How sleep disorders affect patients with Alzheimer's disease
Sleep disorders are common in patients with Alzheimer's disease. These disorders are highly related to the cognitive impairment and have as main risk factor the time of disease. Additionally, they can damage the patient’s quality of life, as well as their family’s and caregivers’. The aim of this study was to clarify which changes in sleep patterns occur in patients with Alzheimer's disease and how they occur. This narrative literature review was performed using five databases: MEDLINE, LILACS, Web of Science, Scopus, and Science Direct. Search terms were: Alzheimer’s disease, sleep-wake disorders, and dyssomnias. The research included articles published between 2000 and 2018, written in English, Portuguese and Spanish. Results showed that Alzheimer's disease is related mainly to REM sleep alterations, day-time sleepiness and napping, increased sleep fragmentation, and other less frequent disorders, such as decreased sleep efficiency and total sleep time, breathing disorders, and increased motor activity. Deposition of β-amyloid protein is the main pathophysiological substrate of sleep disorders, combined with increased orexin levels due to cholinergic deterioration in the central nervous system, and elevation of serum proinflammatory cytokines, associating circadian alterations with neuroinflammation. Therefore, sleep disorders are an important comorbidity in Alzheimer's disease, and can present in several ways, impairing the quality of life of these patients. The pathophysiological mechanisms of these comorbidities have not yet been fully elucidated, and further research that seeks to explain all these gaps is warranted.
Bokenberger K, Ström P, Dahl Aslan AK, Johansson AL, Gatz M, Pedersen NL, Åkerstedt T. Association between sleep characteristics and incident dementia accounting for baseline cognitive status: a prospective population-based study. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences. 2016; 72(1): 134-139.
Bonakis A, Economou NT, Paparrigopoulos T, Bonanni E, Maestri M, Carnicelli L, Di Coscio E, Ktonas P, Vagiakis E, Theodoropoulos P, Papageorgiou SG. Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an earlier stage, when compared to sleep in Alzheimer's disease. Journal of Alzheimer's Disease, (2014). 38(1), 85-91.
Burke SL, Maramaldi P, Cadet T, Kukull W. Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia. International psychogeriatrics. 2016; 28(9): 1409-1424.
Camargos EF, Pandolfi MB, Dias MP, Quintas JL, Guimarães RM, Nóbrega ODT. Incidência de distúrbios do sono em pacientes com doença de Alzheimer. Einstein. 2011; 9(4): 461-465.
Chen, R., Yin, Y., Zhao, Z., Huang, L., Huang, S., Zhuang, J., Wu, H., Peng, H. & Li, P. Elevation of serum TNF-α levels in mild and moderate Alzheimer patients with daytime sleepiness. Journal of neuroimmunology. 2012; 244(1-2): 97-102.
Chwiszczuk L, Breitve M, Hynninen M, Gjerstad MD, Aarsland D, Rongve A. Higher frequency and complexity of sleep disturbances in dementia with Lewy bodies as compared to Alzheimer's disease. Neurodegenerative Diseases. 2016; 16(3-4): 152-160.
Colby-Milley J, Cavanagh C, Jego S, Breitner JC, Quirion R, Adamantidis A. Sleep-wake cycle dysfunction in the TgCRND8 mouse model of Alzheimer’s disease: From early to advanced pathological stages. PloS one. 2015; 10(6), e0130177: 1-22.
Cruz AV, Fulone I, Alcalá M, Fernandes AA, Montebelo MI, Lopes LC. Uso crônico de diazepam em idosos atendidos na rede pública em Tatuí-SP. Revista de Ciências Farmacêuticas Básica e Aplicada. 2009; 27(3): 259-267.
Gagnon J, Petit D, Fantini ML, Rompré S, Gauthier S, Panisset M, Robillard A, Montplaisir J. REM Sleep Behavior Disorder and REM Sleep Without Atonia in Probable Alzheimer Disease. SLEEP. 2006; 29(10): 1321-1325.
García-Alberca JM, Lara JP, Cruz B, Garrido V, Gris E, Barbancho MÁ. Sleep disturbances in Alzheimer’s disease are associated with neuropsychiatric symptoms and antidementia treatment. The Journal of nervous and mental disease. 2013; 201(3): 251-257.
Guarnieri B, Adorni F, Musicco M, Appollonio I, Bonanni E, Caffarra P, Caltagirone C, Cerroni G, Concari L, Cosentino FII., Ferrara S, Fermi S, Ferri R, Gelosa G, Lombardi G, Mazzei D, Mearelli S, Morrone E, Murri L, Nobili FM, Passero S, Perri R, Rocchi R, Sucapane P, Tognoni G, Zabberoni S, Sorbi S. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dementia and geriatric cognitive disorders. 2012; 33(1): 50-58.
Gerstner JR, Lenz O, Vanderheyden WM, Chan MT, Pfeiffenberger C, Pack AI. Amyloid‐β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila. Journal of neuroscience research. 2017; 95(8): 1548-1564.
Hita-Yañez E, Atienza M, Cantero JL. Polysomnographic and subjective sleep markers of mild cognitive impairment. Sleep. 2013; 36(9): 1327-1334.
Ismail Z, Herrmann N, Francis PL, Rothenburg LS, Lobaugh NJ, Leibovitch FS, Black SE, Lanctot KL. A SPECT study of sleep disturbance and Alzheimer’s disease. Dementia and geriatric cognitive disorders. 2009; 27(3): 254-259.
Ju YES, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, Morris JC, Holtzman DM. Sleep quality and preclinical Alzheimer disease. JAMA neurology. 2013; 70(5): 587-593.
