Fragmented Circadian Rhythm Associated with Preclinical Alzheimer’s Disease Interview with:
“mirror clock” by tourist_on_earth is licensed under CC BY 2.0Yo-El Ju, MD

Assistant Professor of Neurology
Sleep Medicine Section
Washington University School of Medicine What is the background for this study? What are the main findings?

Response: The background for this study is that prior studies have shown that people with Alzheimer’s Disease have poor circadian clock function, for example sleeping during the day and being awake or agitated at night. Autopsy studies have shown that people with Alzheimer’s Disease have degeneration in the “clock” part of their brains. In this study, we wanted to examine whether there were any circadian problems much earlier in Alzheimer’s Disease, when people do not have any memory or thinking problems at all.

We measured circadian function in 189 people with an actigraph, which is an activity monitor worn like a watch, for 1-2 weeks. Brain scans and studies of cerebrospinal fluid were used to determine who had preclinical Alzheimer’s Disease, meaning they have the brain changes of Alzheimer’s but do not have symptoms yet. What should readers take away from your report?

Response: We found that people with preclinical Alzheimer’s Disease had fragmentation of their circadian rest-activity patterns, meaning they had more brief spurts of rest or sleep during the day, and brief episodes of activity at night, even after accounting for the decline in circadian function related to aging.

The more Alzheimer’s Disease-related brain changes someone had, the worse their circadian function. What recommendations do you have for future research as a result of this work?

Response: We hope to follow these individuals over time and re-study them, to tease apart the chicken-and-egg question, of whether Alzheimer’s Disease brain changes are causing circadian problems, or whether circadian problems can contribute to Alzheimer’s Disease.

Also, these circadian findings echo what our group and other researchers have found in terms of nighttime sleep disturbance being associated with preclinical Alzheimer’s Disease. In this circadian study, we used information from over the 24-hour day, including the daytime. The circadian system and sleep system in the brain are separate, although they do interact, as anyone who has had jet lag has experienced. We need additional research to find out whether the relationship with Alzheimer’s Disease occurs due to the interaction of circadian and sleep function, or whether the two systems separately affect Alzheimer’s Disease pathology.

Lastly, we need to develop effective interventions to improve circadian function. Since light exposure and voluntary activity levels directly affect circadian function, it is quite possible we could improve circadian function without the risk of medications or procedures. Is there anything else you would like to add? 

Response: There is a related mouse study by Dr Musiek which will be published on 1/30/18 in the Journal of Experimental Medicine. This study shows that disrupting the circadian system accelerates Alzheimer’s Disease pathology. This suggests that poor circadian function is not just a symptom of Alzheimer’s Disease, but rather, perhaps we can intervene on the circadian system to affect the course of Alzheimer’s Disease.
(Kress, GJ, Liao F, Dimitry J, Cedeno MR, Fitzgerald GA, Holtzman DM, Musiek ES. Regulation of amyloid-beta dynamics and pathology by the circadian clock. The Journal of Experimental Medicine, Jan. 30, 2018)

My disclosures include that I am the recipient of an investigator-initiated research grant from Philips-Respironics; that grant was not related to this study.


Musiek ES, Bhimasani M, Zangrilli MA, Morris JC, Holtzman DM, Ju YS. Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol. Published online January 29, 2018. doi:10.1001/jamaneurol.2017.4719

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