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Sleep Quality and Preclinical Alzheimer Disease
Open accessAbstract
IMPORTANCE: Sleep and circadian problems are very common in Alzheimer disease (AD). Recent animal studies suggest a bidirectional relationship between sleep and β-amyloid (Aβ), a key molecule involved in AD pathogenesis. OBJECTIVE: To test whether Aβ deposition in preclinical AD, prior to the appearance of cognitive impairment, is associated with changes in quality or quantity of sleep. DESIGN: Cross-sectional study conducted from October 2010 to June 2012. SETTING: General community volunteers at the Washington University Knight Alzheimer's Disease Research Center. PARTICIPANTS: Cognitively normal individuals (n = 145) 45 years and older were recruited from longitudinal studies of memory and aging at the Washington University Knight Alzheimer's Disease Research Center. Valid actigraphy data were recorded in 142. The majority (124 of 142) were recruited from the Adult Children Study, in which all were aged 45 to 75 years at baseline and 50% have a parental history of late-onset AD. The rest were recruited from a community volunteer cohort in which all were older than 60 years and healthy at baseline. MAIN OUTCOME MEASURES: Sleep was objectively measured using actigraphy for 2 weeks. Sleep efficiency, which is the percentage of time in bed spent asleep, was the primary measure of sleep quality. Total sleep time was the primary measure of sleep quantity. Cerebrospinal fluid Aβ42 levels were used to determine whether amyloid deposition was present or absent. Concurrent sleep diaries provided nap information. RESULTS: Amyloid deposition, as assessed by Aβ42 levels, was present in 32 participants (22.5%). This group had worse sleep quality, as measured by sleep efficiency (80.4% vs 83.7%), compared with those without amyloid deposition, after correction for age, sex, and APOEε4 allele carrier status (P = .04). In contrast, quantity of sleep was not significantly different between groups, as measured by total sleep time. Frequent napping, 3 or more days per week, was associated with amyloid deposition (31.2% vs 14.7%; P = .03). CONCLUSIONS AND RELEVANCE: Amyloid deposition in the preclinical stage of AD appears to be associated with worse sleep quality but not with changes in sleep quantity.
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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 [217]
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Metadata
- Authors
- Ju, Y.-E. S., McLeland, J. S., Toedebusch, C. D., Xiong, C., Fagan, A. M., Duntley, S. P., Morris, J. C., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2013-05-01
- Volume
- 70
- Issue
- 5
- Pages
- 587
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC3676720
- OpenAlex
- W2143790126
- Cited by
- 744
- References
- 39
- Citations by year
- 2026: 45 · 2025: 74 · 2024: 59 · 2023: 67 · 2022: 53 · 2021: 68 · 2020: 86 · 2019: 65 · 2018: 49 · 2017: 51 · 2016: 44 · 2015: 40 · 2014: 31 · 2013: 12
- FWCI
- 30.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR000450, UL1TR000448)
- National Institute on Aging (P 50 AG05681, L30 AG043312, P50AG005681, P01 AG0 3991, P01AG003991, P01AG026276)
- National Institute of Neurological Disorders and Stroke (P01NS074969)
- National Center for Research Resources (KL2RR024994, UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- preclinical Alzheimer's disease, sleep quality, sleep efficiency, total sleep time, amyloid deposition, amyloid-beta, napping, actigraphy, APOE ε4, circadian rhythm, cognitively normal older adults
- MeSH terms
- Aged, Alzheimer Disease, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Peptide Fragments, Sleep Wake Disorders, Time Factors, Amyloid beta-Peptides, Actigraphy, Prodromal Symptoms
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