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Are subjective cognitive complaints relevant in preclinical

Alzheimer's disease? A review and guidelines for
healthcare professionals
Ruth E Mark and Margriet M Sitskoorn

Reviews in Clinical Gerontology / Volume 23 / Issue 01 / February 2013, pp 61 ­ 74

DOI: 10.1017/S0959259812000172, Published online: 06 November 2012

Link to this article: http://journals.cambridge.org/abstract_S0959259812000172

How to cite this article:

Ruth E Mark and Margriet M Sitskoorn (2013). Are subjective cognitive complaints relevant in
preclinical Alzheimer's disease? A review and guidelines for healthcare professionals. Reviews in
Clinical Gerontology, 23, pp 61­74 doi:10.1017/S0959259812000172

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Reviews in Clinical Gerontology 2013 23; 61–74 First published online 6 November 2012
C Cambridge University Press 2012 doi:10.1017/S0959259812000172

Are subjective cognitive complaints relevant in

preclinical Alzheimer’s disease? A review and
guidelines for healthcare professionals
Ruth E Mark and Margriet M Sitskoorn
Department of Cognitive Neuropsychology, Tilburg University, The Netherlands

Summary may aid diagnostic accuracy. Molinuevo et al.5

Identifying what makes people vulnerable to developing recently reported that the preclinical stage of AD
Alzheimer’s disease (AD) is at the forefront of many is biologically active even before cognitive changes
research programmes, while early diagnosis is the goal are evident, while at the same time not all ApoE-ε4
in clinical practice. What individuals themselves tell carriers go on to develop AD. What the protective
their general practitioners (GPs) is clearly important factors are for these individuals is not yet known.6
because these subjective complaints may be a clue What has become clear is that AD has a long
that something is wrong. More specifically, subjective prodromal/preclinical phase lasting from 10–20
cognitive complaints (SCC) may be the first sign of years before the diagnosis is made.7–9 In the
AD in individuals whose cognitive performance on first preclinical phase, patients are asymptomatic
standard neuropsychological tasks is normal for their or have subtle symptoms and complaints. The
age. The challenge for researchers in this field is twofold: new guidelines see this phase as essential for
(a) determining when SCC do or do not predict
research purposes3,4,10 while also highlighting
current cognitive functioning and future dementia; and
the importance of much earlier diagnosis and
(b) estimating how relevant they are for patients and
their proxies. The current article addresses these issues,
treatment than has hitherto been the case. The
while guidelines are also provided in an attempt to help National Alzheimer’s Project Act (NAPA) has
clinicians interpret and make treatment decisions about recently established five goals, which they aim
their patients’ SCC. to achieve by 2025, the most important being:
‘to prevent and effectively treat AD’. In a
Key words: subjective cognitive complaints, objective
recent editorial in Lancet Neurology,11 specific
cognitive performance, mild cognitive impairment,
Alzheimer’s disease, risk factors, predictor variables.
knowledge gaps in this field were highlighted
and included the identification of ‘modifiable risk
factors to prevent cognitive decline or AD, effective
Introduction pharmacological agents, and validated diagnostic
criteria’ (p. 201). Identifying what the risk factors
With Alzheimer’s disease (AD) now described as are for specific cognitive deficits (as assessed
an ‘epidemic’ and a worldwide ‘crisis’ with a recent both subjectively by patients and objectively via
prevalence estimate set at 35.6 million worldwide1 neuropsychological tests) is clearly a priority in
and the projected costs deemed ‘unsustainable’,2 both AD research and clinical practice.
the race is on to develop a cure that will The aim of this review is to determine when
work not only at the symptom level but as one subjective cognitive complaints (SCC) do or do not
treatment (or a combination) which will stop the predict current cognitive functioning and future
neurodegenerative process before it can begin. Last dementia, and to estimate how relevant they are
year, new AD guidelines3,4 appeared with the focus for patients and their proxies. We also attempt
shifting from symptoms and diagnosis to both the to provide guidelines to assist clinicians in their
early preclinical stages and to how biomarkers interpretation of their patients’ SCC and to help
them make the correct treatment decisions.
The literature for this review was identified
Address for correspondence: Ruth Elaine Mark, Depart-
by searching PubMed, Google Scholar and
ment of Cognitive Neuropsychology, Tilburg University,
Postbox 90153, 5000 LE Tilburg, The Netherlands. the Social Science Citation Index for articles
Email: [email protected] published between 1975 and the present.
62 Ruth E Mark and Margriet M Sitskoorn

