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SLEEP
MEDICINE
CLINICS
Sleep Med Clin 3 (2008) 347–360
Sleep disturbances in patients who have demen- to maximize quality of life for patients and their
tia are common and are a major cause of reduced bed partners, and to enable patients who have chal-
patient, and particularly caregiver, quality of life, lenging sleep disturbances to remain in the home
often leading to patient institutionalization. The lit- environment as long as possible.
erature has several excellent reviews on sleep distur- Cognitive impairment and dementia have several
bances in dementia. The principal goals of this dozen causes. The principal causes of irreversible
article are to (1) review the most common and per- dementia are shown in Box 1; the reader is directed
tinent sleep disturbances in the home/ambulatory to other sources for a more complete discussion of
setting, (2) provide a simple diagnostic scheme irreversible dementing illnesses [1–3].
for clinicians (and caregivers) to determine the Alzheimer’s disease (AD) is the most common
likely cause or causes of the sleep disturbances, such cause, with the dysfunctional proteins in this
and (3) provide a summary of nonpharmacologic disorder being amyloid (the major constituent of
and pharmacologic strategies for managing the dis- neuritic plaques) and tau (the major constituent
turbances. The ultimate purpose of such a review is of neurofibrillary tangles). Thus, AD is considered
Center for Sleep Medicine and Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN
55905, USA
E-mail address: bboeve@mayo.edu
1556-407X/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jsmc.2008.04.010
sleep.theclinics.com
348 Boeve
Box 1: Principal causes of irreversible whose onset of cognitive decline begins before age
dementia 65, the FTLD disorders are particularly common
(in the 20%–50% range). Pick’s disease, cortico-
Degenerative basal degeneration, progressive supranuclear palsy,
Alzheimer’s disease
argyrophilic grain disease, and the rare, genetically
Dementia with Lewy bodies
Parkinson’s disease with dementia mediated disorder of FTD with parkinsonism
Pick’s disease linked to chromosome 17 associated with muta-
Corticobasal degeneration tions in the gene encoding microtubule-associated
Progressive supranuclear palsy protein tau are collectively considered ‘‘tauopa-
Argyrophilic grain dementia thies.’’ FTLD with ubiquitin- and TAR-DNA binding
Frontotemporal dementia with parkinson- protein-43-positive inclusions, FTLD with motor
ism linked to chromosome 17 associated neuron disease, and FTD with parkinsonism linked
with mutations in the gene encoding micro- to chromosome 17 associated with mutations in
tubule-associated protein tau the gene encoding progranulin are considered ‘‘tar-
Frontotemporal lobar degeneration with
dopathies.’’ Approximately 40% of patients present-
ubiquitin- and TAR-DNA binding protein-
43-positive inclusions ing with an FTD or primary progressive aphasia
Frontotemporal lobar degeneration with syndrome have an underlying tauopathy, 40%
motor neuron disease have a tardopathy, and the other 20% have either
Frontotemporal dementia with parkinsonism atypical AD or a more obscure disorder. Hunting-
linked to chromosome 17 associated with ton’s disease is an uncommon, genetically medi-
mutations in the gene encoding progranulin ated disorder associated with the dysfunctional
Huntington’s disease gene product from huntingtin. Therefore, a spectrum
Vascular of disorders and their associated proteinopathies
Vascular dementia can underlie the symptoms of the neurodegenera-
tive disorders that present in an insidious fashion
Prion
and have a slowly progressive course. The primary
Creutzfeldt-Jacob disease
Fatal familial insomnia symptoms and inherent sleep disturbances are
Gerstmann-Straussler-Scheinker disease likely linked to the dysfunctional proteins and asso-
ciated topography of neurodegeneration and neu-
rochemical alterations.