Jyoti A, Plano A, Riedel G, Platt B. Progressive age-related changes in sleep and EEG profiles in the Maestri M, Carnicelli L, Tognoni G, Di Coscio E, Giorgi FS, Volpi L, Economou NT, Ktonas P, Ferri F, Bonuccelli U, Bonanni E. Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot study. Sleep medicine. 2015; 16(9): 1139-1145.
Minakawa EN, Miyakazi K, Maruo K, Yagihara K, Fujita H, Wada K, Nagai Y. Chronic sleep fragmentation exacerbates amyloid β deposition in Alzheimer’s disease model mice. Neuroscience Letters. 2017; 635: 362-369.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009; 151(4): 264-269.
Moran M, Lynch CA, Walsh C, Coen R, Coakley D, Lawlor BA. Sleep disturbance in mild to moderate Alzheimer's disease. Sleep medicine. 2005; 6(4): 347-352.
Most EI, Scheltens P, Van Someren, EJ. Increased skin temperature in Alzheimer’s disease is associated with sleepiness. Journal of Neural Transmission. 2012; 119(10): 1185-1194.
PLB1Triple mouse model of Alzheimer’s disease. Neurobiology of aging. 2015; 36(10): 2768-2784.
Liguori C, Romigi A, Nuccetelli M, Zannino S, Sancesario G, Martorana A, Albanese M, Mercuri NB, Izzi F, Bernardini S, Nitti A, Sancesario GM, Sica F, Marciane MG, Placidi F. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA neurology. 2014; 71(12): 1498-1505.
Liguori C, Nuccetelli M, Izzi F, Sancesario G, Romigi A, Martorana A, Amoroso C, Bernardini S, Marciani MG, Mercuri, NB, Placidi F. Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer's disease. Neurobiology of aging. 2016; 40: 120-126.
Ohadinia S, Noroozian M, Shahsavand S, Saghafi S. Evaluation of insomnia and daytime napping in Iranian Alzheimer disease patients: relationship with severity of dementia and comparison with normal adults. The American journal of geriatric psychiatry. 2004; 12(5): 517-522.
Ojopi EPB, Bertoncini AB, Dias Neto E. Apolipoproteína E e a doença de Alzheimer. Archives of Clinical Psychiatry. 2004; 31(1): 26-33.
Oliveira FF, Bertolucci PHF, Chen ES, Smith MDAC. Assessment of sleep satisfaction in patients with dementia due to Alzheimer’s disease. Journal of Clinical Neuroscience. 2014; 21(12): 2112-2117.
Ownby RL, Peruyera G, Acevedo A, Loewenstein D, Sevush S. Subtypes of sleep problems in patients with Alzheimer disease. The American Journal of Geriatric Psychiatry. 2014; 22(2): 148-156.
Park M, Shah RC, Fogg LF, Wyatt JK. Daytime sleepiness in mild Alzheimer’s disease with and without parkinsonian features. Sleep medicine. 2011; 12(4): 397-402.
Pereira AA, Ceolim MF. Relação entre problemas do sono, desempenho funcional e ocorrência de quedas em idosos da comunidade. Revista Brasileira de Geriatria e Gerontologia. 2011; 14(4): 769-778.
Sateia MJ. International classification of sleep disorders. Chest. 2014; 146(5): 1387-1394.
Shih YH, Pai MC, Huang YC, Wang JJ. Sundown syndrome, sleep quality, and walking among community-dwelling people with Alzheimer disease. Journal of the American Medical Directors Association. 2017; 18(5): 396-401.
Torres KCL, Santos RR, Mapa FC, Moraes FL, Moraes EM, Silva MAR. Biomarcadores na doença de Alzheimer. Geriatrics, Gerontology and Aging. 2012; 6(3): 273-282.
Tractenberg RE, Singer CM, Cummings JL, Thal LJ. The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer's disease. Journal of sleep research. 2003; 12(4): 331-337.
Tractenberg, R. E., Singer, C. M., & Kaye, J. A. Symptoms of sleep disturbance in persons with Alzheimer's disease and normal elderly. Journal of sleep research. 2005; 14(2): 177-185.
Tractenberg RE, Singer CM, Kaye, JA. Characterizing sleep problems in persons with Alzheimer's disease and normal elderly. Journal of sleep research. 2006; 15(1): 97-103.
Volicer L, Harper DG, Manning, BC, Goldstein R, Satlin A. Sundowning and circadian rhythms in Alzheimer’s disease. American Journal of Psychiatry. 2001; 158(5): 704-711.
Yesavage JA, Taylor JL, Kraemer H, Noda A, Friedman L, Tinklenberg JR. Sleep/wake cycle disturbance in Alzheimer's disease: how much is due to an inherent trait?. International psychogeriatrics. 2002; 14(1): 73-81.
You SC, Walsh CM, Chiodo LA, Ketelle R, Miller BL, Kramer JH.
Neuropsychiatric symptoms predict functional status in Alzheimer’s disease. Journal of Alzheimer's Disease. 2015; 48(3): 863-869.
Pase MP, Himali JJ, Grima NA, Beiser AS, Satizabal CL, Aparicio HJ, Thomas RJ, Gottlieb DJ, Auerbach SH, Seshadri S. Sleep architecture and the risk of incident dementia in the community. Neurology. 2017; 89(12): 1244-1250.
Yin Y, Liu Y, Pan X, Chen R, Li P, Wu HJ, Zhao ZQ, Li YP, Huang LQ, Zhuang JH, Zhao ZX. Interleukin-1β promoter polymorphism enhances the risk of sleep disturbance in Alzheimer’s disease. PloS one. 2016; 11(3), e0149945: 1-16.
Copyright (c) 2021 Juliana Ciarlini Costa, Gleiry Yuri Rodrigues Cardoso, Matheus Eugênio de Sousa Lima, Gislei Frota Aragão, TATIANA PASCHOALETTE RODRIGUES BACHUR
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