Handbook of Clinical Neurology, Vol.

167 (3rd series)

Geriatric Neurology
S.T. DeKosky and S. Asthana, Editors
https://doi.org/10.1016/B978-0-12-804766-8.00026-1
Copyright © 2019 Elsevier B.V. All rights reserved

Chapter 26

Sleep physiology and disorders in aging and dementia

RUTH M. BENCA1* AND MIHAI TEODORESCU2
1
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, United States
2
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States

Abstract
Sleep problems occur commonly in normal and pathologic aging. Older adults typically have more
difficulty falling asleep and remaining asleep, report more daytime napping, and have an increased prev-
alence of primary sleep disorders such as insomnia, parasomnias, sleep apnea, and sleep-related movement
disorders. Medical and psychiatric disorders as well as medications used to treat them also contribute to
sleep disturbances in aging. Patients with mild cognitive impairment and dementia have more severe sleep
problems, and disturbed sleep and sleep disorders contribute to earlier onset and more rapid progression of
neurodegenerative disorders. Approaches to diagnosing and treating sleep disorders in the elderly are
discussed.

Sleep is a universal physiologic and behavioral state
characterized by specific patterns of neuronal activity,
decreased awareness of the environment, adoption of a
characteristic posture and reduced sensitivity to stimuli.
Stages of sleep and wakefulness are identified through
specific waveforms recorded during electroencephalo-
gram (EEG), eye movements measured by the electrooc-
ulogram (EOG), and muscle activity measured by the
electromyogram (EMG).
Sleep states are divided into two major kinds of sleep,
nonrapid eye movements sleep (NREM) and rapid eye
movements sleep (REM). Nocturnal sleep in adults con-
sists of alternating bouts of NREM and REM sleep.
NREM sleep is further subdivided into stage N1, N2,
and N3 sleep. Individuals usually enter sleep through
stage N1 sleep, which generally occupies a small propor-
tion (5%–10%) of the entire sleep time; N1 is considered
light sleep and characterized by slow rolling eye move-
ments. Stage N2 is the most common stage of sleep
(about half of the entire sleep time) and contains charac-
teristic sleep waveforms of sleep spindles and large
vertex waves (K complexes). Stage N3 is also referred
to as slow-wave sleep (SWS) because it contains delta
waves (0.5–2 Hz). The arousal threshold increases from
stage N1 to stage N3 sleep. N2 and N3 sleep together
usually amount to about 70%–75% of adults’ total sleep
time. REM sleep derives its name from the frequent fast
eye movements, is characterized by an activated EEG
pattern, while tonic muscle tone is the lowest (muscle
atonia) with superimposed phasic muscle twitches;
dreaming is most common during this stage.
The underlying physiologic mechanisms that serve to
regulate organization of sleep and wakefulness consist of
two main processes, the homeostatic drive for sleep and
the circadian rhythm. The homeostatic drive for sleep
(called process S) increases with prolonged wakefulness
and diminishes with sleep. The circadian rhythm
(called process C) is an endogenously generated biologic
rhythm that has a cycle period of about 24 h and responds
(is “entrained”) to a variety of cues (called “zeitgebers”
or “time-givers”), such as light, feeding schedules, phys-
ical activity, and social interactions. Melatonin secretion
by the pineal gland during the night serves to reinforce
the circadian entrainment.
Sleep architecture changes throughout the life span.
Young children spend larger amounts of time sleeping
than adults and have more SWS; sleep changes
during the first 3 decades of life are associated with

*Correspondence to: Ruth M. Benca, M.D., Ph.D., 101 The City Drive South, Bldg 3, Rt. 88, Irvine, CA 92697, United States.
Tel: +1-714-456-7209, E-mail: rbenca@uci.edu
478 R.M. BENCA AND M. TEODORESCU
developmental changes in the brain. During adult years,
SWS continues to decline, with increasing fragmentation
by brief arousals. Small declines in REM sleep also may
occur with advancing age.
Changes in sleeping brain activity reflect underlying
changes in anatomy and neurophysiology during both
development and aging (Nir et al., 2011). Age-related
alterations in gray and white matter structure, brain metab-
olism, and connectivity show substantial regional varia-
tion. The rate and the trajectories of change vary among
the brain regions and among individuals (Dumitriu
et al., 2010). As such, it is becoming increasingly apparent
that sleep is a regional phenomenon and does not occur
uniformly throughout the brain. Some regions can be
active during sleep while others are silent, constraining
intracerebral communication (Hughes et al., 2012).
With increasing age, slow wave (SW) amplitude and
density decline significantly, likely driven by anatomical
changes, which may also reflect a subtler reorganization
of cortical circuits, with some classes of synapses appear-
ing more vulnerable to aging than others (Dumitriu et al.,
2010). These not only include widespread atrophy as
well as a regional thinning of gray matter (Redline
et al., 2004), but also age-dependent atrophy of the ante-
rior and medial aspects of the thalamus and their
projections to the frontal cortex (Dumitriu et al., 2010;
Hughes et al., 2012). Interestingly, the volume of
thalamic projections to parietal, temporal, and occipital
cortex show no significant relationship with age
(Hughes et al., 2012).
Older adults exhibit marked, yet regionally selective,
deficits in fast sleep spindle (13–15 Hz) density relative
to young adults, with the greatest impairment (>40%)
over prefrontal derivations (Mander et al., 2014). This
may be particularly relevant since it is thought that
fast sleep spindles promote bidirectional communication
between the hippocampus and the neocortex, reflecting
a coordinated NREM sleep-dependent memory mecha-
nism, capable of restoring hippocampal-dependent
neuroplasticity and associated encoding ability; these
deficits in older adults lead to a deficient sleep-dependent
restoration of next day learning ability (Mander
et al., 2014).
SLEEP PATTERNS IN AGING
POPULATIONS
Sleep patterns are significantly affected by aging, both in
terms of changes in normal sleep patterns as well as
increased rates of sleep disorders. In a large prospective
cohort study (Sleep Health Heart Study—2685 subjects),
across an age range of 37–92 years, older age (>61 years)
was associated with increased percentages of stages N1
and N2, decreased percentage stage N3 and REM, lower
sleep efficiency, and a higher arousal index, independent
of potential confounders such as obesity, sleep-disordered
breathing, and comorbidity (Monk et al., 2006).
Later bedtimes in the elderly seem to be associated
with less time in bed and less time asleep. One study
of healthy subjects, 70–92 years of age, reported that
each 10-min delay in bedtime from 19:00 h was associ-
ated with about 7–8 min of less time in bed and total sleep
time (Monk et al., 2006). Compared to the young, older
subjects were not only waking earlier relative to clock
time, but also earlier relative to the phase of the melatonin
rhythm (Monk et al., 2006).
The prevalence of sleep difficulties increases with
age. Sleep is considered to be reflective of overall health
and is susceptible to the influence of many endogenous
and exogenous factors. In a study comparing “old old”
subjects (>75 years of age) with “young old” subjects
(60–74 years of age) who were followed longitudinally
for 2 years, age, cognitive status, and medical burden
at baseline also predicted subsequent declines in sleep
efficiency (Hoch et al., 1994). Changes in sleep in
older adults appear even more strongly associated with
psychosocial and health factors than with aging itself
(Wolff et al., 2002; Foley et al., 2004).
Health problems appear to have additive effects in
contributing to sleep complaints. The 2003 “Sleep and
Aging” survey (part of Sleep in America poll) reported
that perception of quality of sleep was highly associated
with the number of medical conditions as approximately
40% of those with major medical comorbidity perceived
their sleep to be of only fair or poor quality. In contrast,
among those without medical conditions, only 10%
reported their sleep quality as “fair” or “poor.” Multiple
chronic diseases and other medical conditions such as
bodily pain and obesity substantially reduced the quality
of sleep among older adults. Having heart disease,
arthritis, diabetes, stroke, and lung diseases were inde-
pendently associated with having one or more sleep
problems nearly every night or day such as difficulty
falling asleep and staying asleep, snoring, breathing
pauses, restless legs, or daytime sleepiness (Foley
et al., 2004).
