Received: 16 February 2016 | Accepted: 26 May 2016

DOI: 10.1002/jgf2.27

REVIEW ARTICLE

Sleep disorders in the elderly: Diagnosis and management

Keisuke Suzuki MD, PhD1 | Masayuki Miyamoto MD, PhD2 | Koichi Hirata MD, PhD1

1
Department of Neurology, Dokkyo Medical
University, Shimotsuga, Tochigi, Japan Abstract
2
Department of Clinical Medicine for Compared with younger people, elderly people show age-­related sleep changes, in-
Nursing, Dokkyo Medical University School of
cluding an advanced sleep phase and decreased slow-­wave sleep, which result in frag-
Nursing, Shimotsuga, Tochigi, Japan
mented sleep and early awakening. Multiple etiologies contribute to insomnia in the
Correspondence
elderly, consistent with the observation that elderly people are likely to have comorbid
Keisuke Suzuki, Department of Neurology,
Dokkyo Medical University, Shimotsuga, conditions and medications. When elderly individuals complain of insomnia, it is im-
Tochigi, Japan.
portant to assess treatable medical conditions and medication use that may be respon-
Email: [email protected]
sible for the insomnia before the use of hypnotics is initiated. Also, screening for
primary sleep disorders, such as sleep apnea syndrome, restless legs syndrome and
rapid eye movement sleep behavior disorder, is essential. We review sleep disorders
commonly observed in the elderly and describe their diagnosis and management.

KEYWORDS
diagnosis, elderly, management, sleep disorders

1 | INTRODUCTION important in the elderly due to age-­related increases in comorbid

medical conditions and medication use as well as age-­related changes
Sleep disturbances are common symptoms in adults and are related to in sleep structure, which shorten sleep time and impair sleep quality.
various factors, including the use of caffeine, tobacco, and alcohol; sleep Spielman et al.8 proposed the 3P model of insomnia, which in-
habits; and comorbid diseases. Sleep apnea syndrome (SAS), rapid eye cludes the following components: (i) predisposing factors: genetic,
movement (REM) sleep behavior disorder (RBD), restless legs syndrome physiological, or psychological predispositions that increase the risk of
(RLS), and psychiatric diseases such as depression and anxiety should insomnia (gender differences, vulnerability to stress, etc.); (ii) precip-
always be screened for in subjects who present with sleep disturbances. itating factors: physiological, environmental, or psychological stress-
Modern life is characterized by reduced sleep times and worsened sleep ors that trigger the onset of insomnia (life events, acute stress, etc.);
quality due to changes in modern lifestyles (working late and using the and (iii) perpetuating factors: behavioral, psychological, environmen-
computer and internet and watching TV late at night).1 An epidemio- tal, and physiological factors that maintain insomnia (increase in the
logical survey performed in Japan reported an insomnia prevalence amount of time spend in bed, taking more naps, etc.). In this model, the
of 21.4% when insomnia was defined to include at least one instance predisposing and precipitating factors contribute to the development
of difficulty initiating sleep (8.3%), maintaining sleep (15.0%), or early of insomnia, while the additional perpetuating factors are responsible
morning awakening (8.0%).2 More than half of older adults suffer from for the maintenance of insomnia.9
3
insomnia, and these subjects are often undertreated. The annual inci- When daytime sleepiness or sleep problems are present in older
dence of insomnia in older people is reported to be 5-­8%.4–6 In a large people, it is essential to assess whether sleep duration, quality, and
epidemiological study of 28 714 subjects, the prevalence of excessive timing are adequate. Hypersomnia disorders such as narcolepsy and
daytime sleepiness, defined as a self-­reported feeling of excessive day- idiopathic hypersomnia, which are conditions characterized by the im-
time sleepiness “always” or “often” among five choices, was 2.5%.7 pairment of arousal systems, typically emerge in younger subjects and
At any age, managing insomnia is a challenging issue that may are rare in older subjects. Table 1 lists causes of chronic insomnia in
require lifestyle changes. The recognition of insomnia is especially older people.3 Mental disorders or medical conditions that may cause

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medium, provided the original work is properly cited and is not used for commercial purposes.
© 2017 The Authors. Journal of General and Family Medicine published by John Wiley & Sons Australia, Ltd on behalf of Japan Primary Care Association.

J Gen Fam Med. 2017;18:61–71. 

wileyonlinelibrary.com/journal/jgf2 | 61
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62 | SUZUKI et al.

