Circadian Rhythm Disturbance and Alzheimer’s Disease

Circadian rhythm disturbances in older adults may be markers of Alzheimer’s Disease (AD) and its progression, according to new research released this month at SLEEP 2019: 33rd Annual Meeting of the Associated Professional Sleep Societies.

Investigators discovered that dementia results in an accelerated rate of disturbances in circadian rhythm in older adults. This suggests that those disturbances may be integral to the dementia process itself.

Medscape Medical News author Megan Brooks quotes lead researcher Peng Li, PhD of Harvard Medical School with the following synopsis: “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.”

Alterations in circadian rhythm occur in patients with Alzheimer’s disease even at the preclinical stages of the disease. Until now, no studies have examined the changes in circadian rhythm which parallel the progression of AD over time.

This was a longitudinal study of 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 and determine the inter-day and intra-day variability. During the study participants also underwent annual cognitive assessments where they were classified as (1) cognitively normal, (2) mild cognitive impairment (MCI), or (3) Alzheimer’s dementia on the basis of standardized criteria.

At the start, 202 patients had MCI and 36 had AD. From the remaining 794 cognitively normal participants, 328 developed MCI during follow-up and 115 of those developed AD. Additionally, of the 202 with MCI at baseline, 90 developed AD during follow-up.

For those developing MCI, the average time from baseline to MCI was 3.4 years. For those developing AD from MCI it was around 2.5 years on average.

After MCI set in, stability of daily rhythms decreased about 90% faster and variability increased 120% faster, relative to normal cognition. Following an AD diagnosis, the rate of decline in stability doubled while the rate of decrease in variability was over 3.4 times faster than following an MCI diagnosis.

Li states in conclusion, “As people age, daily activity rhythms became less stable and more fragmented. The progression of Alzheimer’s dementia accelerates the rhythmic degradation, suggesting that circadian disturbance may be an integral part of the process of Alzheimer’s disease.”

What does this mean for us in our practice? There are several takeaways. First and foremost is circadian rhythm preservation should be a top priority in preserving cognitive function. And believe me, we take this very seriously in our practice. We are fanatical in everything related to these sleep and wakefulness rhythms. The other takeaway is an acknowledgement of the frightening rate of decline to full-blown Alzheimer’s following the transition from cognitively normal to MCI (mild cognitive impairment, aka, pre-Alzheimer’s). We must act swiftly at the earliest signs of cognitive impairment in order to have a chance at preventing progression. Better yet? Let’s act pro-actively before any symptoms of cognitive decline even start.

Source information:

Peng Li, Ph.D.1,2, Wenqing Fan3, Lei Yu, Ph.D.3, Andrew S. P. Lim, M.D.4, Aron S. Buchman, M.D.3, David A. Bennett, M.D.3,
Kun Hu, Ph.D.1,2
1Brigham and Women’s Hospital, Boston, MA, USA, 2Harvard Medical School, Boston, MA, USA, 3Rush University Medical Center, Chicago, IL, USA, 4University of Toronto, Toronto, ON, Canada.

You can find the abstract here: SLEEP: Official Publication of the Sleep Research Society Volume 42, 2019 | Abstract Supplement  (Search for abstract no. 0301)

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