Drowsiness is a common side effect of medications;
many block the actions of acetylcholine or histamine,
both regulatory neurotransmitters for wakefulness. Med-
ications can also produce sleepiness via other mecha-
nisms; e.g., individuals taking levodopa or dopamine
agonists may have an increased prevalence of excessive
daytime sleepiness and sleep attacks (Table 26.1). Alter-
natively, a large number of medications disturb sleep via
activation of the central nervous system. Sleep quality
could be affected if these agents are taken prior to the
patient’s bedtime or have a sustained half-life that
extends into the typical sleep period (Table 26.2). In
 SLEEP PHYSIOLOGY AND DISORDERS IN AGING AND DEMENTIA 479
Table 26.1 disruption appears to precede the onset of relevant neu-
Common drowsiness inducing medications ropsychologic deficits (Tranah et al., 2011; Jaussent
et al., 2012). Findings include increased wakefulness
Antihistamines after sleep onset, reduced sleep efficiency, a subjective
Antispasmodics global sleep misperception, decreased REM sleep, and
Antidiarrheal agents (diphenoxylate, loperamide) increased arousal index in NREM sleep, particularly in
Antipsychotics
SWS (Hita-Yanez et al., 2012). Amnestic MCI subjects
Antiemetics
demonstrate a reduction of stage 2 sleep spindles and
Antiparkinsonian drugs (levodopa, dopamine agonists)
Tricyclic antidepressants (amitriptyline, doxepin, and decreased delta and theta power (Westerberg et al.,
imipramine) 2012). NREM sleep organization and microstructure
Selective serotonin reuptake inhibitors (citalopram, fluoxetine, have been found to be impacted in preclinical stages of
fluvoxamine, paroxetine, sertraline) dementia; these sleep changes parallel the cognitive
Trazodone, nefazodone decline, suggesting an early vulnerability to neurodegen-
Cimetidine eration of the basal forebrain cholinergic system and
Mirtazapine brainstem cholinergic neurons (Maestri et al., 2015).
Oxybutynin Persons with Alzheimer’s disease (AD) experience
Anticonvulsant agents (gabapentin, lamotrigine, tiagabine, significant sleep difficulties, including difficulty remain-
levetiracetam)
ing asleep at night and staying awake during the day.
Morphine and other opiate analgesics
Disturbed nocturnal sleep, particularly when accompa-
Benzodiazepines
Non-BZD GABA receptor agents nied by agitation, is one of the most significant factors
Melatonin receptor agonists leading to institutionalization. The interaction between
Skeletal muscle relaxants sleep and AD appears to be bidirectional. Production
a-adrenergic blocking agents of Ab peptides in the brain appears closely connected
to the 24-h sleep–wake cycle, with higher extracellular
levels during wakefulness compared to sleep (Kang
Table 26.2 et al., 2009). Ab production was postulated (Xie et al.,
2013) to decrease during SWS through decreased neuro-
Behaviors and habits contributing to insomnia
nal activity in this sleep stage and increased clearance of
1. Frequent daytime napping Ab during sleep (Cedernaes et al., 2016). Insomnia,
2. Spending too much time in bed decline in sleep duration, impaired sleep consolidation,
3. Insufficient daytime activities delayed or decreased circadian rhythms, and sleep disor-
4. Late evening exercises dered breathing (SDB) have all been shown to increase
5. Insufficient bright light exposure the risk and/or progression of AD (Yaffe et al., 2014).
6. Excess caffeine
Reciprocally, patients with Alzheimer’s dementia have
7. Evening alcohol consumption
been shown to have increased amounts of sleep fragmen-
8. Smoking in the evening
9. Late heavy dinner tation with lower sleep efficiency and an increase in stage
10. Watching television or engaging in other stimulating N1 sleep and a decrease in stage N3 sleep (with an
activities at night impaired regulation of delta waves (Crowley et al.,
11. Anxiety and anticipation of poor sleep 2005)) amounts. The amount of SWS appears to
12. Clock watching inversely correlate with cognitive decline, possibly by
13. Environmental factors such as the room being too warm, indicating less brain atrophy but also possibly less
too noisy, or too bright. impairment of sleep-dependent cognitive and brain-
14. Pets on the bed or in the bedroom, and/or active or noisy restorative processes (Gelber et al., 2015). REM sleep
bed partners appears to be decreased to a larger extent in AD
compared with MCI.
Daytime sleepiness and napping are common in AD
addition, medications can sometimes interfere with sleep
(Klaffke and Staedt, 2006), which, although are different
by worsening an underlying medical or psychiatric con-
phenomena, could be considered as altered sleep–wake
dition that impacts sleep.
behaviors (Maestri et al., 2015). A decreased amplitude
and robustness of the sleep–wake cycle has been cor-
SLEEP AND NEURODEGENERATION
related with an increased risk of cognitive decline or
Sleep–wake disorders represent a major and challenging dementia (Tranah et al., 2011). As dementia progresses,
issue in neurodegenerative disorders, and especially in it may be associated with reduced activity levels
dementia (Maestri et al., 2015). In many cases, sleep and more phase delay (Ancoli-Israel et al., 1997).
480 R.M. BENCA AND M. TEODORESCU
In AD, patients have increased motor activity during
night time, a phase delay averaging 2 h, as well as a
dampening of the motor activity circadian rhythm com-
pared with healthy elderly patients (Satlin et al., 1991).
Patients with Lewy body disease (LBD) tend to have a
higher index of disturbed sleep, more movements while
asleep, and more abnormal daytime sleepiness than
patients with AD (Grace et al., 2000). This is likely
related to a marked loss of nucleus basalis Meynert
(NBM), a large group of cholinergic neurons (75%–
80%), in conjunction with reduced cholinergic activity
in the reticular thalamic nucleus leading to hallucinations
and fluctuating consciousness (Klaffke and Staedt,
2006). There is a decreasing activity of the suprachias-
matic nuclei (SCN) and decreased synthesis of melato-
nin, with eventual disappearance of the circadian
melatonin rhythm while serotonin appears to show step-
wise depletion during the course of dementia (Wu et al.,
2003). LBD is associated with fluctuations in arousal
and alertness, thought to be related to the subcortical
and cortical cholinergic deficits, in about 80% of these
patients (Byrne, 1997). LBD patients specifically have
more abnormalities in areas such as control of move-
ment, periodic limb movements, nightmares, and confu-
sion upon waking (Bliwise et al., 2011).
SUNDOWNING
Sundowning refers to the recurring onset of confusion
or agitation in some elderly patients in the evening and
can be a significant clinical problem (Bliwise, 1994).
Circadian rhythms may play an important role in the
pathogenesis of sundowning (Klaffke and Staedt,
2006). Neurophysiologically, it appears to be mediated
by degeneration of the suprachiasmatic nucleus of the
hypothalamus and decreased production of melatonin
(Khachiyants et al., 2011). Maximal behavioral disrup-
tion most commonly occurs in the late afternoon or
evening. In community dwelling patients, the phenome-
non has been reported to be associated with significant
caregiver stress (Gallagher-Thompson et al., 1992),
likely contributing to an increased risk of institution-
alization. Sundowning ranks second only to wandering
in disruptive behaviors in institutionalized patients
(Khachiyants et al., 2011).
Factors that contribute to sundowning include
increased patient fatigue, pain, hunger, or anxiety,
excessive environmental stimulation, and changes in
caregiver environment (e.g., fatigue, caregiver change,
lower caregiver availability) (Khachiyants et al., 2011).
For community-based patients, caregiver stress and
burnout may lead to conflicts, frustration, and distress,
increasing the likelihood for sundowning. In the case
of institutionalized patients, an increase in the number
of patients assigned to a caregiver not only changes the
intensity of the structure and/or stimulation for patients
but also increases boredom and can lead to agitation
and restlessness (Khachiyants et al., 2011). Medications
may have anticholinergic effects or induce restlessness.
