkinson's disease in grade 2 to 3 on the modified Hoehn and Yahr scale

Sample size (planned): 40

Sample size (actual): NR

Interventions Nordic walking plus respiratory training vs. Nordic walking vs. respiratory training

Outcomes Measurement of lipid peroxidation, respiratory function

Starting date Study start: 2019

Study completion: 2020

Recruitment status: recruiting

Contact information Rodrigo Santiago Barbosa Rocha, Universidade Metodista de Piracicaba

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NCT04135924 (Continued)

Notes clinicaltrials.gov/ct2/show/record/NCT04135924

NCT04194762
Study name PARK-FIT. Treadmill vs cycling in Parkinson's disease. Definition of the most effective model in gait
reeducation

Methods Randomized controlled trial

Participants Inclusion criteria:

• Participant is diagnosed with idiopathic Parkinson's disease according to criteria from the United
Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB)
• HY less than or equal to 2
• Stable drug treatment in the six weeks prior to the start of training and during the study

Sample size (planned): 48

Sample size (actual): 48

Interventions Treadmill training vs. cycling

Outcomes Step length, MDS-UPDRS-M, PDQ-39

Starting date Study start: 2019

Study completion: 2020

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04194762

NCT04215900
Study name High-Speed yoga and executive function

Methods Randomized controlled trial

Participants Inclusion criteria:

• Men and women between 50 and 85 years of age

• Diagnosis of Parkinson's Disease (Hoehn and Yahr scale 1 to 3)
• Ability to ambulate with or without an assistive device for at least 50 feet
• Ability to get up and down from the floor with minimal assistance
• No medical contraindication to participation in an exercise program including unstable or active
untreated major medical illness
• A score of 23 or above on the Montreal Cognitive Assessment
• Not currently participating in yoga more than one time per week

Sample size (planned): 90

Sample size (actual): NR

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NCT04215900 (Continued)

Interventions High-Speed multi-directional yoga vs. wait-list control

Outcomes MoCA, executive function (Wisconsin Card Sort task, Inhibition of Cognitive Inference, Visual Spa-
tial Ability and Task-switching), Stroop color word test, 6-MIN-W, body weight, fat-free mass, Mi-
ni-BESTest, TUG, PDQ-39, Reactive Balance Distance and Time, Modified Fall Efficacy Scale, UP-
DRS-M

Starting date Study start: 2020

Study completion: 2021

Recruitment status: suspended

Contact information Joseph Signorile, University of Miami

Notes clinicaltrials.gov/ct2/show/record/NCT04215900

NCT04379778
Study name Aerobic exercise and brain health in Parkinson's

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: ≥ 40 years
• Idiopathic Parkinson's disease diagnosis (within the previous five years)
• Participants in symptomatic therapy / not in therapy
• Participants who are not already taking medication are not expected to need medication within
6 months of inclusion (in case of drug startup, this is noted)
• Hoehn and Yahr ≤ 3
• Ability to transport oneself to and from exercise and testing

Sample size (planned): 70

Sample size (actual): NR

Interventions Aerobic exercise vs. standard care

Outcomes Effective transverse relaxation rate; quantitative susceptibility mapping (QSM MRI); Diffusional Kur-
tosis Imaging (DKI MRI); neuromelanin MRI change; volumetry MRI; blood markers; levodopa equiv-
alents; MDS-UPDRS; VO2max test; TUG; 6-MIN-W; Mini BESTest; Montreal Cognitive Assessment
(MoCA); PDQ-39; BDI-II; Non-Motor Symptoms Questionnaire (NMSQ)

Starting date Study start: 2020

Study completion: 2023

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04379778

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 306
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT04558879
Study name Exercise and sleep in Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 45 to 80 years old

• Mild to moderate idiopathic Parkinson's disease (Modified Hoehn and Yahr Scale stages 1 to 3)
• On a stable dosage of medication during the previous month
• Having poor sleep quality defined as a score > 18 in the PDSS-2 (scores above this cut-off value
define clinically relevant sleep disorders)

Sample size (planned): 60

Sample size (actual): NR

Interventions Cardiovascular training vs. resistance training

Outcomes Actigraphy/Sleep efficiency (SE = total sleep time/time spent in bed); Parkinson's Disease Sleep
Scale version 2 (PDSS-2); polysomnography combined with electroencephalogram; MDS-UPDRS-M;
Scale for Outcomes in Parkinson's Disease-Cognition; Parkinson's Disease Fatigue Scale; Scale for
Outcomes in Parkinson's Disease-Psychosocial; Parkinson's Disease Quality of Life Scale; visuomo-
tor tracking task

Starting date Study start: 2020

Study completion: 2023

Recruitment status: not yet recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04558879

NCT04613141
Study name The WalkingTall study: comparing WalkingTall with Parkinson's disease (WalkingTall-PD) with mo-
bility-plus to reduce falls and improve mobility (WalkingTall-PD)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 years and older

• Diagnosed with idiopathic Parkinson's disease (according to UK PD Society Brain Bank Criteria)
• Mild to severe (Hoehn and Yahr stage 1 to 4 idiopathic Parkinson's disease)
• Ability to walk 18 meters with or without an aid
• At least one fall in the past 6 months, or at least 2 falls in the past 12 months, or severe mobility
impairment such as freezing of gait, or history of near falls
• Being stable on anti-Parkinsonian medications for > 1 month

Sample size (planned): 122

Sample size (actual): 60

Interventions WalkingTall-PD vs. body weight exercise program

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 307
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT04613141 (Continued)

Outcomes Standard deviation of step times, assessed by a wearable device (McRoberts); rate of falling; lev-
odopa equivalency daily dosage; Mini-BEST test; Physical Activity Enjoyment Scale Questionnaire;
System Usability Scale Questionnaire; Attitudes to Fall-Related Intervention Scale Questionnaire;
exercise self-efficacy; EuroQoL-5 dimensions (EQ-5D); Short Physical Performance Battery; Move-
ment Disorders Society - Unified Parkinson's Disease Rating Scale; FOG-Q; ADL; exercise adherence;
simple stepping ability; Stroop stepping test

Starting date Study start: 2020

Study completion: 2022

Recruitment status: enrolling by invitation

Contact information Matthew A Brodie, University of New South Wales

Notes clinicaltrials.gov/ct2/show/record/NCT04613141

NCT04644367
Study name Effects of a biomechanical-based tai chi program on gait and posture in people with Parkinson's
disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 75 years
• Diagnosed with Parkinson's disease and demonstrate a disease severity ranging from 1 to 3 on
the Hoehn and Yahr (HY) scale
• Have no fluctuations in motor symptoms as reported by the motor section of the Unified Parkin-
son's Disease Rating Scale (UPDRS-III)
• Have stable medication use
• Can stand and walk independently

Sample size (planned): 40

Sample size (actual): NR

Interventions Tai chi group vs. regular physical activity

Outcomes Walking speed, walking cadence, walking step length, Center of Mass-Center of Pressure (COM-
COP), Montreal Cognitive Assessment (MoCA), single-leg stance test, TUG, Wisconsin Card Sorting
Test (WCST), Trail Making Test Part B (TMT-B), Stroop Test

Starting date Study start: 2020

Study completion: 2022

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04644367

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 308
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT04665869
Study name Long-term effects of combined balance and brisk walking in Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 30 to 80 years old

• Parkinson's disease diagnosed by neurologist with Hoehn and Yahr stage 2 or 3
• Having a 30-meter walking ability

Sample size (planned): 92

Sample size (actual): 44

Interventions Combined balance and brisk walking training vs. flexibility and strengthening exercise

Outcomes MDS-UPDRS-M, MDS-UPDRS-I, Mini-BESTest, 6-MIN-W, TUG, Dual-task timed-up-and-go (DTUG),

Five-times-sit-to-stand (FTSTS), Non-Motor Symptoms Scale for Parkinson's Disease (NMSS), gait
analysis, Activities-specific Balance Confidence (ABC) Scale, PDQ-39, Pittsburgh Sleep Quality Index
(PSQI), fall rate

Starting date Study start: 2021

Study completion: 2022

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04665869

NCT04699617
Study name The feasibility and efficacy of an immersive virtual reality software in Parkinson's disease patients

Methods Randomized controlled trial

Participants Inclusion criteria:

• People diagnosed with Parkinson's disease according to MDS criteria

• Hoehn and Yahr stages between 1 and 3
• Ability to perform the Timed Up and Go (TUG) test in normal pace and without assistance, in less
than 11.5 seconds in ON state
• Stable medication for the past 1 month
• Ability to communicate with the investigator, to understand and comply with the requirements
of the study

Sample size (planned): 30

Sample size (actual): NR

Interventions Active training with the Dolphin 2.0 vs. delayed-start

Outcomes TUG, MDS-UPDRS, Mini-BESTest, Scales for Outcomes in Parkinson's Disease-COGnition (SCO-
PA-COG), PDQ-39, Clinical Global Improvement, System Usability Scale, Simulator Sickness Ques-

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 309
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT04699617 (Continued)
tionnaire, number of steps/day, BMI, Schwab and England scale, patients' satisfaction and per-
ceived exertion (7-point Likert scale)

Starting date Study start: 2020

Study completion: 2022

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/study/NCT04699617

NCT04863118
Study name Acute effects of strength training and high intensity training on functional and biochemical mea-
surements of individuals with Parkinson's disease in different environments and depths

Methods Randomized controlled trial

Participants Inclusion criteria:

• Intervention group:
◦ Diagnosed with Parkinson's disease for at least 6 months
◦ Age: 50 to 70 years
◦ Classified on the Hoehn and Yahr scale from 1 to 3
◦ Rigid-akinetic and/or tremor-dominant type
◦ Individuals who have preserved their cognitive skills, assessed by means of the MMSE and who
have a cut-off score of 23/24
• Control group:
◦ Age: 50 to 70 years
◦ Individuals who have preserved their cognitive skills (with the same cut-off score as the inter-
vention group in the MMSE)
◦ Walk independently

Sample size (planned): 60

Sample size (actual): NR

Interventions Strength training protocol performed in shallow water and on dry land vs. high-intensity training
protocol performed in shallow and deep water

Outcomes Postural stability (stabilometry), strength (isokinetic dynamometry), spatiotemporal gait variables
(kinematic analysis), BBS, TUG, biochemical analysis of the serum brain-derived neurotrophic fac-
tor level (venous blood collection)

Starting date Study start: 2021

Study completion: 2022

Recruitment status: not yet recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04863118

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 310
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

NCT04872153
Study name Exergames in in-patient rehabilitation

Methods Randomized controlled trial

Participants Inclusion criteria:

• People with prescription for rehabilitation

• Age: ≥ 50 years old
• Able to score ≥ 20 on the Mini Mental State Examination (MMSE)
• Able to provide signed informed consent
• Physically able to stand for at least 3 minutes without external support (self-report)

Sample size (planned): 120

Sample size (actual): NR

Interventions Cognitive-motor training in form of exergames and standard rehabilitation treatment plan vs. stan-
dard rehabilitation treatment plan

Outcomes System Usability Scale (SUS); NASA Task Load Index (NASA-TLX); adverse Events; attrition rate; ad-
herence rate; Reaction Time Test (6-RTT); Trail Making Test (TMT); Color-Word Interference Test; the
Go/No-Go Test; TUG; Short Physical Performance Battery (SPPB); Single and Dual Walking Task (10-
meter distance)

Starting date Study start: 2021

Study completion: 2021

Recruitment status: recruiting

Contact information [email protected]

Notes clinicaltrials.gov/ct2/show/record/NCT04872153

NCT04878679
Study name Effect of WB-EMS on Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: from 50 to 80 years old

• Clinical diagnosis of Parkinson's disease from 1 to 3 of Hoehn and Yahr Scale
• No participation in other physical activity program

Sample size (planned): 36

Sample size (actual): NR

Interventions Strength training vs. cardiovascular training vs. no physical activity

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 311
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
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Library Better health. Cochrane Database of Systematic Reviews

NCT04878679 (Continued)

Outcomes 30-second arm curl test; 30-second sit-to-stand test; Soda Pop Test; 8 Feet up and Go Test; 6-MIN-W;
Hand Grip Test; Chair Sit and Reach Test; Tinetti Balance and Gait Evaluation Test; Stroop Test; Rey
Auditory Verbal Learning Test; Trail Making Test Change; Blood Draw

Starting date Study start: 2021

Study completion: 2021

Recruitment status: enrolling by invitation

Contact information Alessandra di Cagno, Università degli studi di Roma Foro Italico

Notes clinicaltrials.gov/ct2/show/record/NCT04878679

RBR-26kn3b
Study name Comparison between training of upper limb respiratory and peripheral resistance on the respirato-
ry function of patients with Parkinson's disease: a randomized clinical trial

Methods Randomized controlled trial

Participants Inclusion criteria:

• Being on regular medication for Parkinson's disease

• Being on the medication "on" period
• Age: 50 to 80 years
• Present stage 2, 2.5 or 3 according to the modified Hoehn and Yahr classification

Sample size (planned): 42

Sample size (actual): NR

Interventions Aerobic training and resistance training of the inspiratory musculature vs. aerobic training and up-
per limb resistance training

Outcomes Forced expiratory volume in one second (FEV1, by spirometry), forced vital capacity (FVC), FEV1 /
FVC ratio, maximum inspiratory pressure (Pimax), maximum expiratory pressure (Pemax), peak ex-
piratory flow (PEF), chest expansion at axillary, xiphoid and umbilical level, 6-MIN-W, Stand-up test