an ‘‘amyloidopathy’’ and also a ‘‘tauopathy.’’ De- Multi-infarct dementia is now considered within
mentia with Lewy bodies (DLB) and Parkinson’s the spectrum of vascular dementia (VaD). Although
disease with dementia (PDD) are the primary de- the prevalence of VaD continues to be debated, and
mentia syndromes associated with underlying cerebrovascular disease is common in cognitively
Lewy body disease (LBD). The choice of the DLB impaired and cognitively normal elderly individ-
versus PDD label relates to the timing of the onset uals [4,5], pure VaD as the sole cause of dementia
of dementia and parkinsonism; DLB is applied to appears to be uncommon. Several sets of criteria
those who develop dementia prior to the onset of exist for the diagnosis of VaD, with the main con-
parkinsonism or within 1 year of the onset of cept being the onset of dementia occurring within
parkinsonism, whereas PDD is applied to those the 3 months after a cerebral infarct, particularly
who develop dementia anytime after 1 year from when the infarct involves the neocortex or
the onset of parkinsonism. Alpha-synuclein is the thalamus.
primary dysfunctional protein in the Lewy bodies Sleep disturbances are also common in the prion
and Lewy neurites of LBD, and LBD, along with disorders (eg, Creutzfeldt-Jacob disease, fatal famil-
multiple system atrophy and primary autonomic ial insomnia, and Gerstmann-Straussler-Scheinker
failure, are collectively considered ‘‘synucleinopa- disease), and marked insomnia is a defining feature
thies.’’ LBD is now considered the second most com- of fatal familial insomnia.
mon irreversible cause of degenerative dementia, Most of the literature on sleep disturbances in de-
accounting for approximately 15% to 25% of cases. mentia involve patients clinically diagnosed with
Frontotemporal lobar degeneration (FTLD) is AD. However, as noted earlier, a few patients who
a spectrum of disorders that principally affect the have typical AD clinical features do not have AD
frontal and temporal lobes. It typically manifests when examined postmortem, and instead have he
clinically as a behavioral/dysexecutive syndrome non-AD disorders listed in Box 1. Therefore, readers
(known as frontotemporal dementia [FTD]) or an of this literature must keep in mind that these stud-
aphasic syndrome (known as primary progressive ies have likely included cases with non-AD disor-
aphasia). FTLD likely accounts for 5% to 15% of ders and thus the findings may not be specific for
dementia cases. Among those who have dementia, AD. Despite these inconsistencies, ample data and
Diagnosis and Management of Sleep Disturbances 349
clinical experience exist from which to develop Such disturbances, which include insomnia, circa-
strategies for managing common, and often chal- dian dysrhythmia, nocturnal awakenings and agita-
lenging, clinical problems in the demented tion, and nocturnal wandering, can cause
population. considerable caregiver burden and lead families to
decide on nursing home placement [7,10,11]. The
medications used to treat these disturbances can
Diagnostic approach
worsen obstructive sleep apnea (OSA) and daytime
This article provides data and strategies that are up- symptoms [12]. Thus, the management of sleep dis-
dated from an earlier article [6] using a diagnostic turbances in patients who have dementia is a com-
approach, as shown in Box 2. Essentially, all sleep plicated and important clinical and societal
disturbances in dementia relate to one of four pri- problem. Issues relating to specific sleep distur-
mary symptom complexes: insomnia, hypersom- bances are described in the following sections. In-
nia, excessive motor activity at night, and somnia as an isolated disturbance may improve
nocturnal hallucinations/behavioral problems. with one or more of the agents presented in Table
Within each symptom, the author reviews how 1. Studies using sodium oxybate and ramelteon in
the symptom relates to the dementing illnesses patients who have dementia and insomnia are
themselves, which primary sleep disorders may be underway.
at play, which medications used for dementia may
impact on the symptom, the role of depression in Sleep disorders
that symptom, and finally, how circadian dysrhyth- Restless legs syndrome
mias can underlie that symptom. Pharmacologic The incidence and prevalence of restless legs syn-
and nonpharmacologic management strategies are drome (RLS) in patients who have AD and other de-
then reviewed. Details regarding specific medica- menting conditions are not known, nor do any
tions are presented in Table 1. studies address the safety and efficacy of various
agents in this population. Insomnia or hypersom-
nia can result from untreated RLS. RLS is a clinical
Symptom complex: insomnia diagnosis and is purely based on a patient’s symp-
Dementing illness toms. If a patient who has dementia does not al-
ready carry an RLS diagnosis, one must rely on
The incidence and prevalence of insomnia, per se, in
the patient’s response, which, by virtue of his/her
patients who have dementing illnesses are not
illness, may or may not accurately reflect whether
known, although sleep disturbances, in general,
any symptom is present or not. One must therefore
are known to exist in patients who have AD [7–9].
