The older patient population is growing rapidly around the world and in the USA. Almost half of seniors over age 65 who live at home are dissatisfied with their sleep, and nearly two-thirds of those residing in nursing home facilities suffer from sleep disorders. Chronic and pervasive sleep complaints and disturbances are frequently associated with excessive daytime sleepiness and may result in impaired cognition, diminished intellect, poor memory, confusion, and psychomotor retardation all of which may be misinterpreted as dementia. The key sleep disorders impacting patients with dementia include insomnia, hypersomnolence, circadian rhythm misalignment, sleep disordered breathing, motor disturbances of sleep such as periodic leg movement disorder of sleep and restless leg syndrome, and parasomnias, mostly in the form of rapid eye movement (REM) sleep behavior disorder (RBD). RBD is a pre-clinical marker for a class of neurodegenerative diseases, the “synucleinopathies”, and requires formal polysomnographic evaluation. Untreated sleep disorders may exacerbate cognitive and behavioral symptoms in patients with dementia and are a source of considerable stress for bed partners and family members. When left untreated, sleep disturbances may also increase the risk of injury at night, compromise health-related quality of life, and precipitate and accelerate social and economic burdens for caregivers.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Bhatt MH, Podder N, Chokroverty S. Sleep and neurodegenerative diseases. Semin Neurol. 2005;25:39–51.
Keage HA, Banks S, Yang KL, et al. What sleep characteristics predict cognitive decline in the elderly? Sleep Med. 2012;13:886–92.
Scullin MK, Bliwise DL. Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research. Perspect Psychol Sci. 2015;10:97–137. A nicely written article reviewing a perplexing question on whether the alterations in sleep physiology can impact cognition. The authors review 50 years of research across diverse experimental protocols concluding that maintenance of adequate sleep in younger-middle age promotes better cognitive functioning and may even be protective against age-dependent cognitive declines.
Bliwise DL. Sleep in normal aging and dementia. Sleep. 1993;16:40–81.
Bliwise DL. Sleep disorders in Alzheimer’s disease and other dementias. Clin Cornerstone. 2004;6(Suppl 1A):S16–28.
Avidan AY. Sleep and neurologic problems in the elderly. Sleep Med Clin. 2006;1:273–92.
Prince M, Bryce R, Albanese E, et al. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9:63–75. e62.
Wimo A, Jonsson L, Bond J, et al. The worldwide economic impact of dementia 2010. Alzheimers Dement. 2013;9:1–11. e13.
Guarnieri B, Adorni F, Musicco M, et al. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dement Geriatr Cogn Disord. 2012;33:50–8.
Guarnieri B, Musicco M, Caffarra P, et al. Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review. Neurol Sci. 2014;35:1329–48.
Landry GJ, Liu-Ambrose T. Buying time: a rationale for examining the use of circadian rhythm and sleep interventions to delay progression of mild cognitive impairment to Alzheimer’s disease. Front Aging Neurosci. 2014;6:325.
Cipriani G, Lucetti C, Danti S, Nuti A. Sleep disturbances and dementia. Psychogeriatrics. 2015;15:65–74. A timely review covering the etiology and consequences of and potential interventions for disrupted sleep in patients with dementia.
Motohashi Y, Maeda A, Wakamatsu H, et al. Circadian rhythm abnormalities of wrist activity of institutionalized dependent elderly persons with dementia. J Gerontol A Biol Sci Med Sci. 2000;55:M740–3.
Pace-Schott EF, Spencer RM. Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment. Curr Top Behav Neurosci. 2015;25:307–30.
Lucey BP, Bateman RJ. Amyloid-beta diurnal pattern: possible role of sleep in Alzheimer’s disease pathogenesis. Neurobiol Aging. 2014;35 Suppl 2:S29–34. An important paper from the Washington University group examining the circadian patterns of Aβ concentrations, reviewing animal models that depict that changes in sleep time alter Aβ deposition. The investigators suggest that sleep may play an important role in AD pathogenesis, and propose a hypothetical model for examining the role of sleep and the Aβ diurnal pattern in promoting to the pathogenesis of AD.
