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Original Investigation
August 30, 2021

Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging

Author Affiliations
  • 1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California
  • 2Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
  • 3Sierra-Pacific Mental Illness Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
JAMA Neurol. 2021;78(10):1187-1196. doi:10.1001/jamaneurol.2021.2876
Key Points

Question  What role does self-reported sleep duration play in brain amyloid-β accumulation, cognitive performance, and lifestyle factors in the context of healthy aging?

Findings  In this cross-sectional study of 4417 older adults with normal cognition, a higher amyloid-β burden was associated with short sleep duration. Sleeping duration of 6 hours or less or 9 hours or more was associated with distinct deficits in cognitive performance as well as greater depressive symptoms, body mass index, and daytime napping.

Meaning  Short and long sleep durations were associated with multiple adverse health outcomes, highlighting the importance of healthy sleep in aging.

Abstract

Importance  Disrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid β [Aβ]), depression, and cardiovascular disease.

Objective  To investigate the associations between self-reported sleep duration and brain Aβ burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition.

Design, Setting, and Participants  This cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study, which is being conducted in 67 sites in the United States, Canada, Australia, and Japan. The sample for this analysis consisted of individuals aged 65 to 85 years who underwent an Aβ positron emission tomography (PET) scan, had complete apolipoprotein E (APOE) genotype data, and were identified as clinically normal (per a Clinical Dementia Rating score of 0) and cognitively unimpaired (per a Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Data were analyzed from April 3, 2020, to June 20, 2021.

Main Outcomes and Measures  The outcome was self-reported nightly sleep duration (grouped by short sleep duration: ≤6 hours, normal sleep duration: 7-8 hours, and long sleep duration: ≥9 hours) compared with demographic characteristics, Aβ burden (as measured with a fluorine 18–labeled-florbetapir PET scan), objective and subjective cognitive function measures, and lifestyle variables.

Results  The 4417 participants in the study included 2618 women (59%) and had a mean (SD) age of 71.3 (4.7) years. Self-reported shorter sleep duration was linearly associated with higher Aβ burden (β [SE] = –0.01 [0.00]; P = .005), and short sleep duration was associated with reduced cognition that was mostly in memory domains. No difference in Aβ was found between long and normal sleep duration groups (β [SE] = 0.00 [0.01]; P = .99). However, compared with normal sleep duration, both short and long sleep durations were associated with higher body mass index (short vs normal sleep duration: β [SE] = 0.48 [0.17], P = .01; long vs normal sleep duration: β [SE] = 0.97 [0.31], P = .002), depressive symptoms (short vs normal sleep duration: β [SE] = 0.31 [0.05], P < .001; long vs normal sleep duration: β [SE] = 0.39 [0.09], P < .001), and daytime napping (short vs normal sleep duration: β [SE] = 2.66 [0.77], P = .001; long vs normal sleep duration: β [SE] = 3.62 [1.38], P = .01). Long sleep duration was associated with worse performance across multiple cognitive domains.

Conclusions and Relevance  In this cross-sectional study, both short and long sleep durations were associated with worse outcomes for older adults, such as greater Aβ burden, greater depressive symptoms, higher body mass index, and cognitive decline, emphasizing the importance of maintaining adequate sleep.

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    1 Comment for this article
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    RE: Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging
    Tomoyuki Kawada, MD | Nippon Medical School
    Winer et al. conducted a cross-sectional study to investigate the association between self-reported sleep duration and brain amyloid beta (Aβ) burden (1). Self-reported shorter sleep duration was linearly associated with higher Aβ burden and associated with reduced cognition that was remarkable in memory domains. In contrast, there was no significant difference in brain Aβ between long and normal sleep duration groups. But long sleep duration was associated with worse performance across multiple cognitive domains. The authors emphasized the importance of maintaining adequate sleep, and I have a comment about their study, presenting two meta-analyses.
    Hudon et al. conducted a meta-analysis,
    presenting that depression, short and long sleep duration were significantly associated with behavioral/psychological symptoms and cognitive decline (2). Fan et al. also conducted a meta-analysis of prospective studies (3). Pooled hazard ratios (95% confidence intervals) of long sleep duration for all-cause dementia and Alzheimer disease (AD) were 1.77 (1.32-2.37) and 1.63 (1.24-2.13), respectively. In contrast, there was no significant association between short sleep duration, all-cause dementia and AD, which was inconsistent with data by Winer et al. Although neural biomarkers were not used in meta-analyses, increased brain Aβ burden by short sleep duration could not be explained by past epidemiologic data.
    In any case, more prospective data are needed to identify the association between sleep duration and subsequent brain Aβ burden.

    References
    1. Winer JR, Deters KD, Kennedy G, et al. Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging. JAMA Neurol 2021;78(10):1187-96.
    2. Hudon C, Escudier F, De Roy J, et al. Behavioral and Psychological Symptoms that Predict Cognitive Decline or Impairment in Cognitively Normal Middle-Aged or Older Adults: a Meta-Analysis. Neuropsychol Rev 2020;30(4):558-79.
    3. Fan L, Xu W, Cai Y, et al. Sleep Duration and the Risk of Dementia: A Systematic Review and Meta-analysis of Prospective Cohort Studies. J Am Med Dir Assoc 2019;20(12):1480-7.e5.

    CONFLICT OF INTEREST: None Reported
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