Circadian Rhythm Disturbances May Be an Alzheimer's Marker

Megan Brooks

June 17, 2019

SAN ANTONIO — Circadian rhythm disturbances in older adults may be markers of Alzheimer disease (AD) and its progression, new research suggests.

Investigators found that dementia is associated with an acceleration of circadian rhythm disturbances in older adults, suggesting that such disturbances may be integral to the dementia process.

"Our findings suggest that the daily activity rhythm may potentially serve as an unobtrusive tool for the early detection of Alzheimer's disease, monitoring of the disease progression, and the evaluation of disease treatments," Peng Li, PhD, instructor in medicine, Harvard Medical School, and associate physiologist, Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Medical News.

The findings were presented here at SLEEP 2019: 33rd Annual Meeting of the Associated Professional Sleep Societies.

Alterations in circadian rhythms occur in patients with AD even at preclinical stages of the disease. Until now, however, no study has examined changes in circadian rhythm in parallel with AD progression over time.

The longitudinal study included 1032 older men and women in the Rush Memory and Aging Project who were followed for up to 13 years. The investigators used actigraphy to assess motor activities for up to 10 days annually and to quantify the inter-daily stability and intra-daily variability of the daily/circadian activity rhythms.

Participants underwent annual cognitive assessments and were classified as being cognitively healthy, as having mild cognitive impairment (MCI), or as having Alzheimer's dementia on the basis of standard criteria.

At baseline, 202 patients had MCI, and 36 had AD. Among the remaining 794 cognitively healthy participants, 328 developed MCI during follow-up. Of those patients, 115 developed AD. In addition, among the 202 participants with MCI at baseline, 90 developed AD during follow-up.

For those who develped MCI, the average time to MCI from baseline was around 3.4 years. For those who develped Alzheimer's dementia, the average time from MCI to dementia was around 2.5 years.

Over time, daily rhythms of motor activity in the elderly became "less stable and more fragmented," said Li.

After MCI set in, stability of daily rhythms decreased roughly 90% faster, and variability increased roughly 120% faster, relative to normal cognition. Following a diagnosis of Alzheimer's dementia, the rate of decline in stability doubled, and the rate of variability decrease was 3.4 times faster than at MCI diagnosis.

"The progression of these daily rhythm disturbances was much faster at the stage of MCI — twice the rate at the stage without cognition impairment. The degradation was even faster after the onset of Alzheimer's dementia — over three times the rate at the stage of MCI," Li said.

The researchers hope to validate their findings using other circadian measures. They want to examine the effect of circadian dysfunction on cognitive changes and confirm the findings in patients with Alzheimer's dementia whose conditions have been determined pathologically.

Commenting on the findings for Medscape Medical News, Andrew Varga, MD, assistant professor of medicine, pulmonary medicine, critical care medicine, and sleep medicine at the Icahn School of Medicine at Mount Sinai in New York City, said the study's strengths include its large sample size and long follow-up.

"The results conform to our expectations about breakdown of circadian rhythm as neurodegeneration advances," he said.

The study was supported by grants from the National Institutes of Health. Li and Varga have disclosed no relevant financial relationships.

SLEEP 2019: 33rd Annual Meeting of the Associated Professional Sleep Societies: Abstract 0301. Presented June 12, 2018.

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