TABLE 1 Causes of chronic insomnia in older people (modified from ref. 3)

(1) Primary sleep disorders

Sleep apnea syndrome
Restless legs syndrome, periodic limb movement disorder
Rapid eye movement sleep behavior disorder
Circadian rhythm sleep-­wake disorders (advanced and delayed sleep-­wake phase disorder)
(2) Acute and chronic medical illness
Allergy (allergic rhinitis, hay fever); Pain (arthritis, musculoskeletal pain); Cardiovascular (heart failure, acute coronary syndrome); Pulmonary
(pneumonia, chronic obstructive pulmonary disease); Metabolic (diabetes, thyroid disorders), Gastrointestinal (gastroesophageal reflux disease,
constipation/diarrhea, acute colitis, gastric ulcer); Urinary (nocturia, incontinence, overactive bladder, benign prostate hypertrophy for men);
Psychiatric diseases (depression, anxiety, psychosis, delirium, alcoholism); Neurological disorders (Alzheimer’s disease, Parkinson’s disease,
cerebrovascular disease, epilepsy); Pruritus; Menopause
(3) Behavioral causes and psychological/physical stressors
Daytime napping; go to bed too early; use the bed for other activities (watching TV, reading); lack of exercise during daytime; death of a partner/
spouse; loneliness; hospitalization
(4) Environmental causes
Noise, light, cold/hot temperature, humidity, uncomfortable bedding, lack of light exposure during daytime
(5) Medications
Psychostimulants; antidepressants (selective serotonin reuptake inhibitors); antihypertensives (beta-­blocker, alpha-­blocker); antiparkinsonian drugs
(levodopa); bronchodilators (theophylline); steroids; antihistamines (H1 and H2 blockers); anticholinergics; alcohol; interferons

insomnia should also be checked. Loss of appetite and interest in addi- peak levels when it is darkest (3-­5 am).13,14 The two-­process model of
tion to insomnia may suggest depression. In addition, delirium related sleep regulation, which has been used to explain 24-­hour sleep regula-
to dementia, anxiety disorders, alcoholism, psychological factors, and tion in humans, includes the following: Process S, which is entirely de-
life events (loneliness, the death of a partner/spouse or hospitalization) termined by the temporal sequence of behavioral states; and Process
may also cause insomnia in the elderly. Habitual snoring and witnessed C, which is totally controlled by the circadian pacemaker, irrespective
apnea during sleep are signs of obstructive sleep apnea (OSA). Greater of behavioral state.15
functional impairment is more strongly associated with older subjects In the elderly, reduced homeostatic sleep pressure decreases the
with insomnia comorbid with SAS than with those having neither in- amount of slow-­wave sleep.16 Additionally, reduced circadian signals
somnia nor SAS.10 Sleep-­initiation and/or maintenance problems that in the elderly result in reduced core body temperature and a phase
are accompanied by restlessness of the legs should prompt evalua- advance of wake and sleep times.
tion for RLS. RBD should be suspected when nocturnal vocalization, Sleep is divided into non-­rapid eye movement (NREM) and REM
sleep talking, and abnormal movements or behavior related to dream sleep. NREM sleep is further divided into light sleep (stages N1 and
content are witnessed by a bed partner. In this review, we describe N2) and slow-­wave sleep (stage N3).6 REM sleep occurs periodically
sleep disturbances commonly observed in older people as well as their in cycles of approximately 90-­120 minutes of sleep. In polysomno-
causes and treatment. graphic studies, four consistent changes related to aging are observed:
decreased total sleep time, sleep efficiency, and slow-­wave sleep; and
increased waking after sleep onset.17 A meta-­analysis of 3577 sub-
2 | PHYSIOLOGY OF SLEEP AND AGE-­ jects aged 5-­102 years demonstrated age-­related changes in sleep
RELATED CHANGES IN SLEEP architecture (Figure 1).17 In adults, total sleep time, sleep efficiency,
percentage of slow-­wave sleep, percentage of REM sleep, and REM la-
The human 24-­hour sleep/wake cycle is tightly regulated by the cir- tency all decreased with age. Sleep latency increased with age, but this
cadian master clock located in the suprachiasmatic nuclei of the hy- change was very subtle. Only sleep efficiency continued to decrease
pothalamus; this clock is synchronized by external entrainers such as after 60 years of age.
light and food. It is well known that on the day after sleep loss, more
sleep is needed to compensate (homeostatic sleep pressure). Thus, the
homeostatic system promotes the amount of sleep we need, whereas 3 | DIAGNOSTIC CRITERIA OF
the circadian system optimizes the best timing to sleep.11 The su- INSOMNIA DISORDER
prachiasmatic nucleus regulates melatonin secretion by the pineal
gland.12 Melatonin modifies circadian rhythm and signals day-­night Insomnia is a subjective sleep problem that is typically defined by dif-
transitions. Melatonin levels in the pineal gland are low during the ficulty with sleep initiation, duration, consolidation, or quality that
daytime and increase after the onset of darkness (9-­10 pm), reaching occurs despite adequate opportunities and situations for sleep.18
 21897948, 2017, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jgf2.27 by Readcube (Labtiva Inc.), Wiley Online Library on [04/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SUZUKI et al. | 63