Search terms included ‘subjective cognitive SCC be used to aid early diagnosis of a dementing
complaints’, ‘subjective memory complaints’, illness? This article attempts to address these issues.
‘objective cognitive performance’, ‘mild cognitive
impairment’, ‘elderly’, ‘older people’, ‘Alzheimer’s
dementia/disease’, ‘(early) diagnosis’, ‘community Importance of early diagnosis of AD
samples’, ‘proxy reports’, ‘self report’, ‘risk factors’
Both the UK National Dementia Strategy20 and
and ‘predictor variables’.
the US Preventive Services Task Force21 emphasize
the need for early recognition of cognitive decline.
Clinicians should investigate cognitive impairment
Subjective cognitive complaints if there are concerns from the patient or informants
or from direct observation. As such then, many
Some researchers have suggested that SCC can be
see SCC as a crucial part of the initial assessment
evident in the first stage of the progression to AD,
(see for example22 ). Most clinicians recognize that
with mild cognitive impairment (MCI; especially
biomarker techniques are (a) not yet standardized,
the subtype amnestic-MCI) recognized as a kind of
(b) unavailable to the general practitioner, and
‘in-between’ station. Furthermore, at a relatively
(c) often too expensive for routine assessment.
recent consensus conference, SCC were said to
Not enough attention, however, has yet been
precede MCI and/or AD by around 15 years.12
paid to how individuals are expected to present
SCC are essentially what individuals can tell us
(psychologically, biologically, etc.) in the early
about how they perceive their own cognition and
stages. Current research suggests that preclinical
are also often used as a diagnostic criterion for
AD begins in mid-life, so more research efforts
MCI,13 something not all researchers agree with
should be directed at this population.23
(MCI remains a much-debated construct – see14 ).
Early diagnosis is so important for a number of
Indeed, some researchers believe that SCC should
reasons, including: (a) to reduce the public health
be excluded from the MCI diagnostic criteria (see
burden of AD by identifying possible reversible
e.g.16 ). SCCs are different from actual cognitive
causes and treating them once diagnosed:24
performance on standard neuropsychological tests
treatment for AD is very often started too late
in that the former depend on patient self-reports,
when neuropathology is advanced;25 (b) to attempt
while the latter depend on actual cognitive ability.
to prevent the development of other/secondary
It is not therefore surprising that SCC and objective
health problems; and (c) to inform both patients
cognitive performance (OCP) are not always
and their caregivers and provide subsequent
strongly related; people can and do under- or over-
education, management tips and counseling, and
estimate their cognitive functioning.
in this way increase quality of life (QoL) for all
SCCs are common not only in general practice
affected and delay the need for nursing home
and memory clinic settings, but also in the
placement/institutional care.26 There are, however,
community. Population studies typically estimate
barriers to diagnosis including those at the patient,
the prevalence of SCC to be around 22–56%, the
caregiver, health care system and GP level.27 The
percentage depending on how it is measured.17
problem at the primary care level is that GPs have
Many older people over the age of 65 talk
often limited time to assess each individual and
about having ‘senior moments’, typically problems
older patients often present with co-morbidities,
finding words (often saying ‘it is on the tip of my
making an AD diagnosis even more difficult (see1
tongue’) and general forgetfulness.18 SCC might
for a discussion of these issues).
also include slowed thinking, being less capable
of doing more than one task at the same time
(multi-tasking), general clumsiness, and decreased
Subjective memory complaints
attention and concentration. The problem of
course is how to differentiate between normal Due to the fact that episodic memory is widely
and abnormal changes in ageing (see e.g.19 ). In recognized as one of the first signs of early AD,
other words, when should we take these concerns memory has been the focus of most studies in this
seriously? When do they indicate an underlying field.28 Subjective memory complaints (SMCs) are
cognitive decline or the beginning of AD, and when the most widely studied cognitive complaints,29,30
do they indicate normal ageing? Ultimately, can but unfortunately there is no consensus on how
 Are subjective cognitive complaints relevant in preclinical Alzheimer’s disease? 63

