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Disrupted sleep-wake cycle might be measure for preclinical Alzheimer’s

People with dementia due to Alzheimer’s disease are known to have disrupted sleep. New NIH-funded research, published online Jan. 29, 2018, in JAMA Neurology, links a disrupted sleep-wake cycle to an earlier, preclinical disease phase, in which people have evidence of the disease but no symptoms. The study, by researchers at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis, Missouri, suggests that a fragmented sleep-wake cycle might be explored as a biomarker for preclinical Alzheimer’s.

For the study, 189 people (average age, 66 years) wore watch-like sensors for 7 to 14 days to collect data about their rest and activity levels. These participants also kept a sleep diary. In addition, they had positron emission tomography (PET) brain scans, cerebrospinal fluid analysis, or both to look for any biological signs of Alzheimer’s, including abnormal levels of the proteins amyloid and tau.

The researchers found that cognitively normal participants who had biological changes related to Alzheimer’s were more likely than those without these changes to have fragmented sleep-wake cycles, with higher-than-normal periods of rest during the day and more periods of activity at night.

Of the participants, 139 showed no evidence of Alzheimer’s, but 50 had abnormal amyloid plaques seen on PET scans or other signs of the disease. These 50 participants had more disruption in their circadian rest-activity (sleep-wake) cycles than those without evidence of Alzheimer’s. There were no significant differences between people with and without the ApoE4 genetic risk factor.

Increasing age also was associated with circadian dysfunction, particularly in men, the researchers found. However, after adjusting for age and gender, they concluded that aging and preclinical Alzheimer’s disease pathology have separate negative effects on circadian rhythm.

The question of whether circadian dysfunction contributes to Alzheimer’s disease pathology or vice versa is still being explored. Previous studies have shown a link between poor sleep quality and beta-amyloid levels in the brain, and findings in this study also suggest circadian dysfunction could contribute to early Alzheimer’s changes in the brain. Given that Alzheimer’s disease starts years before symptoms appear, these differences in the sleep-wake cycle could merit further study as an early indicator of disease.

Reference: Musiek ES, et al. Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurology. 2018 Jan 29. doi:10.1001/jamaneurol.2017.4719. [Epub ahead of print]