Starting date Study start: 2019

Study completion: NR

Recruitment status: recruiting

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-26kn3b

RBR-277fqv
Study name Effects of physical training with exergames on the respiratory function and on the balance of indi-
viduals with Parkinson's disease

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 312
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

RBR-277fqv (Continued)

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 50 to 80 years old

• People with moderate stages of Parkinson's disease
• Both genders
• Autonomy to perform the exercises
• Identified through the Mini Mental State Examination

Sample size (planned): 34

Sample size (actual): NR

Interventions Video-game-based physical training vs. functional training vs. no physical training

Outcomes Respiratory capacity (spirometer, manovacuometer, 6-minute walk test), balance (BBS, TUG,
baropodometry), quality of life (PDQL), perceived state of depression (Beck Depression Inventory)

Starting date Study start: 2017

Study completion: NR

Recruitment status: completed

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-277fqv/

RBR-5r5dhf
Study name Effectiveness of virtual and augmented reality versus neurofunctional physiotherapy in the treat-
ment of motors and non motors [sic] symptoms in patients with Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: over 50 years

• Medical diagnosis of Parkinson's disease according to the criteria of the London Brain Bank
• Mini Mental Score that does not characterize cognitive deficit
• Hoehn and Yahr between 1.5 to 3.0

Sample size (planned): 40

Sample size (actual): NR

Interventions Virtual reality-based rehabilitation vs. augmented reality-based rehabilitation vs. neurofunctional
physiotherapy

Outcomes Postural control, executive function, "COP" amplitude, velocity & area, conclusion time of trail
making test

Starting date Study start: 2018

Study completion: NR
Recruitment status: recruiting

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 313
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

RBR-5r5dhf (Continued)

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-5r5dhf/

RBR-5yjyr7
Study name Parkinson's disease and physiotherapy: analysis of the impact of intervention programs with ter-
restrial and aquatic physical activities - FisioPark

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 60 years or older

• Diagnosis of idiopathic Parkinson's disease
• Between stages 2 to 4 of the Hoehn and Yahr scale
• Present medical certificate clearing to practice physical activity
• Present medical certificate clearing to practice aquatic physical activity
• "Present independent march" [understood to mean having the ability to walk independently]
• Present visual, auditory, and cognitive skills to follow verbal instructions during evaluations and
interventions

Sample size (planned): 70

Sample size (actual): NR

Interventions Exercises of simple terrestrial task vs. dual terrestrial task exercises vs. simple aquatic task exercis-
es vs. dual aquatic task exercises vs. usual activities

Outcomes MoCA, MMSE, Trail Making test parts A and B, Stroop Task test, UPDRS-M, UPDRS-II, PDQ-39, TUG,
Five Times-sit to-stand test, Dynamic Gait Index scale score, Gait Speed test, Functional Reach Test,
BBS, FES, FOG-Q, Aquatic Functional Assessment Scale

Starting date Study start: 2019

Study completion: 2021

Recruitment status: not yet recruiting

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-5yjyr7

RBR-74683n
Study name Efficacy of aerobic training in immunological and neurotrophic parameters and in clinical mea-
sures in subjects with Parkinson's disease: a randomized clinical trial

Methods Randomized controlled trial

Participants Inclusion criteria:

• Clinical diagnosis of idiopathic Parkinson's disease according to the criteria of clinical diagnosis
of the United Kingdom Parkinson's Disease Society Brain Bank

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RBR-74683n (Continued)
• Age: above 40 years
• To be in stage 1,5 to 3 of Hoehn and Yahr
• Be in use of levadopa and clinically stable
• Being able to wander independently or with the use of auxiliary devices
• Have medical release for performing aerobic training

Sample size (planned): 40

Sample size (actual): NR

Interventions Aerobic training vs. stretching exercise and functional training of activities of daily living

Outcomes Serum concentration of inflammatory mediators and neurotrophic factors, leukocyte analysis, lac-
tate level, hematological parameters, brain-derived neurotrophic factor (BDNF) polymorphism,
MoCA, Fatigue Severity Scale (FHS), BDI, Mini-BESTest, TUG, 10-meter test (T10m), five-sit-up test
(TLS), co-operability test for exercise test, questionnaire for daily life activities for patients with
Parkinson's disease, PDQ-39

Starting date Study start: 2019

Study completion:NR

Recruitment status: not yet recruiting

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-74683n

RBR-8s5v5f
Study name Comparison between the effects of neuromuscular training and video game rehabilitation in the
treatment of Parkinson's disease patients

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: between 40 and 80 years

• Presents with Parkinson's disease in stage 1 to 3 according to the modified Hoehn and Yahr clas-
sification
• Signs the Free and Informed Consent Form and the Authorization of Images and Testimonials

Sample size (planned): 22

Sample size (actual): NR

Interventions Video game rehabilitation vs. neuromuscular training

Outcomes Respiratory muscle strength, lung compliance, maximal inspiratory and expiratory pressures (eval-
uated by manovacuometry), forced vital capacity (FVC), TUG, pulmonary function and performance

Starting date Study start: 2019

Study completion: NR

Recruitment status: recruitment completed

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Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

RBR-8s5v5f (Continued)

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-8s5v5f

RBR-9v7gj4
Study name The impact of adapted functional training and the solo Pilates method on motor and non-motor
symptoms of individuals with Parkinson's disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• A clinical diagnosis of Parkinson's disease following the UKPDSBB criteria

• Both sexes
• Age: 50 years or over
• With stable doses at least two weeks
• No change in medication
• Without any functional training for at least three months

Sample size (planned): 45

Sample size (actual): NR

Interventions Adapted functional training vs. routine activities

Outcomes Mini-BESTest, cardiorespiratory fitness verified by ergospirometry, BDI, mood (Brunel Mood Scale
[BRUMS]), the Sheppard Inventory, TUG, muscle strength of lower limbs (Biodex System 4 PRO iso-
kinetic dynamometer), handgrip strength (hydraulic dynamometer), range of motion of shoulders,
“Sit and reach” test

Starting date Study start: 2020

Study completion: NR

Recruitment status: not yet recruiting

Contact information [email protected]

Notes ensaiosclinicos.gov.br/rg/RBR-9v7gj4

TCTR20201009001
Study name Effects of mindful walking meditation on gait, balance and disease severity in patients with Parkin-
son disease

Methods Randomized controlled trial

Participants Inclusion criteria:

• Age: 40 to 85 years
• Clinical diagnosis of Parkinson's disease, with a disease severity rating of stage 1 to 3 on the Hoehn
and Yahr scale
• Stable medication use
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TCTR20201009001 (Continued)
• Able to stand unaided and walk without an assistive device

Sample size (planned): 32

Sample size (actual): NR

Interventions Mindful walking meditation vs. usual care group

Outcomes TUG, 10 meter walk test, Sit to stand test, MOCA test, UPDRS, World Health Organization Quality of
Life (WHOQOL-BREF), PDQ-39, Hamilton Rating Scale for Depression, Patient Health Questionnaire
(PHQ-9), Hospital anxiety and depression score (HADS), complications, compliance

Starting date Study start: 2020

Study completion: NR

Recruitment status: completed

Contact information [email protected]

Notes www.thaiclinicaltrials.org/show/TCTR20201009001

ADL: activities of daily living; BBS: Berg Balance Scale; BDI: Beck Depression Inventory; BMI: body mass indexBESTest: Balance Evaluation
Systems Test; EQ-5D: EuroQoL 5 Dimensions; FES: Falls Efficacy Scale; FOG-Q: Freezing of Gait Questionnaire; HADS: Hospital Anxiety and
Depression Scale; HY: Hoehn and Yahr scale; LSVT BIG: Lee Silverman Voice training BIG; MDS: Movement Disorder Society; MDS-UPDRS-
M: Movement Disorder Society Unified Parkinson Disease Rating Scale/Motor Score; MHY: Modified Hoehn and Yahr scale; Mini-BESTest:
Mini-Balance Evaluation Systems Test; MMSE: Mini Mental State Examination; MoCA: Montreal Cognitive Assessment; MRI: magnetic
resonance imaging; N-FOG-Q: New Freezing of Gait Questionnaire; PDQ-39: Parkinson's Disease Questionnaire 39; PDQ-8: Parkinson's
Disease Questionnaire 8; PDQOL: Parkinson's disease quality of life; SAFEx: Sensory Attention Focused Exercise; SF-36: Short-Form Health
Survey-36 item questionnaire; 6-MIN-W: 6-minute walk test; TUG: Timed up and go; UKPDSBB: UK Parkinson's Disease Society Brain Bank
diagnostic criteria; UPDRS-M: Unified Parkinson's Disease Rating Scale/Motor Score

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 317
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Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review)
ADDITIONAL TABLES
Table 1. Results of network meta-analysis for severity of motor signs
Heterogeneity/Inconsistency: Qtotal = 163.38, df = 68, P < 0.001, Qwithin = 87.87, df = 40, P < 0.001; Qbetween = 75.51, df = 28, P < 0.001; I2 = 58.4%, Tau2 = 0.1501

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Cochrane
Dance . . -0.29 [-1.11, . -0.06 [-1.06, . . -1.41 -0.70 [-1.18, .
0.54] 0.94] [-2.92, -0.22]
0.09]

-0.19 [-0.74, Aqua-based -0.33 [-0.93, 0.18 [-0.34, . . . . . -0.62 [-1.53, .

Better health.
Informed decisions.
Trusted evidence.
0.36] training 0.28] 0.70] 0.30]

-0.22 [-0.69, -0.03 [-0.43, Gait/bal- -0.15 [-0.57, -0.07 [-0.61, 1.53 [ 0.48, . . -0.45 -0.94 [-1.52, .
0.25] 0.37] ance/func- 0.27] 0.47] 2.58] [-0.96, -0.36]
tional train- 0.07]
ing

-0.24 [-0.67, -0.06 [-0.44, -0.03 [-0.30, Multi-domain 0.16 [-0.58, -0.07 [-0.71, 0.07 [-0.42, -0.29 -0.11 -0.63 [-1.02, .
0.18] 0.32] 0.25] training 0.91] 0.56] 0.56] [-1.34, [-0.67, -0.23]
0.77] 0.44]

-0.25 [-0.77, -0.06 [-0.55, -0.03 [-0.40, -0.00 [-0.37, Strength/ 0.17 [-0.49, 0.83 [-0.54, . -0.24 -1.25 [-2.06, -0.60
0.27] 0.43] 0.34] 0.36] resistance 0.83] 2.20] [-1.07, -0.44] [-1.43,
training 0.60] 0.24]

-0.28 [-0.73, -0.09 [-0.55, -0.06 [-0.42, -0.04 [-0.35, -0.03 [-0.43, Mind-body 0.19 [-0.94, . . -0.43 [-0.77, -0.41
0.17] 0.37] 0.29] 0.27] 0.36] training 1.32] -0.09] [-1.06,
0.24]

-0.28 [-0.77, -0.10 [-0.57, -0.07 [-0.44, -0.04 [-0.36, -0.04 [-0.46, -0.00 [-0.37, En- 0.26 [-0.73, -0.30 -0.21 [-0.67, -1.02
0.20] 0.38] 0.31] 0.28] 0.39] 0.36] durance 1.25] [-1.01, 0.26] [-1.75,
training 0.41] -0.29]

-0.35 [-1.13, -0.17 [-0.93, -0.14 [-0.85, -0.11 [-0.79, -0.11 [-0.85, -0.07 [-0.79, -0.07 LSVT BIG . -0.31 [-1.30, .

