INTRODUCTION
Sleep disorders are common in the elderly. It is estimated that 40-70% of elderly
experience chronic sleep problems. Higher rates of sleep problems are observed in
those elderly with medical and psychiatric comorbidity. The comorbid disorders have
additive effects on sleep disturbances, i.e. higher the number of comorbidities, higher
the rates of sleep problems.
Elderly subjects have initial insomnia, wake up earlier than usual, have higher time
spent in bed, have nighttime awakenings, nap more, and have decreased total sleep
as compared to younger adults. With increasing age lighter stages of sleep becomes
more, whereas, REM and slow-wave sleep reduce; up to 6 years of age there is 2% decrease
in slow-wave sleep every decade. Slow-wave sleep does not change much from 60 to 90
years of age. However, sleep efficiency, i.e. the duration of sleep relative to total
time in bed, continue to decrease over time. Sleep in the elderly is fragmented, lighter
and is characterized by episodes of arousals and awakenings.
Certain changes in circadian physiology occur with age. They include sleeping before
the desirable sleep and wake times, earlier clock hour of internal circadian time,
alteration in the relationship between the internal circadian time and sleep, reduction
in circadian amplitude, and reduced sensitivity to low to moderate light levels. Among
the elderly, core body temperature, and cortisol and melatonin rhythms occur at an
earlier time. The changes in sleep that occur with age are summarized in Table 1.
However, these changes are not the common sleep complaints of the elderly population.
Table 1
Sleep changes in the elderly
Indian Psychiatric Society (IPS) published Clinical Practice Guideline (CPG) for management
of sleep disorders, for the first time in the year 2006 and a revised version in the
year 2017. The current version of the CPG is an update of the earlier versions which
specifically focuses on management of sleep disorders in the elderly. The current
version of the CPG for sleep disorders in elderly must be read in conjunction with
the previous versions of CPG for sleep disorders in the adult population. These guidelines
provide a broad framework for assessment and management of sleep problems in elderly
patients. Most of the recommendations made as part of the guidelines are evidence-based.
However, these guidelines should not be considered as a substitute for professional
knowledge and clinical judgment. The recommendations made as part of these guidelines
are best available options that have to be modified as per the clinical needs of the
individual patient and the treatment setting.
SLEEP DISORDERS IN ELDERLY
Insomnia and daytime sleepiness are the common sleep complaints in older individuals
(table 2). Among the elderly, the prevalence of initial insomnia are found in 15%–45%,
middle insomnia in 20%–65%, late insomnia in 15%–54%, and 10% have poor sleep quality.
Those having sleep complaints report poor quality of life and higher rates of depression
and anxiety. Cognitive deficits can appear because of chronic sleep problems in the
elderly that include attentional impairment, difficulties in short-term memory, increase
inresponse time and decreased performance. Furthermore, sleep problems increase mortality
in older individuals; lower sleep efficiency (<80%) almost doubles the risk of all-cause
mortality. The common primary sleep disorders thatare seen in older adults include
chronic insomnia disorder (CID), sleep-disordered breathing (SDB), restless legs syndrome(RLS)/periodic
limb movements in sleep (PLMS), REM sleep behavior disorder (RBD) and advanced sleep-wake
phase disorder (ASWPD).
Table 2
Common sleep complaints in the elderly
CHRONIC INSOMNIA DISORDER
Insomnia is commonly defined as recurring problems in sleep initiation (sleep onset
insomnia) or maintaining asleep (sleep maintenance insomnia). The former is also called
initial insomnia, and the later can be either middle or terminal insomnia. Without
distinguishing between primary and secondary, ICSD-3 identifies insomnia disorder,
that can be divided on the basis of its duration into transient or short-term (lasting
only a few days to three to four weeks) or chronic (persisting for more thanthree
months). Clinically (as well as using polysomnographic criteria) insomnia is defined
as a sleep latency of more than 30 minutes, remaining awake after sleep onset formore
than 30 minutes, sleep efficiency of less than 85%, or less than 6 to 6.5 hours total
time asleep, occurring on three nights per week or more. Complaints of only non-restorative
sleep are no longer sufficient to diagnose insomnia disorder. The diagnostic criteria
for chronic insomnia disorder are in table 3.
Table 3
Diagnostic criteria for chronic insomnia disorder
Insomnia is the most common sleep complaint in the elderly. Insomnia is seen in 20
to 40% of older adults as compared with 9% to 15% in the general adult population.
Sleep maintenance insomnia is more common in elderly than sleep onset insomnia. Insomnia
disorder leads to fatigue, mood changes, poor cognition, daytime sleepiness and impairment
in functioning. Other consequences of untreated insomnia disorder include increased
chances of developing mental illness, accidents, poorer quality of life, and greater
healthcare utilization.