rely on the bed partner’s determination of the de-
gree of restlessness at night, rather than solely bas-
ing one’s impression on the patient’s recall of
Box 2: Diagnostic approach for assessing typical RLS symptoms. The author’s clinical experi-
sleep disturbances in patients ence suggests that RLS occurs with frequency in pa-
who have dementia tients who have AD, DLB, FTD, and VaD. Several
Essentially, all sleep disturbances in patients agents (eg, carbidopa/levodopa, pergolide, prami-
who have dementia fall into one of four major pexole, and gabapentin [see Table 1]) appear to
symptom complexes. Within each symptom be generally well tolerated and efficacious. How-
complex, one can then consider five potential ever, the dopaminergic agents should be used
underlying causes for that symptom, which with caution in patients who have psychotic fea-
can then be pursued further and managed. tures because these agents can escalate hallucina-
Symptom complex tions and delusions.
Insomnia Clinicians should keep in mind the association
Hypersomnia between iron deficiency and RLS; when these coex-
Excessive motor activity at night ist, it is often challenging, if not impossible, to treat
Nocturnal hallucinations/behavioral problems RLS effectively. One should not rely on routine re-
Underlying causes sults obtained from a standard complete blood
Dementing illness and its associated neuro- count; it is the ferritin level that is most important.
nal degeneration/ischemia/death and alter- Those who have RLS and ferritin levels below
ations in neurochemical systems 50 ng/mL typically have limited responses to ther-
Primary sleep disorder apy. In such patients, daily use of iron supplemen-
Medication effect tation is recommended (ferrous fumarate plus
Depression
vitamin C is particularly well tolerated) for at least
Circadian dysrhythmia
2 months, and perhaps longer, to achieve and
350 Boeve
Table 1: (continued)
Symptom/ Suggested Typical
behavior/ Starting titrating therapeutic
disorder Medication dose schedule range
Dextroamphetamine 5 mg qam Increase in 5-mg increments 5 mg qam–20 mg
every 3–5 d as necessary and bid (AM and noon)
tolerated in bid dosing (AM and
noon), up to 40 mg bid
Dextroamphetamine 5 mg qam Increase in 5-mg increments 5–20 mg qam
every 3–5 d as necessary and
tolerated, up to 40 mg bid
Amphetamine/ 5 mg qam Increase in 5-mg increments 5 mg qam–20 mg
dextroamphetamine every 3–5 d as necessary and bid (AM and noon)
tolerated in bid dosing (AM and
noon), up to 40 mg bid
REM sleep Clonazepam 0.25 mg qhs Increase in 0.25-mg increments 0.25–1 mg/night
behavior every 3–7 d as necessary and
disorder tolerated, up to 2 mg qhs
Melatonin 3 mg Increase in 3-mg increments 3–12 mg/night
every 3–7 d as necessary and
tolerated, up to 12 mg/night
Carbidopa/levodopa 25/100 CR 1 tab qhs; increase to 2 tabs 1–2 tabs/night
1 wk later if necessary
Quetiapine 25 mg qhs Increase in 25-mg increments 25–100 mg/night
every 3–7 d as necessary and
tolerated, up to 300 mg qhs
Nocturnal Donepezil 5 mg qam Increase to 10 mg qam 5–10 mg qam
hallucinations 2–4 wk later
or delusions Rivastigmine 1.5 mg bid Increase in 1.5-mg increments 1.5 mg bid–6.0 mg
or behavioral for both doses every 2–4 wk, bid
dyscontrol or to a maximum 6 mg bid
agitation/ Rivastigmine 4.6 mg/24-h Increase to the 9.5 mg/24-h 4.6 mg/24 h–9.5 mg/
aggression or transdermal patch daily patch 2–4 wk later 24 h
nocturnal patch qam
wandering or Galantamine 4 mg bid Increase in 4-mg increments 4 mg bid–12 mg bid
disinhibition for both doses every 2–4 wk,
to a maximum 12 mg bid
Galantamine ER 8 mg qam Increase in 8-mg increments 8–24 mg qam
every 2–4 wk, to a maximum
24 mg qam
Memantine 5 mg qd Increase gradually over 5 mg qd–10 mg bid
3–4 wk, up to 10 mg bid
Melatonin 3 mg Increase in 3-mg increments 3–12 mg/night
every 3–7 d as necessary and
tolerated, up to 12 mg/night
Quetiapine 25 mg qhs Increase in 25-mg increments 25–100 mg/night
every 3–7 d as necessary and
tolerated, up to 300 mg qhs
Olanzapine 5 mg qhs Increase in 5-mg increments 5 mg qhs–10 mg bid
q7 d in bid dosing (AM and hs)
Disclaimer and important points: The choice of which agents to use and which dosing schedules to recommend must be in-