F I G U R E 1 Age-­related trends for

stage 1 sleep (stage N1), stage 2 sleep
(stage N2), slow-­wave sleep (SWS), rapid
eye movement (REM) sleep, wake after
sleep onset (WASO), and sleep latency (in
minutes)17

In contrast, “insomnia disorder” is a syndrome characterized by in- TABLE 2 Chronic insomnia disorder (ref. 20)
somnia complaints, as defined by the International Classification of
Diagnostic criteria
Sleep Disorders (ICSD), 2nd or 3rd edition. In the ICSD-­2,19 primary
insomnia includes various subtypes, such as psychological insomnia, Criteria A-­F must be met

idiopathic insomnia, paradoxical insomnia, and inadequate sleep hy- A. The patient reports, or the patient’s parent or caregiver observes,
one or more of the following:
giene. Psychological insomnia is characterized by hyperarousal and
1. Difficulty initiating sleep.
learned sleep-­preventing associations, while paradoxical insomnia is
characterized by the misperception of sleep, including a propensity to 2. Difficulty maintaining sleep.

underestimate the amount of actual sleep time. Secondary insomnia 3. Waking up earlier than desired.

includes insomnia attributed to medical conditions and mental disor- 4. Resistance to going to bed on appropriate schedule.
ders such as depression, pain, or anxiety disorders (ICSD-­2). However, 5. Difficulty sleeping without parent or caregiver intervention.
the various subtypes of primary sleep disorders often co-­occur, the B. The patient reports, or the patient’s parent or caregiver observes,
symptoms of these disorders can overlap with those of both primary one or more of the following related to the nighttime sleep
difficulty:
and secondary insomnia. Also, because it is often unclear whether
insomnia is the result of co-­occurring comorbid disorders or condi- 1. Fatigue/malaise.

tions, in the latest ICSD, the 3rd version, 20

regardless of whether 2. Attention, concentration, or memory impairment.
the insomnia is classified as primary or secondary, all subtypes of 3. Impaired social, family, occupational, or academic performance.
insomnia disorders that occur at least three nights per week for at 4. Mood disturbance/irritability.
least 3 months are included as “chronic insomnia disorder” (ICSD-­3) 5. Daytime sleepiness.
(Table 2). According to ISCD-­3,20 when insomnia symptoms indepen- 6. Behavioral problems (eg, hyperactivity, impulsivity, aggression).
dently develop from the co-­occurring sleep disorders including RLS, 7. Reduced motivation/energy/initiative.
SAS, and RBD, medical disorders or psychiatric disorders, or insomnia
8. Proneness for errors/accidents.
symptoms persist despite adequate treatment for the co-­occurring
9. Concerns about or dissatisfaction with sleep.
sleep and psychiatric disorders, a chronic insomnia disorder diagnosis
C. The reported sleep/wake complaints cannot be explained purely by
would apply. Conversely, a chronic insomnia disorder diagnosis would inadequate opportunity (ie, enough time is allotted for sleep) or
not apply, when treatment of the co-­occurring sleep, medical, or psy- inadequate circumstances (ie, the environment is safe, dark, quiet,
chiatric disorder resolves the insomnia symptoms. and comfortable) for sleep.
These criteria clearly state that insomnia sufferers experi- D. The sleep disturbance and associated daytime symptoms occur at
ence daytime dysfunction such as fatigue and daytime sleepi- least three times per week.

ness. Nonrestorative sleep remains a factor in the International E. The sleep disturbance and associated daytime symptoms have been
present for at least 3 mo
Classification of Disease 10th edition (ICD-­10), which requires a du-
ration of one month for an insomnia diagnosis, but was eliminated F. The sleep/wake difficulty is not better explained by another sleep
disorder.
from the Diagnostic and Statistical Manual, version 5 (DSM-­V), which
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64 | SUZUKI et al.

requires a duration of at least 3 months for a diagnosis of insomnia.