best to define them.31 Most studies find that assess change of cognition over time, including
about one-third of their non-institutionalized older frequency and severity, while others ask close
populations report memory complaints32–34 and informants to (also) fill in the questionnaires in
that the frequency of these complaints typically order to enable a comparison between patient and
rises in a linear fashion with age (quoted at so-called proxy reports (incidentally this is also
43% in the age range 65–74 years, 51% for often used as a way to assess a patient’s awareness
those between 75 and 84 years, and 88% for – see e.g.45 ).
those aged 85 and older35 ). On the other hand, Questionnaires have the advantage over simple
memory complaints in populations with cognitive yes/no questions in that they use specific examples
impairments (MCI/early AD) have been found to from daily living, and in that sense might be
be changeable depending on the specific questions more easily understood by responders and less
asked and the patient’s level of awareness. In a susceptible to age-bias (older patients saying they
recent meta-analysis36 SMC were found in 43% of have memory complaints because they think that
AD patients, 38% in those with MCI and 17% in is what is expected of them because of their age).
healthy older controls. In other words, the majority However, questionnaires also have their disadvant-
of the patients (57% with AD and 62% with MCI) ages, including: unwillingness to admit to com-
denied or did not report SMC when they were plaints, inability to remember (i.e. an actual/real
questioned directly. Patients’ awareness is clearly memory problem) and other factors including
an issue as to whether they will complain about mood (e.g. anxiety46 , depression47 ). Pre-morbid
their cognition or not. While most studies in this personality characteristics (e.g. neuroticism48 ) and
field have focused on SMC, the term SCC will be embarrassment at perceived failure could also
used in the remainder of this review except when affect how people respond to questions about how
making a specific distinction between SMC and the they evaluate their own current level and/or change
more widespread SCC. in cognitive functioning. Furthermore, none of the
SCC questionnaires has been extensively validated
to date and there is a huge variability in how SCC
are assessed between and across studies.49
Measuring SCC
The issue of whether SCC are directly
Some (especially population and/or large scale measured (via direct questioning or self-report
research) studies have started to more thoroughly questionnaires) or spontaneously offered by
investigate SCC using detailed questionnaires patients in their GPs’ surgeries has also been a topic
asking specific questions about general daily of scientific study.50 Some researchers find that
cognitive functioning. There are a number of direct questioning may be more clinically relevant
these self-report questionnaires covering various than self-report questionnaires for older people
aspects of cognition including among others: the living in the community.51 For example, Mattos
Cognitive Failures Questionnaire (CFQ37 ); the et al.51 stated that people who cannot judge their
Memory Functioning Questionnaire (MFQ38 ); own memory may engage in risky activities putting
the Memory self-rating scale (MAC-S39 ); the themselves and others at risk, and may not seek
McNair & Kahn;40 the Everyday Memory Ques- help when they actually need it.
tionnaire (EMQ41 ); and the Ruff Neurobehavioral
Inventory (RNBI42 ), etc. A more recent and AD-
related scale, the Alzheimer Questionnaire (AQ43 )
Pre-existing factors that enhance the likelihood
is filled in by a close informant or proxy and it in-
of reporting SCC
cludes SCC items that the authors claim can detect
MCI and AD. The AQ’s short administration time There seem to be pre-existing factors that
(3 minutes) and easy interpretation makes it a good determine whether a patient will have SCC in
instrument for time-strapped GPs.43 the first place. These are female sex (e.g.29,52,53 );
Other investigators use interview (or single) a history of/or current depression (e.g.35,52,54–57 );
questions to assess SCC in their patients, for perceived daily stress;58 personality traits like
example the Cambridge Mental Disorders of high neuroticism and low extroversion;58–60 low
the Elderly Examination-Revised (CAMDEX-R44 ). education (e.g.29,35 but see61 for conflicting findings
Some of these questionnaires and/or interviews also with education and SCC); age (SCC increase
64 Ruth E Mark and Margriet M Sitskoorn