dividualized. It is the responsibility of the clinician to consider potential side effects, drug interactions, allergic response, life-
threatening reactions, dosing changes due to renal or hepatic dysfunction, and so forth, before administering any drug to
any patient, including those listed above. Dr. Boeve, Mayo Foundation, and the publisher will not be responsible for any ad-
verse reactions of any kind to any patient regarding the content of this information. The Food and Drug Administration (FDA)
has issued warnings about the increased frequency of hyperglycemia/diabetes, stroke, and mortality associated with some or
all of the atypical neuroleptics, and increased mortality associated with galantamine in patients who have mild cognitive im-
pairment. (For these and other warnings, refer to the FDA Web site [www.fda.gov].) The FDA has also issued a warning about
the increased frequency of cardiac dysrhythmia, other morbidity, and death associated with psychostimulant use. Clinicians,
patients, and their families must carefully weigh the risks and benefits before commencing any of these agents.
Abbreviations: AM, morning; CR, controlled release; ER, extended release; qam, every morning; qhs, every night.
352 Boeve
maintain ferritin levels well above 50 ng/mL. It is least for trial periods to determine if efficacy war-
reasonable to also administer a dopaminergic agent rants continued use.
or gabapentin over this same time period, and some
patients no longer require continued use of dopa- Tacrine
minergic therapy or gabapentin once ferritin levels Tacrine was the first AChEI marketed for the man-
exceed 50 ng/mL. agement of cognitive impairment in AD, but it is
The same logic as that for assessing iron defi- rarely used anymore because of liver toxicity and
ciency and treating it with iron replacement therapy the need for frequent dosing during the day. Insom-
applies to periodic limb movement disorder nia can occur with this agent.
(PLMD) (see section on excessive motor activity
a night). Donepezil
Donepezil was the second AChEI to become avail-
Central sleep apnea able on the market, and it is widely used in the
Central sleep apnea (CSA) can cause profound hy- United States and abroad. Donepezil affects acetyl-
persomnia or insomnia; this topic is discussed in cholinesterase activity. The manufacturer recom-
the section on hypersomnia. mends that it be dosed at night to minimize the
development of nausea, although many clinicians
now dose this agent with breakfast because nausea
Medication effects tends to be mild and infrequent, and insomnia,
The only agents approved by the United States Food nightmares, and nocturnal hallucinations can be
and Drug Administration for the management of problematic for some patients.
dementia are the acetylcholinesterase inhibitors
(AChEIs) (ie, tacrine, donepezil, rivastigmine, and Rivastigmine
galantamine) and the N-methyl-D-aspartate Rivastigmine affects acetylcholinesterase and butyl-
(NMDA) antagonist memantine. The AChEIs act cholinesterase activity, and this agent is also widely
by blocking acetylcholinesterase activity, thereby used in patients who have dementia. Oral and
leaving more acetylcholine in the synaptic cleft to transdermal formulations are available. The manu-
continue activating the postsynaptic neuron. Mem- facturer recommends that the oral form be admin-
antine blocks NMDA receptors and is believed to istered twice daily, and most patients take the pill
provide benefits by decreasing glutaminergic excito- with breakfast and supper. If insomnia is problem-
toxicity. The usual starting doses and titration atic with this agent, the latter dose can be taken ear-
schedules are shown in Table 1. The AChEI agents lier in the day, such as with lunch. The transdermal
and memantine can improve cognitive and neuro- formulation should be applied each morning, with
psychiatric symptoms and functional abilities; evi- the previous day’s patch removed and the current
dence is not convincing that any of the agents day’s patch placed on a different location of the
slow the course of any of the dementing conditions. skin (often changed after a patient takes a shower
It is common practice for patients to be com- in the morning).