5 | DIFFERENTIAL DIAGNOSIS OF
Therefore, depending on the insomnia criteria used, the prevalence
INSOMNIA
of insomnia can vary widely: The reported prevalence of insomnia
among adults was 15% and 4% according to the ICSD-­2 and ICD-­10,
When making a diagnosis of insomnia, sleep habits (sleep/wake
respectively.6
schedule, sleep time, and naps) should be assessed. A sleep diary is
a useful tool to assess sleep patterns and usual sleep times and thus
also in diagnosing sleep problems. A flowchart for the screening of
4 | INSOMNIA IN THE ELDERLY sleep problems is illustrated in Figure 2.29 When patients have sleep
problems, changes in environmental conditions, physical/psychosocial
In elderly individuals, sleep-­maintenance insomnia and early awak- stressors, medications, and chronic and acute medical illnesses should
ening are more common complaints than sleep-­onset insomnia; this be screened first. Then, accompanying symptoms or a detailed sleep
is likely due to the age-­related changes in sleep architecture and history may reveal psychiatric diseases such as depression, SAS, RLS,
circadian rhythm described above.21 Unruh et al.22 administered or parasomnia. Additionally, when patients present with abnormal
unattended home polysomnography (PSG) and sleep question- nocturnal behaviors and are unaware of them, epilepsy, night delirium,
naires to 5407 community-­dwelling adults aged 45-­99 years (mean or metabolic disorders such as hypoglycemia due to insulinoma should
age, 63 years) who were members of the Sleep Heart Health Study be ruled out (Table 3).30 NREM parasomnia is common in younger sub-
Cohort. The results showed that in both men and women, older age jects, whereas REM parasomnia, such as RBD, is common in subjects
was associated with shorter sleep duration, reduced sleep efficiency, aged 50 years or older. The RBD screening questionnaire (RBDSQ) is
and increased arousal. In men but not women, older age was inde- a widely used,31 including in Japan,32 and useful way of screening for
pendently associated with increased light stages of sleep (Stage 1 RBD (a cutoff RBDSQ score ≥5 suggests probable RBD).
and Stage 2), while older women had more trouble falling asleep and
tended to have more problems with waking up during the night and
waking up too early. In a cross-­sectional study of 13 563 adults aged 6 | MANAGEMENT OF INSOMNIA
47-­69 years who were participants in a prospective population-­based
study of cardiovascular disease, the prevalence of sleep complaints There are both nonpharmacological approaches and pharmacological
involving difficulty falling asleep, difficulty staying asleep, and non- treatments for insomnia. Sleep hygiene education should be the first
restorative sleep was 22%, 39%, and 35%, respectively.23 Increasing approach because the development of good sleep habits benefits all
age was associated with difficulty staying asleep but not with diffi- insomnia sufferers. As mentioned previously, when other sleep disor-
culty falling asleep or nonrestorative sleep. In a cross-­sectional, mul- ders or mental/physical illnesses related to insomnia are suspected,
ticenter study of 2862 community-­dwelling men at least 65 years of prompt screening for each condition is needed. In parallel, treatment
age, greater sleep fragmentation (sleep efficiency <80% and/or wak- for insomnia is recommended; it is not necessary to wait for a re-
ing after sleep onset) and hypoxia (>1% of sleep time with O2 satura- sponse to treatment for comorbid conditions. However, the use of
tion <90%) were associated with poorer physical function, such as benzodiazepines should be avoided when severe SAS is strongly sus-
decreased grip strength and gait speed.24 pected, as these drugs aggravate sleep apnea. Also, antidepressants
Falls and fractures in older people are significant problems that such as selective serotonin reuptake inhibitors can worsen or trigger
affect their quality of life. Stone et al.25 investigated the risk of falls RLS or RBD. Good sleep hygiene includes regular exercise and meals,
in 2978 community-­dwelling women 70 years and older using ac- the avoidance of stimulants such as caffeine and tobacco, and the
tigraphy. The authors showed that short nighttime sleep duration creation of a comfortable sleep environment (Table 4).33 Table 5 lists
(<5 hours; odds ratio, 1.52; 95% CI, 1.03-­2.24) and increased sleep nonpharmacological treatments for insomnia in the elderly, including
fragmentation increased the risk of falls (odds ratio, 1.36; 95% CI, stimulus control, sleep restriction, and cognitive behavioral therapy
1.07-­174) in older women, independent of benzodiazepine use, and for insomnia (CBT-­I). CBT-­I has been shown to be useful in elderly
other risk factors for falls. Although the results remain controver- subjects,34 although in Japan, CBT-­I is available in a limited number of
26 27
sial, Morimoto et al. demonstrated that obstructive, central, and facilities. Insomnia can co-­occur with medical diseases, which some-
mixed SAS were associated with an increased risk of cardiovascular-­ times result in secondary insomnia, and in these cases, it is important
related and all-­cause mortality. Elderly participants with persistent to treat the primary disease. However, all subtypes of insomnia dis-
insomnia have also been reported to have an increased risk for devel- orders are included in the ICSD-­3 classification of chronic insomnia
oping depression.28 Despite the fact that sleep becomes increasingly disorders, without any differentiation between secondary insomnia
fragmented with age, several studies have shown that older people and primary insomnia, suggesting that treatment of insomnia should
are less likely to complain of sleep problems than younger people, be initiated along with treatment for comorbid diseases, rather than
possibly because of age-­related adjustments of sleep status in older waiting to determine the effect that treating the primary disease has
adults or because older adults tend to be more tolerant of sleep on the insomnia. If left untreated, insomnia is known to have a nega-
6
deprivation. tive impact on the quality of life of sufferers.
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SUZUKI et al. | 65