Cochrane Database of Systematic Reviews

0.42] 0.60] 0.58] 0.57] 0.64] 0.64] [-0.76, 0.67]
0.62]

-0.59 [-1.11, -0.41 [-0.90, -0.38 [-0.75, -0.35 [-0.71, -0.35 [-0.79, -0.32 [-0.75, -0.31 -0.24 Active . .
-0.08] 0.09] -0.01] 0.01] 0.10] 0.12] [-0.73, [-0.99, control
0.10] 0.51] group

-0.77 [-1.16, -0.58 [-0.99, -0.55 [-0.85, -0.52 [-0.77, -0.52 [-0.89, -0.49 [-0.76, -0.48 -0.41 -0.17 Passive con- .
-0.37] -0.17] -0.25] -0.27] -0.15] -0.21] [-0.80, [-1.10, [-0.56, trol group
-0.17] 0.27] 0.22]
318
Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review)
Table 1. Results of network meta-analysis for severity of motor signs (Continued)

-0.92 [-1.55, -0.73 [-1.36, -0.70 [-1.25, -0.68 [-1.20, -0.67 [-1.22, -0.64 [-1.14, -0.64 -0.57 -0.33 -0.15 [-0.67, Flexibility
-0.29] -0.11] -0.16] -0.16] -0.13] -0.14] [-1.14, [-1.39, [-0.92, 0.36] training

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Cochrane
-0.13] 0.25] 0.26]

Treatment effects are expressed as standardized mean differences with 95% confidence intervals. Treatments are ordered by P-score (descending). Upper triangle: direct
estimates. Lower triangle: network estimates.
Number of studies: 71. Number of treatments: 11. Number of pairwise comparisons: 85. Number of designs: 31

Better health.
Informed decisions.
Trusted evidence.
Table 2. Results of network meta-analysis for quality of life
Heterogeneity/Inconsistency: Qtotal = 125.02, df = 50, P < 0.001, Qwithin = 71.91, df = 26, P < 0.001; Qbetween = 53.11, df = 24, P < 0.001; I2 = 60.0%, Tau2 = 0.1210

Aqua-based . . . . -0.94 [-1.58, -0.15 [-0.86, . . . -0.57 .

training -0.30] 0.57] [-1.74,
0.59]

-0.32 [-0.88, Endurance -0.42 [-1.50, -0.05 . -0.15 [-0.67, -0.09 [-0.75, . . . -0.65 .
0.23] training 0.67] [-0.97, 0.38] 0.56] [-1.24,
0.88] -0.05]

-0.35 [-0.91, -0.03 [-0.47, Mind-body . -0.50 . -0.43 [-1.19, 0.15 . -0.72 -0.44 .
0.21] 0.42] training [-1.11, 0.33] [-0.85, [-1.49, [-0.89,
0.11] 1.14] 0.04] 0.02]

-0.45 [-1.21, -0.12 [-0.78, -0.10 [-0.80, Gaming . -0.35 [-1.27, 0.15 [-0.82, . . . . .
0.32] 0.54] 0.61] 0.56] 1.13]

-0.49 [-1.03, -0.16 [-0.62, -0.14 [-0.54, -0.04 Strength/ -0.06 [-0.57, 0.18 [-0.71, . . -0.28 -0.90 0.03
0.06] 0.29] 0.26] [-0.74, resistance 0.44] 1.06] [-1.04, [-1.50, [-0.74,
0.66] training 0.49] -0.30] 0.80]

Cochrane Database of Systematic Reviews

-0.53 [-0.99, -0.21 [-0.57, -0.18 [-0.56, -0.08 -0.04 Gait/bal- -0.06 [-0.52, . . . -0.35 -0.67
-0.07] 0.16] 0.20] [-0.72, [-0.39, ance/func- 0.40] [-0.71, [-1.20,
0.56] 0.30] tional train- 0.00] -0.14]
ing

-0.55 [-1.02, -0.23 [-0.60, -0.20 [-0.56, -0.11 -0.07 -0.02 [-0.29, Multi-domain 0.60 -0.42 . -0.24 -0.44
-0.09] 0.14] 0.16] [-0.74, [-0.42, 0.24] training [-0.46, [-1.43, [-0.57, [-0.92,
0.53] 0.29] 1.67] 0.58] 0.09] 0.05]
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Table 2. Results of network meta-analysis for quality of life (Continued)

-0.61 [-1.22, -0.29 [-0.82, -0.26 [-0.74, -0.17 -0.13 -0.08 [-0.54, -0.06 [-0.50, Dance . . -0.08 0.46
0.00] 0.24] 0.22] [-0.92, [-0.64, 0.37] 0.38] [-0.59, [-0.91,

Library
Cochrane
0.58] 0.38] 0.42] 1.83]

-0.97 [-2.08, -0.65 [-1.72, -0.62 [-1.69, -0.53 -0.49 -0.44 [-1.48, -0.42 [-1.43, -0.36 LSVT . . .
0.13] 0.42] 0.44] [-1.72, [-1.55, 0.59] 0.58] [-1.46, BIG
0.66] 0.58] 0.73]

Better health.
Informed decisions.
Trusted evidence.
-0.92 [-1.76, -0.59 [-1.37, -0.57 [-1.26, -0.47 -0.43 -0.39 [-1.12, -0.36 [-1.09, -0.30 0.06 Flexi- . .
-0.08] 0.18] 0.13] [-1.42, [-1.12, 0.34] 0.36] [-1.11, [-1.18, bility
0.47] 0.26] 0.50] 1.30] training

-0.85 [-1.32, -0.52 [-0.89, -0.50 [-0.83, -0.40 -0.36 -0.32 [-0.57, -0.30 [-0.53, -0.23 0.13 0.07 Passive .
-0.37] -0.16] -0.17] [-1.05, [-0.70, -0.07] -0.06] [-0.64, [-0.91, [-0.65, control
0.25] -0.02] 0.17] 1.16] 0.79] group

-0.90 [-1.47, -0.58 [-1.07, -0.55 [-1.03, -0.45 -0.41 -0.37 [-0.76, -0.35 [-0.72, -0.29 0.07 0.02 -0.05 Active
-0.33] -0.08] -0.07] [-1.17, [-0.87, 0.02] 0.03] [-0.82, [-1.00, [-0.77, [-0.46, control
0.26] 0.04] 0.24] 1.15] 0.80] 0.35] group

Treatment effects are expressed as standardized mean differences with 95% confidence intervals. Treatments are ordered by P-score (descending). Upper triangle: direct
estimates. Lower triangle: network estimates.
Number of studies: 55. Number of treatments: 12. Number of pairwise comparisons: 67. Number of designs: 29

Table 3. Results of network meta-analysis for freezing of gait

Heterogeneity/Inconsistency: Qtotal = 22.36, df = 13, P = 0.050, Qwithin = 14.83, df = 9, P = 0.096; Qbetween = 7.53, df = 4, P = 0.110; I2 = 41.9%, Tau2 = 0.0632

Strength/resistance train- . . . -1.16 [-2.25, -0.10 [-0.70, 0.50] . .

ing -0.08]

Cochrane Database of Systematic Reviews

0.06 [-1.13, 1.25] Aqua-based train- . . . -0.45 [-1.52, 0.61] . .
ing

-0.15 [-0.78, 0.49] -0.21 [-1.33, 0.92] Dance . . -0.19 [-0.58, 0.20] -0.49 [-1.23, .
0.24]

-0.08 [-1.13, 0.97] -0.14 [-1.54, 1.25] 0.06 [-0.92, Mind-body . -0.31 [-1.22, 0.60] . .
1.04] training
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Table 3. Results of network meta-analysis for freezing of gait (Continued)

-0.20 [-0.77, 0.37] -0.26 [-1.36, 0.85] -0.05 [-0.50, -0.11 [-1.07, Gait/bal- -0.28 [-0.60, 0.04] -0.50 [-1.45, -0.42 [-1.02,
0.40] 0.84] ance/function- 0.45] 0.18]

Library
Cochrane
al training

-0.39 [-0.92, 0.13] -0.45 [-1.52, 0.61] -0.25 [-0.61, -0.31 [-1.22, -0.20 [-0.49, Passive control group 0.33 [-0.61, .
0.12] 0.60] 0.10] 1.28]

-0.44 [-1.14, 0.26] -0.50 [-1.67, 0.67] -0.29 [-0.80, -0.36 [-1.38, -0.24 [-0.73, -0.05 [-0.53, 0.43] Multi-domain -0.41 [-1.21,

Better health.
Informed decisions.
Trusted evidence.
0.22] 0.67] 0.25] training 0.39]

-0.70 [-1.45, 0.05] -0.76 [-1.96, 0.44] -0.55 [-1.18, -0.62 [-1.68, -0.50 [-1.02, -0.31 [-0.87, 0.25] -0.26 [-0.83, Active con-
0.08] 0.45] 0.01] 0.31] trol group

Treatment effects are expressed as standardized mean differences with 95% confidence intervals. Treatments are ordered by P-score (descending). Upper triangle: direct
estimates. Lower triangle: network estimates.
Number of studies: 20. Number of treatments: 8. Number of pairwise comparisons: 20. Number of designs: 11

Table 4. Results of network meta-analysis for functional mobility and balance

Heterogeneity/Inconsistency: Qtotal = 204.30, df = 48, P < 0.001, Qwithin = 108.31, df = 27, P < 0.001; Qbetween = 95.99, df = 21, P < 0.001; I2 = 76.5%, Tau2 = 0.3436

Aqua-based train- . . . . -0.69 . -0.92 [-1.71, . . . -0.70

ing [-1.48, -0.13] [-2.11,
0.10] 0.70]

-0.39 [-1.70, 0.92] LSVT BIG . . -0.50 . . . . . . -0.72

[-1.81, [-2.03,
0.82] 0.60]

-0.52 [-1.19, 0.15] -0.13 [-1.36, Mind- 0.00 [-1.32, . -0.49 -0.26 0.41 [-0.47, . . -0.78 -0.96
1.10] body 1.32] [-1.83, [-1.17, 1.30] [-1.68, [-1.45,

Cochrane Database of Systematic Reviews

training 0.85] 0.64] 0.13] -0.48]

-0.56 [-1.34, 0.23] -0.16 [-1.46, -0.03 Dance . . . -1.62 [-3.17, . -1.15 . -0.46
1.13] [-0.67, -0.07] [-2.86, [-1.08,
0.60] 0.55] 0.17]

-0.61 [-1.42, 0.21] -0.21 [-1.39, -0.08 -0.05 En- . . -1.33 [-2.78, . -0.03 -1.00 -0.53
0.97] [-0.77, [-0.84, durance 0.12] [-1.28, [-2.55, [-1.35,
0.60] 0.75] training 1.22] 0.55] 0.28]
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Table 4. Results of network meta-analysis for functional mobility and balance (Continued)

-0.63 [-1.19, -0.06] -0.23 [-1.47, -0.10 -0.07 -0.02 Gait/bal- -0.13 -0.51 [-1.12, . -0.49 . -0.26
1.00] [-0.61, [-0.72, [-0.70, ance/func- [-1.03, 0.10] [-1.12, [-1.00,

Library
Cochrane
0.40] 0.58] 0.66] tional 0.76] 0.13] 0.47]
training

-0.71 [-1.40, -0.01] -0.31 [-1.56, -0.18 -0.15 -0.10 -0.08 Strength/ 0.17 [-1.14, . -0.05 -0.25 -0.92
0.94] [-0.71, [-0.83, [-0.82, [-0.60, resis- 1.49] [-1.25, [-1.44, [-1.55,
0.34] 0.54] 0.61] 0.44] tance 1.15] 0.95] -0.30]

Better health.
Informed decisions.
Trusted evidence.
training

-0.77 [-1.33, -0.20] -0.37 [-1.61, -0.24 -0.21 -0.16 -0.14 -0.06 Multi-do- -0.13 . . -1.61
0.86] [-0.74, [-0.85, [-0.84, [-0.56, [-0.60, main train- [-1.50, [-2.44,
0.25] 0.43] 0.51] 0.28] 0.48] ing 1.25] -0.78]

-0.90 [-2.38, 0.59] -0.50 [-2.35, -0.37 -0.34 -0.29 -0.27 -0.19 -0.13 [-1.50, Gaming . . .
1.35] [-1.83, [-1.86, [-1.82, [-1.71, [-1.67, 1.25]
1.09] 1.18] 1.24] 1.17] 1.29]

-1.07 [-1.83, -0.32] -0.68 [-1.97, -0.55 -0.51 -0.47 -0.45 -0.36 -0.30 [-0.94, -0.18 Active . .
0.61] [-1.22, [-1.27, [-1.21, [-0.99, [-1.03, 0.33] [-1.69, control
0.13] 0.24] 0.28] 0.10] 0.30] 1.34] group

-1.33 [-2.29, -0.37] -0.94 [-2.32, -0.81 -0.77 -0.72 -0.70 -0.62 -0.56 [-1.41, -0.43 -0.26 Flexi- .
0.45] [-1.58, [-1.71, [-1.61, [-1.55, [-1.44, 0.29] [-2.05, [-1.20, bility
-0.04] 0.17] 0.17] 0.15] 0.20] 1.18] 0.69] training

-1.40 [-2.01, -0.79] -1.01 [-2.18, -0.88 -0.84 -0.79 -0.77 -0.69 -0.63 [-1.07, -0.50 -0.33 -0.07 Passive
0.17] [-1.27, [-1.39, [-1.40, [-1.20, [-1.15, -0.20] [-1.94, [-0.94, [-0.87, control
-0.48] -0.30] -0.18] -0.35] -0.23] 0.94] 0.29] 0.73] group

Treatment effects are expressed as standardized mean differences with 95% confidence intervals. Treatments are ordered by P-score (descending). Upper triangle: direct

Cochrane Database of Systematic Reviews

estimates. Lower triangle: network estimates.
Number of studies: 54. Number of treatments: 12. Number of pairwise comparisons: 64. Number of designs: 27
322
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Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Table 5. Comparison of direct and indirect evidence (in closed loops) for severity of motor signs
Comparison Number of Network esti- Direct estimate Indirect esti- Test for dis-
studies mate mate agreement

Aqua-based training vs gait/bal- 3 -0.03 [-0.43, 0.37] -0.33 [-0.93, 0.28] 0.20 [-0.33, 0.73] 0.1962
ance/functional training

Aqua-based training vs multi-do- 4 -0.06 [-0.44, 0.32] 0.18 [-0.34, 0.70] -0.33 [-0.88, 0.23] 0.1972
main training

Aqua-based training vs passive con- 2 -0.58 [-0.99, -0.62 [-1.53, 0.30] -0.57 [-1.03, 0.9315
trol group -0.17] -0.11]

Dance vs active control group 1 -0.59 [-1.11, -1.41 [-2.92, 0.09] -0.48 [-1.03, 0.07] 0.2545
-0.08]

Dance vs mind-body training 1 -0.28 [-0.73, 0.17] -0.06 [-1.06, 0.94] -0.34 [-0.85, 0.17] 0.6252