menced on either an AChEI or memantine first
and, once the maintenance dose is achieved, to Galantamine
then add the other class or agent such that a combi- Galantamine affects acetylcholinesterase and nico-
nation of memantine and one of the AChEIs is be- tinic receptor activity. This agent comes in liquid
ing administered. Although the clinical benefit and capsule (given twice daily) and extended-
from these agents is typically modest at best, rare release capsule (given once daily) formulations.
patients do experience rather dramatic improve- The extended-release pill should be given in the
ment in symptoms and functional abilities, morning. If insomnia is problematic with the liquid
particularly with the AChEIs. Based on head- or standard capsule formulations, the latter dose
to-head studies and clinical experience, none of can be taken earlier in the day, such as with lunch.
the AChEIs appears to be superior to the others.
However, the clinical benefits and side effects are Memantine
variable for each individual, so changing from Memantine is an NMDA receptor antagonist, and it
one AChEI to one of the others is reasonable, de- is often used in combination with one of the
pending on the response to therapy. Despite the of- AChEIs mentioned earlier. The medication is typi-
ten disappointing efficacy of these agents, and cally titrated upward over 3 to 4 weeks to a mainte-
potential side effects that can impact sleep and nance dose of 10 mg twice daily. Although efficacy
alertness, the progressive nature and universally fa- has been demonstrated in placebo-controlled trials,
tal result of the irreversible dementing disorders cer- clinical experience has shown that improvement in
tainly justify using the AChEIs or memantine at cognition and neuropsychiatric issues is typically
Diagnosis and Management of Sleep Disturbances 353
subtle, rather than dramatic. Side effects are uncom- Symptom complex: hypersomnia
mon and minor. Insomnia due to memantine is
rare; when it does occur, taking the latter dose ear- Dementing illness
lier in the day, such as with lunch, often alleviates it. The incidence and prevalence of hypersomnia in
the various dementing conditions are not known,
and reports of hypersomnia directly related to an
Depression underlying degenerative dementing disorder have
Depression is common in patients who have de- not been published. Experience at the author’s cen-
mentia, and can cause insomnia in demented indi- ter indicates that some individuals who have DLB
viduals, similar to those who do not have any or FTD have objective evidence of hypersomno-
cognitive impairment. Antidepressant medications lence, as measured by the multiple sleep latency
can also lead to insomnia, particularly those with test, that is not associated with another primary
‘‘activating’’ properties such as fluoxetine, venlafax- sleep disorder, and such hypersomnolence can im-
ine, and bupropion. The choice of when to treat de- prove with psychostimulant therapy. More recent
pression and with which agent is up to the clinician, evidence in DLB patients from the author’s center
but because tricyclic antidepressants have mild to has revealed marked hypersomnolence (mean ini-
severe anticholinergic side effects, these agents tial sleep latencies less than 5 minutes), sometime
should generally be avoided in patients who have associated with two or more sleep-onset rapid eye
dementia. Sertraline also has some anticholinergic movement (REM) periods, on the multiple sleep la-
activity and is not ideal for patients who have tency test, suggesting a ‘‘narcoleptic’’ profile (Fer-
dementia. man and colleagues, unpublished data, 2008).
Low-dose methylphenidate (5 mg or less) has been
shown to improve alertness in older patients resid-
ing in nursing homes [24], and recent evidence sug-
Circadian dysrhythmia
gests methylphenidate in older individuals might
Although precise data on the incidence and preva- reduce fall risk [25]. In the author’s experience, mod-
lence of circadian dysrhythmia in the demented afinil, methylphenidate, dextroamphetamine, and
population do not exist, several groups have ob- dextroamphetamine/methamphetamine have been
served a high frequency of sleep fragmentation helpful in managing hypersomnolence in patients
and circadian dysrhythmia in the institutionalized who have dementia, without inducing untoward
elderly [8,9,13,14]. The symptoms of insomnia neurobehavioral or cardiovascular side effects (see
and hypersomnia can reflect a primary circadian Table 1). The anatomicophysiologic underpinnings
dysrhythmia. Degenerative changes in the supra- of hypersomnia in dementing conditions are un-
chiasmatic nucleus of the hypothalamus and de- clear, although alterations in hypocretin production
creased melatonin production are thought to be or physiology may be at play [26].
