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The sleep–wake Cycle and Alzheimer’s Disease: What do We know?
Open accessAbstract
Sleep-wake disturbances are a highly prevalent and often disabling feature of Alzheimer's disease (AD). A cardinal feature of AD includes the formation of amyloid plaques, associated with the extracellular accumulation of the amyloid-β (Aβ) peptide. Evidence from animal and human studies suggests that Aβ pathology may disrupt the sleep-wake cycle, in that as Aβ accumulates, more sleep-wake fragmentation develops. Furthermore, recent research in animal and human studies suggests that the sleep-wake cycle itself may influence Alzheimer's disease onset and progression. Chronic sleep deprivation increases amyloid plaque deposition, and sleep extension results in fewer plaques in experimental models. In this review geared towards the practicing clinician, we discuss possible mechanisms underlying the reciprocal relationship between the sleep-wake cycle and AD pathology and behavior, and present current approaches to therapy for sleep disorders in AD.
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“Agitation is common in Alzheimer's disease, with 60% of people with MCI and 76% of people with Alzheimer's dementia experiencing agitation.”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [63]
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“For example, increases in beta‐amyloid and tau may interrupt the sleep‐wake cycle, 217 leading to increased sleep fragmentation and wakefulness and decreased slow‐wave sleep. 63”
From 2024 Alzheimer's disease facts and figures (2024) · cites this paper as [63]
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“In contrast to SD, enhancing normal sleep patterns may alleviate AD pathogenesis, as extension of sleep duration decreases plaque deposition in animal models [574].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [574]
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Metadata
- Authors
- Lim, M. M., Gerstner, J. R., & Holtzman, D. M.
- Affiliations
- Oregon Health & Science University (US)
- Washington State University Spokane (US)
- Washington University in St. Louis (US)
- Venue
- Neurodegenerative Disease Management
- Publisher
- Informa UK Limited
- Published
- 2014-10
- Volume
- 4
- Issue
- 5
- Pages
- 351-362
- ISSN
- 1758-2024 (ISSN-L)
- 1758-2032
- PMC
- PMC4257134
- OpenAlex
- W1984375619
- Cited by
- 168
- References
- 105
- Citations by year
- 2026: 17 · 2025: 15 · 2024: 15 · 2023: 8 · 2022: 20 · 2021: 14 · 2020: 16 · 2019: 16 · 2018: 17 · 2017: 14 · 2016: 11 · 2015: 4
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurodegenerative Disease Management (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01 AG0 3991, P01AG003991)
- National Heart, Lung, and Blood Institute (T32HL007713)
- National Institute of Neurological Disorders and Stroke (P01NS080675, 1P01NS074969-A1, P01NS074969)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, sleep-wake cycle, sleep-wake disturbances, amyloid-beta, amyloid plaques, sleep fragmentation, chronic sleep deprivation, sleep extension, disease progression
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Sleep, Amyloid beta-Peptides, Disease Progression, Sleep Disorders, Circadian Rhythm, Plaque, Amyloid
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