Assessment and Evaluation
In the diagnostic evaluation of patients presenting with insomnia, detailed sleep,
medical and psychiatric history is essential. Detailed information has to be obtained
regarding the initiation of symptoms, its course, and progression. Also, information
from the bedpartner is invaluable in arriving at the correct diagnosis. There are
several conditions that can be mistaken for insomnia and need to be ruled out before
making a diagnosis of insomnia (table 4). Insomnia is associated with several psychiatric
disorders (table 5) and medical disorders (table 6) in the elderly. It is pertinent
to ask about the prescription as well as non-prescription medications that a person
is taking several classes of medications are associated with insomnia (table 7). Sleep
log or diary is a primary subjective method which gives nightly information on perceived
sleep patterns and quality. It not only aids in the assessment of insomnia but also
in monitoring treatment outcomes. Simple forms of sleep diaries may only include information
on how much time a person spends in bed, approximate durations of sleeping and waking
time, and estimation of sleep efficiency. While starting therapy, sleep diaries are
typically filled two weeks prior and continued during treatment and follow up period.
An algorithm for the diagnosis of insomnia disorder is presented in figure 1.
Table 4
Conditions are mistaken for insomnia
Table 5
Insomnia in psychiatric disorders
Table 6
Medical conditions associated with insomnia in elderly
Table 7
Medications associated with insomnia
Figure 1
Algorithm for diagnosis of insomnia disorder
There are specific scales and other rating instruments available for assessment of
sleep and insomnia symptoms (table 8). These instruments aid in the evaluation of
patients with insomnia and may be used in addition to history and examination. Objective
methods such as polysomnography (PSG) and actigraphy are used in special laboratories
for measuring sleep initiation and maintenance variables. PSG is not indicated routinely
in the evaluation of insomnia but may be used to rule out other sleep disorders or
in non-responders (i.e. when patients do not respond to the first-line medications).
Actigraphy is a small device that is worn as a wristwatch that records movement frequency
and is a reliable and valid tool for assessing sleep duration.
Table 8
Objective assessment scales in insomnia
Non-pharmacological management
The initial treatment for insomnia in the elderly should include non-pharmacological
approaches. Several treatment options for the older individuals are available (see
Table 9).
Table 9
Non-pharmacological treatment for chronic insomnia disorder
Sleep hygiene education can be used which includes certain lifestyle changes such
as diet control, regular exercise and reducing stimulant and alcohol use, in addition
to controlling environmental factors such as ambient noise, light, and temperature
that may disturb sleep. Also, it is advised to avoid frequent daytime napping, late
evening exercises, and late heavy dinner. A regular exercise regimen and adequate
light exposure during daytime have been found useful forinsomnia in elderly.
Stimulus Control Therapy: The theory behind stimulus control treatment is maladaptive
conditioning between the bedroom environment and bedtime with behaviors that are incompatible
with sleep. These behaviors include worrying, reading, using a smartphone or watching
TV while in bed. Stimulus control aims at reducing the association between these maladaptive
behaviors which maintain arousal during bedtime and increasing the association between
sleep and sleep-promoting stimuli. This is achieved by restricting the time one is
awake in bed by reducing the sleep-interfering activities, and by maintaining a regular
sleep-wake schedule. Instructions to patients for stimulus control include:1) Lie
on the bed only when feeling sleepy, 2) Avoid any activity that keeps you awake in
the bedroom, other than sex, 3) Sleep only on bed in the bedroom, and not on other
places such as sofa, 4) To leave the bedroom soon after waking, 5) To come to bedroom
only when feel sleepy, 6) Keep the waking up time fixed, irrespective of the hours
of sleep during night, and 7) Avoid napping during day.
Sleep Restriction: It includes reducing the duration spent in bed to the actual time
asleep, thus creating sleep deprivation and subsequent increase in sleep drive. Before
starting sleep restriction therapy, a sleep log for 2 weeks is maintained which gives
an estimate of average sleep time versus actual time in bed, i.e. sleep efficiency
(SE). The allowed sleep time is the average subjective sleep time but is never less
than 5 hours. As SE improves (more than 90%), time in bed is increasedby 15-minute
increments until adequate sleep duration is attained.
Relaxation therapy and imagery: Thoughts can be detrimental to sleep and anxiety may
cause sleep onset insomnia. Relaxation training originally used to alleviate anxiety
is used for the treatment of sleep onset insomnia. Several techniques have been used
in the treatment of insomnia that includes 1) Progressive muscle relaxation, 2) Autogenic
training (induction of sensations of warmth and heaviness are used to promote somatic
relaxation), 3) Imagery (pleasant imagery can be used along with relaxation to improve
sleep). Individuals must practice the chosen technique at least twice a day, and itmay
require several weeks of practice before the skill is acquired.
Cognitive behavioral therapy for insomnia (CBT-I): This has been specifically developed
for insomnia that comprises of cognitive approaches that target cognitive distortions
and misconceptions related to insomnia, behavioral approaches such as stimulus control
and sleep restriction, and educational approaches such as sleep hygiene. This can
be delivered in several different formats either face-to-face individual or in a group
setting, through the telephone- or internet-based modules, and also through self-help
books. CBT-I in elderly has mild effect for sleep problems and works best for sleep
maintenance insomnia. Multi-component therapy involves a different combination of
all the treatment approaches listed above. Brief behavioral therapy (BBT) is also
used for insomnia in older adults.