They also may inappropriately change the level of
alertness, such as sedation during daytime or excessive
alertness during the night. Certain medications used for
behavioral changes associated with dementia, such as
benzodiazepines (e.g., lorazepam), may actually induce
paradoxical agitation, worsen behavior disinhibition, or
increase confusion in certain patients.
DELIRIUM
Sleep–wake cycle disturbances are one of the most
salient features of delirium; in a series of 600 consecutive
patients admitted to the intensive care unit for more
than 24 h, sleep disturbance occurred in almost 70% of
patients with delirium as compared with 12% of patients
without delirium (Marquis et al., 2007). Another study of
100 cases of delirium in a palliative care inpatient service
reported sleep disturbances in 97% of patients (Meagher
et al., 2007). In a study of 13 patients (6 with delirium and
7 without delirium) employing actigraphy, delirious
patients showed less time resting over 24 h, greater mean
activity at night, reduced consolidation of rest and
activity throughout the day, and reduced amplitude of
day–night differences in rest and activity (Jacobson
et al., 2008).
SLEEP DISORDERS WITH INCREASED
PREVALENCE IN AGING
Insomnia
DEFINITION
The International Classification of Sleep Disorders, third
edition (ICSD-3) (American Academy of Sleep Medi-
cine, 2014), defines insomnia as repeated difficulty
(occurring at least 3 times/week) in initiating or main-
taining sleep or waking up earlier than desired, which
is associated with daytime symptoms and is not
explained purely by inadequate opportunity or circum-
stances for sleep. Chronic insomnia has a duration of
at least 3 months.
PREVALENCE
Using cross-sectional data from the National Health
Interview Survey (available for the years 2002, 2007,
and 2012, involving 23–34 thousand subjects), insomnia
is estimated to affect over 20% of individuals both in the
65–74 age group and the >75 years of age group (Ford
et al., 2015).
 SLEEP PHYSIOLOGY AND DISORDERS IN AGING AND DEMENTIA
CONSEQUENCES
Insomnia is linked to psychologic distress in the older
person and may place them at greater risk for daytime
fatigue, diminished cognitive ability including attention
and memory, disturbances in psychomotor functioning
and slowed response time, dependence on hypnotic med-
ication, depression, dementia, falls, and residential care
(Alessi and Vitiello, 2015).
COMORBIDITIES
Most insomnia in the elderly is comorbid with other
medical or psychiatric disorders. Insomnia is frequently
a symptom of anxiety or depression; difficulty initiating
sleep was found to be associated with the presence of
depression 3 years later in the elderly in a large Japanese
longitudinal study (Yokoyama et al., 2010).
Insomnia can also be comorbid with other primary
sleep disorders in the elderly, including sleep apnea
and restless legs. In a study of 112 community-based
older adults, a substantial percentage of subjects with
insomnia endorsed snoring (46%), breathing problems
at night (27%), daytime sleepiness (36%), while those
diagnosed with sleep apnea reported high frequencies
of insomnia problems (57%) and fatigue (77%) (Bailes
et al., 2005).
ASSESSMENT AND TREATMENT
Since insomnia in late life tends to be chronic and
recurring (Morgan and Clarke, 1997; Reynolds et al.,
1999), long-term disease management strategies are
needed. Multiple factors, including biologic (circadian),
psychologic, and social factors need to be considered
(Table 26.3). In addition, changes in cognitive function,
visual acuity, hearing impairment, and mobility
limitations are common. Older adults can have physical
restrictions or become socially isolated, reducing social
interactions, exposure to sunlight, and the melatonin-
mediated circadian rhythmicity. These often need to be
addressed in treatment of insomnia in this population
(Fiorentino and Martin, 2010).
Sleep hygiene measures are often the first line of
intervention, since poor sleep habits such as irregular
sleep schedules, napping, and use of substances such
as caffeine and alcohol can contribute to insomnia
(Table 26.4). Sleep hygiene alone can sometimes
improve subjective sleep (Friedman et al., 2009).
Moderate-intensity exercise (30–40 min of walking
or low-impact aerobics 4 times per week, or Tai Chi 3
times per week) was reported to possibly be more
effective than no treatment in improving sleep quality
at 16–25 weeks in people with primary insomnia
(Alessi and Vitiello, 2015).
481
Table 26.3
Sleep history sample
Sample initial questions
1. What time do you normally go to bed at night? What time
do you normally wake up in the morning?
2. Do you often have trouble falling asleep at night?
3. About how many times do you wake up at night?
4. If you do wake up during the night, do you usually have
trouble falling back asleep?
5. Does your bed partner say (or are you aware) that you
frequently snore, gasp for air, or stop breathing?
6. Does your bed partner say (or are you aware) you kick or
thrash about while asleep?
7. Are you aware that you ever walk, eat, punch, kick, or
scream during sleep?
8. Are you sleepy or tired during much of the day?
9. Do you usually take one or more naps during the day?
10. Do you usually doze off without planning to during the
day?
11. How much sleep do you need to feel alert and function
well?
12. Are you currently taking any type of medication or other
preparation to help you sleep?
Sample follow up questions
1. Do you have the urge to move your legs or do you
experience uncomfortable sensations in your legs during
rest or at night?
2. Do you have to get up often to urinate during the night?
3. If you nap during the day, how often and for how long?
4. How much physical activity or exercise do you get daily?
5. Are you exposed to natural outdoor light most days?
6. What medications do you take, and at what time of day and
night?
7. Do you suffer any uncomfortable side effects from your
medications?
8. How much caffeine and alcohol do you consume each day/
night?
9. Do you often feel sad or anxious?
10. Have you suffered any personal losses recently?
Insufficient evidence has been reported with regard to
the effect of timed exposure to bright light on sleep qual-
ity in the elderly with insomnia (Alessi and Vitiello,
2015). In a single-blind, placebo controlled, 12 week ran-
domized study, both evening and morning bright light
were able to evoke a significant change in the timing
of the circadian pacemaker; bright light in the morning
was associated with an average phase advance of
0.49
0.66 h and evening bright light was associated
with an average phase delay of 0.53
0.97 h. However,
no consistent effects on subjective or objective measures
of sleep were found (Friedman et al., 2009).
482 R.M. BENCA AND M. TEODORESCU
Table 26.4
Cognitive behavior therapy for insomnia
Combines multiple behavioral approaches, usually
incorporating sleep restriction, stimulus control, and
cognitive therapy, with or without relaxation therapy
1. Sleep hygiene and sleep education are frequently included
2. Sleep restriction therapy—limiting time in bed to
consolidate actual time sleeping. The patient is counseled to
reduce the amount of time in bed to correlate closely with
actual time sleeping. The recommended sleep times are
based upon sleep logs kept for 2 weeks before sleep
restriction therapy is begun
3. Sleep compression (variant of sleep restriction) patients are
counseled to decrease their time in bed gradually to match
total sleep time rather than making an immediate substantial
change
4. Stimulus control therapy attempts to eliminate coping
strategies actually perpetuating the problem (e.g., watching
television or reading in bed, worrying about falling asleep,
using the bedroom for different activities, including
spending excessive time in bed to rest) and strengthen the
association between sleep and the bed and bedroom
5. Relaxation therapy to lead to a calm, steady state around
planned sleep time. Methods include progressive muscle
relaxation (tensing and then relaxing each muscle group),
guided imagery, diaphragmatic breathing, meditation, and
biofeedback
6. Cognitive interventions target misperceptions regarding
normal aging and sleep. May employ motivational strategies
to increase compliance with the other interventions
Cognitive behavioral therapy for insomnia (CBT-I) is
a multidimensional approach that combines psychologic
and behavioral therapies to treat insomnia (Table 26.5).
These include sleep hygiene, sleep restriction, stimulus
control, relaxation techniques, and cognitive therapy.
Any single therapy does not appear as effective as when
interventions are combined (Morin et al., 2006).
