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Less Sleep in Midlife Is Linked to Dementia in Later Life ... and a Possible Mechanism

Journal Watch NEJM

Anthony L. Komaroff, MD, reviewing Sabia S et al. Nat Commun 2021 Apr 20 Da Mesquita S et al. Nature 2021 Apr 28

People who sleep for less than 7 hours nightly at age 50 are at excess risk for cognitive impairment at age 75.

Past studies that linked lack of sleep to dementia have involved small numbers of participants, included assessment of sleep duration only in later life, relied on self-reports of sleep duration, and had follow-up durations of only about 1 decade. In two new studies, researchers assessed the long-term relation of sleep and dementia and a possible mechanism that links them.

In one study, researchers assessed sleep duration (beginning at age 50) in 8000 people who were followed for a mean 25 years. Accuracy of self-reported sleep duration was confirmed by accelerometry. Compared with people who averaged 7 hours of sleep nightly at ages 50 and 60, those who averaged 6 hours nightly at those ages were significantly more likely to develop dementia (hazard ratios for those with short sleep at age 50 and 60 were 1.22 and 1.37, respectively). For people who averaged even less than 6 hours nightly at those ages, risks were much greater. These statistically robust risk estimates were adjusted for multiple dementia risk factors.

Another study suggests a mechanism by which less sleep might increase risk for dementia. Previously, researchers identified a “glymphatic” system in the brain that, particularly during sleep, flushes toxins in the interstitial fluid out of the brain, including two toxins central to the pathology of Alzheimer disease, β-amyloid (Aβ) and tau (NEJM JW Gen Med Jan 15 2020 and Science 2019; 366:628). Investigators ablated the meningeal lymphatic system in mice that overexpressed Aβ: Aβ deposits built up, and the mice developed cognitive defects. Then, the researchers used a gene therapy technique to enhance growth of lymphatic vessels; in such mice, monoclonal antibodies targeted against Aβ were much more effective in clearing Aβ from the brain and preventing cognitive deterioration.

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