Pharmacological management
In the elderly, the ideal hypnotic should 1) be able to induce sleep rapidly, 2) have
no adverse effects on normal sleep architecture, 3) demonstrate no significant residual
effects, 4) be safe in patients with respiratory and cardiac conditions, 5) have minimal
effects on memory, 6) not impair functioning, 7) have no risk of tolerance or rebound
insomnia, 8) be safe during overdose, and 9) possess no potential for abuse or dependence.
However, there is no ideal hypnotic available till date.
The basic rules of rational pharmacotherapy for insomnia in the elderly includes prescribing
the lowest effective dose (which is usually half of adult dose), for shortest possible
time (no more than 3–4 weeks), intermittent dosing (two to four times weekly) if possible,
using drugs that have shorter elimination half-lives and lesser daytime sedation,
and which can be gradually discontinued without causing rebound insomnia.
The first line drugsfor chronic insomnia disorder includes nonbenzodiazepine Z-drugs,
benzodiazepines and melatonin receptor agonist ramelteon (table 10). Other medications
include orexin receptor antagonist suvorexant, the antidepressants such as doxepin,
antihistamines, antipsychotics, and melatonin. There is no evidence of superior efficacy
of either of the agents in insomnia treatment.
Table 10
First line medications† for chronic insomnia in elderly
Non-benzodiazepine benzodiazepine receptor agonists: The Z-drugs in this group include
zolpidem, zaleplon, zopiclone, and eszopiclone. These medications target the GABA-A
receptor complexes and have preferential affinity for the α-1 subunit. For sleep onset
insomnia, medications with a shorter half-life (zaleplon or zolpidem) are preferred,
whereas, for sleep maintenance insomnia, those with a longer half-life (zolpidem sustained
release or eszopiclone) are needed. Zaleplon can be used specifically for the treatment
of mid-night awakenings because of its short half-life and ensures 4 hours of sleep.
Owing to less adverse effects, Z-drugs are considered as the first-line agents for
chronic insomnia wherever available.
Melatonin agonists: Ramelteon, a selective melatonin MT1 and MT2 receptor agonist,
has been used for chronic insomnia at 4 to 8 mg/day. It probably acts through suprachiasmatic
nucleus by influencing homeostatic sleep signaling. Ramelteon reduces sleep onset
latency and total sleep timein older adults with insomnia and wastolerated well up
to one year. Studies suggest that low doses of melatonin (0.5-6 mg) improve initial
sleep quality in older adults with insomnia. There is some evidence to suggest that
agomelatine at 25 mg isuseful for the treatment of insomnia in the elderly.
Orexin receptor antagonist: Suvorexant is a newer medication for treating insomnia
that blocks orexin-mediated wake signaling. It improves initial and maintenance insomnia
at 10-20 mg dosage. Suvorexant is usually taken on an empty stomach so that sleep
onset is faster. It is recommended that it is taken at a time when one plans to sleep
for at least 7 hours continuously. Common side effects include somnolence, fatigue,
and headache. Suvorexant improves sleep onset and maintenance and is tolerated well
bythe elderly.
Very low dose doxepin: Doxepin 3-6 mg through its H1 antagonism action has been found
to be safe and effective in the treatment of sleep maintenance insomnia in the elderly.
It improves sleep maintenance, total sleep time and sleep quality, but has no effect
on sleep onset. There are no residual symptoms the next day. However, long-term studies
are lacking.
Several benzodiazepines such as estazolam, temazepam, triazolam, flurazepam have been
used for the treatment of chronic insomnia. In absence of benzodiazepines approved
as hypnotics, other agents such as lorazepam, oxazepam, clonazepam or diazepam can
be used. The strategy is to use long-acting benzodiazepines if comorbid anxiety is
present. In other situations, either short- or intermediate-acting agent are preferred
for sleep onset and sleep maintenance insomnia, respectively. However, benzodiazepines
should be used with caution in the elderly, as it can lead to falls and fractures,
motor vehicle accidents, cognitive decline, delirium, dependence and are best avoided
if possible. Sedating tricyclic antidepressants may be used as hypnotics in low doses,
e.g. amitriptyline 10-50 mg, imipramine 25-50 mg. Other commonly used medication for
insomnia, mostly available as over-the-counter agents includes diphenhydramine (50-100
mg) and promethazine (25-100 mg). However, these medications are best avoided in elderly
and are included in Beers list for potentially inappropriate medication use in the
elderly.