Cognitive-behavioral interventions (CBT-I) for
insomnia have been demonstrated to be effective in older
adults (Buysse et al., 2011). In a randomized controlled
trial of 78 older adults (mean age 65), behavioral and
pharmacologic therapies, alone or in combination, were
found to be effective in the short-term (3 months) man-
agement of late-life insomnia; however, long-term (12-
and 24-month) follow-up data showed that only behav-
ioral treatment produced durable changes while clinical
benefits obtained by subjects treated with drug therapy
alone were gradually lost (Morin et al., 1999).
Efficacy coupled with minimal side effects makes
behavioral techniques highly recommended for treating
insomnia, particularly in the elderly. In a study of 536
younger veterans and 121 older veterans who received
CBT-I, 64% of younger and 77% of older patients
Table 26.5
Cognitive behavioral therapy for insomnia-specific issues
for older adults
1. Use large print fonts (to account for visual decrements in
older adults)
2. Keep instructions concise and ensure patients have them
handy at home
3. Educate about normal age-related changes in sleep
4. Educate about comorbidities and medications effects on
sleep
5. Evaluate coping mechanisms with fatigue, and if and why
the patient spends excessive time in bed
6. If the patient uses to bed excessively to “rest”, explore
alternative options to rest without sleeping
7. Account for napping when calculating overall amount of
time spent asleep over 24 h
8. Daytime napping/dozing off should be accounted for and
limited according to therapy plan. Naps may be considered
but with some limits (e.g., 30 min, proper timing, use an
alarm to ensure adherence)
9. Remind patients to use an assistive device and ensure
adequate environment (lighting, obstacle removal,
distance to bathroom) if up at night
10. Assess fall risk and apply fall prevention measures
11. Ensure lifestyle recommendations account for executive
dysfunction, physical limitations, dietary restrictions,
comorbidities control
12. Behavioral measures regarding nocturia—first line of
approach
13. Discussion on goals of therapy—ensuring they are realistic
and account for the often multimorbidity and functional
limitations
14. Evaluate and address psychologic issues, such as
“excessive worry,” and designate “worry time”
15. Account for patient preferences and activities and try to
blend them in treatment plan
completed all sessions or finished early due to symptom
relief (Karlin et al., 2015). Mean insomnia scores
declined from 19.5 to 9.7 in the older group and from
20.9 to 11.1 in the younger group. CBT-I yielded sig-
nificant improvements in depression and quality of life
for both age groups. Another study employing a 4 week,
group-based treatment program of CBT-I including bed-
time restriction therapy, sleep education, and cognitive
restructuring, noted improvements in the timing and
quality of sleep including later bedtimes, earlier out-of-
bed times, reduced wake after sleep onset, and improved
sleep efficiency in 118 older adults (mean age 64 years)
(Lovato et al., 2014).
PHARMACOLOGIC MANAGEMENT
Explicit criteria have evolved as important clinical and
educational tools to guide prescribing in older adults and
 SLEEP PHYSIOLOGY AND DISORDERS IN AGING AND DEMENTIA
are a valuable resource for clinicians who seek
consensus-based support regarding both potentially
inappropriate medication (PIM) use and potential
prescribing omissions (PPOs). The two most widely
accepted explicit criteria are the US-based American
Geriatrics Society (AGS) Beers Criteria and the
European-based Screening Tool of Older People’s
Prescriptions/Screening Tool to Alert to Right Treat-
ment (STOPP/START) (Barenholtz Levy and Marcus,
2016). They recommend increased caution regarding
benzodiazepine (BZD) and non-BZD hypnotic use,
including fall-risk concerns. AGS Beers uniformly
recommends avoiding all BZD and non-BZD hypnotics,
regardless of duration of use, and all three US-approved
non-BZD hypnotics are included as drugs to avoid in
dementia. STOPP now includes both short- and long-
acting BZDs as PIMs, but allows their use for up to
4 weeks. Non-BZD hypnotics are newly included along
with BZDs in the fall-risk category (Barenholtz Levy
and Marcus, 2016).
A 2005 meta-analysis of 24 randomized trials (2417
patients) that evaluated the impact of pharmacotherapy
in adults older than 60 with insomnia with no psychiatric
or psychologic disorders, found improvements in sleep
quality, increased total sleep time and decreased number
of night time awakenings with use of sedative agents.
Adverse cognitive events were 4.78 times more com-
mon, adverse psychomotor events were 2.61 times more
common, and reports of daytime fatigue were 3.82 times
more common (Glass et al., 2005). Not surprisingly, a
2003 paper reporting on 599 subjects older than 85 years
of age and part of a prospective study of community-
dwelling elderly individuals found an increase of mortal-
ity related to fracture in individuals who used benzo-
diazepines (Vinkers et al., 2003). However, use of
benzodiazepines was not found to be related to all-cause
mortality. In support of the latter finding, a population-
based retrospective cohort study of 2224 residents of
Lepp€avirta, Finland, aged 65 years and older (325 users
of BZD and non-BZD agents), found that, after multivar-
iate adjustments, use of these drugs was not associated
with excess mortality (Gisev et al., 2011). A long-term
national health study of almost 150,000 postmenopausal
women (ages of 50–79, median follow-up 8 years, also
reported no strong independent association of hypnotic
use with mortality, myocardial infarction, stroke, diabe-
tes, or cancer (except for melanoma) (Hartz and
Ross, 2012).
In view of the above, implicit judgment is necessary,
especially for the complex or frail elderly (Lang
et al., 2016).
Management of insomnia in older adults remains a
challenge in light of potential adverse events. Comor-
bidities and concomitant medications likely play an
483
important role in determining a patient’s susceptibility
to adverse events and need to be individually assessed
before a hypnotic is considered (Levy, 2014). It is to be
noted that non-BZDs may not necessarily be a safer alter-
native to traditional BZDs (Levy, 2014). Short acting
drugs may be useful when initiating sleep is the main
problem, whereas somewhat longer acting substances
may be needed for maintaining sleep. Choice among spe-
cific agents should not only depend on the clinician’s
assessment of the vulnerability of the patient but also
should take into account other drug characteristics that
may be important for optimal treatment of the individual
patient (e.g., speed of onset, duration of action, likelihood
of next-day carryover effects). Possible interactions with
preexisting medications must also be taken into consider-
ation. Intermittent use of hypnotics should be preferred
to regular use. Starting low and carefully titrating up is
usually the best approach. For some agents (e.g., zolpi-
dem, eszopiclone, zaleplon, temazepam, triazolam), the
recommended dose is usually half that recommended
for younger patients. Some agents, such as antipsychotics,
antidepressants, melatonin, and herbal products (usually
over the counter), are sometimes used, but only a few
of these have proven tolerability in the elderly.
INSOMNIA IN COGNITIVELY IMPAIRED PATIENT
In the case of elderly patients with dementia, caretaker
assessments of the sleep–wake pattern demonstrate
either inverted or irregular sleep–wake patterns in most
individuals, with an overall increased fragmentation
and decrease in the amplitude of the rest–activity rhythm
(Abbott and Zee, 2015). The magnitude of decreased
amplitude and increased fragmentation of the rest–
activity pattern appears to correlate with the severity of
dementia.
A behavioral approach should always be considered
as the initial step in managing a patient’s insomnia symp-
toms, which frequently overlap with other behaviors
(agitation, increased confusion). An algorithm named
Treatment Routes for Exploring Agitation (TREA) has
been proposed which may provide a systematic method-
ology for individualizing nonpharmacologic interven-
tions (Cohen-Mansfield et al., 2012). Accommodation
and flexibility are essential elements of intervention.
Activities need to be meaningful to the patient, easily
administered, and match the affected individual’s level
of functioning. Implementation of TREA in a group of
89 nursing home residents improved agitation and
increased pleasure and interest compared with a control
group (Cohen-Mansfield et al., 2012).
