Circadian Rhythm Changes Linked to Future Parkinson's Risk

June 19, 2020

Abnormalities in circadian rhythm may represent an important feature in the very early stages of Parkinson's disease before symptoms develop, a new study suggests.

"We found that men with abnormal circadian rhythms had 3 times the risk of developing Parkinson's disease over an 11-year follow-up period," lead author, Yue Leng, MD, University of California, San Francisco, told Medscape Medical News.

"If confirmed to be a risk factor for Parkinson's disease, then circadian rhythmicity could be a promising intervention target and will open new opportunities for the prevention and management of Parkinson's disease," the researchers conclude.

The study was published online in JAMA Neurology on June 15.

Circadian disruption is very common in neurodegenerative diseases such as Parkinson's, but there isn't much information on how it may predict the disease, Leng explained. "We wanted to see whether circadian abnormalities may predict Parkinson's," she said.

"Parkinson's disease has a long prodromal phase where brain changes have started to occur but no clinical symptoms have become evident. It would be useful to be able to identify these patients and maybe changes in circadian rhythms may help us to do that," she added.

For the study, the researchers analyzed data from 2930 community-dwelling men aged 65 years or older (mean age, 76 years) who participated in the Osteoporotic Fractures in Men Study in which they underwent comprehensive sleep and rest-activity rhythms assessment.

"Patterns of rest and activity were measured with an actigraph device, which is worn on the wrist like a watch and captures movements which are translated into a rest-activity rhythm model — one of the most commonly used and evidence-based measures of circadian rhythm," Leng said. Men were asked to wear the actigraphs continuously for a minimum of three 24-hour periods.

Results showed that 78 men (2.7%) developed Parkinson's during the 11-year follow-up. After accounting for all covariates, the risk of Parkinson's increased with decreasing circadian amplitude (strength of the rhythm) with an odds ratio per 1-standard deviation decrease of 1.77; mesor (mean level of activity) with an odds ratio of 1.64; or robustness (how closely activity follows a 24-hour pattern) with an odds ratio of 1.54.

Those in the lowest quartile of amplitude, mesor, or robustness had approximately 3 times the risk of developing Parkinson's compared with those in the highest quartile of amplitude. The association remained after further adjustment for nighttime sleep disturbances.

"It has previously been shown that daytime napping has been linked to risk of developing Parkinson's. Now we have shown that abnormalities in the overall 24-hour circadian rest activity rhythm are also present in the prodromal phase of Parkinson's, and this association was independent of several confounders, including nighttime sleep disturbances," Leng commented.

"This raises awareness of the importance of circadian rhythm in older individuals and changes in their 24-hour pattern of behavior could be an early signal of Parkinson's disease," she said.

"This study does not tell us whether these circadian changes are causal for Parkinson's or not," Leng noted.

Future studies are needed to explore underlying mechanisms and to determine whether circadian disruption itself might contribute to the development of Parkinson's disease, the researchers say.

"If there is a causal link, then using techniques to improve circadian rhythm could help to prevent or slow the onset of Parkinson's," Leng suggested. There are many established therapies that act on circadian rhythm including bright light therapy, melatonin, and chronotherapy, she added.

Support for this study was provided by the National Institute on Aging (NIA); the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and the Weill Pilot Award. Leng reported grants from the NIA and the University of California, San Francisco, Weill Institute for Neurosciences during the conduct of the study; and grants from Global Brain Health Institute, the Alzheimer’s Association, and the Alzheimer’s Society outside the submitted work.

JAMA Neurol. Published online June 15, 2020. Abstract

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