Dance vs multi-domain training 2 -0.24 [-0.67, 0.18] -0.29 [-1.11, 0.54] -0.23 [-0.73, 0.27] 0.9036

Dance vs passive control group 5 -0.77 [-1.16, -0.70 [-1.18, -0.91 [-1.61, 0.6338
-0.37] -0.22] -0.20]

Endurance training vs active control 2 -0.31 [-0.73, 0.10] -0.30 [-1.01, 0.41] -0.32 [-0.83, 0.19] 0.9677
group

Endurance training vs flexibility 2 -0.64 [-1.14, -1.02 [-1.75, -0.29 [-0.99, 0.41] 0.1587
training -0.13] -0.29]

Endurance training vs LSVT BIG 1 -0.07 [-0.76, 0.62] 0.26 [-0.73, 1.25] -0.39 [-1.37, 0.58] 0.3546

Endurance training vs mind-body 1 0.00 [-0.36, 0.37] -0.19 [-1.32, 0.94] 0.03 [-0.36, 0.41] 0.7246
training

Endurance training vs multi-domain 5 0.04 [-0.28, 0.36] -0.07 [-0.56, 0.42] 0.12 [-0.30, 0.54] 0.5652
training

Endurance training vs passive con- 5 -0.48 [-0.80, -0.21 [-0.67, 0.26] -0.72 [-1.15, 0.1117
trol group -0.17] -0.29]

Endurance training vs strength/re- 1 0.04 [-0.39, 0.46] -0.83 [-2.20, 0.54] 0.13 [-0.32, 0.57] 0.1929
sistance

Flexibility training vs mind-body 2 0.64 [0.14, 1.14] 0.41 [-0.24, 1.06] 0.97 [0.19, 1.75] 0.2806
training

Flexibility training vs strength/resis- 1 0.67 [0.13, 1.22] 0.60 [-0.24, 1.43] 0.73 [0.01, 1.45] 0.8158
tance training

Gait/balance/functional vs active 3 -0.38 [-0.75, -0.45 [-0.96, 0.07] -0.31 [-0.83, 0.22] 0.7170
control group -0.01]

Gait/balance/functional vs mind- 1 -0.06 [-0.42, 0.29] 1.53 [0.48, 2.58] -0.27 [-0.64, 0.11] 0.0015
body training

Gait/balance/functional training vs 6 -0.03 [-0.30, 0.25] -0.15 [-0.57, 0.27] 0.06 [-0.30, 0.42] 0.4590
multi-domain training

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Informed decisions.
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Table 5. Comparison of direct and indirect evidence (in closed loops) for severity of motor signs (Continued)

Gait/balance/functional vs passive 3 -0.55 [-0.85, -0.94 [-1.52, -0.40 [-0.76, 0.1250

control group -0.25] -0.36] -0.05]

Gait/balance/functional training vs 3 -0.03 [-0.40, 0.34] -0.07 [-0.61, 0.47] 0.00 [-0.50, 0.51] 0.8562
strength/resistance training

LSVT BIG vs multi-domain training 1 0.11 [-0.57, 0.79] 0.29 [-0.77, 1.34] -0.02 [-0.90, 0.87] 0.6690

LSVT BIG vs passive control training 1 -0.41 [-1.10, 0.27] -0.31 [-1.30, 0.67] -0.51 [-1.45, 0.44] 0.7813

Mind-body training vs multi-domain 2 0.04 [-0.27, 0.35] 0.07 [-0.56, 0.71] 0.02 [-0.33, 0.38] 0.8996
training

Mind-body training vs passive con- 10 -0.49 [-0.76, -0.43 [-0.77, -0.59 [-1.05, 0.5918
trol group -0.21] -0.09] -0.13]

Mind-body training vs strength/re- 2 0.03 [-0.36, 0.43] -0.17 [-0.83, 0.49] 0.14 [-0.35, 0.63] 0.4556
sistance training

Multi-domain training vs active con- 3 -0.35 [-0.71, 0.01] -0.11 [-0.67, 0.44] -0.52 [-0.99, 0.2784
trol group -0.05]

Multi-domain training vs passive 7 -0.52 [-0.77, -0.63 [-1.02, -0.45 [-0.77, 0.5040
control group -0.27] -0.23] -0.13]

Multi-domain training vs strength/ 2 -0.00 [-0.37, 0.36] 0.16 [-0.58, 0.91] -0.06 [-0.47, 0.36] 0.6148
resistance training

Strength/resistance vs active con- 1 -0.35 [-0.79, 0.10] -0.24 [-1.07, 0.60] -0.39 [-0.92, 0.13] 0.7568
trol group

Strength/resistance vs passive con- 2 -0.52 [-0.89, -1.25 [-2.06, -0.32 [-0.74, 0.10] 0.0455
trol group -0.15] -0.44]

Estimates are expressed as standardized mean differences with 95% confidence intervals.
Results of tests for disagreements between direct and indirect estimates are reported as P values.
Only comparisons for which both direct and indirect evidence were available are shown.

Table 6. Comparison of direct and indirect evidence (in closed loops) for quality of life
Comparison Number of Network esti- Direct estimate Indirect esti- Test for dis-
studies mate mate agreement

Aqua-based training vs gait/bal- 3 -0.53 [-0.99, -0.94 [-1.58, -0.10 [-0.76, 0.56] 0.0746
ance/functional training -0.07] -0.30]

Aqua-based training vs multi-do- 2 -0.55 [-1.02, -0.15 [-0.86, 0.57] -0.85 [-1.46, 0.1448
main training -0.09] -0.24]

Aqua-based training vs passive con- 1 -0.85 [-1.32, -0.57 [-1.74, 0.59] -0.90 [-1.43, 0.6159
trol group -0.37] -0.38]

Dance vs active control group 1 -0.29 [-0.82, 0.24] 0.46 [-0.91, 1.83] -0.42 [-1.00, 0.16] 0.2468

Dance vs mind-body training 1 0.26 [-0.22, 0.74] -0.15 [-1.14, 0.85] 0.39 [-0.16, 0.93] 0.3601

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Table 6. Comparison of direct and indirect evidence (in closed loops) for quality of life (Continued)

Dance vs multi-domain training 1 0.06 [-0.38, 0.50] -0.60 [-1.67, 0.46] 0.20 [-0.28, 0.68] 0.1788

Dance vs passive control group 4 -0.23 [-0.64, 0.17] -0.08 [-0.59, 0.42] -0.52 [-1.20, 0.17] 0.3186

Endurance training vs gait/bal- 4 -0.21 [-0.57, 0.16] -0.15 [-0.67, 0.38] -0.27 [-0.78, 0.25] 0.7469
ance/functional training

Endurance training vs Gaming 1 -0.12 [-0.78, 0.54] -0.05 [-0.97, 0.88] -0.21 [-1.16, 0.75] 0.8124

Endurance training vs mind-body 1 -0.03 [-0.47, 0.42] -0.42 [-1.50, 0.67] 0.05 [-0.44, 0.54] 0.4400
training

Endurance training vs multi-domain 2 -0.23 [-0.60, 0.14] -0.09 [-0.75, 0.56] -0.29 [-0.73, 0.15] 0.6273
training

Endurance training vs passive con- 3 -0.52 [-0.89, -0.65 [-1.24, -0.45 [-0.91, 0.01] 0.6097
trol group -0.16] -0.05]

Flexibility training vs mind-body 1 0.57 [-0.13, 1.26] 0.72 [-0.04, 1.49] -0.12 [-1.74, 1.50] 0.3546
training

Flexibility training vs strength/resis- 1 0.43 [-0.26, 1.12] 0.28 [-0.49, 1.04] 1.13 [-0.50, 2.77] 0.3546
tance training

Gait/balance/functional vs active 3 -0.37 [-0.76, 0.02] -0.67 [-1.20, -0.01 [-0.59, 0.57] 0.0971
control group -0.14]

Gait/balance/functional training vs 1 0.08 [-0.56, 0.72] 0.35 [-0.56, 1.27] -0.17 [-1.07, 0.72] 0.4199
gaming

Gait/balance/functional training vs 4 -0.02 [-0.29, 0.24] -0.06 [-0.52, 0.40] -0.00 [-0.32, 0.32] 0.8303
multi-domain training

Gait/balance/functional training vs 5 -0.32 [-0.57, -0.35 [-0.71, 0.00] -0.28 [-0.64, 0.08] 0.7796
passive control group -0.07]

Gait/balance/functional training vs 3 0.04 [-0.30, 0.39] 0.06 [-0.44, 0.57] 0.03 [-0.45, 0.50] 0.9135
strength/resistance

Gaming vs multi-domain training 1 -0.11 [-0.74, 0.53] 0.15 [-0.82, 1.13] -0.30 [-1.14, 0.54] 0.4875

Mind-body training vs multi-domain 1 -0.20 [-0.56, 0.16] -0.43 [-1.19, 0.33] -0.14 [-0.55, 0.27] 0.5055
training

Mind-body training vs passive con- 5 -0.50 [-0.83, -0.44 [-0.89, 0.02] -0.57 [-1.05, 0.6978
trol group -0.17] -0.08]

Mind-body training vs strength/re- 2 -0.14 [-0.54, 0.26] -0.50 [-1.11, 0.11] 0.14 [-0.39, 0.66] 0.1239
sistance training

Multi-domain training vs active con- 3 -0.35 [-0.72, 0.03] -0.44 [-0.92, 0.05] -0.21 [-0.81, 0.38] 0.5625
trol group

Multi-domain training vs passive 7 -0.30 [-0.53, -0.24 [-0.57, 0.09] -0.36 [-0.70, 0.6206
control group -0.06] -0.01]

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Table 6. Comparison of direct and indirect evidence (in closed loops) for quality of life (Continued)

Multi-domain training vs strength/ 1 0.07 [-0.29, 0.42] -0.18 [-1.06, 0.71] 0.11 [-0.28, 0.50] 0.5567
resistance training

Strength/resistance training vs ac- 1 -0.41 [-0.87, 0.04] 0.03 [-0.74, 0.80] -0.65 [-1.21, 0.1589
tive control group -0.09]

Strength/resistance vs passive con- 3 -0.36 [-0.70, -0.90 [-1.50, -0.10 [-0.52, 0.32] 0.0309
trol group -0.02] -0.30]

Estimates are expressed as standardized mean differences with 95% confidence intervals.
Results of tests for disagreements between direct and indirect estimates are reported as P values.
Only comparisons for which both direct and indirect evidence were available are shown.

Table 7. Comparison of direct and indirect evidence (in closed loops) for freezing of gait
Comparison Number of Network esti- Direct estimate Indirect esti- Test for dis-
studies mate mate agreement

Dance vs multi-domain training 2 -0.29 [-0.80, 0.22] -0.49 [-1.23, 0.24] -0.10 [-0.81, 0.60] 0.4537

Dance vs passive control group 4 -0.25 [-0.61, 0.12] -0.19 [-0.58, 0.20] -0.58 [-1.52, 0.36] 0.4537

Gait/balance/functional training vs 1 -0.50 [-1.02, 0.01] -0.42 [-1.02, 0.18] -0.72 [-1.70, 0.25] 0.6058
active control group

Gait/balance/functional training vs 1 -0.24 [-0.73, 0.25] -0.50 [-1.45, 0.45] -0.15 [-0.72, 0.42] 0.5438
multi-domain training

Gait/balance/functional training vs 5 -0.20 [-0.49, 0.10] -0.28 [-0.60, 0.04] 0.23 [-0.51, 0.97] 0.2190
passive control group

Gait/balance/functional training vs 1 0.20 [-0.37, 0.77] 1.16 [0.08, 2.25] -0.17 [-0.84, 0.50] 0.0395
strength/resistance training

Multi-domain training vs active con- 1 -0.26 [-0.83, 0.31] -0.41 [-1.21, 0.39] -0.10 [-0.93, 0.72] 0.6058
trol group

Multi-domain training vs passive 1 0.05 [-0.43, 0.53] -0.33 [-1.28, 0.61] 0.18 [-0.38, 0.74] 0.3608
control group

Strength/resistance training vs pas- 2 -0.39 [-0.92, 0.13] -0.10 [-0.70, 0.50] -1.44 [-2.56, 0.0395
sive control group -0.31]

Estimates are expressed as standardized mean differences with 95% confidence intervals.
Results of tests for disagreements between direct and indirect estimates are reported as P values.
Only comparisons for which both direct and indirect evidence were available are shown.