Redline S, Kirchner HL, Quan SF, et al. The effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture. Arch Intern Med. 2004;164:406–18.
Mander BA, Rao V, Lu B, et al. Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. Nat Neurosci. 2013;16:357–64.
Mendelsohn AR, Larrick JW. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases. Rejuvenation Res. 2013;16:518–23. A beautifully illustrated review summarizing the glymphatic system in humans which opens up new possibilities for the therapy and prevention of dementia. The paper illustrates how healthy sleep as a public health initiative in middle-aged and older people could play a vital role in protecting from and preventing the future development of AD, especially among those with the apolipoprotein E (ApoE) ɛ4 allele.
Kress BT, Iliff JJ, Xia M, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76:845–61. A pivotal investigation proposing that an impaired glymphatic clearance could contribute to cognitive decline among older patients, which could constitute a novel therapeutic target for the management of neurodegenerative diseases associated with the abnormal accumulation of misfolded protein aggregates.
Huang Y, Potter R, Sigurdson W, et al. Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system. Arch Neurol. 2012;69:51–8. A succinct review, appraising the current literature related to the mechanisms by which disturbed sleep and circadian rhythms could play a role in the pathogenesis of AD. The authors discuss potential therapeutic strategies directed at these systems for the prevention of AD.
Roh JH, Huang Y, Bero AW, et al. Disruption of the sleep-wake cycle and diurnal fluctuation of beta-amyloid in mice with Alzheimer’s disease pathology. Sci Transl Med. 2012;4:150ra–122. In this comprehensive review, the authors argue that fluctuations in sleep-wake behavior and diurnal variations of Aβ in the CNS could be surrogate functional and biochemical biomarkers of Aβ -associated pathology. The authors suggest that abnormalities in sleep-wake rhythmicity should be explored given potential therapeutic opportunities.
Kang JE, Lim MM, Bateman RJ, et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009;326:1005–7.
Mander BA, Marks SM, Vogel JW et al. beta-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat Neurosci 2015. Fascinating new data demonstrates amyloid pathology with non-REM sleep disruption and memory impairment in older adults and connecting disturbed sleep as a potential mechanism by which β-amyloid pathology could induce cognitive decline in older adults.
Lee SD, Kang SH, Ju G, et al. The prevalence of and risk factors for sleep-disordered breathing in an elderly Korean population. Respiration. 2014;87:372–8.
Olson EJ, Park JG, Morgenthaler TI. Obstructive sleep apnea-hypopnea syndrome. Prim Care. 2005;32:329–59.
Sforza E, Roche F, Thomas-Anterion C, et al. Cognitive function and sleep related breathing disorders in a healthy elderly population: the SYNAPSE study. Sleep. 2010;33:515–21.
Carelli G, Krieger J, Calvi-Gries F, Macher JP. Periodic limb movements and obstructive sleep apneas before and after continuous positive airway pressure treatment. J Sleep Res. 1999;8:211–6.
Berger K, Luedemann J, Trenkwalder C, et al. Sex and the risk of restless legs syndrome in the general population. Arch Intern Med. 2004;164:196–202.
Trenkwalder C, Hening WA, Montagna P, et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord. 2008;23:2267–302.
Aurora RN, Zak RS, Maganti RK, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010;6:85–95.
Malhotra R, Avidan AY. Neurodegenerative disease and REM behavior disorder. Curr Treat Options Neurol. 2012;14:474–92.
Trotti LM. REM sleep behaviour disorder in older individuals: epidemiology, pathophysiology and management. Drugs Aging. 2010;27:457–70.
Foley D, Monjan A, Masaki K, et al. Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men. J Am Geriatr Soc. 2001;49:1628–32.
Jaussent I, Bouyer J, Ancelin ML, et al. Excessive sleepiness is predictive of cognitive decline in the elderly. Sleep. 2012;35:1201–7.
Merlino G, Piani A, Gigli GL, et al. Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: a population-based study. Sleep Med. 2010;11:372–7.