A recent review reported a lack of evidence to help
guide drug treatment of sleep problems in patients with
AD, with no randomized controlled trials of many drugs,
484 R.M. BENCA AND M. TEODORESCU
including BZD and non-BZD hypnotics, despite consid-
erable uncertainty about the balance of benefits and risks
associated with these treatments (McCleery et al., 2014).
Circadian rhythm disturbances
The major feature of these disorders is a misalignment
between the patient’s sleep pattern and the sleep pattern
that is desired or regarded as the societal norm. When
internal factors, such as neurologic disease, or external
factors, such as environmental or social circumstances,
produce a circadian rhythm sleep disorder, diagnostic
subtypes can be specified with the diagnosis of intrinsic
type or extrinsic type, respectively. The inadequate influ-
ence of external zeitgebers, such as irregular or reduced
light exposure, meals, social interactions, and physical
activity, may contribute to the disturbances. In most
circadian rhythm sleep disorders, the underlying problem
is that the patient cannot sleep when sleep is desired,
needed, or expected. Therefore, the patient complains
of insomnia or excessive sleepiness.
Irregular sleep–wake rhythm disorder (ISWRD) is a
circadian rhythm disorder where there is no longer a clear
24-h sleep–wake pattern. Individuals present with symp-
toms of either insomnia, excessive daytime sleepiness, or
both, related to being awake during traditional sleep
periods, and napping during the daytime.
DIAGNOSIS
The diagnosis of a circadian rhythm disorder depends on
obtaining sleep-logs and/or actigraphy recordings from
the individual for at least 1 but preferably 2 weeks. For
ISWRD, sleep logs generally need to be completed by
a caretaker given the high prevalence of neurologic
impairment associated with this disorder (Abbott and
Zee, 2015).
MANAGEMENT
Light is the most potent entraining factor for the circadian
clock and has direct effects on behavior that include
increased alertness and mood. Recent studies have found
that photoreceptors for the circadian and alerting effects
of light are distinct from those involved in vision and are
mediated by melanopsin receptors that have greatest
sensitivity for light in the 460–480 nm (blue) range
(Martin et al., 2014). Light therapy may be attempted
to reset the phase of the circadian rhythm relative to
the light–dark cycle and may influence the production
of melatonin, which helps synchronize an individual’s
circadian rhythm. The best time of day to offer light
therapy remains unknown.
Light therapy is generally well tolerated. Bright light
poses a theoretical threat of retinal damage in susceptible
individuals (proliferative diabetic retinopathy, moderate
or severe macular degeneration, or absence of a natural
or artificial lens in either eye). While bright white light
(similar to daylight) was initially employed, short-
wavelength blue light (approximately 460 nm) may have
greater phase-shifting properties than the rest of the
visible light spectrum; it is still unclear whether this is
becoming the preferred method to influence the biologic
clock in the elderly (Herljevic et al., 2005).
INTERVENTIONS IN DEMENTIA
Elderly individuals, particularly those with cognitive
impairment, are likely to be more sedentary and, as a
result, less likely to get light exposure, which likely con-
tributes to their sleep difficulties. Numerous studies have
assessed the effects of light therapy on subjects with AD
in nursing homes. For example, AD patients treated
with 2 h of morning bright light for 4 weeks showed
increased nocturnal sleep, decreased napping, and
improved scores on the Mini-Mental-State Examination
(Monk et al., 2009). In contrast to these findings, effects
of light therapy alone on cognition, function, sleep,
behavioral disturbances, and psychiatric disturbances
associated with dementia were reported to be of unclear
benefit in a Cochrane review (Forbes et al., 2014). How-
ever, when used in conjunction with other interventions,
such as in a randomized, controlled trial of patients with
dementia and their family caregivers employing light
exposure and behavioral techniques (specifically, sleep
hygiene education, daily walking), it was shown to
improve sleep (McCurry et al., 2005). Severity of demen-
tia was found to influence results (Forbes et al., 2014).
Use of melatonin has shown mixed results. In a
randomized, placebo controlled study of nursing home
subjects, using melatonin administered at 10 pm for
10 consecutive nights, no beneficial effects were noted
with regard to sleep, circadian rhythms, and agitation
(Gehrman et al., 2009). However, in an open-label
study employing actigraphy, use of 3 mg melatonin
in day–night rhythm disturbances in a sundowning
community-based patients every evening for 3 weeks
was well tolerated and was associated with complete
remission in 4 out of 7 patients (Mahlberg et al.,
2004). A significant decrease in sundowning was also
reported in another study of 11 nursing home patients
(Cohen-Mansfield et al., 2000). A recently published
Cochrane meta-analysis with regard to use of melatonin
in dementia found significant improvement in psycho-
pathologic behavior from data analysis of the ADAS
noncognitive scale (3 mg melatonin, 4 week change
score from baseline) and the Neuropsychiatric Inventory
(7 weeks at endpoint from baseline, 2.5 mg melatonin)
(Jansen et al., 2006). While the meta-analysis did not
 SLEEP PHYSIOLOGY AND DISORDERS IN AGING AND DEMENTIA
support the use of melatonin for treatment of cognitive
impairment associated with dementia, authors did
find that melatonin treatment might be effective in
dementia-related behavioral disturbances.
PARASOMNIAS
Parasomnias are characterized by undesirable behaviors
or experiences arising during sleep and are classified in
NREM and REM parasomnias.
NREM parasomnias are considered disorders of par-
tial or incomplete arousal from sleep. These disorders
typically arise in childhood and are most likely to occur
during the first few hours of sleep. In adults, these para-
somnias can be triggered by a variety of medications or
primary sleep disorders (such as sleep apnea or periodic
limb movements’ disorder).
REM sleep behavior disorder (RBD) is a type of para-
somnia manifested by vivid, often frightening dreams
associated with motor behaviors during REM sleep,
sometimes causing injuries to patients themselves or to
their bed partners. Polysomnographic features of RBD
include increased muscle activity during REM sleep
(REM sleep without atonia).
The majority of RBD-affected persons are older men
(about 90% cases). Prevalence is estimated at 0.5% of
the general population. The disorder might be idiopathic
or associated with neurologic disorders (secondary or
symptomatic RBD), most commonly a synucleinopathy.
Among the neurodegenerative disorders associated
with RBD, almost all (94%) were synucleinopathies
(Boeve et al., 2013); a high proportion of idiopathic
RBD patients convert to Parkinson’s disease, dementia
with LBD, or multiple system atrophy (MSA)
(Claassen et al., 2010). The vast majority of patients
older than 50 years of age (late onset) who were initially
diagnosed with idiopathic RBD eventually develop a
parkinsonian disorder/dementia, with the mean interval
being 14 years while the range extended to 29 or more
years (Schenck et al., 2013). The RBD-synucleinopathy
association is particularly high when RBD preceded the
onset of other neurodegenerative syndrome features
(Boeve et al., 2013). Over time, many patients seem to
develop nonmotor signs (decreased olfaction and color
vision, orthostatic hypotension, altered visuospatial abil-
ities) as well as electroencephalographic (EEG) slowing
occurring while awake and asleep (Inoue et al., 2015).
PATHOPHYSIOLOGY
The specific nuclei or the precise neuronal network is still
unclear. Recent studies found that reduction of signal
intensity in locus coeruleus/subcoeruleus areas in
patients with both PD and RBD was more marked than
in those with PD without RBD, suggesting that the
485
degeneration of these areas would cause RBD
(Ehrminger et al., 2016). Selective serotonin reuptake
inhibitors (e.g., fluoxetine, venlafaxine, and paroxetine)
and those that block acetylcholine transmission (tricy-
clics such as clomipramine) can induce RBD, possibly
because they prevent normal sleep-related hypotonia
(serotoninergic drugs) or normal REM sleep-related
atonia (anticholinergics) (Winkelman and James, 2004).