Table 8. Comparison of direct and indirect evidence (in closed loops) for functional mobility and balance
Comparison Number of Network esti- Direct estimate Indirect esti- Test for dis-
studies mate mate agreement

Aqua-based training vs gait/bal- 3 -0.63 [-1.19, -0.69 [-1.48, 0.10] -0.56 [-1.36, 0.24] 0.8223
ance/functional training -0.06]

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Table 8. Comparison of direct and indirect evidence (in closed loops) for functional mobility and balance (Continued)

Aqua-based training vs multi-do- 3 -0.77 [-1.33, -0.92 [-1.71, -0.61 [-1.41, 0.20] 0.5840
main training -0.20] -0.13]

Aqua-based training vs passive con- 1 -1.40 [-2.01, -0.70 [-2.11, 0.70] -1.56 [-2.24, 0.2831
trol group -0.79] -0.88]

Dance vs active control group 1 -0.51 [-1.27, 0.24] -1.15 [-2.86, 0.55] -0.36 [-1.20, 0.49] 0.4114

Dance vs mind-body training 1 0.03 [-0.60; 0.67] -0.00 [-1.32; 1.32] 0.05 [-0.68, 0.77] 0.9528

Dance vs multi-domain training 1 -0.21 [-0.85, 0.43] -1.62 [-3.17, 0.09 [-0.62, 0.79] 0.0495
-0.07]

Dance vs passive control group 5 -0.84 [-1.39, -0.46 [-1.08, 0.17] -2.03 [-3.13, 0.0153
-0.30] -0.92]

Endurance training vs active control 1 -0.47 [-1.21, 0.28] -0.03 [-1.28, 1.22] -0.70 [-1.62, 0.22] 0.3991
group

Endurance training vs flexibility 1 -0.72 [-1.61, 0.17] -1.00 [-2.55, 0.55] -0.59 [-1.68, 0.50] 0.6736
training

Endurance training vs LSVT BIG 1 0.21 [-0.97, 1.39] 0.50 [-0.82, 1.81] -0.97 [-3.64, 1.71] 0.3357

Endurance training vs multi-domain 1 -0.16 [-0.84, 0.51] -1.33 [-2.78, 0.12] 0.16 [-0.60, 0.92] 0.0748
training

Endurance training vs passive con- 3 -0.79 [-1.40, -0.53 [-1.35, 0.28] -1.13 [-2.05, 0.3451
trol group -0.18] -0.20]

Flexibility training vs mind-body 2 0.81 [0.04, 1.58] 0.78 [-0.13, 1.68] 0.88 [-0.56, 2.33] 0.9007
training

Flexibility training vs strength/resis- 1 0.62 [-0.20, 1.44] 0.25 [-0.95, 1.44] 0.96 [-0.17, 2.09] 0.3971
tance training

Gait/balance/functional training vs 4 -0.45 [-0.99, 0.10] -0.49 [-1.12, 0.13] -0.30 [-1.40, 0.81] 0.7618
active control group

Gait/balance/functional training vs 1 0.10 [-0.40, 0.61] 0.49 [-0.85, 1.83] 0.04 [-0.51, 0.58] 0.5411
mind-body training

Gait/balance/functional training vs 5 -0.14 [-0.56, 0.28] -0.51 [-1.12, 0.10] 0.20 [-0.39, 0.79] 0.0995
multi-domain training

Gait/balance/functional training vs 3 -0.77 [-1.20, -0.26 [-1.00, 0.47] -1.04 [-1.57, 0.0935
passive control group -0.35] -0.51]

Gait/balance/functional training vs 2 -0.08 [-0.60, 0.44] -0.13 [-1.03, 0.76] -0.06 [-0.69, 0.58] 0.8946
strength/resistance training

LSVT BIG vs passive control group 1 -1.01 [-2.18, 0.17] -0.72 [-2.03, 0.60] -2.17 [-4.83, 0.48] 0.3357

Mind-body training vs multi-domain 2 -0.24 [-0.74, 0.25] 0.41 [-0.47, 1.30] -0.54 [-1.13, 0.06] 0.0809
training

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Table 8. Comparison of direct and indirect evidence (in closed loops) for functional mobility and balance (Continued)

Mind-body training vs passive con- 8 -0.88 [-1.27, -0.96 [-1.45, -0.70 [-1.39, 0.0809
trol group -0.48] -0.48] -0.02]

Mind-body training vs strength/re- 2 -0.18 [-0.71, 0.34] -0.26 [-1.17, 0.64] -0.15 [-0.79, 0.50] 0.5406
sistance training

Multi-domain training vs passive 3 -0.63 [-1.07, -1.61 [-2.44, -0.27 [-0.78, 0.24] 0.0071
control group -0.20] -0.78]

Multi-domain training vs strength/ 1 0.06 [-0.48, 0.60] -0.17 [-1.49, 1.14] 0.11 [-0.48, 0.70] 0.7037
resistance training

Strength/resistance training vs ac- 1 -0.36 [-1.03, 0.30] -0.05 [-1.25, 1.15] -0.50 [-1.30, 0.30] 0.5383
tive control group

Strength/resistance training vs pas- 5 -0.69 [-1.15, -0.92 [-1.55, -0.42 [-1.10; 0.25] 0.2884
sive control group -0.23] -0.30]

Estimates are expressed as standardized mean differences with 95% confidence intervals.
Results of tests for disagreements between direct and indirect estimates are reported as P values.
Only comparisons for which both direct and indirect evidence were available are shown.

APPENDICES

Appendix 1. Categorization of interventions and control groups

Physical exercise categorized using an adaptation of the ProFaNE taxonomy (Lamb 2011)

Type of physical exer- Description Examples of interventions in-

cise cluded in this review

Aqua-based training Interventions that are delivered in an aquatic setting Aquatic ai chi, aquatic exercise
training, Halliwick aquatic exer-
cises, water-based physiotherapy

Dance Dance interventions or interventions that comprise components typ- Dance therapy, Ronnie Gardiner
ically involved in dancing rhythm and music method, tan-
go, waltz/foxtrot

Endurance training Interventions that primarily address participants' endurance Aerobic training, brisk walking,
high-cadence cycling, Nordic
walking, speed treadmill training

Flexibility training Interventions that primarily address participants' flexibility Flexibility exercises, stretching

Gait/balance/functional Interventions that involve gait training (i.e. training that involves cor- Functional mobility training, Hi-
training rection of walking technique and changes of pace, level and direc- Balance training, treadmill train-
tion), and/or balance training (i.e. training that involves the efficient ing
transfer of body weight or challenges aspects of the balance sys-
tems) or balance retraining activities and/or functional training (i.e.
training that utilises functional activities as the training stimulus)

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Gaming Interventions that involve structured, physical exercises delivered via Exergaming, Nintendo Wii train-
video-games and/or virtual reality applications, and may not be cate- ing
gorized using any of the other exercise categories

LSVT BIG Interventions that deliver the 'Lee Silverman Voice Training BIG' pro- LSVT BIG
gram

Mind-body training Interventions that primarily address the mind and body Tai chi, qigong, yoga

Multi-domain training Interventions that involve a balanced combination of components Multidisciplinary intensive reha-
associated with multiple exercise categories bilitation treatment, multimodal
exercise training, physiotherapy,
rehabilitation exercises

Strength/resistance Interventions that involve all types of weight training (i.e. training Muscle power training, progres-
training that involves contracting the muscles against a resistance to over- sive resistance exercise
load and bring about a training effect in the muscular system)

Control groups

Type of control group Description Examples of interventions included in this review

Active control group Structured, supervised, non-physical inter- Education program, mental/leisure program, speech
ventions and communication training

Passive control group No intervention, unstructured interventions Conventional care, educational brochure, home walking,
without supervision (including general physi- medication only, wait-list control
cal activity), or usual care

Appendix 2. CENTRAL search strategy

Cochrane Central Register of Controlled Trials (via CRSonline)

# Searches

1 MESH DESCRIPTOR Parkinson Disease EXPLODE ALL TREES

2 parkinson*

3 #1 or #2

4 MESH DESCRIPTOR Software EXPLODE ALL TREES

5 software:TI,AB,KY

6 (game or gaming or play* or simulation* or program* or techni* or video):TI,AB,KY

7 MESH DESCRIPTOR Virtual Reality Exposure Therapy EXPLODE ALL TREES

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8 (user-computer interface or interactive or virtual* or vr or augmented or exergam* or kinect or nin-

tendo wii or microsoft xbox):TI,AB,KY

9 #4 OR #5 OR #6 OR #7 OR #8

10 biofeedback:TI,AB,KY

11 MESH DESCRIPTOR movement EXPLODE ALL TREES

12 movement:TI,AB,KY

13 MESH DESCRIPTOR Physical Therapy Modalities EXPLODE ALL TREES

14 MESH DESCRIPTOR Physical Fitness EXPLODE ALL TREES

15 fitness:TI,AB,KY

16 MESH DESCRIPTOR Muscle Strength EXPLODE ALL TREES

17 (strength or muscle or locomot*):TI,AB,KY

18 MESH DESCRIPTOR Muscle Strength EXPLODE ALL TREES

19 ((weight* next body*) or (weight* near2 training*) or motor activity):TI,AB,KY

20 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19

21 MESH DESCRIPTOR Exercise EXPLODE ALL TREES

22 (exercise* or activit* or sport* or train* or intervention* or condition*):TI,AB,KY

23 MESH DESCRIPTOR Physical Endurance EXPLODE ALL TREES

24 endurance:TI,AB,KY

25 MESH DESCRIPTOR Gait EXPLODE ALL TREES

26 (gait* or postural balance):TI,AB,KY

27 MESH DESCRIPTOR Dancing EXPLODE ALL TREES

28 (danc* or tango):TI,AB,KY

29 MESH DESCRIPTOR Martial Arts EXPLODE ALL TREES

30 (martial art* or aerobic or boxing or shadowboxing or treadmill* or karate):TI,AB,KY

31 MESH DESCRIPTOR Walking EXPLODE ALL TREES

32 walking:TI,AB,KY

33 MESH DESCRIPTOR Bicycling EXPLODE ALL TREES

34 (bicycle* or cycl*):TI,AB,KY

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35 #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR
#34

36 MESH DESCRIPTOR Medicine, Chinese Traditional EXPLODE ALL TREES

37 (traditional chinese exercise):TI,AB,KY

38 #36 OR #37

39 MESH DESCRIPTOR Mind-Body Therapies EXPLODE ALL TREES

40 ((mind near1 body)):TI,AB,KY

41 MESH DESCRIPTOR Tai Ji EXPLODE ALL TREES

42 ((chi near1 tai) or (tai near1 ji*) ):TI,AB,KY

43 (taiji* or taichi* or t'ai chi or wuqinxi or baduanjin or yijiejing):TI,AB,KY

44 MESH DESCRIPTOR Qigong EXPLODE ALL TREES

45 (qi-gong* or qigong* or (qi* near2 (gong* or kung* or chung* or gung*)) or (chi* near2 (gong* or
kung* or chung* or gung*))):TI,AB,KY

46 (yoga or asana or pranayama or dhyana or pilates):TI,AB,KY

47 #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46

48 MESH DESCRIPTOR Rehabilitation EXPLODE ALL TREES

49 (rehab* or telerehab*):TI,AB,KY

50 MESH DESCRIPTOR Therapeutics EXPLODE ALL TREES

51 therap* or physical* or physiotherapy or exercise therapy

52 MESH DESCRIPTOR Exercise Test EXPLODE ALL TREES

53 (exercise test or strengthening program* or progressive resistance training or cardiorespirato-

ry):TI,AB,KY

54 MESH DESCRIPTOR Cardiovascular System EXPLODE ALL TREES

55 (cardiovascular or aqua* or hydrotherapy or lsvt-big or lsvtbig or ("Lee Silverman Voice Treatment"

and big) or periodicity or socio environmental):TI,AB,KY

56 (whole body near1 vibration*):TI,AB,KY

57 #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56

58 #9 OR #20 OR #35 OR #38 OR #47 OR #57

59 #3 AND #58

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Appendix 3. MEDLINE search strategy

Medline (via OvidSP)

# Searches

1 exp PARKINSON DISEASE/

2 parkinson*.tw,kf.

3 or/1-2

4 exp SOFTWARE/

5 software.mp.

6 game.mp.

7 gaming.mp.

8 play*.mp.

9 simulation*.mp.

10 program*.mp.

11 techni*.mp.

12 video.mp.

13 VIRTUAL REALITY EXPOSURE THERAPY/

14 user-computer interface.mp.

15 interactive.mp.

16 virtual*.mp.

17 vr.mp.

18 augmented.mp.

19 exergam*.mp.

20 kinect.mp.

21 nintendo wii.mp.

22 microsoft xbox.mp.

23 or/4-22

24 biofeedback.mp.

25 exp MOVEMENT/

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26 movement.mp.

27 exp PHYSICAL THERAPY MODALITIES/

28 exp PHYSICAL FITNESS/

29 fitness.mp.

30 exp MUSCLE STRENGTH/

31 strength.mp.

32 muscle.mp.

33 locomot*.mp.

34 exp BODY WEIGHT/

35 (weight* adj1 body*).mp.

36 (weight* adj2 training*).mp.

37 motor activity.mp.

38 or/24-37

39 exp EXERCISE/

40 exercise*.mp.

41 activit*.mp.

42 sport*.mp.

43 train*.mp.

44 intervention*.mp.

45 condition*.mp.

46 exp PHYSICAL ENDURANCE/

47 endurance.mp.

48 exp GAIT/

49 gait*.mp.

50 postural balance.mp.

51 exp DANCING/

52 danc*.mp.

53 tango.mp.

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54 exp MARTIAL ARTS/

55 martial art*.mp.

56 aerobic.mp.

57 (boxing or shadowboxing).mp.

58 treadmill*.mp.

59 karate.mp.

60 exp WALKING/

61 walking.mp.

62 BICYCLING/

63 bicycle*.mp.

64 or/39-63

65 MEDICINE, CHINESE TRADITIONAL/

66 traditional chinese exercise.mp.

67 or/65-66

68 exp MIND-BODY THERAPIES/

69 (mind adj1 body).mp.

70 Tai ji/

71 ((chi adj1 tai) or (tai adj1 ji*) or taiji* or taichi* or t'ai chi).mp.

72 (wuqinxi or baduanjin or yijiejing).mp.

