People who log seven to eight hours of sleep per night have less amyloid and perform better on memory and other tests than do people who reported sleeping for six hours or less. This is the main finding from a study published August 30 in JAMA Neurology. Those who spent the most time under the covers—longer than nine hours per night—had different problems, doing poorly on tests of executive function and on daily tasks. At 4,417 participants, the study was the largest yet to relate sleep duration to both amyloid burden and cognition.
- In A4 trial, more than 4,400 people reported their sleep habits.
- Short sleep meant more plaques and memory deficits.
- Excessive sleep came with poor executive function.
Although the findings hint at links between sleep patterns and Alzheimer's pathophysiology, this cross-sectional study cannot disentangle cause and effect. Led by Joseph Winer and Elizabeth Mormino at Stanford University in Palo Alto, California, the study also found that race or ethnicity as well as health and lifestyle factors influenced sleep patterns, complicating interpretation of these association data.
Prior epidemiological research has supported the idea of a sweet spot for shut-eye. Both too much and too little sleep have been tied to cognitive impairment, producing a classic U-shaped curve where just the right amount of zzz’s appears protective (Kronholm et al., 2009; Ma et al., 2020). Understanding the mechanisms underlying these patterns has been difficult, although some small studies have tied insufficient sleep to elevated Aβ in the brain (Spira et al., 2013; Sep 2009 news; Jan 2018 news).
Winer and colleagues wanted to measure in a larger sample how sleep duration relates to both cognitive performance and amyloid burden. To do that, they tapped screening data from A4—an ongoing secondary prevention trial evaluating the anti-Aβ antibody solanezumab in cognitively unimpaired people who had signs of brain amyloid (Jan 2013 news; Jun 2017 news). As part of the massive recruiting effort for the trial, people whose cognition was normal were screened with an amyloid-PET scan and filled out health questionnaires that included questions about their sleep habits. Specifically, participants were asked how long they slept each night, and whether, and for how long, they napped during the day.
The researchers categorized participants into three groups: short duration, who reported getting on average six or fewer hours sleep per night; normal, i.e., seven to eight hours; and long, at longer than nine hours. The scientists acknowledge that, as opposed to objective measures such as actigraphy or EEG, self-reported sleep duration is not highly accurate, does not reflect sleep quality or disruption, and can change over time.
First, the researchers analyzed how self-reported sleep duration related to amyloid burden among these participants. They found that the fewer hours people reported sleeping each night, the more brain amyloid they had. Broken down by group, short sleepers, but not long sleepers, had slightly more amyloid than did normal-length sleepers (see image below).
What about cognition? Compared to people who reportedly got the recommended seven to eight hours of sleep each night, those who snoozed less than six hours scored slightly lower both on the mini mental state examination (MMSE) and on the logical memory delayed recall test. Short sleepers were also less likely to achieve the maximum score on the free and cued selective reminding test, a measure of episodic memory. Long sleepers, on the other hand, fell short on the digit symbol substitution test, a measure of executive function. Scores on the cognitive function instrument, a self- and partner-reported measure of everyday functioning, were lower in both short and long sleepers than in normal sleepers (Mar 2015 news).
Health and lifestyle factors also appeared to play into how much people reported sleeping. Both short and long sleepers were more likely to be depressed, to have a higher body mass index, and to take daytime naps than normal-length sleepers. The association between alcohol consumption and sleep duration was particularly robust. People who slept more than nine hours a night drank more than normal or short sleepers. This supports the idea that different etiologies may underlie the cognitive slips among long- and short-duration sleepers.
Winer emphasized that this data cannot prove what causes what. That said, the findings do imply that short sleep duration aligns with both the amyloid pathology and the subtle memory deficits that crop up in the preclinical stage of AD. In contrast, the reasons why people spend excessive amounts of time in bed at night appear unrelated to amyloid; they may reflect other health issues.
The scientists also found that sleep duration differed markedly by race and ethnicity. Compared to non-Hispanic white people, participants who self-identified as non-Hispanic black, African American, Asian, Latino, or Hispanic white all slept less. The difference was largest for non-Hispanic black people and African Americans, who reported sleeping 38 minutes less than did non-Hispanic white people per night. The findings jibe with previous studies that have tied racial and ethnic differences to sleep patterns (Kingsbury et al., 2013; Carnethon et al., 2016; Grandner et al., 2016).
Sigrid Veasey of the University of Pennsylvania School of Medicine in Philadelphia pointed out that short and long sleep are not two distinct conditions or behaviors; rather, they are symptoms of diverse sleep behaviors and disorders, such as sleep apnea. “The higher body mass indices and depression scores, and the presence of daytime napping for both short and long sleepers, are consistent with obstructive sleep apnea,” Veasey said. She thinks it will be important to understand the underlying causes of different sleep durations, and then identify how those underlying causes relate to amyloid burden and cognitive function.
Erik Musiek of Washington University in St. Louis noted that the large numbers of people with amyloid PET imaging was a major strength of the study, though it was limited by its assessments at a single time point. “This study provides more strong evidence that brain amyloid is associated with short sleep in cognitively normal individuals, even though directionality cannot be proven,” he wrote. “The integration of objective sleep measurements with multimodal AD biomarkers in longitudinal studies of preclinical AD is the ultimate goal, and this study is an important step in that direction.”—Jessica Shugart
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- Kronholm E, Sallinen M, Suutama T, Sulkava R, Era P, Partonen T. Self-reported sleep duration and cognitive functioning in the general population. J Sleep Res. 2009 Dec;18(4):436-46. PubMed.
- Ma Y, Liang L, Zheng F, Shi L, Zhong B, Xie W. Association Between Sleep Duration and Cognitive Decline. JAMA Netw Open. 2020 Sep 1;3(9):e2013573. PubMed.
- Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, Zhou Y, Wong DF, Ferrucci L, Resnick SM. Self-reported Sleep and β-Amyloid Deposition in Community-Dwelling Older Adults. JAMA Neurol. 2013 Oct 21; PubMed.
- Kingsbury JH, Buxton OM, Emmons KM. Sleep and its Relationship to Racial and Ethnic Disparities in Cardiovascular Disease. Curr Cardiovasc Risk Rep. 2013 Oct;7(5) PubMed.
- Carnethon MR, De Chavez PJ, Zee PC, Kim KY, Liu K, Goldberger JJ, Ng J, Knutson KL. Disparities in sleep characteristics by race/ethnicity in a population-based sample: Chicago Area Sleep Study. Sleep Med. 2016 Feb;18:50-5. Epub 2015 Jul 26 PubMed.
- Grandner MA, Williams NJ, Knutson KL, Roberts D, Jean-Louis G. Sleep disparity, race/ethnicity, and socioeconomic position. Sleep Med. 2016 Feb;18:7-18. Epub 2015 Feb 28 PubMed.
No Available Further Reading
- Winer JR, Deters KD, Kennedy G, Jin M, Goldstein-Piekarski A, Poston KL, Mormino EC. Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging. JAMA Neurol. 2021 Aug 30; PubMed.