contributing factors in the circadian dysrhythmic
abnormalities in patients who have AD and other
dementing conditions [15,16]. Sleep disorders
Two primary management strategies center Obstructive sleep apnea
around this knowledge: exogenous melatonin and The relationships among OSA, cognitive status, and
phototherapy. Data from small numbers of patients dementia are complex and not fully understood. Al-
who have dementia suggest that melatonin can im- though OSA and dementia appear to be associated,
prove sleep continuity and lengthen total sleep time data are conflicting as to whether OSA is causally re-
[17,18]. A multicenter, placebo-controlled trial us- lated to dementia [27–32]. Because intracranial
ing 2.5 mg slow-release and 10 mg formulations pressure increases markedly and cerebral perfusion
of melatonin failed to demonstrate efficacy over changes during apneic events [33,34], one would
placebo, although individual patients clearly ap- expect that if OSA is causally related to any etiologic
peared to benefit from melatonin [19]. Studies mechanism for dementia at all, VaD would most
with ramelteon for the management of circadian likely be related. Evidence accumulated over the
dysrhythmia in patients who have dementia are in past 20 years indicates that untreated OSA in the
progress, and clinical experience thus far has nondemented population causes cognitive impair-
yielded variable efficacy but good tolerability. Pho- ment, excessive daytime somnolence (EDS), and di-
totherapy has shown some promise in the manage- minished mood and quality of life, and that
ment of circadian dysrhythmia in demented treatment of OSA (particularly with nasal continu-
individuals, although the optimal timing and dura- ous positive airway pressure [CPAP]) improves cog-
tion of phototherapy and illumination intensity nitive performance, EDS, mood, and quality of life
have not yet been determined [20–23]. [35–50]. Neuropsychologic analyses have revealed
354 Boeve
that in patients who have OSA, cognitive flexibility, responsible for CSA in degenerative dementing ill-
attention, processing speed, and memory all im- nesses, and likely contributes similarly in VaD.
prove with CPAP therapy [39,46,51]. The challenge The frequency of CSA in the degenerative and vas-
is that many patients who have OSA do not experi- cular dementing conditions is not known, but in
ence an obvious clinical benefit from CPAP therapy, the author’s experience, it is far less common than
or cannot tolerate nightly CPAP use, so compliance OSA in those who have mild to moderate dementia.
with CPAP therapy, even in nondemented individ- As in CSA related to cardiac dysfunction, manage-
uals, is far from ideal. ment can be challenging. Nasal CPAP therapy, bile-
In some instances, patients have been diagnosed vel positive airway pressure therapy, adaptive
with delirium [52,53], dementia (not otherwise servoventilation devices, supplemental oxygen,
specified) [54], and a degenerative dementing ill- benzodiazepines, or a combination of two or three
ness [55], who are found to have untreated OSA, of these can provide symptomatic improvement in
and delirium or dementia disappears with CPAP some cases. Therapeutic trials typically require 1 or
therapy. Hence, OSA can be considered one of the 2 nights of PSG to determine which single therapy
reversible causes of delirium and dementia. The fre- or combination of therapies provides the maximal
quency of such cases is not known, but the fact that benefit.
some individuals have dramatic functional and
neuropsychometric improvement with CPAP ther- Complex sleep apnea syndrome
apy, and the high prevalence of OSA in the elderly Some patients who have OSA develop a high fre-
[28], underscore the need to consider OSA in any quency of central apneas or a disruptive Cheyne-
patient who has cognitive impairment. Further- Stokes respiratory pattern after application of
more, because CPAP therapy has now been shown CPAP, which has been termed ‘‘complex sleep ap-
to improve the sleep quality in bed partners of pa- nea syndrome’’ (CompSAS) [59,60]. Adaptive ser-
tients who have OSA [56], caregivers of patients voventilation has been shown to be effective in
who have dementia and OSA could enjoy improved treating CompSAS [61]. The incidence and preva-
quality of sleep/quality of life with their bed part- lence of CompSAS in patients who have dementia
ners’ use of CPAP therapy. have not been well studied, but in the author’s expe-
Recent data show that cognition and alertness rience, this disorder does occur with some fre-
improve with CPAP therapy in patients who have quency in the dementia population, and adaptive
OSA and a coexisting dementing illness, and that servoventilation can be tolerated and effective.
