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Circadian Abnormalities Linked to Increased Risk of Parkinson’s Disease

Circadian rhythm disruptions are associated with an increased risk of incident Parkinson's disease (PD), according to a longitudinal cohort study published online first on June 15 in JAMA Neurology.

Circadian disruption is often more severe among patients with PD compared with healthy older adults, the study authors noted, and they may occur in early stages of the disease. But they said it is unknown whether these abnormalities precede the development of PD.

Yue Leng, MD, PhD, of the University of California, San Francisco, and colleagues set out to evaluate the association between rest-activity rhythm (RAR) and whether that link occurred independent of nighttime sleep disturbances.

Dr. Leng's group assessed 2,930 men from the Osteoporotic Fractures in Men Study, a cohort of community-dwelling older men from six clinical in the US. Participants—who were asked to wear a small commercially available actigraph on the wrist—did not have PD at baseline. Over the 11 year follow up period, 2.7 percent of the participants developed PD. Mean age was 76.3 years.

During an 11- year follow-up, the investigators also observed that decreased circadian amplitude, mesor, or robustness at baseline were consistently associated with a higher risk of development of PD.

With decreasing circadian amplitude, robustness (OR per 1-SD decrease 1.54), or mesor (OR per 1-SD decrease 1.64), the risk of incident PD increased significantly, the researchers found.

Compared with those in the highest quartile for mesor (OR 3.24), robustness (OR 3.34), and amplitude (OR 3.56), participants in the lowest quartile for these factors had about a three-fold risk of developing PD, the investigators found.

"Our results suggest that the reduced amplitude and/or robustness of the rhythms rather than disrupted timing (acrophase) are most indicative of a subsequent risk of PD, independent of nighttime sleep disturbances. Markers of circadian rhythmicity might be valuable as a prodromal feature to help with the early detection of PD," the authors wrote.

Limitations of the study included the fact that it relied on physician diagnosis of PD, which might have involved some misclassification and a dearth of data on the exact time of diagnosis. These limitations made it difficult to compare the incident rate of PD, the authors noted. Another limitation is that the results may not be generalizable to younger or more ethnically diverse groups or even to women, they added.

"Future studies are needed to explore underlying mechanisms and to determine whether circadian disruption itself might contribute to the development of PD. If confirmed to be a risk factor for PD, then circadian rhythmicity could be a promising intervention target and will open new opportunities for the prevention and management of PD," the authors concluded.

Disclosures:

Dr. Leng disclosed relationships with the Alzheimer's Society, the National Institute on Aging, Global Brain Health Institute, the Alzheimer's Association, and the University of California, San Francisco, Weill Institute for Neurosciences.

Link Up For More Information:

Leng Y, Blackwell T, Cawthon PM, et al. Association of circadian abnormalities in older adults with an increased risk of developing Parkinson disease. JAMA Neurol 2020; Epub 2020 June 15.