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Amyloid-Sleep Link Emerges in Alzheimer's Trial Screening Data

— Both short and long sleepers self-reported worse cognitive function

Ƶ MedicalToday
A senior man sleeping in his bed.

Sleep duration was tied to early Alzheimer's disease pathology in cognitively normal older adults, a large cross-sectional analysis showed.

Among 4,417 people screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial, short sleep (6 hours or less a night) was linearly associated with higher amyloid beta (Aβ) burden (β=-0.01, P=0.005) and lower memory performance, reported Joseph Winer, PhD, of Stanford University School of Medicine in California, and co-authors.

Long sleep (9 hours or more) was linked with worse executive function performance but not with elevated Aβ, the researchers wrote in .

Both short and long sleep were associated with worse self-reported cognitive function and multiple lifestyle outcomes, including higher BMI, greater depressive symptoms, and more time spent napping during the day, suggesting a U-shaped association between sleep duration and these variables.

People sleeping shorter or longer than the normal sleep duration of 7 to 8 hours a night have been shown to be at greater risk of cognitive decline, Winer noted. Earlier research in smaller samples has evaluated relationships of both amyloid and tau with sleep.

"However, since PET imaging studies that measure amyloid plaques are expensive and typically enroll fewer than 100 people, it has been difficult to determine whether healthy older adults with short and long sleep durations are at equal risk for Alzheimer's disease," Winer told Ƶ.

As part of its screening process, the ongoing of the investigational anti-amyloid drug solanezumab used fluorine 18-labeled-florbetapir PET to measure brain amyloid accumulation in .

Participants were clinically normal (Clinical Dementia Rating score of 0) and cognitively unimpaired (Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Mean age was about 71, and 59% were women.

Most of the 4,417 people included in the analysis (67%) reported sleeping 7 to 8 hours a night; 27% were short sleepers and 6% were long sleepers. Female sex (β=0.07) and greater years of education (β=0.02) were tied to longer nightly sleep duration.

The researchers found no difference in Aβ burden association between long and normal sleepers (β=0.00, P=0.99). "To our knowledge, this study was the first to examine whether long sleep duration, which is believed to be a marker of poor health in older adults, is associated with Aβ levels," Winer and colleagues wrote.

Other studies have shown inconsistent relationships between sleep duration and specific cognitive domains, but this analysis found that people with short sleep performed worse on memory tests and people with long sleep performed worse in an executive function task, they added.

Both short (β=0.34) and long (β=0.57) sleepers reported worse subjective cognitive function than people who slept 7 to 8 hours a night. Compared with normal sleep duration, both short and long sleep were associated with higher BMI (short β=0.48, long β=0.97), depressive symptoms (short β=0.31, long β=0.39), and daytime napping (short β=2.66, long β=3.62).

The analysis had several limitations, Winer and co-authors acknowledged. It lacked information about sleep-disordered breathing, which is a risk factor for cognitive decline and elevated Aβ. The researchers also did not have data on medications that may affect sleep duration or cognitive function.

The study used self-reported sleep duration instead of actigraphy or polysomnography data; subjective and objective sleep times may differ. The cross-sectional design of the analysis could not determine the direction of associations between sleep and outcomes.

In addition, "the modest effect sizes of some of the associations with self-reported sleep duration limited the clinical implications of these findings," the researchers noted.

  • Judy George covers neurology and neuroscience news for Ƶ, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more.

Disclosures

The analysis was supported by grants from the National Institute on Aging.

Winer reported no disclosures. Other researchers reported relationships with NIH, Michael J. Fox Foundation for Parkinson's Research, Roche, Eli Lilly, and CuraSen Therapeutics.

Primary Source

JAMA Neurology

Winer JR, et al "Association of short and long sleep duration with amyloid-β burden and cognition in aging" JAMA Neurol 2021; DOI: 10.1001/jamaneurol.2021.2876.