Circadian Abnormalities Tied to Increased Risk of Parkinson Disease in Older Men

By Lisa Rappaport

July 24, 2020

(Reuters Health) - Circadian rhythm disruption in older men may be a sign of increased risk for developing Parkinson disease, a longitudinal cohort study suggests.

Researchers examined data on 2,930 community-dwelling participants in the Osteoporotic Fractures in Men Study who didn't have Parkinson disease at baseline, when their mean age was 76.3 years, and who also enrolled in an ancillary sleep study. The sleep study provided 24-hour data on rest-rhythm activity (RAR) including amplitude, mesor, robustness, and acrophase using wrist actigraphy.

During 11 years of follow-up, 78 men (2.8%) developed Parkinson disease. Compared to participants with the highest RAR scores, those with the lowest scores for amplitude (odds ratio 3.11), mesor (OR 3.04), or robustness (OR 2.65) were more likely to develop Parkinson disease.

Once researchers adjusted for sleep duration and nighttime sleep disturbances, the increased risk of Parkinson disease with the lowest RAR scores compared with the highest scores was less pronounced, but still significant for amplitude (OR 2.40), mesor (OR 2.76), and robustness (OR 2.33).

Acrophase was not significantly associated with Parkinson risk, the authors report in JAMA Neurology.

"Our study is the first to report a longitudinal association between circadian disruption and subsequent risk of Parkinson disease in community-dwelling older adults," said coauthor Dr. Yue Leng, an assistant professor of psychiatry at the University of California, San Francisco.

"This is important for clinicians because markers of circadian rhythmicity might be valuable as a prodromal feature to help with the early detection of Parkinson disease," Dr. Leng said by email. "In addition, if circadian disruption is confirmed to be a risk factor for Parkinson disease, then circadian rhythmicity could be a promising intervention target for the prevention of Parkinson disease."

It's not clear from the study results whether circadian disruption is a risk factor for Parkinson disease or if it's a prodromal feature, Dr. Leng said. It's possible, however, that circadian abnormalities might cause Parkinson disease through a disruption of sleep-wake patterns or disregulation of immune and protein homeostasis in the brain, Dr. Leng said.

One limitation of the study is that it relied on physician diagnosis of Parkinson disease, and it's possible some participants had preclinical disease or had not yet been diagnosed, the study team notes.

Another is that Parkinson disease develops gradually and has a long preclinical window, making it hard to determine the exact timing of circadian abnormalities relative to preclinical Parkinson.

"We also cannot rule out reverse causation bias - i.e. circadian disruptions could be the result of preclinical Parkinson's Disease that has not yet been detected," said Aiden Doherty, an associate professor at the University of Oxford in the UK who wasn't involved in the study.

"If confirmed to be a risk factor for Parkinson disease, then circadian rhythmicity could be a promising intervention target - but there's much work to be done before that stage is reached," Doherty said by email.

Even so, markers of circadian abnormalities might aid early detection of Parkinson disease, and potentially help clinicians pursue early interventions, Dr. Leng said.

"There are a number of established circadian interventions - e.g. bright light therapy, etc - to treat circadian abnormalities," Dr. Leng said.

"At this point, since we don't know whether circadian disruption itself causes Parkinson disease, it is unclear to what extent can treatment reduce the risk of Parkinson disease," Dr. Leng added. "However, this is a very important future research direction to pursue."

SOURCE: JAMA Neurology, online June 15, 2020.