FIGURE 2 Flowchart of screening for sleep disturbances (modified from ref. 29) [Colour figure can be viewed at wileyonlinelibrary.com]

When nonpharmacological strategies do not work well, pharma- significantly increased sleep efficiency and reduced sleep latency and
cological treatments should be considered. Hypnotic drugs should waking after sleep onset. There were also no differences in efficacy
be used in the lowest effective dose, and short-­term use is recom- between women and men, and rebound insomnia and dose escala-
mended. The hypnotics available in Japan are listed in Table 6. For tion were also absent.36 Eszopiclone has been reported to be effica-
sleep-­onset insomnia, ultra-­short-­acting or short-­acting types are cious in treating patients with insomnia with comorbid diseases such
used, while for frequent arousal during sleep or early morning awaken- as depression37 and Parkinson’s disease.38 Compared to nonbenzo-
ing, intermediate types or long-­acting types may be chosen. However, diazepine drugs, benzodiazepine drugs have more anxiolytic effects,
attention should be paid to potential next-­day hangover effects when which are dependent on the integrity of the α2 subunit, but postwith-
prescribing intermediate or long-­acting hypnotics, especially in the drawal rebound, tolerance, and dependence are more important is-
elderly. Both benzodiazepine and nonbenzodiazepine drugs (eszopi- sues.39 Although the association between the use of hypnotics and
clone, zopiclone, and zolpidem) bind to GABAA receptors in the brain, the subsequent risk of dementia is inconclusive, several studies have
exerting hypnotic effects. Benzodiazepine hypnotics bind equivalently demonstrated an association between the use of benzodiazepines
to all GABAA receptors (α1-­, α2-­, α3-­, and α5-­containing subtypes). and subsequent dementia. In prospective studies that included older
In contrast, nonbenzodiazepine hypnotics (zolpidem, zopiclone, and people, long-­term use of benzodiazepines was related to an increased
eszopiclone) preferentially bind α1-­containing subtypes, and the risk of dementia (odds ratio 1.6-­3.5).40,41 In addition, over 8 years of
shorter half-­life of the effects of binding to these receptors lowers the follow-­up of 8204 people aged 65 or greater, Shash et al.42 showed
risk of fall and residual sleepiness.35 In a recent randomized placebo-­ that the use of long-­half-­life benzodiazepine was associated with
controlled study that was conducted over 12 months of observation an increased risk of dementia (adjusted hazard ratio=1.62; 95% CI,
and included 89 patients with primary insomnia, 10 mg/day zolpidem 1.11-­2.37). However, because untreated insomnia can impair daytime
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66 | SUZUKI et al.

TABLE 3 Differential diagnosis of abnormal nocturnal behavior: sleep disorders versus disturbance of consciousness (ref. 30)

Sleep disorders

REM parasomnia Non-­REM parasomnia Disturbance of consciousness

REM sleep Arousal disorder (sleep- Hypoglycemia due to

behavior disorder walking and sleep terrors) Epilepsy Night delirium insulinoma

Peak onset age >50 y of age Child Child/elderly Elderly Any age (middle age)
Time of day of the occurrence Early morning First half of the night Anytime Night (anytime) Early morning
of abnormal behavior
Type of movement Complex Complex Stereotyped Complex Complex, stereotyped
Walking ±/+ + + + +
Urinary incontinence − − ±/+ ±/+ +
Nightmares + ± − − −
Dream recall + − − − −
Arousal in response to Quick to awaken Difficult to arouse Difficult to Difficult to Difficult to arouse
external stimuli arouse arouse
Electroencephalographic REM sleep Epileptic Slow dominant Slow dominant rhythm
findings without atonia discharge rhythm
Relevant sleep stage REM sleep Non-­REM sleep Non-­REM
Stage N3 sleep