Trazodone 50 mg improves sleep parameters in Alzheimer's disease and is tolerated
well. Mirtazapine (7.5-15 mg) and esmirtazapine (1.5-4.5 mg) has also been reported
to be effective in the treatment of insomnia. Atypical antipsychotics such as a low
dose of quetiapine (25-100 mg) may be useful in some patients with insomnia if other
agents are not effective. Tiagabine, a selective inhibitor of GABA transporter, at
4-6 mg dose increase slow-wave sleep and was well tolerated in elderly. Gabapentin
(100-600 mg) and pregabalin (150-300 mg) may sometimes be used for insomnia, specifically
for those with comorbid neuropathic pain symptoms.
SLEEP-DISORDERED BREATHING (SDB)
SDB is an umbrella term encompassing obstructive sleep apnoea (OSA), primary or secondary
centralsleep apnoea (CSA), high-altitude periodic breathing, Cheyne–Stokes respiration,
nonobstructive hypoventilation, or hypoxemia disorders secondary to pulmonary parenchymal,
vascular, neuromuscularor chest wall disorders. OSA, which is the most common SDB,
is characterized by a distinctive snoring pattern caused by intermittent airway collapse.
In this condition, there are of periods of loud snoring or brief gasping followed
by cessation of respiration lasting 20 to 30 seconds. This leads to sleep arousals,
possibly due to arterial oxygen desaturation. Often the patient is not aware of his
or her snoring and nighttime arousals, and a subset of patients complain of excessive
daytime sleepiness (EDS).
In patients having SDB, apneas (complete cessation of respiration) and/or hypopneas
(30% reduction in airflow with 4% oxygen desaturation) occur during sleep. SBD is
diagnosed when these episodes last more than 10 sec and occurseveral times during
the night, leading to frequent arousals and fall in oxygen saturation. The total number
of apnoea and hypopnea episodes per hour of sleep is known as apnea-hypopnea index
(AHI). For the diagnosis of SBD, an AHI morethan 5 is required. SDB in > 65-year-olds
is found in >20%(as defined by AHI ≥10) and can be up to 60% in frail elderly patients
(Netzer et al. 2016). The known risk factors for SDB in older adults include male
gender, positive family history, smoking, several craniofacial abnormalities such
as retrognathia, retrusion of the maxilla, macroglossia, central obesity, concomitant
pulmonary diseases that reduce the chest wall compliance or any condition reducing
diaphragmatic movement. Therisk of SBD becomes more if there is alcohol consumption
sedating medication use. In elderly patients with severe SDB (AHI≥30), cognitive impairments
are frequent that includes poor attention and recall, slowed response time and impairments
in executive function.
Central sleep apnea (CSA) is characterized by loss of ventilatory drive leading to
stoppage of breathing (at least 5 or more per hour) during sleep. On the basis of
etiology, CSA in the older population can be broadly classified as primary CSA, Cheyne–Stokes
breathing pattern inheart failure, and CSA in neurodegenerative disease and stroke.
Assessment and Evaluation
Evaluation of SDB includes a complete sleep history that covers the history of snoring,
snorting, non-refreshing sleep, nocturia >2/night, nocturnal gastro-esophageal reflux,
sleep-talking, increased dreaming, daytime fatigue and in a subset of patients, excessive
daytime sleepiness. Preferably, in all cases, parallel information must be obtained
from bed-partners who complain of witnessed pauses in breath during sleep. Also, details
of medical and psychiatric disorders, prescribed medications, alcohol use, as well
as cognitive impairment should be elicited. Formal evaluation for OSA should be considered
in elderly patients who exhibit typical symptoms, but also should be considered in
patients with comorbid cardiovascular risk factors or atypical symptoms such as nocturia,
un explainedfalls, automobile accidents, or cognitive decline.
Findings on physical examination that supports OSA include: 1) neck circumference
>40 cm in males and 37 cm in females, measured at cricothyroid level, 2) body mass
index (BMI) >25 kg/mm2, 3) low-lying soft palate, 4) elongated or large uvula, 5)
large tongue (often noted by the presence of tongue edge crenations), or 6) large
tonsils or narrow distance between the tonsillar pillars. In older adults, an additional
risk factor is an edentulous state, i.e. when patients remove their dentures at night,
this leads to a reduction in the vertical dimension that increases the occurrence
of upper airway obstructive events.
Screening tools, such as the Berlin Questionnaire can be used for estimation of OSA
risk, which has been validated for Indian population. Epworth Sleepiness Scale may
be used to document sleepiness.
The SDB is diagnosed based on overnight sleep recording, i.e. nocturnal PSG. A full
night polysomnography in the sleep laboratory is considered as the gold standard method
for diagnosis of SDB. In this method, sleep data of entire night is recorded and is
scored by a trained scorer. The subsequent night is used to manually titrate the pressure
of PAP device. Thus, each study requires at least two nights. However, in extreme
cases where pre-test clinical data suggests severe OSA and patient is not having any
other comorbidity, split-night study may be done. During “split study” the initial
half of the night is used for diagnosis, whereas, the second half is used to titrate
positive arterial pressure (PAP) if the OSA is severe. The limited-channel home-based
testing (respiratory polygraphy) has also been studied in making the diagnosisof SDB.