EVALUATION AND DIFFERENTIAL DIAGNOSIS
Individuals at risk, such as patients with PD or related
neurodegenerative disorders or narcolepsy, should be
screened by interview. RBD should be considered in
any patient presenting with violent or injurious behavior
during sleep. Patients who suffer from severe obstructive
sleep apnea (OSA), posttraumatic stress disorder, noctur-
nal seizures, and parasomnias arising from NREM sleep
and the use or withdrawal of certain drugs or alcohol
may also exhibit phenomena like enacting their dreams.
Thus, to differentiate from these circumstances, detailed
medical histories and video polysomnography (vPSG)
records are essential in diagnosing RBD. REM sleep
without atonia is a major finding and supports the
diagnosis.
Management includes ensuring a safe sleep environ-
ment for patient and bed partner (as applicable), such as
moving sharp and edged objects out of patient’s reach,
placing a mattress or cushion of some type on the floor
adjacent to the bed (if patient is at risk of falling out of
bed). Clonazepam is the most commonly employed phar-
macologic agent, and reduces both dream intensity and
acting-out behaviors and remains effective even after a
few years (Maestri et al., 2015). Clonazepam suppresses
behavioral symptoms and reduces phasic REM muscle
activity but does not restore REM sleep muscle atonia.
However, it can be associated with significant risks
(please see discussion on hypnotics use in the elderly).
Use of melatonin was found to yield a statistically sig-
nificant decrease in REM sleep without atonia in one
randomized placebo-controlled trial and two open-label
trials (McGrane et al., 2015). Besides these two thera-
pies, other agents demonstrated no clear systematic
benefits (Jiang et al., 2016).
OBSTRUCTIVE SLEEP APNEA
Age-related changes in the upper airway anatomy
include an increase in the soft palate length and para-
pharyngeal fat pads independent of body mass index
(BMI), and a decrease in the upper airway size
(Malhotra et al., 2006). Aging also affects upper airway
function, bringing a decrease in genioglossus response
to negative pressure, greater reduction in genioglossus
and tensor palatini activity at sleep onset, and an
486 R.M. BENCA AND M. TEODORESCU
increase in pharyngeal collapsibility and resistance
independent of BMI and gender (Malhotra et al., 2006).
PREVALENCE
Prevalence estimates for OSA among persons over
65 years of age, as compared to the middle aged, are
approximately 2–3 times higher (Young et al., 2002).
In a large cohort of healthy older persons, the prevalence
of OSA as defined by apnea–hypopnea index (AHI) >
15 respiratory events/h of sleep was found to be more
than 50%, while more than one-third had severe OSA
(AHI > 30) (Sforza et al., 2010). In addition to age,
OSA prevalence increases with male gender, higher body
mass index (BMI), but also in conditions such as neuro-
muscular disorders, epilepsy, multiple sclerosis, and
stroke (Kaminska et al., 2015). However, while popula-
tion sampling of middle aged adults have reported men
approximately 3 times more likely than women to have
sleep apnea, the gender difference diminishes with age,
as the protective advantage of estrogen appears to wane
for postmenopausal women (Bixler et al., 2001).
COMORBIDITIES
OSA likely contributes to decreased quality of life,
increased neurocognitive impairment, and greater risk
of nocturia and cardiovascular disease (Launois et al.,
2007). Cardiovascular comorbidities (arterial hyperten-
sion, heart failure, and stroke) are common in OSA
populations; OSA was also found to be associated with
new-onset hypertension in the normotensive elderly
(mean age 68) (Guillot et al., 2013). In a case–control
study including 158 elderly individuals (ages 67–89),
healthcare costs 2 years before OSA diagnosis were
more than 1.8 times as high for the elderly and
middle-aged patients with OSA as for controls. Further-
more, expenditures of elderly patients with OSA were
1.9 times as high as for middle-aged patients with
OSA, with cardiovascular disease being an independent
determinant of high healthcare utilization (Tarasiuk
et al., 2008).
ASSESSMENT
Traditional risk factors for OSA such as snoring, body
mass index, and neck circumference may not be as com-
mon in the elderly; patients may rather complain of not
feeling well rested in the morning, of daytime sleepiness,
and a high frequency of nocturia (Endeshaw, 2006).
Daytime sleepiness is a frequently reported problem
in the elderly and often is not specific to OSA. The more
risk factors are present in a given individual, the higher
the risk for excessive sleepiness. For example, in a group
of nondemented, nondepressed subjects, significant risk
factors for excessive sleepiness were male gender, severe
sleep-disordered breathing (apnea–hypopnea index
>30 episodes/h), poor sleep quality, increased percent-
age of time in REM sleep, pain at night at least 3 times
per week, wheezing or whistling from chest at night,
and medications with sleepiness as a side effect (Pack
et al., 2006).
History should be obtained from the patient and the
bed partner or care giver and should include questions
not only on OSA symptoms but also on nocturia and
comorbidities. It should be noted that men are more
likely to have a partner than the women do (Bailes
et al., 2005).
CONSERVATIVE MEASURES
Treatment of disorders that reduce nasal airflow, such as
chronic rhinitis, nasal polyps, or septal deviation, is
important because reduced nasal airflow increases the
propensity to snore and can lead to upper airway closing.
Patients with OSA should avoid alcohol and other sedat-
ing agents. Because patients with sleep apnea tend to
sleep poorly, they are more likely to turn to sedatives
to promote sleep. However, these may cause snoring in
persons who normally do not snore, while persons
who already snore may become apneic due to muscle
relaxation of the tongue and parapharyngeal muscles,
and increased arousal threshold.
Raising the head of the bed or avoiding the supine
position during sleep may help decrease the frequency
of apnea. Elevation of the head tends to bring the ton-
gue forward, while sleeping on the side moves the
tongue laterally. Positional therapy may be sufficient
for some patients with mild sleep apnea.
In an interventional study employing exercise train-
ing and dietary-induced weight loss, reduction in body
weight (9%) in 19 subjects older than 60 years of age
was associated with a decrease of 10 events/h in the
apnea–hypopnea index and an improvement in mean
nocturnal oxygen saturation from 94.9% to 95.2%
(Dobrosielski et al., 2015).
CONTINUOUS POSITIVE AIRWAY PRESSURE
Patients with moderate to severe sleep apnea (AHI > 15)
generally require more than conservative therapy.
Continuous positive airway pressure (CPAP) is the most
consistently successful and extensively studied treatment
for OSA. Treatment with CPAP must be based on a pre-
viously established diagnosis of OSA (Kushida et al.,
2006a). In a randomized trial comparing CPAP with sup-
portive care, enrolling 278 aged 65 years or older patients
with newly diagnosed OSA syndrome, CPAP was found
 SLEEP PHYSIOLOGY AND DISORDERS IN AGING AND DEMENTIA
to improve sleepiness, mobility, total cholesterol, and
LDL cholesterol in 3 months (McMillan et al., 2014).
Optimal pressure settings for CPAP are determined
either by titration during a nocturnal polysomnogram
or using auto-adjusting PAP machines in a home setting.
Diagnostic-titration (split-night) studies may be adequate
for some patients (Kushida et al., 2006a). The pressure
required to control sleep apnea depends on the upper
airway collapsibility, which can vary with position, sleep
stage, fluid status, substance, or medication use.
While acceptance of and compliance with CPAP treat-
ment was reported to be as good in the older age group
as in younger patients, with noted effectiveness in terms
of improvement in daytime sleepiness and cognitive
function (Planchard et al., 2004), in real-life, immediate
and long-term compliance with CPAP therapy may be
more challenging. In older male patients with OSA, com-
pliance with CPAP therapy was associated with atten-
dance of patient CPAP education and support groups.
Resolution of symptoms correlated with enhanced
compliance, while nocturia and the existence of benign
prostatic hypertrophy in older men correlated with
noncompliance (Russo-Magno et al., 2001). Cognitive-
behavioral interventions increased CPAP use and vigi-
lance in older adults, with greater improvement on
vigilance at 12 weeks follow-up (Aloia et al., 2001).
