Original Contribution |

Sleep Quality and Preclinical Alzheimer Disease

Yo-El S. Ju, MD; Jennifer S. McLeland, MSW, MA; Cristina D. Toedebusch, BS; Chengjie Xiong, PhD; Anne M. Fagan, PhD; Stephen P. Duntley, MD; John C. Morris, MD; David M. Holtzman, MD
JAMA Neurol. 2013;70(5):587-593. doi:10.1001/jamaneurol.2013.2334.
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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 APOE ϵ4 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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Figure 1. Distribution of sleep and napping parameters. A, Time in bed (blue bars) and total sleep time (red bars) were normally distributed, with mean values of 486.4 minutes and 402.6 minutes, respectively. B, Sleep efficiency was also normally distributed, with a mean value of 82.9%. C, Nap days per week was skewed toward zero. Vertical axes represent absolute frequency.

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Figure 2. Prevalence of amyloid deposition by sleep efficiency group. Participants were grouped by sleep efficiency, at cutoffs of less than 75% and more than 89% for poor and good sleep efficiency, respectively. The proportion in each group with abnormal β-amyloid 42 (Aβ42) level (≤500 pg/mL) decreases with better sleep efficiency. The group with worst sleep efficiency compared with best sleep efficiency had an odds ratio of 5.6 (95% CI, 0.965-32.5) of having amyloid deposition (P = .06).

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Figure 3. Model of sleep and Alzheimer disease (AD). The interrelationships and positive feedback loops between sleep, β-amyloid (Aβ)/amyloid, AD, and related factors are schematized. OSA indicates obstructive sleep apnea.





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