However, this must be used cautiously only in selected cases as it provides data only
regarding sleep discorded breathing and can miss other information which may be important
for patient's management.
Non-pharmacological management
Treatments for SDB depend on the symptoms and disease severity, and the presence of
cardiovascularor metabolic disease. Treatment options in OSA are summarized in table
11. Treatment for mild OSA (AHI 6-15) without any other medical comorbidity includes
lifestyle modification strategies such as regular exercise and weightloss, smoking
cessation and reducing caffeine, alcohol, and avoiding the use of sedatives and other
recreational drugs, and optimizing sleep and medical management of comorbidities.
These patients should be followed up every three months to clinically assess symptoms
and progress of weight reduction.
Table 11
Treatment options for OSA
Inmild-to-moderate SDB, positional measures and oral mandibular advancement splints
are used. Positional therapy consists of techniques intended to increase the time
spent in the lateral sleeping position as opposed to the supine position. These include
using pillows to prop up while lying or even sewing a ball into the back of the shirt
to make the supine position more uncomfortable. There are sleep shirts available to
facilitate lateral positional therapy. Positional therapy is indicated specifically
for positional sleep apnea. In a meta-analysis, both continuous positive airway pressure
(CPAP) and positional modification techniques were effectivein reducing AHI in those
with positional OSA; however, the former was better.
Oral appliances are helpful in improving respiration and sleep quality in patients
with OSA. It is recommended that for OSA in adults, a custom, titratable appliance
is prescribed in consultation with a qualified dentist. However, their effectiveness
in elderly is poorly studied.
In moderate to severe cases of OSA or symptomatic cases (associated with other comorbidities)
mainstay of therapy is positive airway pressure devices and it is considered the gold
standard treatment. Usually, manual CPAP device is preferred. Bilevel PAP device is
advisable when the patient is not able to tolerate CPAP pressure or when PAP pressure
requirement is beyond 20 cmH2O. In a network meta-analysis, CPAP was found to the
most effective treatment for OSA. Older adults whoadhere to at least three months
of CPAP treatment show improvements in cognitive functions such as psychomotor speed,
executive functioning, and non-verbal delayed recall. Auto-PAP has limited efficacy
in the management of OSA.
Surgical modifications of upper airway include procedures such as maxillomandibular
advancement (MMA), laser-assisted uvulopalatoplasty (LAUP), uvulopharyngopalatoplasty
(UPPP) and radiofrequency ablation (RFA). In a meta-analysis, MMA resulted in improvements
in the AHI, whereas, pharyngeal surgeries had less consistent outcomes. Several studies
have found good results with newer pharyngeal surgeries and multi-level techniques,
which needs replication. However, due to limited data, recurrence rates falling close
to 50%, surgical methods are restricted to only a selected group of patients with
major anatomical issues and PAP failure.
Hypnotics and other sedating medications worsen SDB by inducing or worsening OSA and
CSA. These medications should be avoided if SBD is suspected.
Sometimes, modafinil or armodafinil can be used if daytime sleepiness persists in
spite of compliance to PAP therapy.
SLEEP-RELATED MOVEMENT DISORDERS
Sleep-related movement disordersinclude conditions that have stereotyped movements
that disrupt sleep. The common presenting features are initial or maintenance insomnia.
It includes restless leg syndrome (RLS), periodic limb movement disorder (PLMD) and
REM sleep behavior disorder (RBD).
RESTLESS LEGS SYNDROME (RLS)
Restless legs syndrome (RLS) (also called Willis-Ekbom disease) is featured by dysesthesia
in the legs which are usually described as bubbly or a “creepy and crawly” sensation,
tingling, tickling, just restlessness, stretching sensation in the leg muscles that
occurs during rest and is relieved by movement. Indian data suggests that most of
the patients adopt one of the four strategies: moving legs, coming out of bed and
walking, asking somebody to massage their legs and tying a rope on their legs. These
complaints are almost always seen at night. A number of conditions may be mistaken
for RLS, so they should be ruled out carefully, before diagnosing RLS. The prevalence
of RLS in >65-year-olds is 10-35%.
Certain medications are seen in those having RLS. These are commonly seen in elderly,
increasing the chances of having RLS. These include iron deficiency, uremia, neuropathies
and cardiovascular disorders. Hence, these disorders must be ruled out in all patients
of RLS. Serum ferritin level <50 μg/L has been found to correlate with severe RLS
symptoms in comparison with serum iron levels, total iron binding capacity (TIBC)
or transferrin saturation percentage. The prevalence of RLS is typically between 15to
40% in patients with uremia. It affects hemodialysis, as patients are required to
lie still during the procedure. There is some evidence to suggest that RLS is associated
with diabetic or alcoholic neuropathy and spinocerebellar ataxia type 3.