with increasing age29,35,62,63 ) and those who are have been associated with poorer QoL,80 impaired
in poor health, are less physically active or physical functioning,81 a higher risk for a number
actually physically disabled.19,54 Reduced activities of diseases, diminished therapy adherence, the
in daily living (ADL) have also been linked to increased likelihood of institutionalization, and
SCC.64 premature death.81,82
Most researchers recognize the importance of Studies that have assessed the link between SCC
the positive link between depressive symptoms and OCP have been carried out in a variety of
and SCC,46,65,66 while causality (i.e what comes chronic patient populations. They have typically
first) is debated.23 Indeed, some researchers believe found that when OCP were equivalent in the two
that all SCC depend mainly on the psychological groups, patients nevertheless tended to report more
state of the person rather than on their actual SCC than controls. This has been interpreted to
cognitive difficulties.56,67,68 This relationship may, mean that patients tend to be poor at evaluating
however, be due to the overlap between cognitive their own cognitive functioning: most of them
symptoms of depression as assessed for example underestimate their performance, in other words,
by the Geriatric Depression Scale (GDS)69 and complaining more than their OCP would suggest.
patients complaining of poor concentration,70
and/or that both SCC and depressive symptoms
tend to be assessed by self-report questionnaires.71
When the link (SCC-OCP) is typically found
It might also be more likely that SCC are linked
to affective disturbances rather than cognitive Positive links between SCC and OCP have been
performance only in specific populations (e.g. Gulf found when participants had clear cognitive
War veterans56 ). impairments at baseline measurement17,33,35,52
Some authors have also suggested that and/or when both specific objective memory tasks
depressive symptoms in and of themselves may be (e.g. free recall, orientation to time and place,
a manifestation of pre-AD in some older cohorts, category fluency and factual memory) and specific
and/or that a continuum exists between depression, SMC questions have been employed.54 The time
MCI and AD.72 It is also possible that depressive interval between SCC and OCP measurement
symptoms are part of the AD profile.57 can also play a role with longer retention
intervals increasing the link between SCC and
OCP found in epileptic patients,90 while others
SCC and the brain have found a stronger link when SCC are
assessed immediately after performing on a test
Positive links have been found between SCC
assessing the same cognitive ability.83 Furthermore,
and neuropathology,31 including: white matter
individual factors such as insight, level of pre-
lesions;73 reduced grey matter in some brain
morbid functioning, education level, stage of
regions and smaller left hippocampal volumes;50
neuropsychological decline, personality,84 coping
temporal lobe atrophy;74 ApoE-ε4 allele carriage;75
style and social support are all likely to be
but see50 ); and more general AD pathology.76
important in ascertaining whether a link between
SCC have also been linked with AD biomarkers
SCC and OCP will be found or not.
(e.g. amyloid;77 FDG78 ).
Reid and MacLullich’s review85 suggested that
SCC are linked more with future than current
cognitive decline (corroborated more recently
Objective cognitive performance and the
by7,86,87 ). In a community sample of older people,
link with SCC
Tobiansky et al.34 found that those with SCC
Objective cognitive performance (OCP) refers to at baseline were both four times more likely to
how a person actually performs on (usually stand- develop dementia and two times more likely to
ard) neuropsychological tests. Neuropsychological develop depression when followed up after 2 years.
assessment is of course not only used for diagnosis The problem is, however, that not every study
but also to estimate how suitable someone will confirms this link (see Table 1 in50 for a list of
be for a specific rehabilitation programme, and/or studies (n = 10) that found a link between SCC
whether they are able to return to work or and future AD, those that found a link between
should drive or not, etc.79 Impairments in OCP SCC and future cognitive decline (n = 4) and those
 Are subjective cognitive complaints relevant in preclinical Alzheimer’s disease? 65

who failed to find a link (n = 5)). Furthermore, SMC exclusively.95 Individuals with EF complaints
the large-scale Kungsholmen cohort study88 found can have lower IADL and this can lead to safety
that only 18% of AD patients screened positive for problems not only for the patient but also for the
SCC in the preclinical phase.89 people living with them.30