73 QIGONG/

74 (qi-gong* or qigong*).mp.

75 ((qi* adj2 (gong* or kung* or chung* or gung*)) or (chi* adj2 (gong* or kung* or chung* or
gung*))).mp.

76 yoga.mp.

77 (asana or pranayama or dhyana).mp.

78 pilates.mp.

79 or/68-78

80 exp REHABILITATION/

81 rehab*.mp.

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82 exp THERAPEUTICS/

83 therap*.mp.

84 physical*.mp.

85 physiotherapy.mp.

86 exercise therapy.mp.

87 exp EXERCISE TEST/

88 exercise test.mp.

89 strengthening program*.mp.

90 progressive resistance training.mp.

91 cardiorespiratory.mp.

92 exp CARDIOVASCULAR SYSTEM/

93 cardiovascular.mp.

94 aqua*.mp.

95 hydrotherapy.mp.

96 (lsvt-big or lsvtbig).mp.

97 ("Lee Silverman Voice Treatment" and big).mp.

98 periodicity.mp.

99 socio environmental.mp.

100 (whole body adj1 vibration*).mp.

101 or/80-100

102 23 or 38 or 64 or 67 or 79 or 101

103 randomized controlled trial.pt.

104 controlled clinical trial.pt.

105 randomi?ed.ab.

106 placebo.ab.

107 clinical trials as topic.sh.

108 randomly.ab.

109 trial.ti.

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110 or/103-109

111 exp animals/ not humans/

112 110 not 111

113 3 and 102 and 112

key: exp # /: explode # MeSH subject heading, tw: text word. kf: keyword heading word mp: multiple purpose, ti: title, ab: abstract, pt:
publication type, *: truncation, ?: wildcard, adj#: adjacent within # number of words
searchline #103-#112 Cochrane RCT-Filter, sensitivity- and precision-maximizing version

Appendix 4. Embase search strategy

Embase (via Ovid)

# Searches

1 PARKINSON DISEASE/

2 parkinson*.tw.

3 or/1-2

4 exp SOFTWARE/

5 software.tw.

6 game.tw.

7 gaming.tw.

8 play*.tw.

9 simulation*.tw.

10 program*.tw.

11 techni*.tw.

12 video.tw.

13 VIRTUAL REALITY EXPOSURE THERAPY/

14 user-computer interface.tw.

15 interactive.tw.

16 virtual*.tw.

17 vr.tw.

18 augmented.tw.

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19 exergam*.tw.

20 kinect.tw.

21 nintendo wii.tw.

22 microsoft xbox.tw.

23 or/4-22

24 biofeedback.tw.

25 exp "MOVEMENT (PHYSIOLOGY)"/

26 movement.tw.

27 exp PHYSIOTHERAPY/

28 exp FITNESS/

29 fitness.tw.

30 MUSCLE STRENGTH/

31 strength.tw.

32 muscle.tw.

33 locomot*.tw.

34 exp BODY WEIGHT/

35 (weight* adj1 body*).tw.

36 (weight* adj2 training*).tw.

37 motor activity.tw.

38 or/24-37

39 exp EXERCISE/

40 exercise*.tw.

41 activit*.tw.

42 sport*.tw.

43 train*.tw.

44 intervention*.tw.

45 condition*.tw.

46 ENDURANCE/

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47 endurance.tw.

48 exp GAIT/

49 gait*.tw.

50 postural balance.tw.

51 exp DANCING/

52 danc*.tw.

53 tango.tw.

54 exp MARTIAL ART/

55 martial art*.tw.

56 aerobic.tw.

57 (boxing or shadowboxing).tw.

58 treadmill*.tw.

59 karate.tw.

60 exp WALKING/

61 walking.tw.

62 CYCLING/

63 (bicycle* or cycling).tw.

64 or/39-63

65 CHINESE MEDICINE/

66 traditional chinese exercise.tw.

67 or/65-66

68 (mind adj1 body).tw.

69 TAI CHI/

70 ((chi adj1 tai) or (tai adj1 ji*) or taiji* or taichi* or t'ai chi).tw.

71 (wuqinxi or baduanjin or yijiejing).tw.

72 QIGONG/

73 (qi-gong* or qigong* or chi kung* or chigung*).tw.

74 ((qi* adj2 (gong* or kung* or chung* or gung*)) or (chi* adj2 (gong* or kung* or chung* or
gung*))).tw.

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75 yoga.tw.

76 (asana or pranayama or dhyana).tw.

77 pilates.tw.

78 exp ALTERNATIVE MEDICINE/

79 or/68-78

80 REHABILITATION/

81 rehab*.tw.

82 THERAPEUTICS/

83 therap*.tw.

84 physical*.tw.

85 physiotherapy.tw.

86 exercise therapy.tw.

87 exp EXERCISE TEST/

88 exercise test.tw.

89 strengthening program*.tw.

90 progressive resistance training.tw.

91 cardiorespiratory.tw.

92 exp CARDIOVASCULAR SYSTEM/

93 cardiovascular.tw.

94 aqua*.tw.

95 hydrotherapy.tw.

96 (lsvt-big or lsvtbig).tw.

97 ("Lee Silverman Voice Treatment" and big).tw.

98 periodicity.tw.

99 socio environmental.tw.

100 or/80-99

101 (whole body adj1 vibration*).tw.

102 23 or 38 or 64 or 67 or 79 or 100 or 101

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103 3 and 102

104 (double adj1 blind*).sh,ab,ti. or placebo*.ab,ti. or blind*.ab,ti.

105 3 and 102 and 104

106 limit 105 to medline

107 105 not 106

Appendix 5. CINAHL search strategy

CINAHL (via EBSCO)

# Searches

1 (MH "PARKINSON DISEASE")

2 TX parkinson*

3 software*

4 game OR gaming OR play*

5 program* OR techni* OR video

6 (MH "VIRTUAL REALITY EXPOSURE THERAPY")

7 user-computer interface

8 interactive OR virtual* OR vr

9 augmented OR exergam* OR kinect OR nintendo wii OR microsoft xbox

10 S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9

11 (MH "BIOFEEDBACK")

12 biofeedback

13 (MH "MOVEMENT+")

14 movement

15 (MH "PHYSICAL THERAPY+")

16 (MH "PHYSICAL FITNESS+")

17 fitness

18 (MH "MUSCLE STRENGTH+")

19 strength OR muscle OR locomot*

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20 (MH "BODY WEIGHT+")

21 (weight* N1 body*) OR (weight* N2 training*) OR motor activity

22 S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21

23 (MH "EXERCISE+")

24 exercise* OR activit* OR sport*

25 train* OR intervention* OR condition*

26 (MH "PHYSICAL ENDURANCE+")

27 endurance

28 (MH "Gait+") OR (MH "Gait Training+")

29 gait* OR postural balance

30 (MH "Dancing+")

31 danc* OR tango

32 (MH "MARTIAL ARTS")

33 martial art* OR aerobic OR ( (boxing or shadowboxing) ) OR treadmill* OR karate

34 (MH "WALKING+")

35 walking

36 (MH "CYCLING")

37 bicycle* OR cycl*

38 S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR
S36 OR S37

39 (MH "MEDICINE, CHINESE TRADITIONAL+")

40 traditional chinese exercise

41 S39 OR S40

42 (MH "MIND BODY TECHNIQUES+")

43 mind body

44 (MH "TAI CHI")

45 chi N1 tai OR tai N1 ji* OR taiji* OR taichi* OR t'ai chi

46 wuqinxi OR baduanjin OR yijiejing

47 (MH "QIGONG")

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48 qi-gong* OR qigong*

49 ( qi* N2 (gong* OR kung* OR chung* OR gung*) ) OR ( chi* N2 (gong* OR kung* OR chung* OR

gung*) )

50 (MH "YOGA+")

51 yoga OR asana OR pranayama OR dhyana

52 (MH "PILATES")

53 S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51 OR S52

54 (MH "REHABILITATION+")

55 rehab*

56 (MH "THERAPEUTICS")

57 therap* OR physical* OR physiotherapy OR exercise therapy

58 (MH "EXERCISE TEST")

59 exercise test OR strengthening program* OR progressive resistance training

60 (MH "CARDIOVASCULAR SYSTEM+")

61 cardiorespiratory OR cardiovascular

62 (MH "HYDROTHERAPY+")

63 aqua* OR hydrotherapy

64 ( lsvt-big OR lsvtbig ) OR ( "Lee Silverman Voice Treatment" AND big )

65 periodicity OR socio environmental OR (whole body vibration*)

66 S54 OR S55 OR S56 OR S57 OR S58 OR S59 OR S60 OR S61 OR S62 OR S63 OR S64 OR S65

67 S10 OR S22 OR S38 OR S41 OR S53 OR S66

68 (S1 or S2) and S67

69 randomized OR randomised OR treatment outcome* OR clinical trial*

70 S68 AND S69

Appendix 6. SPORTDiscus search strategy

SPORTDiscus (via EBSCO)

# Searches

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1 DE "PARKINSON'S disease"

2 TX parkinson*

3 S1 OR S2

4 DE "ELECTRONIC games" OR DE "COMPUTER games" OR DE "INTERNET games" OR DE "MULTI-

PLAYER games" OR DE "VIDEO games" OR DE "EXERCISE video games" OR DE "NINTENDO Wii Fit
games"

5 TX software OR TX game OR TX gaming OR TX play*

6 TX simulation* OR TX program* OR TX video

7 VIRTUAL REALITY EXPOSURE THERAPY

8 TX user-computer interface OR TX interactive OR TX virtual*

9 TX vr OR TX augmented OR TX exergam*

10 TX kinect OR TX nintendo wii OR TX microsoft xbox

11 S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10

12 TX biofeedback

13 (DE "BODY movement" OR DE "ABDUCTION (Kinesiology)" OR DE "ADDUCTION" OR DE "MOVE-

MENT therapy")

14 TX movement OR TX fitness

15 DE "PHYSICAL therapy" OR DE "BALNEOLOGY" OR DE "COLD therapy" OR DE "ELECTROTHER-

APEUTICS" OR DE "HYDROTHERAPY" OR DE "LIANGONG" OR DE "MANIPULATION therapy" OR
DE "OCCUPATIONAL therapy" OR DE "PHOTOTHERAPY" OR DE "RECREATIONAL therapy" OR DE
"SPORTS physical therapy" OR DE "THERMOTHERAPY" OR DE "VETERINARY physical therapy"

16 DE "PHYSICAL fitness" OR DE "ANAEROBIC exercises" OR DE "ASTROLOGY & physical fitness" OR

DE "BODYBUILDING" OR DE "CARDIOPULMONARY fitness" OR DE "CARDIOVASCULAR fitness" OR
DE "CIRCUIT training" OR DE "COMPOUND exercises" OR DE "EXERCISE tolerance" OR DE "ISO-
LATION exercises" OR DE "LIANGONG" OR DE "MUSCLE strength" OR DE "PERIODIZATION training"
OR DE "PHYSICAL fitness for children" OR DE "PHYSICAL fitness for girls" OR DE "PHYSICAL fitness
for men" OR DE "PHYSICAL fitness for older people" OR DE "PHYSICAL fitness for people with dis-
abilities" OR DE "PHYSICAL fitness for women" OR DE "PHYSICAL fitness for youth" OR DE "SPORT
for all"

17 DE "HUMAN locomotion" OR DE "GAIT in humans" OR DE "HOPPING (Locomotion)" OR DE "HUMAN

climbing" OR DE "JUMPING" OR DE "PARKOUR" OR DE "RUNNING" OR DE "SKIPPING" OR DE "STAIR
climbing" OR DE "SWIMMING" OR DE "WALKING" OR DE "LOCOMOTION" OR DE "ANIMAL locomo-
tion" OR DE "AUTOMOBILES" OR DE "BOATS & boating" OR DE "CYCLING" OR DE "FLIGHT" OR DE
"HORSEMANSHIP" OR DE "HUMAN locomotion" OR DE "TURNING (Locomotion)"

18 DE "MUSCLE strength" OR DE "GRIP strength" OR DE "KRAUS-Weber test"

19 DE "STRENGTH training" OR DE "WEIGHT lifting"

20 TX strength OR TX muscle OR TX locomot*

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21 DE "BODY weight" OR DE "LEANNESS" OR DE "OBESITY"