Assessment and Evaluation
Diagnosis of RLS is purely clinical and depends upon the information provided by the
patient (table 12). All the criteria need to be met to diagnose RLS. Also, the RLS
mimics (table 13) need to be differentiated. Additional supportive criteria include
treatment response with dopaminergic agents (60-75%). Iron deficiency frequently coexists
and needs investigation. Low serum ferritin (<50 μg/L) is a sensitive marker for iron
deficiency. The recommended investigations in elderly include hemogram, serum ferritin,
blood urea and serum creatinine in all cases, and if possible, serum folate, vitamin
B12, and magnesium levels.
Table 12
Diagnostic Criteria for RLS/WED
Table 13
RLS Mimics
Salient features of patient workup have been summarized in table 14.
Table 14
Work up of a suspected case of RLS at baseline and on each follow-up visit
International Restless Legs Scale (IRLS) is a 10-item measure of disease severity
in RLS that is easy to use and has been used extensively. Actigraphy or polysomnographic
assessment is usually not required.
The Suggested Immobilization Test (SIT) was developed for evaluation of RLS, however,
it has limited clinical utility. In the standard procedure of the SIT, the patient
lies down with legs straight for one hour starting at 9pm. Patients are encouraged
to resist any urge to move during the SIT. Also, the SIT gives information on the
propensity to symptom onset because immobilization provokes RLS symptoms. A modification
of SIT, Multiple Suggested Immobilization Test (m-SIT) is also validated which consists
of several tests in the afternoon and evening hours.
Non-pharmacological Treatment
Several dietary and lifestyle modifications are useful to control RLS. Patients are
instructed to take a hot shower or massage their legs before bedtime, have regular
sleeping and waking timings, regular exercise, and avoiding sleep deprivation and
caffeine, cigarettes, andalcohol. Several over-the-counter medications such as antihistamines
worsen RLS symptoms and are better avoided. Other medications such as antipsychotics,
antiemetics, antidepressants, beta blockers, some anticonvulsants and lithium are
known to exacerbate RLS and should be discontinued if possible.
Pharmacological Treatment
Pharmacotherapy is indicated when RLS symptoms impair functioning, sleep, and quality
of life. The medication options in RLS are summarized in table 15. The first-line
treatment of primary RLS includes non-ergot based dopamine agonists (ropinirole, pramipexole,
and rotigotine), which have the highest level of evidence for efficacy and safety.
The dopamine precursors (levodopa) and ergot-based dopamine agonists (e.g. cabergoline)
are effective, but more likely to cause augmentation, hence, are considered as second-line
agents. In general, longer acting dopamine agents are preferred and the dopaminergic
load should be decreased by prescribing the lowest dose that is effective for the
shortest time.
Table 15
Pharmacotherapy of RLS
One of the major problem during treatment with short-acting dopaminergic agents is
augmentation, which is characterized by either worsening of the severity of symptomsor
by an earlier onset of symptoms as compared to baseline. This condition worsened by
increasing the dose of dopaminergic agents. This must be differentiated from the end
of dose phenomenon. The Max Planck Institute's operationalcriteria for augmentation
is summarized in table 16.
Table 16
Max Planck Institute criteria for augmentation
If augmentation limits the use of dopamine agonists, non-dopaminergic agents such
as gabapentin and pregabalin are preferred agents and have a fair level of evidence
for their efficacy. In some recent guidelines, use of these drugs is considered as
first-line to prevent the development of augmentation. Specifically, gabapentin enacarbil
(the pro-drug of gabapentin) is preferred considering its longer half-life. Use of
opioids is limited by their possible abuse potential but may be usefulin non-responders,
specifically those having severe augmentation features. Benzodiazepines such as clonazepam
do not reduce PLMS, but improves sleep; therefore, they are indicated if sleep disturbance
is prominent.
For secondary RLS, the underlying condition needs treatment along with specific treatment
with dopamine agonists. Iron therapy is indicated in those with lower ferritin levels.
Oral supplementation or intravenous formulations are indicated so that the ferritin
levels increase to more than 50 μg/L. It is not effective if ferritin levels are higher
than 100 μg/L and anemia is absent. In those with RLS associated with end-stage renal
disease, dialysis improves the symptoms.
RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER (RBD)
The prevalence of RBD is 0.5% in the general population. Among the elderly, 7% have
RBD. It is predominantly seen in males after the age of 50 years. The plausible reasons
for lower rates in females are summarized in table 17.
Table 17
Plausible reasons for lower rates of RBD in females
RBD is featured by dream enactment behavior (DEB) that ranges from simple to complex
vocalizations and motoric behaviors that occur during REM sleep. These behaviors occur
because there are periods where there is no loss of muscle tone that is typically
found in REM sleep, i.e. REM sleep without atonia (RSWA). Typically, RBD behaviors
are more prominent during the latter part of the night when REM sleep predominates.
Common RBD behaviors are walking, speaking and eating. Occasionally, they can be violent
and the patient or their bed partner may be hurt; however, most are unaware of these
actions. It is likely that some patients with RBD involve impressive and obvious DEB,
whereas, most DEB may be unobtrusive movements limited to the hands, otherwise known
as hand babbling.