Vitiello MV, Borson S. Sleep disturbances in patients with Alzheimer’s disease: epidemiology, pathophysiology and treatment. CNS Drugs. 2001;15:777–96.
Association AP. Diagnostic and statistical manual of mental disorders. 5th ed. DC:: Washington; 2013.
Tay L, Lim WS, Chan M et al. New DSM-V neurocognitive disorders criteria and their impact on diagnostic classifications of mild cognitive impairment and dementia in a memory clinic setting. Am J Geriatr Psychiatry 2015.
Avidan AY. Clinical neurology of insomnia in neurodegenerative and other disorders of neurological function. Rev Neurol Dis. 2007;4:21–34.
Beydoun MA, Beydoun HA, Gamaldo AA, et al. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health. 2014;14:643.
McCurry SM, Gibbons LE, Logsdon RG, et al. Nighttime insomnia treatment and education for Alzheimer’s disease: a randomized, controlled trial. J Am Geriatr Soc. 2005;53:793–802.
Avidan A, Hays RD, Diaz N, et al. Associations of sleep disturbance symptoms with health-related quality of life in Parkinson’s disease. J Neuropsychiatry Clin Neurosci. 2013;25:319–26.
Bliwise DL, Mercaldo ND, Avidan AY, et al. Sleep disturbance in dementia with Lewy bodies and Alzheimer’s disease: a multicenter analysis. Dement Geriatr Cogn Disord. 2011;31:239–46.
Boeve BF, Silber MH, Ferman TJ, et al. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology. 1998;51:363–70.
Elwood PC, Bayer AJ, Fish M, et al. Sleep disturbance and daytime sleepiness predict vascular dementia. J Epidemiol Community Health. 2011;65:820–4.
Pollak CP, Perlick D, Linsner JP, et al. Sleep problems in the community elderly as predictors of death and nursing home placement. J Community Health. 1990;15:123–35.
Kim YH, Choi SH, D’Avanzo C et al. A 3D human neural cell culture system for modeling Alzheimer’s disease. In: Nat Protoc. 2015/06/13. 2015. pp. 985–1006.
Ringman JM, Goate A, Masters CL, et al. Genetic heterogeneity in Alzheimer disease and implications for treatment strategies. Curr Neurol Neurosci Rep. 2014;14:499.
Del Ser T, Hachinski V, Merskey H, Munoz DG. Alzheimer’s disease with and without cerebral infarcts. J Neurol Sci. 2005;231:3–11.
Jahn H. Memory loss in Alzheimer’s disease. Dialogues Clin Neurosci. 2013;15:445–54.
Nikolaev A, McLaughlin T, O’Leary DD, Tessier-Lavigne M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature. 2009;457:981–9.
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14:388–405.
Lim AS, Yu L, Kowgier M, et al. Modification of the relationship of the apolipoprotein E epsilon4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurol. 2013;70:1544–51.
O’Hara R, Schroder CM, Kraemer HC, et al. Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE epsilon4 carriers. Neurology. 2005;65:642–4.
Osorio RS, Ayappa I, Mantua J, et al. Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer’s disease in cognitively normal elderly individuals. Neurobiol Aging. 2014;35:1318–24.
Moraes W, Poyares D, Sukys-Claudino L, et al. Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study. Chest. 2008;133:677–83.
Sukys-Claudino L, Moraes W, Guilleminault C, et al. Beneficial effect of donepezil on obstructive sleep apnea: a double-blind, placebo-controlled clinical trial. Sleep Med. 2012;13:290–6.
Moran M, Lynch CA, Walsh C, et al. Sleep disturbance in mild to moderate Alzheimer’s disease. Sleep Med. 2005;6:347–52.
Iranzo A, Isetta V, Molinuevo JL, et al. Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder. Sleep Med. 2010;11:534–9.
Dowling GA, Burr RL, Van Someren EJ, et al. Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease. J Am Geriatr Soc. 2008;56:239–46.
Ancoli-Israel S, Poceta JS, Stepnowsky C, et al. Identification and treatment of sleep problems in the elderly. Sleep Med Rev. 1997;1:3–17.