Specific versus global SCC and the link with OCP

When the link (SCC-OCP) is typically not found
Snitz et al.96 stated that while we still do not
A link is generally not found: when a cross-
know the best way to measure SCC, Item Response
sectional design is employed; when the population
Theory might be the way forward in an attempt
tested are clinic- rather than population-based;
to tease out the individual differences in those
when a control and/or a group with evident
with SCC and their subsequent predictive value.
cognitive impairment are excluded;17,33 when
This suggests that subdivisions of both SCC and
jargon used between professionals and patients is
OCP may be more fruitful than global measures in
different;79 when self-awareness of the patient is
producing links between the two. More researchers
low90 and when the statistical power is too low.
are beginning to look into which specific SCC
Reduced effort on the part of the patient can also
are linked with OCP. For example, Amariglio
reduce the likelihood of a link between SCC and
et al.97 found that some SCC were more strongly
OCP (p. 102).91
linked than others with OCP, namely: finding
Zelinski et al.92 suggested that it was difficult
one’s way around familiar streets and having
to find a link between SCC and OCP for the
trouble following a group conversation. They also
following reasons: (a) memory decline in the
found that instances such as walking into a room
normal older population is modest at best and
and forgetting why you have just done so are
therefore difficult to measure subjectively while
more likely to reflect normal ageing. Finally, these
in the AD population reduced awareness may
authors found that the more SCC a person reported
hinder memory self-reporting; (b) there is selection
the more likely they were to have actual OCP
bias in convenience samples reducing variance
deficits.
(most are highly educated and healthy) while the
In the GuidAge study investigating older
link between SCC and OCP tends to be higher
patients who spontaneously complained about
in population samples due to greater variance;
their memory to their GPs, Coley et al.50 suggested
(c) statistical power needs to be high enough to
that specific items like: ‘I forget the day of the
find a link and most studies are carried out on
week’ etc., as assessed by the McNair & Kahn
sample sizes that are too small; (d) the link tends
scale, rather than treated as general memory
to be increased if the questions/tests are matched
complaints, were more likely to predict future
and/or they measure the same aspects; and (e) the
AD, and SCC should therefore receive attention
link is reduced if cultural assumptions are high (age
in general practice. Calero-Garcia et al.98 stated
bias – see ‘Measuring SCC’ section).
quite rightly that memory is multi-dimensional and
The links between SCC and OCP are difficult to
some aspects are more affected by ageing than
find when traditional neuropsychological tasks are
others. Other researchers are beginning to focus
used, and may be easier to find with ecologically
on different SCC (not just SMC) like language or
valid tests (e.g.93 ), or at least those that assess
executive functioning complaints.99 In summary,
the same aspects of cognition.79 The failure to
assessing specific SCC items might be more fruitful
find links between SCC and OCP are therefore
for GPs and other healthcare workers when they
very likely to lie in the simplicity of the questions
are attempting to predict the likelihood of future
used to date for both measures, or due to the fact
AD in their patients.
that many tests (SCC and OCP) are heterogeneous
and do not measure just one cognitive function.30
At the very least we should measure more than
Risk factors which increase the likelihood that
SMC; executive functioning (EF) also declines with
those with SCC will convert to AD
age, for example.94 We should therefore aim to
assess subjective attention, language and executive Other factors like family history of AD,
functioning complaints in our patients and not just behavioural impairments, depression, vascular
66 Ruth E Mark and Margriet M Sitskoorn