Idiopathic RBD is linked to neurodegenerative disorders, specifically with alpha-synucleinopathies
(e.g. Parkinson's disease, Lewy Body Dementia, multiple system atrophy) (see table
18). Features that suggest the possibility of neurodegenerative disorders include
abnormal smell or vision, constipation, orthostasis and motor slowing. Several medications
and drugs are also associated with RBD (see table 19).
Table 18
Secondary causes of RBD
Table 19
Drugs associated with RBD
Assessment and Evaluation
The observations of a bed partner or someone who has witnessed the patient's sleep
are invaluable. In patientswithout a bed partner, clues suggesting possible RBD include
vivid or terrifying dreams, falling out of bed, or unexplained nocturnal bruising.
RBD can be accurately identified with the following screening question: “Has anyone
ever told that you act out your dreams (e.g. punching or flailing arms in theair or
screaming and shouting in your sleep?)”. RBD need to be distinguished from NREM sleep
disorders. One clue which favors RBD is that patients are alert and immediately have
a vivid dream recall. Another clue is the phenomenon of isomorphism, i.e. the DEB
correlates with a recalled dream, in contrast to confusion and little recall after
NREM sleep disorder. A 16-item Mayo Sleep Questionnaire (MSQ) can be used to screen
for RBD and other sleep disorders. All patients with dream enactment history should
be screened for OSA, which can mimic RBD. The differential diagnosis of RBD is summarized
in table 20. Detailed neurological examination in patients with RBD is summarized
in table 21. Early features of neurodegenerative disorders having RBD is presented
in table 22.
Table 20
Differential diagnosis of RBD in elderly
Table 21
Neurological history and examination: salient features
Table 22
Early features of neurodegenerative disorders that present as RBD
Although history may suggest RBD, PSG is often required for definitive diagnosis.
The diagnosis of RSWA is based on EMG findings during REM sleep. To diagnose RBD,
EMG abnormalities include increase in muscle tone and/or phase twitch during REM sleep.
The duration of RBD may have a wide variation, however, most occur less than once
weekly and last for less than 2 minutes.
Approach to a patient with RBD is depicted in figure 2.
Figure 2
Flowchart showing differential diagnosis, progression monitoring and treatment decision
tree in idiopathic RBD (iRBD)
Non-pharmacological Treatment
The primary goals of treatment in RBD include preventing injury to the patient and
their bed partner during sleep andminimizing sleep disruption.
Injury-preventing techniques: These includes modification of environment such as sleeping
on the floor to avoid falling from bed, padding corners of furniture, keeping the
window and door locked at night and removing potentially dangerous objects from the
room. Using heavy curtains on bedroom windows reduces sleep disruption. The bed partner
may be asked to sleep separately till the condition improves.
Discontinue medications known to exacerbate RBD: Medications that are known to exacerbate
RBD should be discontinued if possible. These include antidepressants (selective serotonin
reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants
and monoamine oxidase inhibitors), beta-blockers (atenolol, bisoprolol), tramadol
and cholinesterase inhibitors. If there is comorbid depression, bupropion is preferred
as it doesn't worsen RBD.
Treat underlying cause: If any specific underlying cause is found (e.g. brain stem
tumor), it requires specific treatment.
Prognostic counseling: Patients need to be educated regarding the possibility of RBD
being an early marker of neurodegenerative disease.
Bed alarm: A bed alarm can be used for the treatment of RBD. It consists of a pressure
sensor that is placed on the shoulders which get activated during dream enactment.
At that time a pre-recorded message is played which tells them that it is a dream,
thereby calming the patient and they go back to sleep.
Pharmacological Treatment
First-line treatment: The preferred treatment for RBD is low-dose clonazepam at doses
from 0.5-1 mg/day. It is a long-acting benzodiazepine that reduces abnormal motor
behavior in 90% of subjects (table 23). However, there are concerns regarding its
use in elderly such as residual sleepiness, unsteadiness leading to falls and fractures,
delirium and cognitive impairment, which limits its use in frail patients. Also, it
should be avoided in RBD patients with comorbid OSA, as it is potential respiratory
suppressant. Furthermore, clonazepam being a cytochrome P450 substrate, drug interactions
needs consideration.
Table 23
Drugs used in treatment of RBD
Melatonin at high-doses is also as effective as clonazepam for RBD and can be considered
as an alternative first-line agent. It is probably better tolerated, specifically
in those with neurodegenerative disease. The recommended dose is 3-15 mg at bedtime
(median effective dose is 6 mg). Other melatonergic agents such as agomelatine (25–50
mg) or ramelteon (8 mg) at bedtime may be helpful, but evidence for their efficacy
is low.
Second-line drugs: Medications such as dopaminergic agonists (pramipexole) and acetylcholinesterase
inhibitors (rivastigmine) have been used with variable success in patients with RBD
and may be considered in treatment-refractory patients as second-line agents. Other
agents that have been used include temazepam, lorazepam, zolpidem, zopiclone, cannabinoids,
and sodium oxybate.
