Circadian rhythm

“Our findings suggest that the circadian 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.

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.

Changes in circadian rhythm

But 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.

However, 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.

But 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.

However, for those who develop 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. But over time, daily rhythms of motor activity in the elderly became “less stable and more fragmented,” said Li.

Diagnosis of Alzheimer’s dementia

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. But 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.