Bombois S, Derambure P, Pasquier F, Monaca C. Sleep disorders in aging and dementia. J Nutr Health Aging. 2010;14:212–7.
Ju YE, McLeland JS, Toedebusch CD, et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013;70:587–93.
Beaulieu-Bonneau S, Hudon C. Sleep disturbances in older adults with mild cognitive impairment. Int Psychogeriatr. 2009;21:654–66.
Yaffe K, Laffan AM, Harrison SL, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011;306:613–9. Important data demonstrating that older women with sleep-disordered breathing had an increased risk of developing cognitive impairment, compared with those without sleep-disordered breathing. Possible mechanisms could include hypoxia, sleep fragmentation, or sleep duration.
Yoon SS, Jo SA. Mechanisms of amyloid-beta peptide clearance: potential therapeutic targets for Alzheimer’s disease. Biomol Ther (Seoul). 2012;20:245–55.
Mayo MC, Bordelon Y. Dementia with Lewy bodies. Semin Neurol. 2014;34:182–8.
Heidebrink JL. Is dementia with Lewy bodies the second most common cause of dementia? J Geriatr Psychiatry Neurol. 2002;15:182–7.
Gagnon JF, Bertrand JA, Genier MD. Cognition in rapid eye movement sleep behavior disorder. Front Neurol. 2012;3:82.
Kosaka K. Diffuse Lewy body disease. Neuropathology. 2000;20(Suppl):S73–8.
Kosaka K. Lewy body disease and dementia with Lewy bodies. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90:301–6.
Benjamin R, Leake A, Edwardson JA, et al. Apolipoprotein E genes in Lewy body and Parkinson’s disease. Lancet. 1994;343:1565.
Gardner RC, Valcour V, Yaffe K. Dementia in the oldest old: a multi-factorial and growing public health issue. Alzheimers Res Ther. 2013;5:27.
Mata IF, Samii A, Schneer SH, et al. Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders. Arch Neurol. 2008;65:379–82.
Nalls MA, Duran R, Lopez G, et al. A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA Neurol. 2013;70:727–35.
Inoue Y, Sasai T, Hirata K. Electroencephalographic finding in idiopathic REM sleep behavior disorder. Neuropsychobiology. 2015;71:25–33.
Claassen DO, Josephs KA, Ahlskog JE, et al. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010;75:494–9.
Munhoz RP, Teive HA. REM sleep behaviour disorder: how useful is it for the differential diagnosis of parkinsonism? Clin Neurol Neurosurg. 2014;127:71–4.
Vendette M, Gagnon JF, Decary A, et al. REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia. Neurology. 2007;69:1843–9.
Latreille V, Carrier J, Lafortune M, et al. Sleep spindles in Parkinson’s disease may predict the development of dementia. Neurobiol Aging. 2015;36:1083–90.
Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996;46:388–93.
Ondo WG, Vuong KD, Jankovic J. Exploring the relationship between Parkinson disease and restless legs syndrome. Arch Neurol. 2002;59:421–4.
Ferini-Strambi L, Marelli S, Galbiati A, et al. REM sleep behavior disorder (RBD) as a marker of neurodegenerative disorders. Arch Ital Biol. 2014;152:129–46.
Roman GC. Vascular dementia. Advances in nosology, diagnosis, treatment and prevention. Panminerva Med. 2004;46:207–15.
Aharon-Peretz J, Masiah A, Pillar T, et al. Sleep-wake cycles in multi-infarct dementia and dementia of the Alzheimer type. Neurology. 1991;41:1616–9.
Elwood P, Hack M, Pickering J, et al. Sleep disturbance, stroke, and heart disease events: evidence from the Caerphilly cohort. J Epidemiol Community Health. 2006;60:69–73.
Merrilees J, Hubbard E, Mastick J, et al. Sleep in persons with frontotemporal dementia and their family caregivers. Nurs Res. 2014;63:129–36.
Anderson KN, Hatfield C, Kipps C, et al. Disrupted sleep and circadian patterns in frontotemporal dementia. Eur J Neurol. 2009;16:317–23.