CIRCADIAN RHYTHM SLEEP-WAKE DISORDERS (CRSWD)
Sleep and circadian rhythm changes with aging, as well as less exposure to light and
reduced activity level, are factors leading to circadian rhythm sleep-wake disorders
(CRSWDs) in the elderly (see table 24). Sleep quality is optimal if there is a match
between the intended sleep times with thetiming of endogenous circadian rhythm. CRSWDs
can occur if the timings of central circadian clock changes or the timing of endogenous
circadian rhythm don't match with the daily social and physical environment. The underlying
cause for CRSWDs is related to circadian timing alterations, however, the clinical
presentation depends on the physiological, behavioral and environmental factors. Shift
work and Jet lag disorder are extrinsic, whereas, rest are intrinsic disorders.
Table 24
Circadian rhythm sleep-wake disorders
In the elderly advanced sleep-wake phase disorder (ASWPD) is most common, which is
characterized by an advancement of the sleep-wake cycle. It presents as regular and
involuntary sleep and wake times which occur several hours before the usual times.
In a large multicenter study on subjects more than 65 years, 20% experienced early
morning awakening.
Evaluation and assessment
To diagnose CRSWDs, clinical sleep history, monitoring with a sleep diary, and if
possible actigraphy for at least one week is required. Patients with ASWPD typically
report sleepiness during the early evening, early sleep onset (between 6-9 PM), and
spontaneous early morning awakening (2-5 AM). Even if they resist evening sleepiness
and sleep at conventional bedtime, they still wakeup early and have daytime sleepiness.
A sleep log or actigraphy monitoring is required to demonstrate a pattern of advancement
in the regular sleep time for at least one week. Psychiatric disorders that cause
early morning awakening such as depression and bipolar disorder need to be ruled out.
Morningness-Eveningness Questionnaire (MEQ) can be used to characterize the chronotype
of an individual, which shows a definite ‘morning type’. Polysomnography is not always
needed for diagnosis of CRSD, but may be indicated to rule out other comorbid conditions
such as OSA or PLMS. If PSG is performed, it is to be done at the usual sleep time
of the patient.
To study the phase and amplitude of circadian rhythm, dim light melatonin onset (DLMO)
and nadir core body temperature (Tmin) can be used. DLMO is considered as the most
reliable among all. It is the timewhen endogenous melatonin levels start rising in
dim light, i.e. approximately 2–3 hours before the usual bedtime. DLMO is used to
estimate the circadian timing of individual so that melatonin and other treatment
can be administered at appropriate times. The intrinsic circadian period can be estimated
under free-running conditions, where the effects of light are controlled.
Management of Advanced sleep-wake phase disorder (ASWPD)
Treatment of ASWPD involves delaying the sleep-wake timing through chronotherapy,
timed-melatonin, and timed-light exposure. Sleep hygiene is not of much use, except
for avoiding long evening naps which may improve nocturnal sleep. The co-morbid conditions
that may contribute to sleep complaints, especially depression should be treated.
Nonpharmacological treatment
Light therapy: The principle involves reducing morning light that advances phase and
increasing evening light which delays phase. Patients are instructed to avoid going
out and stay in a dark room during the early morning and to wear sunglasses while
going out. Also, they are instructed to remain outdoors in the late afternoon and
early evening and use bright lights inside the home during the evening. Bright light
is recommended in the evening, between 7 to 9 PM (at least 5000 lux for 2 hours) todelay
the circadian phase.
Chronotherapy: The goal in the treatment of ASWPD is a correction of abnormal early
sleep phase. Most patients have difficulty delaying their sleep schedule, but find
it easier to advance. Therefore, in some persons, advancing around the clock is preferred.
In ASWPD, typically timing of sleep is advanced by 3 hours every 2 days until the
expected time is reached. However, such schedules may not be liked by many and can
cause disruptions in routine work.
Pharmacological Treatment
Melatonin: Phase delay can be induced by administration of melatonin in the early
morning; the optimal time is in the early morning following spontaneous awakening.
Light exposure should be minimized so that phase delay with melatonin is not countered
by the phase advance effect of early morning light. It is useful at doses ranging
from 0.5 to 10 mg.
CONCLUSION
Sleep in the elderly gets lighter and fragmented, however, very few otherwise healthy
older people complain about their sleep problem. In the majority, sleep disruptions
are associated with medical and psychiatric disorders, use of medications, changes
in circadian rhythm and other sleep disorders such as sleep disordered breathing and
REM behavior disorder. It is important to identify various causes of sleep disturbances
in the elderly and to start treatment at the earliest. Furthermore, the factors that
maintain disrupted sleep are targeted using nonpharmacological and behavioral techniques,
along with medications if needed. This would enhance the quality and duration of sleep,
and improve the overall quality of life in the elderly.