22 TX weight* N1 body* OR TX weight* N2 training* AND TX motor activity

23 S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22

24 DE "EXERCISE" OR DE "ABDOMINAL exercises" OR DE "AEROBIC exercises" OR DE "ANAEROBIC

exercises" OR DE "AQUATIC exercises" OR DE "ARM exercises" OR DE "BACK exercises" OR DE
"BREATHING exercises" OR DE "BREEMA" OR DE "BUTTOCKS exercises" OR DE "CALISTHENICS"
OR DE "CHAIR exercises" OR DE "CHEST exercises" OR DE "CIRCUIT training" OR DE "COMPOUND
exercises" OR DE "COOLDOWN" OR DE "DO-in" OR DE "EXERCISE adherence" OR DE "EXERCISE
for children" OR DE "EXERCISE for girls" OR DE "EXERCISE for men" OR DE "EXERCISE for mid-
dle-aged persons" OR DE "EXERCISE for older people" OR DE "EXERCISE for people with disabili-
ties" OR DE "EXERCISE for women" OR DE "EXERCISE for youth" OR DE "EXERCISE therapy" OR DE
"EXERCISE video games" OR DE "FACIAL exercises" OR DE "FALUN gong exercises" OR DE "FOOT
exercises" OR DE "GYMNASTICS" OR DE "HAND exercises" OR DE "HATHA yoga" OR DE "HIP exer-
cises" OR DE "ISOKINETIC exercise" OR DE "ISOLATION exercises" OR DE "ISOMETRIC exercise"
OR DE "ISOTONIC exercise" OR DE "KNEE exercises" OR DE "LEG exercises" OR DE "LIANGONG"
OR DE "METABOLIC equivalent" OR DE "MULAN quan" OR DE "MUSCLE strength" OR DE "PILATES
method" OR DE "PLYOMETRICS" OR DE "QI gong" OR DE "REDUCING exercises" OR DE "RUNNING"
OR DE "RUNNING -- Social aspects" OR DE "SCHOOL exercises & recreations" OR DE "SEXUAL exer-
cises" OR DE "SHOULDER exercises" OR DE "STRENGTH training" OR DE "STRESS management ex-
ercises" OR DE "TAI chi" OR DE "TREADMILL exercise" OR DE "WHEELCHAIR workouts" OR DE "YO-
GA"

25 TX exercise* OR TX activit* OR TX sport*

26 TX train* OR TX intervention* OR TX condition*

27 PHYSICAL ENDURANCE

28 TX endurance

29 DE "GAIT in humans"

30 TX gait OR TX postural balance

31 DE "DANCE" OR DE "AERIAL dance" OR DE "AEROBIC dancing" OR DE "BALLET" OR DE "BALLROOM

dancing" OR DE "BELLY dance" OR DE "BREAK dancing" OR DE "CHA-cha (Dance)" OR DE "COUN-
TRY dancing" OR DE "DANCE & globalization" OR DE "DANCE for people with disabilities" OR DE
"FLAMENCO" OR DE "FOLK dancing" OR DE "FREE skating" OR DE "HIP-hop dance" OR DE "ICE
dancing" OR DE "JAZZ dance" OR DE "LINE dancing" OR DE "LION dance" OR DE "MODERN dance"
OR DE "MOVEMENT notation" OR DE "ORIGINAL set pattern dance (Skating)" OR DE "POLE danc-
ing" OR DE "ROUND dancing" OR DE "SALSA (Dance)" OR DE "SHISHIMAI (Dance)" OR DE "STEP
dancing" OR DE "TANGO (Dance)" OR DE "TAP dancing"

34 TX danc* OR TX tango

35 DE "MARTIAL arts" OR DE "ARCHERY" OR DE "BUDO" OR DE "DUELING" OR DE "EAST Asian mar-

tial arts" OR DE "ESCRIMA" OR DE "HAND-to-hand fighting" OR DE "JEET Kune Do" OR DE "JU-
kenpo" OR DE "KAJUKENBO" OR DE "KALARIPPAYATTU" OR DE "KENJUTSU" OR DE "KENPO" OR
DE "KICKBOXING" OR DE "KRAV maga" OR DE "KUN-tao" OR DE "KYUDO (Archery)" OR DE "LION
dance" OR DE "MARTIAL arts for children" OR DE "MARTIAL arts for people with disabilities" OR DE
"MIXED martial arts" OR DE "NINJUTSU" OR DE "PENCAK silat" OR DE "SAN-jitsu" OR DE "SHISHI-
MAI (Dance)" OR DE "SPEAR fighting"

36 TX martial art* OR TX aerobic OR TX ( (boxing or shadowboxing) )

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37 TX treadmill* OR TX karate

38 DE "WALKING" OR DE "FITNESS walking" OR DE "GAIT in humans" OR DE "HIKING" OR DE "LONG

distance walking" OR DE "VIERDAAGSE (Walking event)"

39 TX walking

40 DE "CYCLING" OR DE "BICYCLE commuting" OR DE "BICYCLE racing" OR DE "BICYCLE touring" OR

DE "CYCLING ability testing" OR DE "CYCLING competitions" OR DE "CYCLING for people with dis-
abilities" OR DE "MOTORCYCLING" OR DE "MOUNTAIN biking" OR DE "NIGHT cycling" OR DE "RAIL-
BIKING" OR DE "STUNT cycling" OR DE "URBAN cycling" OR DE "WOMEN'S cycling"

41 TX bicycle*

42 DE "HUMAN locomotion" OR DE "GAIT in humans" OR DE "HOPPING (Locomotion)" OR DE "HUMAN

climbing" OR DE "JUMPING" OR DE "PARKOUR" OR DE "RUNNING" OR DE "SKIPPING" OR DE "STAIR
climbing" OR DE "SWIMMING" OR DE "WALKING" OR DE "LOCOMOTION" OR DE "ANIMAL locomo-
tion" OR DE "AUTOMOBILES" OR DE "BOATS & boating" OR DE "CYCLING" OR DE "FLIGHT" OR DE
"HORSEMANSHIP" OR DE "HUMAN locomotion" OR DE "TURNING (Locomotion)"

43 S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR
S37 OR S38 OR S39 OR S40 OR S41OR S42

44 TX traditional chinese N1 exercise

45 DE "MIND & body" OR DE "ALEXANDER technique" OR DE "BIOFEEDBACK training" OR DE "BODY

image" OR DE "INFLUENCE of age on ability" OR DE "MIND-body walking" OR DE "PSYCHOSOMATIC
medicine"

46 mind N1 body

47 (DE "TAI chi" OR DE "TAI chi for children") OR (DE "TAI chi" OR DE "TAI chi for children")

48 TX chi N1 tai OR TX tai N1 ji* OR TX taiji* OR TX taichi* OR TX t'ai chi

49 TX wuqinxi OR TX baduanjin OR TX yijiejing

50 TX qi-gong* OR TX qigong* OR TX ( qi* N2 (gong* OR kung* OR chung* OR gung*) ) OR TX ( chi* N2

(gong* OR kung* OR chung* OR gung*) )

51 DE "YOGA" OR DE "ASTANGA yoga" OR DE "CHAKRAS" OR DE "HATHA yoga" OR DE "KUNDALINI yo-

ga" OR DE "MUSIC for yoga" OR DE "SIDDHA yoga (Service mark)" OR DE "YIN yoga" OR DE "YOGA
for children" OR DE "YOGA for people with disabilities"

52 TX yoga OR TX asana OR TX pranayama OR TX dhyana

53 DE "PILATES method"

54 TX pilates

55 S44 OR S45 OR S46 OR S47 OR S48 OR S49 OR S50 OR S51 OR S52 OR S53 OR S54

56 DE "REHABILITATION" OR DE "AQUATIC exercises -- Therapeutic use" OR DE "MEDICAL rehabilita-

tion" OR DE "NEUROPSYCHOLOGICAL rehabilitation"

57 TX rehab*

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58 DE "THERAPEUTICS"

59 TX therap*

60 TX physical* OR TX physiotherapy OR TX strengthening program*

61 DE "PHYSIOLOGICAL therapeutics" OR DE "CRANIOSACRAL therapy" OR DE "DIET therapy" OR

DE "ELECTROTHERAPEUTICS" OR DE "EXERCISE therapy" OR DE "EXTRACORPOREAL shock wave
therapy" OR DE "MAGNETOTHERAPY" OR DE "MASSAGE therapy" OR DE "MECHANOTHERAPY" OR
DE "OCCUPATIONAL therapy" OR DE "PHOTOTHERAPY" OR DE "PHYSICAL therapy" OR DE "RE-
FLEXOTHERAPY" OR DE "REST" OR DE "PHYSICAL therapy"

62 DE "CARDIOVASCULAR system" OR DE "ANAEROBIC capacity" OR DE "BLOOD-vessels" OR DE

"HEART"

63 TX progressive resistance N1 training OR TX cardiorespiratory OR TX cardiovascular

64 DE "HYDROTHERAPY"

65 TX lsvt-big OR TX lsvtbig OR TX ( ("Lee Silverman Voice Treatment" AND big )

66 TX periodicity OR TX socio environmental

67 TX whole body N1 vibration

68 S56 OR S57 OR S58 OR S59 OR S60 OR S61 OR S62 OR S63 OR S64 OR S65 OR S66 OR S67

69 S11 OR S23 OR S43 OR S55 OR S68

70 S3 AND S69

71 TX ((clinic$ or controlled or comparative or placebo or prospective or randomised or randomized)

and (trial or study))

72 TX (random* and (allocat* or allot* or assign* or basis* or divid* or order*))

73 TX ((singl* or doubl* or trebl* or tripl*) and (blind* or mask*))

74 TX (cross?over or (cross over))

75 TX "randomi?ed control* trial*"

76 TX ((allocat* or allot* or assign* or divid*) and (condition* or experiment* or intervention* or treat-

ment* or therap* or control* or group*))

77 TX placebo*

78 S71 OR S72 OR S73 OR S74 OR S75 OR S76 OR S77

79 S70 AND S78

Appendix 7. AMED search strategy

AMED (Allied and Complementary Medicine) (via Ovid)

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# Searches

1 PARKINSON DISEASE/

2 parkinson*.tw.

3 or/1-2

4 exp SOFTWARE/

5 software.tw.

6 game.tw.

7 gaming.tw.

8 play*.tw.

9 simulation*.tw.

10 program*.tw.

11 techni*.tw.

12 video.tw.

13 VIRTUAL REALITY/

14 user-computer interface.tw.

15 interactive.tw.

16 virtual*.tw.

17 vr.tw.

18 augmented.tw.

19 exergam*.tw.

20 kinect.tw.

21 nintendo wii.tw.

22 microsoft xbox.tw.

23 biofeedback.tw.

24 MOVEMENT/

25 movement.tw.

26 PHYSICAL FITNESS/

27 exp PHYSICAL THERAPY MODALITIES/

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28 MUSCLE STRENGTH/

29 strength.tw.

30 muscle.tw.

31 locomot*.tw.

32 exp BODY WEIGHT/

33 (weight* adj1 body*).tw.

34 (weight* adj2 training*).tw.

35 motor activity.tw.

36 exp EXERCISE/

37 exercise*.tw.

38 activit*.tw.

39 SPORT/

40 sport*.tw.

41 train*.tw.

42 intervention*.tw.

43 condition*.tw.

44 ENDURANCE/

45 endurance.tw.

46 exp GAIT/

47 gait*.tw.

48 postural balance.tw.

49 exp DANCING/

50 danc*.tw.

51 tango.tw.

52 exp MARTIAL ARTS/

53 martial art*.tw.

54 aerobic.tw.

55 BOXING/

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56 (boxing or shadowboxing).tw.

57 treadmill*.tw.

58 karate.tw.

59 exp WALKING/

60 walking.tw.

61 BYCYCLING/

62 (bicycle* or cycling).tw.

63 TRADITIONAL MEDICINE CHINESE/

64 traditional chinese exercise.tw.

65 (mind adj1 body).tw.

66 exp TAI CHI/

67 ((chi adj1 tai) or (tai adj1 ji*) or taiji* or taichi* or t'ai chi).tw.

68 (wuqinxi or baduanjin or yijiejing).tw.

69 QIGONG/

70 (qi-gong* or qigong* or chi kung* or chigung*).tw.

71 ((qi* adj2 (gong* or kung* or chung* or gung*)) or (chi* adj2 (gong* or kung* or chung* or
gung*))).tw.

72 YOGA/

73 yoga.tw.

74 (asana or pranayama or dhyana).tw.

75 pilates.tw.

76 REHABILITATION/

77 rehab*.tw.

78 THERAPEUTICS/

79 therap*.tw.

80 PHYSICAL FITNESS/

81 physical*.tw.

82 physiotherapy.tw.

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83 PHYSICAL THERAPY MODALITIES/ or exp EXERCISE MOVEMENT TECHNIQUES/ or exp EXERCISE

THERAPY/

84 exercise therapy.tw.

85 exp EXERCISE TESTING/

86 exercise test.tw.

87 strengthening program*.tw.

88 progressive resistance training.tw.

89 cardiorespiratory.tw.

90 exp CARDIOVASCULAR SYSTEM/

91 cardiovascular.tw.

92 aqua*.tw.

93 HYDROTHERAPY/

94 hydrotherapy.tw.

95 (lsvt-big or lsvtbig).tw.

96 ("Lee Silverman Voice Treatment" and big).tw.

97 periodicity.tw.

98 socio environmental.tw.

99 (whole body adj1 vibration*).tw.

100 or/4-99

101 randomized controlled trial.tw.

102 controlled clinical trial.tw.

103 randomized.ab.

104 placebo.ab.

105 drug therapy.tw.

106 randomly.ab.

107 trial.ab.

108 groups.ab.