Yamakawa M, Shigenobu K, Makimoto K, et al. Environmental control interventions for frontotemporal dementia with reversed sleep-wake cycles. Am J Alzheimers Dis Other Demen. 2008;23:470–6.
Peter-Derex L, Yammine P, Bastuji H, Croisile B. Sleep and Alzheimer’s disease. Sleep Med Rev. 2015;19:29–38.
Lack L, Wright H. The effect of evening bright light in delaying the circadian rhythms and lengthening the sleep of early morning awakening insomniacs. Sleep. 1993;16:436–43.
McCurry SM, Pike KC, Vitiello MV, et al. Increasing walking and bright light exposure to improve sleep in community-dwelling persons with Alzheimer’s disease: results of a randomized, controlled trial. J Am Geriatr Soc. 2011;59:1393–402.
Riemersma-van der Lek RF, Swaab DF, Twisk J, et al. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008;299:2642–55.
Deschenes CL, McCurry SM. Current treatments for sleep disturbances in individuals with dementia. Curr Psychiatry Rep. 2009;11:20–6.
Sloane PD, Williams CS, Mitchell CM, et al. High-intensity environmental light in dementia: effect on sleep and activity. J Am Geriatr Soc. 2007;55:1524–33.
Lin L, Huang QX, Yang SS, et al. Melatonin in Alzheimer’s disease. Int J Mol Sci. 2013;14:14575–93.
McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer’s disease. Cochrane Database Syst Rev. 2014;3:CD009178. An extensive meta-analysis noting a lack of evidence to help direct pharmacological interventions for the management of sleep problems in AD. Authors note the lack of RCTs examining therapies commonly used in the routine management of sleep problems in AD, including the benzodiazepine and non-benzodiazepine hypnotics and noting lack of evidence to support the use of melatonin in patients with AD, patients who present with sleep disturbances in the setting of moderate to severe dementia.
Medeiros CA, Carvalhedo de Bruin PF, Lopes LA, et al. Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson’s disease. A randomized, double blind, placebo-controlled study. J Neurol. 2007;254:459–64.
Wade AG, Farmer M, Harari G, et al. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014;9:947–61.
Videnovic A, Lazar AS, Barker RA, Overeem S. “The clocks that time us”—circadian rhythms in neurodegenerative disorders. Nat Rev Neurol. 2014;10:683–93. A very elegant review examining whether circadian disturbances could represent cause or a consequence of neurodegeneration. The investigators argue that AD, PD, and HD share an underlying “chronodegeneration” as a common feature. The authors conclude that novel interventions targeting the chronodegeneration may help improve symptoms, quality of life, and perhaps even delay or slow down disease progression.
Asai H, Hirano M, Furiya Y, et al. Cerebrospinal fluid-orexin levels and sleep attacks in four patients with Parkinson’s disease. Clin Neurol Neurosurg. 2009;111:341–4.
Mahowald MW, Schenck CH. REM sleep behavior disorder. Philadelphia: WB Saunders; 1994.
Takeuchi N, Uchimura N, Hashizume Y, et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001;55:267–9.
Boeve B. Melatonin for treatment of REM sleep behavior disorder: response in 8 patients. Sleep. 2001;24(suppl):A35.
This material is the result of work supported with the resources and use of facilities at the UCLA Department of Neurology in Los Angeles, California, USA.
Conflict of Interest
Verna R. Porter and William G. Buxton declare that they have no conflict of interest.
Alon Y. Avidan is a consultant for Vanda, Merck, is on the speaker’s bureau for Merck and Xenoport and received stipends as an author and lecturer on behalf of the Elsevier, LWW, Best Doctors, AAN, AASM, ACCP, and CHEST.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Sleep Disorders
About this article
Cite this article
Porter, V.R., Buxton, W.G. & Avidan, A.Y. Sleep, Cognition and Dementia. Curr Psychiatry Rep 17, 97 (2015). https://doi.org/10.1007/s11920-015-0631-8
- Sleep disorders
- Neurodegenerative disease
- REM sleep behavior disorder
- Alpha synucleinopathies
- Alzheimer’s dementia