disease, other neurological abnormalities and cognitive tests – a delayed verbal recall test and
slowness of gait have been identified as risk factors a verbal fluency test. All of these measures can
which increase the likelihood that people with be relatively easily obtained during a routine GP
SCC will convert to dementia.18,46,99,72 Current appointment.
depressive status is a risk factor for having SCC, Other researchers have also attempted to
but whether it then predicts current or future determine prediction scores. Kivipelto et al.104
OCP is harder to determine. Indeed, some studies studied a younger cohort than Jessen et al.62 and
have found that subjects with either depressive included the following variables in their prediction
symptoms or a clinical depressive disorder tended score: age, education, sex, systolic blood pressure,
to do better on objective memory tests, even body mass index, total cholesterol, physical activity
though they also complained more about their and ApoE-ε4 status. Barnes et al.105 added white
memories.100,101 At the same time some studies matter lesions on MRI scans to their prediction
have found depression to be a better predictor score. This work is, however, still in the early
of OCP than SCC.33,96,102 Furthermore, it has stages and Barnes and Lee8 rightly pointed out
been suggested that SCC in the highly educated that current prediction models have two main
might actually be predictive of AD even when limitations: (a) they do not take the issue of
there is no sign of decline on OCP tests.29,103 mortality into account, and (b) they have not
Indeed, the highly educated are more likely to score investigated all the important variables (imaging,
at ceiling on the cognitive screens like the Mini biomarkers, risk factors) over the entire preclinical
Mental State Examination (MMSE), which many stage, which, as has already been mentioned, can
GPs use.103 A stronger link between SCC and future last anything from 10–20 years. However, such
AD has also been found for individuals with: a high prediction studies/models are crucial because they
level of education, a high socioeconomic status, will pave the way towards helping doctors decide
married patients,61 and those whose partners have which patients may be at a heightened risk for
corroborated their complaints and who have noted developing AD in the future.
cognitive change over time.
Most community/population-based longitudinal
studies have found a link between SCC and
Personal relevance for the patient, quality of life
future cognitive decline.33,34,46,62,67,71 Determin-
and the impact of life events
ing which underlying individual (and environ-
mental) factors are important both within and Begum et al.106 recently suggested that SCC
between patient groups is clearly necessary, as are common and have emotional and functional
is eventually forming a model that can predict importance for older people. These authors found
links between specific SCC and their corresponding that complaints about their memory worried their
OCP at the individual level. As has already been participants more than asthma, previous heart
discussed, some researchers are attempting to do attacks, angina or hypertension, while at the same
just that.62,104,105 time, only one person from a total of 126 older
participants actually sought out medical help for
them, possibly suggesting fear of AD and the stigma
Relevance of SCC many attach to it. However, more effort should be
directed towards encouraging people with SCC to
Prediction of (future) cognitive decline/AD
seek help at the primary care level. Some authors
A number of researchers have taken the relevance see SCC as a somatoform disorder in its own
of SCC to the next level and attempted to right,110 which is common in older people and
develop prediction scores derived from how people can trigger anxiety and fear of possible dementia.
respond on both self-report questionnaires/items Indeed, a new scale to assess fear of AD has recently
and standard neuropsychological tests. In the large been designed.107
longitudinal AgeCoDe cohort study, Jessen and Furthermore, patients who complain about
colleagues62 found that the best set of baseline their cognition tend to have a poorer QoL with
variables which predicted future AD were: age, every dimension of QoL affected.53 Instrumental
SMC (with and without worry), and performance Activities in Daily Living (IADL) performance is
on the MMSE, an IADL scale and on two short also generally lower in those with SCC63 and
 Are subjective cognitive complaints relevant in preclinical Alzheimer’s disease? 67