Bi-level pressure ventilation (BiPAP) uses two levels
of air pressure and may be better tolerated when high
pressure is needed and the patient experiences difficulty
breathing out against CPAP (Kushida et al., 2006a).
SECOND LINE APPROACHES
There is little information on the benefits of oral devices
or surgical approaches in the older adult population; cur-
rent indications are based on younger patients. Oral
appliances are dental devices used to advance the tongue
and mandible forward. The presence and severity of OSA
must be determined before initiating treatment with oral
appliances to identify those patients who would benefit
most and provide a baseline to establish the effectiveness
of treatment. Oral appliances are usually made by dental
personnel experienced in the overall care of oral health,
the temporomandibular joint, dental occlusion, and asso-
ciated oral structures (Kushida et al., 2006b). A follow-
up sleep study is recommended in patients with moderate
to severe sleep apnea with the device in place to assess
effectiveness.
Supplemental oxygen and medications are not indicated
in the treatment of OSA. A meta-analysis of O2 therapy as
part of 14 studies including a total of 359 patients, found
that use of O2 alone, while improving oxygen saturation
in patients with OSA, it may also increase the duration
of apnea–hypopnea events (Mehta et al., 2013).
487
Central sleep apnea
Central sleep apnea (CSA) syndrome is characterized by
a cessation or decrease of ventilatory effort during sleep,
usually associated with brief arousals and decreases
in oxygen saturation. CSA syndrome may have a few
associated obstructive respiratory events or episodes of
hypoventilation; however, the predominant respiratory
disturbance consists of central apneic episodes.
PREVALENCE
CSA is observed with increasing frequency in the
general population as a function of age and frequently
overlaps with OSA. OSA is common in patients with
mild-to-moderate heart failure (HF), while those with
moderate-to-severe HF often have CSA (Oldenburg
et al., 2007). Common associated comorbidities include
systemic arterial hypertension, cardiac arrhythmias, pul-
monary hypertension, and cardiac failure, which may
reflect a primary disorder of the cardiovascular system
that leads to the development of the apnea. Various neu-
rologic lesions may also be part of the etiology. A recent
review of 8 studies including 560 patients taking chronic
opiate therapy found an overall prevalence of CSA of
24% (Correa et al., 2015). The most important risk fac-
tors for severity of CSA were a morphine equivalent dose
of >200 mg/day, and low or normal body mass index.
PROGNOSIS
A recent meta-analysis of 11 studies (1944 participants in
total) that addressed mortality in chronic HF patients
with sleep-disordered breathing (SDB), reported that a
significant increase in risk of mortality was observed
for CSA vs no-SDB (Nakamura et al., 2015).
MANAGEMENT
In the event that CPAP (Correa et al., 2015) or BiPAP are
not effective, the adaptive servo-ventilator (ASV) pro-
vides a baseline degree of ventilatory support superim-
posed on expiratory positive airway pressure (EPAP),
aiming to correlate to the degree of patient’s respiratory
effort, with the goal of maintaining a target ventilation
(usually 90% of the patient’s recent average ventilation).
ASV provides ventilatory support to control different
forms of CSA (CSA), mixed apnea, and periodic breath-
ing, commonly known as Cheyne–Stokes respiration
(CSR). By ventilating the patient during periods of
hypopnea and apnea and reducing support during periods
of hyperventilation and normal breathing, ASV stabilizes
breathing patterns and arterial blood gases. A meta-
analysis of 5 randomized controlled studies (395 partic-
ipants) assessing the effect of positive airway pressure
488 R.M. BENCA AND M. TEODORESCU
(PAP) in chronic HF patients with SDB found that ASV
reduced all-cause mortality (Nakamura et al., 2015).
However, at the current time, ASV is not recommended
for individuals with CSA and systolic heart failure (ejec-
tion fraction <45%), since it may increase mortality risk
(Cowie et al., 2015).
RESTLESS LEGS SYNDROME AND PERIODIC LIMB
MOVEMENTS DISORDER
Restless legs syndrome (RLS) is a disorder characterized
by disagreeable leg sensations occurring in a predictable
circadian pattern, usually prior to sleep onset. Criteria for
RLS diagnosis include a complaint of an unpleasant sen-
sation in the legs (disagreeable sensations of “creeping”
inside the calves are present and may be associated with
general aches and pains in the legs), associated with an
almost irresistible urge to move the legs. The most char-
acteristic feature is the partial or complete relief of the
sensation with leg motion and the return of the symptoms
upon cessation of leg movements. Although usually
bilateral, the symptoms can be asymmetric in severity
and frequency and rarely occur unilaterally. They typi-
cally are present only at rest; while they occur prior to
the patient’s sleep period, they can be present at other
times of the day, particularly when the patient sits for
prolonged periods of time.
Periodic limb movements of sleep (PLMS) are charac-
terized by periodic episodes of repetitive and highly
stereotyped limb movements that occur during sleep.
The movements usually occur in the legs and consist
of extension of the big toe in combination with partial
flexion of the ankle, knee, and sometimes hip; similar
movements can occur in the upper limbs. The move-
ments can be associated with a partial arousal or awa-
kening; the patient is usually unaware of the limb
movements or sleep disruption. The number of move-
ments can be subject to significant nightly variability.
Prevalence
Prevalence of RLS varies from 1% to 15% among dif-
ferent ethnic populations (Hanewinckel et al., 2015).
A large prospective study of close to 6000 general pop-
ulation subjects (mean age approximately 66) found a
prevalence of almost 14% (Hanewinckel et al., 2015).
In a population-based study of more than 2100
subjects, PLMS index >15/h was approximately 29%
(31% in men, 26% in women) (Haba-Rubio et al.,
2016). Compared to subjects with PLMSI 15/h, sub-
jects with PLMSI >15/h were older, were predominantly
males, had a higher proportion of RLS, had a higher body
mass index, and had a lower mean glomerular filtration
rate, also had a higher prevalence of diabetes, hyperten-
sion, and b-blocker or hypnotic treatments.
Pathophysiology
The pathophysiology of RLS is not fully understood.
Changes in iron metabolism and dopaminergic function,
as well as autonomic dysfunction or abnormal activa-
tion of the central pattern generator (network of spinal
neurons involved in the control of rhythmic locomotor
pattern generation and modulation), probably play a role
in the pathophysiology of the disease, but the exact
mechanisms are still somewhat unclear (Hanewinckel
et al., 2015). Other factors that have been associated with
RLS include gender, pregnancy, body mass index (BMI),
diabetes mellitus, renal failure, and socio-economic
status (Hanewinckel et al., 2015).
Management
A Cochrane meta-analysis of 35 placebo controlled and
three active controlled randomized trials (N ¼ 7365)
reported a mean reduction of approximately 6 points
(on the RLS scale) with dopamine agonist treatment
compared to placebo (Scholz et al., 2011). Periodic limb
movements in sleep per hour of sleep were 22.4/h
lower than in placebo. Self-rated quality of sleep and
disease specific quality of life were improved (Scholz
et al., 2011).
In a study of patients older than 65 years of age with
RLS and a ferritin level < 50 ng/mL or transferrin
saturation < 16%, administration of iron (as an intra-
venous infusion) was associated with a significant
improvement of symptoms as assessed by the RLS sever-
ity scale 2 weeks after treatment (Lieske et al., 2015).
The clinical significance of the movements needs to
be decided on an individual basis. Periodic limb move-
ments may be an incidental finding, and medication
targeted at reducing the number of limb movements
can result in little or no change in sleep duration or sleep
efficiency since it is possible that a centrally mediated
event can give rise to both the periodic movements
and the sleep disturbance. Clinical history and poly-
somnographic findings need to be correlated to assess
the role of this phenomenon in a certain sleep-related
symptomatology.