TABLE 4 Sleep hygiene (modified from ref. 33) T A B L E 5 Nonpharmacological treatments for insomnia in the
elderly (modified from ref. 33)
Tips Contents
Stimulus control
(1) Regular exercise Take regular exercise. Adequate aerobic
Ask patients to go to bed only when sleepy. The bed should be used
exercise improves the ability to fall asleep.
for sleep only. If the patient is unable to fall asleep for 20 min,
Exercise in the early morning and early
suggest they get up and go to another room to do something. The
evening promotes deep sleep and improves
patient can go back to the bedroom when sleepy. The patient should
sleep quality; however, exercise just before
get up at the same time every morning, irrespective of how much
bedtime should be avoided.
sleep the patient had during the night. Avoid naps.
(2) Bedroom Keep bedroom dark and quiet. Noises and dim
Sleep restriction
environment light can interrupt sleep. Maintain a
Patients should be instructed to sleep for the average total sleep
comfortable bedroom temperature (below 24
time estimated from a 2-­week sleep diary (minimum 4.5 h). Sleep
degrees Celsius [75 degrees Fahrenheit]).
efficiency, as defined by total sleep time/time spent in bed, should
During the summer season, consider using an
be evaluated regularly. When sleep efficiency improves, the time
air conditioner.
spent in bed can be increased. When sleep efficiency is >90%, the
(3) Regular meals Keep regular eating patterns, 3 times/day. patient go to bed 15 min earlier.
When you feel hungry, eat a light snack
Sleep hygiene (see Table 4)
(cheese, milk, nuts, or carbohydrates) but
For good sleep habits, several tips are recommended: regular
avoid heavy meals before bedtime.
exercise and meals, the avoidance of stimulants such as caffeine and
(4) Limit fluid intake Limit fluid intake before bedtime to reduce tobacco, and the creation of a comfortable sleep environment.
before bedtime the frequency of urination during sleep. In
Cognitive behavioral treatment
cases of cerebral infarction or angina
Identify incorrect thoughts, beliefs, or knowledge about sleep and
pectoris, follow the instructions of your
correct knowledge, emotions, and behaviors related to sleep.
primary physician.
Bright light therapy
(5) Avoid caffeine Caffeine intake before bedtime may result in
When the patients have advances in sleep phases or early awaken-
sleep-­initiation and maintenance problems.
ings, light exposure or bright light therapy in the evening is
Limit caffeinated foods and beverages (Green
recommended.
tea, tea, coffee, cola, and chocolate) to the
equivalent of three cups of coffee and ingest
them no later than 4 h before bedtime.
(6) Avoid alcohol Limit alcoholic beverages, which may promote performance and cognitive function, when the use of benzodiazepines
sleep initiation but cause fragmented and is considered, the balance of risks and benefits should be considered,
unrefreshing sleep. and the lowest effective dose for short-­term use is recommended.
(7) Avoid smoking Avoid smoking in the evening. Nicotine acts as In a single-­center study in Japan that evaluated fall rates among
a stimulant, interfering with sleep.
1469 older inpatients taking different types of hypnotics, eszopiclone
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SUZUKI et al. | 67

TABLE 6 Pharmacological treatment for insomnia: primary hypnotic drugs available in Japan

Class Type Generic name Dose (mg) Half-­life (h)

Benzodiazepine Ultra-­short-­acting Triazolam 0.125–­0.25 2–­4

Short-­acting Etizolam 0.5–­1 6
Brotizolam 0.25 7
Rilmazafone 1–­2 10
Lormetazepam 1–­2 10
Intermediate-­acting Flunitrazepam 0.5–­2 24
Estazolam 1–­4 24
Nitrazepam 5–­10 28
Long-­acting Quazepam 15–­30 36
Flurazepam 10–­30 65
Nonbenzodiazepine Ultra-­short-­acting Zolpidem 5–­10 2
Zopiclone 7.5–­10 4
Eszopiclone 1–­3 (Elderly 1–­2) Adults 5
Elderly 7
Melatonin receptor agonist Ramelteon 8 1–­2
Dual orexin receptor antagonist Suvorexant 20 (Elderly 15) 12