this may in turn be linked to reduced treatment visuospatial disorientation. Abbate et al.16 also
adherence and poorer recovery. Causality is of found that informants tended to overrate episodic
course an issue: as with depression, what comes memory problems and attentional deficits and
first – poor QoL or more SCC?108 Future, underrated other cognitive functions. Specific
prospective longitudinal studies should hopefully items/questions might therefore be more fruitful
shed light on this issue of causality. SCC have also than general questions about memory/other
been found to be an independent predictor not only cognition not only in patients but also in their
for future AD but also for increased healthcare informants. It is important to note that proxy
use and future nursing home placement.109 People reports are not perfect, in the sense that they are not
who do seek help for SCC have access to typically systematic, planned or even complete, and
training programmes to improve their cognitive they are influenced by the proxy’s mood and their
performances and thereby reduce distress and relationship (in turn influenced by length, quality,
improve QoL. However, many patients appear to etc.) with the patient (see also16 ).
be unaware of what treatment options are available
to them.110 Education and more high-profile public
Guidelines/recommendations
awareness campaigns are clearly necessary.
Major stressful life events (e.g. widowhood, In the flowchart we provide some guidelines/
falls, illness, etc.) might also have an impact on recommendations for GPs and other healthcare
the predictive worth of SCC on future OCP in workers who listen to their patients’ SCC and
longitudinal studies. For example, an interesting wonder what to make of them.
study found elevated cortisol levels to be associated The relationship between SCC and OCP is likely
with SCC in their older population while no to be complex and multi-dimensional.114 Many of
subsequent link was found between SCC and the risk factors for having SCC in the first place can
OCP.70 These authors speculated that people with be important in predicting future cognitive decline;
SCC might actually have poorer OCP in situations there is obvious overlap between risk factors and
where their stress is elevated. predictor variables. In the flowchart we highlight
the individual characteristics that are the most
likely signs of underlying neurodegeneration and
subsequent AD in those presenting with SCC at
The importance of proxy reports
baseline.
Proxy reports are an important corroborative Furthermore, as discussed earlier in this review,
technique during both clinical assessment and in the context and time of measurement, study design,
research studies. Some studies have found high demographic characteristics, and the instruments
correlations between proxy and (neurological) and specific questions used to assess both SCC
patient self-report,111 while others have not and OCP are also important. Patients who
always found this overlap.112 Some researchers spontaneously complain to their GPs about their
have even suggested that proxy- may be better cognition may be more likely to convert to AD
than patient-report in predicting future AD.113 versus those who are asked to fill in self-report
Another important consideration is that family questionnaires or those who are directly questioned
members differ in their acceptance (this can be by their doctors.50 Of course it is also true that
complete, passive or partial) of the patient’s GPs can help or hinder patient disclosure and
memory complaints and subsequent MCI or AD educating GPs on the importance of SCC may
diagnosis.14 This research emphasizes the need to be of fundamental importance in the years ahead
include the family in a patient’s diagnosis because as people live longer.115 GPs are after all the
their reactions can influence treatment adherence gatekeepers for patient referral116 and it is a worry
and all of the family members’ QoL. that many AD patients are not diagnosed early
In a recent paper Malek-Ahmadi et al.15 enough.1
suggested that certain, specific proxy-reported Also, as stated earlier, the literature suggests that
symptoms might help clinicians differentiate links between SCC and OCP are more likely to
between MCI and normal ageing. These included be found when longitudinal designs are employed
four types of items, namely: orientation, ability (rather than cross-sectional) (see e.g.29,117,118 ) and
to manage finances, repetition of statements and important variables are controlled (e.g. depression,
68 Ruth E Mark and Margriet M Sitskoorn

First visit to GP
Patient complains about their cognition (SCC)

Ask yourself are these:

• spontaneously offered by patient?

• specific/not global?
• corroborated by a proxy?

Check for co-morbidities:

clinical depression, advanced age, Carry out a short cognitive screen to
female gender, daily perceived check for OCP decline, e.g. a delayed
stress can all account for SCC verbal recall test and a verbal fluency
test. MMSE prone to ceiling effects!

SCC present
with/without
co- No apparent OCP decline
morbidities

SCC are a red flag and require more extensive follow-up in the following patients:

• highly educated
• high socioeconomic status
• married
• specific SCC
• SCC spontaneously offered
• <80 years of age
• IADL decline is also present
• effort on OCP tests is adequate
• other risk factors are present (inc: depression, vascular &/or neurological disease, slow gait)
• other possible reasons for SCC have been ruled out

If most aspects present we recommend: SCC could prove cost- and time-effective
comprehensive neuropsychological work up, to busy GPs and may suggest possible future
brain scanning and biomarker assays if available AD

If MCI or AD is diagnosed provide education about

management, support services and available treatments

Flowchart. How to interpret patients’ subjective cognitive complaints (SCC): recommendations for General
Practitioners and other healthcare workers

gender, age, dementia status, education, premorbid Conclusions and implications

IQ, etc.) in community-based samples.84 At the
very least, doctors should take the age of the The link between SCC and OCP demands
patient, their education level, and their history further investigation and long-term follow-up.
of depression into account when attempting to Unfortunately, AD is under-diagnosed in primary
interpret that patient’s SCC. care centres and often not recognized by GPs
 Are subjective cognitive complaints relevant in preclinical Alzheimer’s disease? 69

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