Inverted U-shaped association seen between sleep and cognitive function

Extremes of sleep duration — 4 hours or less, or 10 hours or more — were associated with faster global cognitive decline than less extreme sleep durations, a longitudinal pooled cohort study showed.

Compared with a reference group that reported 7 hours of sleep nightly, adults in the 4 hours or less group had greater decline in a global cognitive z scores in adjusted results (pooled β −0.022, 95% CI −0.035 to −0.009 SD per year; P = 0.001).

For adults sleeping 10 hours or more, greater cognitive decline was also seen compared with the reference group (pooled β −0.033; 95% CI, −0.054 to −0.011 SD per year; P = 0.003).

“A statistically significant inverted U-shaped association was observed between sleep duration and cognitive function, as well as subsequent decline,” wrote Wuxiang Xie, PhD, of Peking University, China, and coauthors in JAMA Network Open.

“Extreme sleep duration (i.e., 4 or less, or 10 or more hours per night) was associated not only with lower cognitive function at baseline but also with faster cognitive decline during the follow-up assessments,” they noted. “The inverted U-shaped association indicates that cognitive function should be monitored in middle-aged and older individuals with insufficient or excessive sleep duration.”

The interpretation of this study’s public health relevance is limited by small effect sizes and low prevalence of extreme sleep duration, noted Yue Leng, MD, PhD, and Kristine Yaffe, MD, both of the University of California, San Francisco, in an accompanying editorial. “The associations were small, especially for longitudinal analyses,” they wrote.

“Although this investigation is not the first study to report on such an association, the implications of this work go beyond a U-shaped association,” they added.

“Although ample evidence supports the negative impact of sleep deprivation on cognitive aging through the promotion of amyloid and tau deposition, endothelial dysfunction, and inflammation, there are no known biological mechanisms that explain why long sleep duration might cause cognitive impairment,” they noted. Long sleep duration also may reflect other sleep disorders or comorbidities, medication use, or frailty, they observed.

Strong associations between sleep and cognitive function have been seen in earlier research. Both sleep deprivation — which impairs memory consolidation — and long sleep duration have been associated with cognitive changes. Proposed mechanisms associated with sleep deprivation include inflammation, cortical thinning, and increased accumulation of Aβ42 and tau proteins.

A 2013 study of midlife sleep and late life cognition found baseline short and long sleepers had lower cognitive scores than participants sleeping 7 to 8 hours/ day. Two studies — one with all-female and one with twin cohorts — showed inverted U-shaped associations between sleep duration and cognitive decline.

“Numerous prior studies, often on a much smaller scale, have produced inconsistent findings regarding the association between sleep duration and cognitive function, whereas larger studies, including meta-analysis, have mostly identified an inverted U-shaped association,” Leng and Yaffe wrote. “This observation makes one wonder if previous null findings could be partly owing to a lack of statistical power to detect a modest association between sleep duration and cognitive function.”

Xie and colleagues analyzed data from 20,065 participants, including 9,254 from the English Longitudinal Study of Aging data collected 2008-2017; mean age, 64.6; 55.9% women; median follow-up 8 years) and 10,811 from the China Health and Retirement Longitudinal Study (data collected 2011-2015; mean age, 57.8; 50.2% men; median follow-up 4 years). In both cohorts, longitudinal studies were done every 2 years.

Baseline sleep duration was self-reported as “number of hours of sleep on an average week night” in the English cohort and “during the past month, how many hours of actual sleep did you get at night (average hours for one night)?” in the Chinese cohort.

In the English and Chinese cohorts, 4 or less hours was reported by 9.3% and 28.6%, respectively. Corresponding figures for the reference group (7 hours) were 65.6% and 41.6%, respectively; and for 10 or more hours of sleep, 3.4% and 8.2%, respectively.

Cognitive evaluations included simple tests for orientation (day, date, month, and year), memory (summed number of correct words for immediate, then delayed recall) and either animal naming (English cohort) or summed serial sevens and pentagon copying scores for executive function (Chinese cohort).

Cross-sectional analysis showed a significant reduction in baseline global cognitive scores compared with the reference group for those reporting 8, 9, 10 or more hours of sleep in both groups, as well as for those reporting 4 or less.

Longitudinal analysis revealed a inverted U-shaped association between sleep duration and global cognitive decline, which persisted after adjustment. In individual domains, an inverted U-shaped association was seen for memory, but not for executive function or orientation.

The editorialists noted that, at baseline, Chinese participants were much more likely to sleep for less than 6 or 10 or more hours per night and have lower body mass index, a lower level of education, depressive symptoms, coronary heart disease or chronic lung disease, and were less likely to be living alone or to consume alcohol at least once per week, or to have hypertension, stroke, cancer, or asthma than British participants. Cognitive testing showed higher memory, lower executive, and similar orientation for the Chinese cohort compared with the English group.

“Although some of these factors were controlled for in the multivariate model, residual confounding is still a possibility,” Leng and Yaffe wrote. “Future cross-cultural comparative studies would be of particular interest.”

Limitations include those inherent to observational study, and no causal relationships can be inferred. Reverse causation remains a possibility; extreme sleep durations might be a sign of brain impairment. Self-reported sleep duration also may be inaccurate, and the simple cognitive tests used may have limited ability to reflect individual performance.

  1. Extreme sleep duration (4 hours or less, or 10 hours or more) was associated with both lower cognitive function at baseline and faster cognitive decline during the follow-up assessments.

  2. Ample evidence supports the negative effect of sleep deprivation, but no known biological mechanisms explain how long sleep duration might cause cognitive impairment, the editorialists noted.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This work was supported by the National Natural Science Foundation of China, Newton International Fellowship from the Academy of Medical Sciences, Fundamental Research Funds for the Central Universities of China, and Irma and Paul Milstein Program for Senior Health Research Project Award.

Researchers disclosed no conflicts of interest.

Leng reported receiving grants from the National Institute on Aging, Global Brain Health Institute, Alzheimer’s Association, and Alzheimer’s Society. Yaffe reported receiving personal fees from Eli Lilly, the National Institute on Aging, and Alector and being a member of the Beeson Scientific Advisory Board and the Global Council on Brain Health.

Cat ID: 361

Topic ID: 82,361,361,422,192,50,925