CLINICAL EVALUATION OF SLEEP
Sleep complaints
Sleep complaints predict the general physical and mental
health-related quality-of-life status in elderly populations
with comorbid medical and mental illnesses (Reid et al.,
2006). In addition to sleep problems related to age-
related changes in sleep patterns, neurodegenerative
disorders, and other medical factors, primary sleep disor-
ders are also more prevalent in older adults. Thus careful
 SLEEP PHYSIOLOGY AND DISORDERS IN AGING AND DEMENTIA
evaluation for common sleep disorders, such as insom-
nia, sleep apnea, and restless legs syndrome, should be
a necessary and continuous part of the routine care of
all older adults (Zee and Turek, 2006). Most elderly fail
to mention their sleep problems to their physicians out of
a false belief that sleep troubles are just a consequence of
getting older (Quan and Zee, 2004). On the contrary,
sleep disorders in older adults can be often managed,
resulting in a return to more restful sleep. Therefore,
questions regarding sleep should be routinely included
in most clinical evaluations. Given the growing evidence
of a relationship between sleep and health, identification
of sleep disorders could lead to improved management of
common age-related chronic illnesses and quality of life
of elderly patients.
Evaluation begins with identifying the main
complaints with regard to sleep, providing a focus for
delineating the patient’s concerns and further developing
the history. A careful history should be taken that
includes both the patient and, if available, family mem-
bers. People who share living and sleeping spaces may
provide important information about sleep behavior that
the patient may not be able to convey (Mezey, 2003). If
the chief complaint is from the spouse or bed partner, it is
important to determine whether the patient recognizes
the problem, is unaware of it, or denies its existence.
A comprehensive sleep history should cover not only
symptoms related to sleep and nocturnal awakenings but
also those related to the periods of wakefulness. Symp-
toms that occur during sleep concern movements or
behaviors, such as snoring, cessation of breathing, talk-
ing, moving, or abnormal behaviors, often reported by
the spouse or bed partner because the patient may be
unaware of the episodes. Symptoms related to nocturnal
awakenings might include pain, wheezing, or shortness
of breath, chest pain, palpitations, heartburn, leg cramps,
or nocturia. Daytime symptoms include not feeling
refreshed when waking up, sleepiness, fatigue, difficul-
ties with concentration and memory, or increased irrita-
bility, all of which may affect daytime function. Patients
may also report difficulties with the timing of their sleep
across the day. Drowsy driving should always be
assessed, since patients may not bring up this symptom
spontaneously.
After evaluation of a patient’s symptoms, care pro-
viders may be able to determine what the sleep problem
is and if there are multiple sleep problems and contribut-
ing comorbidities. With regard to the amount of optimal
sleep that an individual needs, sleep requirements are
related to levels that prevent daytime dysfunction or mood
impairments rather than sleep time averages (Petit et al.,
2003). If the physician and patient agree that the sleep
problem is substantial enough to need intervention, then
plans to manage the problem can be considered.
489
STANDARDIZED TOOLS FOR ASSESSING SLEEP
SYMPTOMS
A variety of tools are available to aid in sleep assess-
ments. Questionnaires and a sleep diary are often used
as self-reporting methods, while polysomnography and
actigraphy are objective methods used for measuring
sleep initiation and maintenance variables. Studies have
shown important correlations between self-reports and
objective sleep measures, despite potential inaccurate
estimations of sleep initiation and maintenance. For
example, when an awaking during the sleep period lasts
less than 3–4 min, individuals tend not to remember the
episode. Individuals with insomnia, for example, tend to
overestimate the time it takes to fall asleep and how much
time they spend awake during the night, and underesti-
mate their total time asleep.
● Sleep diary. A sleep diary is a form used by patients
for recording sleep/wake schedules. It can vary in
complexity from a simple log marking bedtime,
nighttime awakenings, and morning wake times to
a more detailed diary of daytime activities that may
influence sleep. Sleep diaries should be completed
for at least 1–2 weeks due to night-to-night variability.
Once a baseline sleep pattern is established, sleep
diaries can be used by the patient and provider to
monitor treatment progress and symptom relapse.
● Insomnia Severity Index. This questionnaire used to
assess the severity of insomnia, satisfaction with cur-
rent sleep, sleep interference, and concerns with the
sleeping problem. There are seven items and scores
range from 0 to 28, with scores greater than eight
suggestive of insomnia (Bastien et al., 2001).
● Pittsburgh Sleep Quality Index. This survey mea-
sures the quality and patterns of sleep and differenti-
ates “poor” from “good” sleep by measuring seven
areas: subjective sleep quality, sleep latency, sleep
duration, habitual sleep efficiency, sleep distur-
bances, use of sleeping medication, and daytime
dysfunction over the previous month. The patient
self-rates each of these seven areas of sleep: a sum
of 5 or greater indicated a “poor” sleeper and resulted
in a sensitivity of nearly 99% and specificity of 84%
as a marker for sleep disturbances in patients with
insomnia vs controls (Backhaus et al., 2002).
● Epworth Sleepiness Scale. This is a self-estimate of
sleep propensity in different circumstances and is
commonly used to estimate the degree of sleepiness
(Johns, 1991). Patients rate how likely they are to
doze off or fall asleep in eight different situations
commonly encountered in daily life. Scores higher
than 10 suggest excessive daytime sleepiness.
● Caregiver reports. When the use of self-assessment
tools, such as sleep diaries and self-report sleep
490 R.M. BENCA AND M. TEODORESCU
questionnaires, are not possible (e.g., persons with
severe cognitive impairment), caregiver reports are
referenced. Note that there are major limitations
when someone other than the patient is reporting
the symptoms.
● The Functional Outcomes of Sleep Questionnaire
(FOSQ) was developed to assess the impact of disor-
ders of excessive sleepiness on activities of daily
living (Weaver et al., 1997; Stavem et al., 2004).
The FOSQ is self-administered, consists of 30 items,
and focuses on five domains: general productivity,
social outcome, activity level, vigilance, and intimate
relationships and sexual activity. The potential range
of scores for each subscale is 1 (least dysfunctional)
to 4 (most dysfunctional), for the total score 5–20.
●
The Berlin Questionnaire (Netzer et al., 1999) is a
self-report instrument to determine risk for OSA.
Patients without frequent symptoms or who qualify
in only one category are placed into the lower risk
group. In a large cohort of 643 subjects 65 years of
age studied with an in-home sleep study, the Berlin
questionnaire demonstrated only a moderate level
of accuracy, its sensitivity being 77% but its specific-
ity only 39%. Among categories defining a high
OSA risk, sleepiness was less likely to be the deter-
mining factor for the high risk classification, snoring
criteria alone showing a better sensitivity (63%)
and specificity (59%) (Sforza et al., 2011). While
this is not adequately sufficient to use in a general
population, investigators still saw its value as a
prescreening tool in a high risk older population
(Sforza et al., 2011).
●
The STOP-Bang Questionnaire (Chung et al., 2008)
is another self-report questionnaire to identify indi-
viduals at risk for OSA. It is shorter and more easily
scored that the Berlin, and a recent metaanalysis of
17 studies including 9206 patients reported that a
score of 3 was related to a probability of 25% for
severe OSA (AHI > 30) in sleep clinic patients
and 15% for severe OSA in surgical patients
(Nagappa et al., 2015). Probabilities increased with
higher scores.
OBJECTIVE METHODS
●
Actigraphy. This tool is an accelerometer usually
worn at the wrist and provides valuable data in
evaluating activity–wake patterns in long-term
care settings due to major limitations in obtaining
self-reported data, as well as limited feasibility
of polysomnographic testing in this population.
Actigraphy is usually employed for a period of
7–14 days and may assist with the differential
diagnosis, guide treatment recommendations, and
assess results. Actigraphy should not be used alone,
but rather in conjunction with a sleep diary to guide
scoring and interpretation of data.
● Polysomnography is a multichannel recording includ-
ing measurement of variables to document sleep
breathing disorders (oxygen saturation in arterial
blood, rib cage, and abdominal movement, nasal
and oral airflow, and snoring sounds), data regarding
sleep and stage of sleep (electroencephalography,
electrooculography, and surface electromyography),
and electrocardiogram and leg electromyogram to
document the presence of periodic leg movements.
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