had the lowest fall rate (1.36%), followed by zolpidem (2.32%), zopiclone insomnia in the USA and Japan) in patients with mild-­to-­moderate
43
(3.85%), brotizolam (4.14%), triazolam (12.0%), and estazolam (13.1%). chronic obstructive pulmonary disease49 or mild-­to-­moderate OSA50
However, in this study, confounding factors, such as diabetes, depres- did not have a detrimental effect on respiratory status as measured by
sion, and total sleep time, were not evaluated. Although melatonin re- SpO2 or the apnea hypopnea index (AHI).
ceptor agonists (ramelteon) and orexin receptor antagonists (such as
suvorexant) were not included in this study, they should have a lower
7 | PRIMARY SLEEP DISORDERS AND
risk of falls because their mechanisms differ from GABAA stimulation.
ITS MANAGEMENT
Ramelteon is a selective agonist of MT1 and MT2 melatonin re-
ceptors located in the suprachiasmatic nuclei in the hypothalamus11.
7.1 | Rapid eye movement sleep behavior disorder
Activation of MT1 receptors decreases the alerting signal in the eve-
ning, and activation of MT2 receptors can shift the phase of the cir- Rapid eye movement sleep behavior disorder is a parasomnia that
cadian system. Compared with benzodiazepine hypnotics, ramelteon occurs during REM sleep and is characterized by dream-­enacting be-
is associated with lower risk of falling, withdrawal, and tolerance. havior, which is the acting out of dream content, including talking,
Ramelteon has been shown to be effective in treating sleep-­onset in- shouting, punching, and kicking; REM sleep without atonia (RWA), loss
somnia and delayed sleep phase syndrome. Its half-­life is short (0.83-­ of normal skeletal muscle atonia during REM sleep, as documented
1.90 hours); however, its effects in reducing wakefulness last up to on polysomnography; as well as altered dream mentation—night-
6 hours.11,44 Ramelteon has been reported to be useful in improving mares of being chased or attacked by unfamiliar people or animals
sleep-­onset latency in OSA patients treated with auto-­titrating pos- are common.51 Abnormal nocturnal behaviors due to RBD are often
45
itive airway pressure therapy. Additionally, the administration of associated with injury of the patients and their bed partners during
8 mg/day ramelteon for 7 days to elderly patients admitted for acute sleep. Diagnosis of RBD requires repeated episodes of sleep-­related
care protected against the occurrence of delirium in a multicenter, vocalization and/or complex motor behaviors; these behaviors are
rater-­blinded, randomized, placebo-­controlled setting.46 documented by PSG during REM sleep or presumed to occur during
Suvorexant, a dual orexin receptor antagonist, is a new class REM sleep based on clinical history, and the presence of RWA on PSG
of hypnotic that works by selectively blocking the binding of the (ICSD-­3).20 Upon awakening, individuals with RBD are typically alert
wakefulness-­promoting neuropeptides orexin A and B to OX1 and OX2 and can recall the contents of their dreams. However, approximately
47
receptors, which suppresses wakefulness. Suvorexant has a half-­life 8% of idiopathic RBD subjects did not recall unpleasant dreams, and
of approximately 12 hours and is useful in subjects with sleep-­onset as 46% were unaware of their abnormal night behavior.52 Additionally,
well as sleep-­maintenance insomnia. There was no evidence of with- in patients with RBD, the details of dreams can be almost forgotten
drawal or rebound effects upon discontinuation after up to 1 year of by noon the following day.51 The prevalence of RBD has been esti-
treatment. Based on the drug’s mechanism of action, a benign side ef- mated as 0.5% of the general population.53 In a large, random-­sample
48
fect profile has been suggested. The administration of 30-­40 mg/day survey of 19 961 members of the general population of Finland,
suvorexant (up to twice the maximum recommended dose for treating Germany, Italy, Portugal, Spain, and the United Kingdom who were
 21897948, 2017, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jgf2.27 by Readcube (Labtiva Inc.), Wiley Online Library on [04/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
68 | SUZUKI et al.

TABLE 7 Essential and supportive diagnostic criteria for RLS (ref. T A B L E 8 Essential and supportive criteria for the diagnosis of
62) probable RLS in the cognitively impaired elderly (ref. 64)

Essential diagnostic criteria of RLS Essential diagnostic criteria of RLS in the cognitively impaired elderly
1 An urge to move the legs usually but not always accompanied 1 Signs of leg discomfort such as rubbing or kneading the legs
by, or felt to be caused by, uncomfortable and unpleasant and groaning while holding the lower extremities are present.
sensations in the legs. 2 Excessive motor activity in the lower extremities, such as
2 The urge to move the legs and any accompanying unpleasant pacing, fidgeting, repetitive kicking, tossing and turning in
sensations begin or worsen during periods of rest or bed, slapping the legs on the mattress, cycling movements of
inactivity such as lying down or sitting. the lower limbs, repetitive foot tapping, rubbing the feet
3 The urge to move the legs and any accompanying unpleasant together, and the inability to remain seated, are present.
sensations are partially or totally relieved by movement, such 3 Signs of leg discomfort are exclusively present or worsen
as walking or stretching, at least as long as the activity during periods of rest or inactivity.
continues. 4 Signs of leg discomfort are diminished with activity.
4 The urge to move the legs and any accompanying unpleasant 5 Criteria 1 and 2 occur only in the evening or at night or are
sensations during rest or inactivity only occur or are worse in worse at those times than during the day.
the evening or night than during the day.
Supportive diagnostic criteria of RLS in the cognitively impaired elderly
5 The occurrence of the above features is not solely
­accounted for as symptoms primary to another medical a Dopaminergic responsiveness
or a behavioral condition (eg, myalgia, venous stasis, leg b Patient’s past history—as reported by a family member,
edema, arthritis, leg cramps, positional discomfort, habitual caregiver, or friend—is suggestive of RLS
foot tapping). c A first-­degree, biologic relative (sibling, child, or parent) has RLS
Clinical features supporting the diagnosis of RLS d Observed periodic limb movements while awake or during sleep
The following features, although not essential for diagnosis, are e Periodic limb movements of sleep recorded by polysomnogra-
closely associated with RLS/Willis–Ekbom disease (WED) and should phy or actigraphy
be noted when present:
f Significant sleep-­onset problems
1 Periodic limb movements (PLM): presence of periodic leg
movements in sleep (PLMS) or resting wake (PLMW) at rates g Better quality sleep in the day than at night
or intensity greater than expected for age or medical/ h The use of restraints at night (for institutionalized patients)
medication status.
i Low serum ferritin level
2 Dopaminergic treatment response: reduction in symptoms, at
j End-­stage renal disease
least initially with dopaminergic treatment.
k Diabetes
3 Family history of RLS/WED among first-­degree relatives.
l Clinical, electromyographic, or nerve-­conduction evidence of
4 Lack of profound daytime sleepiness.
peripheral neuropathy or radiculopathy