109 or/101-108

110 ANIMALS/ not HUMANS/

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111 109 not 110

112 3 and 100 and 111

Appendix 8. REHABDATA search strategy

Containing all of the words: Parkinson*,
containing at least one of the word(s): "software" or "game" or "gaming" or "play* or "simulation" or "program*" or "techni*" or "video" or
"interface" or "virtual" or "vr" or "augmented" or "exergam*" or "Kinect" or "Nintendo wii" or "xbox" or "biofeedback" or "movement" or
"fitness" or "strength" or "muscle" or "locomot*" or "body weight" or "exercise" or "activit*" or "sport*" or "train*" or "intervention*" or
"condition*" or "endurance" or "gait" or "danc*" or "tango" or "martial art*" or "aerobic" or "boxing" or "shadowboxing" or "treadmill*"
or "karate" or "walking" or "bicycli*" or "cycl*" or " "mind body" or "body mind" or "tai ji" or "rehab*" or "telerehab*" or "therap*" or
"physical*" or "physiotherapy*" or "strengthening" or "cardiorespiratory" or "cardiovascular" or "aqua*" or "hydrotherapy*" or "lsvtbig"
or "lsvt big" or "periodicity" or "socio environmental" or "whole body"

Appendix 9. PEDro search strategy

Title & abstract: parkinson* and method: clinical trial

Appendix 10. Trial register search strategies (Clinicaltrials.gov, WHO ICTRP, ISRCTN, EUCTR)
Clinicaltrials.gov search strategy:

Advanced search
Conditions: Parkinson
Interventions: software OR game OR play OR simulation OR program OR video OR interface OR virtual OR vr OR augmented OR exergame
OR Kinect OR Nintendo OR wii OR Recruitment: All studies
Study type: Interventional studies
Conditions: Parkinson
Interventions: biofeedback OR movement OR fitness OR strength OR muscle OR locomot OR body weight OR exercise OR activit OR sport*
OR train* OR intervention* OR endurance OR gait Recruitment: All studies
Study type: Interventional studies
Conditions: Parkinson
Interventions: dance OR tango OR martial art OR aerobic OR boxing OR shadowboxing OR treadmill OR karate OR walking OR bicycli OR
cycl OR mind body OR tai ji Recruitment: All studies
Study type: Interventional studies
Conditions: Parkinson
Interventions:rehabilitation OR telerehabilitation OR physical OR physiotherapy OR strengthening OR cardiorespiratory OR cardiovascular
Recruitment: All studies
Study type: Interventional studies
Conditions: Parkinson
Interventions: aqua OR hydrotherapy OR lsvtbig OR lsvt-big OR Lee Silverman Voice OR periodicity OR socio environmental OR whole body
Recruitment: All studies
Study type: Interventional studies

WHO ICTRP search strategy:

Advanced search
Condition: Parkinson*
Intervention: software OR gam*
Recruitment status: ALL
Condition: Parkinson*
Intervention: play* OR simulation OR program* OR techni* OR video OR interface
Recruitment status: ALL
Condition: Parkinson*
Intervention: virtual OR vr OR augmented OR exergam*
Recruitment status: ALL
Condition: Parkinson*
Intervention: kinect OR Nintendo wii OR xbox
Recruitment status: ALL

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Condition: Parkinson*
Intervention: biofeedback OR movement OR fitness
Recruitment status: ALL
Condition: Parkinson*
Intervention: strength OR muscle OR locomot*
Recruitment status: ALL
Condition: Parkinson*
Intervention: body weight OR exercise
Recruitment status: ALL
Condition: Parkinson*
Intervention: activit* OR sport* OR train*
Recruitment status: ALL
Condition: Parkinson*
Intervention: condition* OR endurance OR gait
Recruitment status: ALL
Condition: Parkinson*
Intervention: danc* OR tango
Recruitment status: ALL
Condition: Parkinson*
Intervention: martial art* OR aerobic OR boxing OR shadowboxing OR treadmill* OR karate
Recruitment status: ALL
Condition: Parkinson*
Intervention: walking OR bicycli* OR cycl* OR mind body OR tai ji
Recruitment status: ALL
Condition: Parkinson*
Intervention: rehab* OR telerehab* OR therap* OR physical* OR physiotherapy*
Recruitment status: ALL
Condition: Parkinson*
Intervention: strengthening OR cardiorespiratory OR cardiovascular OR aqua* OR hydrotherapy*
Recruitment status: ALL
Condition: Parkinson*
Intervention: Lee Silverman Voice OR lsvtbig OR lsvt-big OR periodicity OR socio environmental OR whole body
Recruitment status: ALL

ISRCTNsearch strategy:
Condition: Parkinson

EU clinical trials register search strategy:

Parkinson

Appendix 11. Network estimates of effects and prediction intervals for physical exercise in people with Parkinson’s
disease on severity of motor signs

Patient or population: people with Parkinson's disease

Interventions: physical exercise including aqua-based training, dance, endurance training, flexibility training, gait/balance/function-
al training, gaming, LSVT BIG, mind-body training, multi-domain training, and strength/resistance training
Comparison: passive control group (mean [median] UPDRS-M score = 21.34 [19.80])*
Outcome: severity of motor signs, measured with UPDRS-M, scale from 0 to 108 (worse)
Settings: inpatient and outpatient care

Total studies: 71 RCTs Estimated absolute effects on severity of

motor signs (SMD and 95% PI)
Total participants: 3196

Dance -0.77 (-1.64 to 0.11)

(5 RCTs; 169 participants)

Aqua-based training -0.58 (-1.46 to 0.30)

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(2 RCTs; 30 participants)

Gait/balance/functional training -0.55 (-1.38 to 0.28)

(3 RCTs; 137 participants)

Multi-domain training -0.52 (-1.34 to 0.29)

(7 RCTs; 271 participants)

Strength/resistance training -0.52 (-1.38 to 0.34)

(2 RCTs; 52 participants)

Mind-body training -0.49 (-1.31 to 0.34)

(10 RCTs; 323 participants)

Endurance training -0.48 (-1.32 to 0.35)

(5 RCTs; 227 participants)

LSVT BIG -0.41 (-1.45 to 0.63)

(1 RCT; 39 participants)

Flexibility training 0.15 (-0.78 to 1.09)

(No direct evidence, indirect evidence only)

Gaming Not applicable**

(No direct or indirect evidence)

Footnotes

MD: mean difference; PI: prediction interval; SMD: standardized mean difference; UPDRS-M: Unified Parkinson Disease Rating Scale -
motor scale

* Scores were calculated based on mean UPDRS-M scores (post-intervention) reported in 23 studies (317 participants) which were included
in the network meta-analysis.
** None of the studies provided data on the effect of gaming on severity of motor signs.

Appendix 12. Network estimates of effects and prediction intervals for physical exercise in people with Parkinson’s
disease on quality of life

Patients or population: people with Parkinson's disease

Interventions: physical exercise including aqua-based training, dance, endurance training, flexibility training, and gait/bal-
ance/functional training, gaming, LSVT BIG, mind-body training, multi-domain training, and strength/resistance training
Comparison: passive control group (mean [median] PDQ-39 score = 32.72 [29.50])*

Outcome: quality of life, measured with PDQ-39, scale from 0 to 100 (worse)

Settings: inpatient and outpatient care

Total studies: 55 RCTs Estimated absolute effects on quality

of life (SMD and 95% PI)
Total participants: 3283

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Aqua-based training -0.85 (-1.7 to 0.01)

(1 RCT; 18 participants)

Endurance training -0.52(-1.32 to 0.27)

(3 RCTs; 90 participants)

Mind-body training -0.50 (-1.27 to 0.28)

(5 RCTs; 155 participants)

Gaming -0.40 (-1.37 to 0.56)

(No direct evidence, indirect evidence only)

Strength/resistance training -0.36 (-1.14 to 0.42)

(3 RCTs; 87 participants)

Gait/balance/functional training -0.32 (-1.06 to 0.43)

(5 RCTs; 745 participants)

Multi-domain training -0.30 (-1.04 to 0.44)

(7 RCTs; 575 participants)

Dance -0.23 (-1.05 to 0.58)

(4 RCTs; 130 participants)

LSVT BIG 0.13 (-1.14 to 1.39)

(No direct evidence, indirect evidence only)

Flexibility training 0.07 (-0.94 to 1.08)

(No direct evidence, indirect evidence only)

Footnotes

MD: mean difference; PDQ-39: Parkinson's Disease Questionnaire 39; PI: prediction interval; SMD: standardized mean difference

* Scores were calculated based on mean PDQ-39 scores (post-intervention) reported in 21 studies (642 participants) which were included
in the network meta-analysis.

WHAT'S NEW

Date Event Description

16 May 2023 Amended An Editorial note was added to make the interactive summary of
findings table more prominent to readers.

Physical exercise for people with Parkinson’s disease: a systematic review and network meta-analysis (Review) 354
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 Cochrane Trusted evidence.
Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

HISTORY
Protocol first published: Issue 2, 2021
Review first published: Issue 1, 2023

Date Event Description

14 March 2023 Amended An interactive summary of findings table was added to present
key results of the network meta-analyses.

CONTRIBUTIONS OF AUTHORS
ME: methodological expertise, conception, and writing of the review
AF: methodological expertise, conception, and writing of the review
RG: support in data extraction
EL: support in data extraction
JCV: support in data extraction
NC: support in data extraction
AA: carried out the network meta-analyses
IM: development of the search strategy
AD: methodological expertise, conception, and writing of the review
MR: methodological expertise, conception, and writing of the review
CE: clinical expertise and advice
NS: methodological expertise, conception, and writing of the review
EK: methodological expertise, conception, and writing of the review

DECLARATIONS OF INTEREST
ME is associated with the Cochrane Haematology group, but was not involved in the editorial process of this review.
AF has been involved in an ongoing study eligible for inclusion (Gooßes 2020). She was not involved in the assessment of the study's
eligibility and she will not be involved in the data extraction or the assessment of risk of bias in the future.
RG: none known
EL: none known
JCV is associated with the Cochrane Haematology group, but was not involved in the editorial process of this review.
NC is associated with the Cochrane Haematology group, but was not involved in the editorial process of this review.
AA is associated with the Cochrane Haematology group, but was not involved in the editorial process of this review.
IM is associated with the Cochrane Haematology group, but was not involved in the editorial process of this review.
AD: none known
MR: none known
CE: none known
NS is associated with the Cochrane Haematology group, but was not involved in the editorial process of this review.
EK has been involved in an ongoing study eligible for inclusion (Gooßes 2020). She was not involved in the assessment of the study's
eligibility and she will not be involved in the data extraction or the assessment of risk of bias in the future.

SOURCES OF SUPPORT

Internal sources
• University Hospital of Cologne, Faculty of Medicine and University Hospital, University of Cologne, Germany

Cochrane Haematology, Department I of Internal Medicine

External sources
• German Federal Ministry of Education and Research (BMBF), Germany

Grant no: 01KG1902

DIFFERENCES BETWEEN PROTOCOL AND REVIEW

This section records differences between the methods described in the protocol (Roheger 2021), and the methods used in the review.
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Informed decisions.
Library Better health. Cochrane Database of Systematic Reviews

Primary outcomes
One of our primary outcomes was originally labelled 'clinician-rated impairment and disability', based on a previous Cochrane Review. We
rephrased the outcome to 'severity of motor signs' to improve accuracy and readability.

Selection of studies
We had planned to perform the screening of all titles and abstracts in duplicate. In light of the large number of search results (21,981), only
one review author (ME) performed the initial screening of titles and abstracts for clearly irrelevant results (16,129), before the remaining
results were screened in duplicate and independently by two authors (ME, AF).

Measures of treatment effect

For binary outcomes, we had planned to extract number of participants and number of events per arm, whenever possible. However, we
were not able to retrieve the relevant information, and conduct a quantitative synthesis on the number of participants with any adverse
event using a network meta-analysis, given the heterogeneity in measuring and reporting of adverse events. Therefore, we did not calculate
risk ratios with 95% confidence intervals for each trial.

Pairwise comparisons
At protocol stage, we described methods to be used for the conduct of both network meta-analyses and pairwise meta-analyses. However,
pairwise comparisons are part of the network meta-analysis and, based on the available data, we were able to conduct network meta-
analysis for all pre-planned comparisons across the efficacy outcomes, and did not need to perform additional pairwise meta-analyses.
Therefore, we did not explicitly describe the methods to be used for pairwise meta-analyses in the review. Nevertheless, we do present
the estimates for all pairwise comparisons provided by the network meta-analyses, i.e. in the upper triangle of each league table (Table
1; Table 2; Table 3; Table 4).

Risk of bias
We had planned to use the Cochrane risk of bias 2 (RoB 2) tool to assess risk of bias for the severity of motor signs, quality of life (QoL),
and adverse events (Sterne 2019). However, we only used RoB 2 to asses risk of bias for study results on the severity of motor signs and
QoL. Since it was not feasible to retrieve effect estimates for a network meta-analysis and conduct a formal assessment of risk of bias for
adverse events, we made an informal judgment of the risk of bias for this outcome.

Confidence in the evidence and summary of findings tables

We had planned to rate the confidence in the evidence of effects on the severity of motor signs, QoL, and adverse events using the
Confidence in Network Meta-Analysis (CINeMA) approach (Nikolakopoulou 2020). However, as we could not conduct a quantitative
synthesis on the number of participants with any adverse event using a network meta-analysis, we instead used the GRADE approach to
assess our confidence in the evidence for this outcome (Schünemann 2022). Accordingly, the format of the summary of findings (SoF) table
for our main findings on adverse events (Summary of findings 3) differs from the format of the SoF tables for the severity of motor signs
(Summary of findings 1) and QoL (Summary of findings 2). In particular, we did not stratify the narrative summary of adverse events in
the main text by type of intervention. Correspondingly, we did not stratify the results on adverse events by type of intervention in the SoF
table either.

INDEX TERMS

Medical Subject Headings (MeSH)

Exercise; Gait; Network Meta-Analysis; *Parkinson Disease [therapy]; Quality of Life; *Resistance Training

MeSH check words

Adult; Humans

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