CPAP therapy is tolerated in demented individuals
[57,58]. No published data exist on the effects of Periodic limb movement disorder
CPAP therapy on the bed partners/caregivers of pa- See section on excessive motor activity at night.
tients who have OSA and dementia. Experience at
the author’s center has also revealed the following Medication effects
regarding patients who have dementia and OSA: The AChEIs rarely cause hypersomnia, but in those
(1) a few patients do experience significant func- who do experience this side effect, it may be worth-
tional and mild neuropsychometric improvement while to change to another agent in this class be-
with CPAP therapy, (2) a significant proportion of cause it is rare to experience hypersomnia as
patients do tolerate CPAP therapy and use it nightly, a side effect across all of the AChEIs. Hypersomnia
(3) some patients who have positional OSA do tol- due to memantine is also rare.
erate positional therapy and experience mild clini-
cal improvement, and (4) some caregivers of Depression
patients enjoy less fragmented sleep and less EDS
while their bed partners who have dementia use Hypersomnia related to underlying depression can
CPAP therapy. Therefore, importantly, it should certainly occur and, if suspected, an antidepressant
not be assumed that patients who have dementia with few or no sedating properties could be used.
and OSA cannot tolerate or benefit from CPAP ther-
apy; most deserve a polysomnography (PSG) and Circadian dysrhythmia
CPAP trial, similar to any individual who does See the section on insomnia. Also, wake-promoting
not have dementia. agents can be used effectively and without side ef-
fects in patients who have hypersomnia, whether
Central sleep apnea related to a circadian dysrhythmia or not. Some-
CSA is known to occur in patients who have pri- times, strategies directed at minimizing insomnia
mary cardiac and primary central nervous system (eg, a sedative/hypnotic or phototherapy) plus
dysfunction. The dysregulation of the brainstem re- a wake-promoting agent during the day can provide
spiratory neuronal networks is presumed to be the best response.
Diagnosis and Management of Sleep Disturbances 355
night evolves, especially when it does so abruptly. same phenomenon could be occurring with care-
One should also use behavioral techniques before givers of patients residing at home.
proceeding to pharmacologic intervention. Tech- Several different physiologic substrates for the
niques such as acknowledging the source of agita- various problem symptoms and behaviors are
tion if it can be identified, then using gentle likely, and the optimal strategies for management
redirection, can be effective, but the caregiver or may reflect the physiologic underpinnings, which
nursing home staff needs to be trained in how to have yet to be fully characterized. Therefore, in
use behavioral techniques, which some master but communicating among health care professionals,
many do not. Various medications can be effective patients, caregivers, and researchers, it may be
for managing nocturnal agitation (see Table 1). more appropriate to use descriptive terms or
The AChEIs (eg, donepezil, rivastigmine, galant- phrases such as ‘‘agitation and physically aggressive
amine), memantine, atypical neuroleptics (eg, behavior’’ or ‘‘wandering and pacing’’ rather than
olanzapine, quetiapine), antiepileptics (eg, carba- ‘‘sundowning.’’ Furthermore, administering medica-
mazepine, valproic acid), benzodiazepines (eg, clo- tions to patients is only one facet of management;
nazepam), and trazodone and chloral hydrate, can caregiver education, psychologic support, time
be considered if drug therapy is needed [1]. If agi- away from patients by way of respite care, and so
tated depression is suspected, psychiatric consulta- forth, are also critical.
tion for consideration of electroconvulsive therapy Several modalities have been suggested to ame-
can be helpful. liorate various features of the ‘‘sundowning’’ syn-
drome (see excellent review by McGaffigan and
Sleep disorders Bliwise [88].) Table 1 presents several agents that
Rapid eye movement sleep behavior disorder are variably effective for problem symptoms and
RBD is discussed in the section on excessive motor behaviors. The dictums of therapy are (1) use
activity at night. a trial-and-error approach and (2) ‘‘start low and
go slow.’’ Combination therapy is sometimes
Medication effects necessary.
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Health 1990;15:123–5. cell loss in Parkinson’s disease. Brain 2007;130:
[11] Little J, Satlin A, Sunderland T, et al. Sundown 1586–95.
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