15 years and older, 1.6% of the respondents reported violent behavior effective in approximately 90% of patients with RBD, but for elderly
during sleep; 78.7% of these individuals reported vivid dreams, and patients, the potential side effects of daytime sleepiness and dizzi-
54
31.4% hurt themselves or someone else. A study of 349 elderly in- ness should be noted. When patients with dream-­enacting behavior
patients and outpatients at the University of Hong Kong identified 2 also have a history of habitual snoring or witnessed sleep apnea, SAS
(0.57%) with RBD based on polysomnographic findings.55 In a recent should be screened for because clonazepam may worsen sleep apnea
study of 488 subjects aged 60-­97 years (without Parkinson’s disease) in patients with comorbid SAS. Additionally, it is important to note that
representative of the general elderly community, the prevalence of severe SAS can mimic RBD—such cases are called pseudo-­RBD—and
probable RBD was 4.6% and 7.7% according to the RBD screening that the abnormal behavior related to SAS can be effectively treated
questionnaire and Innsbruck RBD-­Inventory, respectively.56 RBD is with continuous positive airway pressure (CPAP) therapy.59 In the USA
more common in males and usually occurs after 50 years of age. Early-­ and Europe, 3-­12 mg melatonin at bedtime has had clinical efficacy in
onset RBD (onset before 50 years of age) has been associated with treating RBD with a reduced risk of fall.60 The efficacy of the herbal
increased gender parity, an increased proportion of idiopathic RBD medicine Yi-­Gan San has also been reported in Japan.61
57
and an increased occurrence of narcolepsy and antidepressant use.
It is becoming increasingly clear that 50% of idiopathic patients with
7.2 | Restless legs syndrome
RBD convert to a parkinsonian disorder within a decade and that 81%-­
90% patients with RBD eventually develop a neurodegenerative disor- Restless legs syndrome is classified as a sleep-­related movement dis-
der.58 Older patients with RBD should be regularly evaluated for the order20 that is typified by an urge to move the legs and abnormal leg
presence of subtle parkinsonism and cognitive and olfactory impairment. sensation, resulting in sleep-­initiation and/or sleep-­maintenance prob-
Hazard avoidance, including removing potentially dangerous ob- lems.62 RLS is also known as Willis–Ekbom disease. The RLS diagnos-
jects from the bedroom or placing a mattress on the floor, is important tic criteria proposed by the International RLS study group (IRLSSG)
to prevent sleep-­related injury in patients with RBD. Clonazepam is include four essential features63: (i) an urge to move the legs; (ii) the
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SUZUKI et al. | 69

symptoms (the urge to move the legs and any accompanying unpleas-
8 | CONCLUSION
ant sensations) begin or worsen during periods of inactivity; (iii) the
symptoms are partially or totally relieved by movement; and (iv) the
Here, we reviewed and discussed the differential diagnosis, clinical
symptoms occur only in the evening or at night or are worse during
diagnosis, and management of insomnia in elderly subjects. In elderly
these times. The latest criteria of the IRLSSG added as a fifth crite-
subjects, the effects on sleep of many comorbid medical conditions,
rion that other conditions or diseases that mimic RLS be ruled out
concomitant medication use, and age-­related physiological changes
(Table 7).62 Clinical features that support a RLS diagnosis include fam-
in sleep architecture and circadian rhythm should be considered.
ily history of RLS (more than 50% of patients with RLS have a family
Comprehensive assessment and management of insomnia along with
history of RLS), a favorable response to dopaminergic treatment, the
treatment of comorbid medical conditions may improve the patient’s
presence of periodic limb movements during sleep or resting wake-
quality of sleep as well as of daytime life.
fulness, and the lack of profound daytime sleepiness. Despite signifi-
cant sleep loss, patients with RLS rarely report daytime sleepiness.64
Using proton magnetic resonance spectroscopy, Allen et al.65 found CO NFL I C T O F I NT ER ES T
increased thalamic glutamate levels in patients with RLS that were
The authors declare no conflict of interests regarding this article.
correlated with wake times during the sleep period, supporting the
concept that the hyperarousal state that characterizes RLS is mediated
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