Can Circadian Abnormalities Lead to Development of Parkinson Disease?

Circadian disruptions were associated with an increased risk of Parkinson disease (PD) in older men, potentially signifying PD’s impact on the internal clock before diagnosis, note study results published in JAMA Neurology.

The complexity of PD has often caused misdiagnoses at symptom onset, which could prove detrimental to disease progression and timely care.

"PD is a disease that probably takes decades to develop, and apart from changes in movement, earlier signs might be critical in understanding the disease and its mechanisms,” said lead author Yue Leng, MD, PhD, an assistant professor of psychiatry at the University of California, San Francisco.

Notably, the circadian rhythm has been shown in prior studies to have adverse health consequences when irregular, including an association with an increased risk of type 2 diabetes. Although sleep-related issues are known to occur more severely in patients with PD, researchers note it is unknown whether circadian abnormalities might precede the development of the disease.

The ancillary sleep study included patient data from the Osteoporotic Fractures in Men Study, with participants (n = 2930; mean [SD] age, 76.3 [5.5] years) having technically adequate 24-hour rest-activity rhythm (RAR) data (amplitude, mesor, robustness, and acrophase) generated by wrist actigraphy—extended cosinor analysis. The researchers sought to determine the association between RAR and risk of incident PD, and whether this link was independent of nighttime sleep disturbances.

The patient cohort had no prevalent PD at baseline (December 1, 2003, to March 31, 2005), and they were analyzed from February 1, 2019, to August 31, 2019. A multivariate logistic regression was used to find the association between quartiles of RAR parameters and risk of incident PD.

Of the study cohort, 78 (2.7%) participants developed PD during 11 years of follow-up. Those who scored lowest in the RAR parameters of amplitude (odds ratio [OR], 3.11; 95% CI, 1.54-6.29), mesor (OR, 3.04; 95% CI, 1.54-6.01), or robustness (OR, 2.65; 95% CI, 1.24-5.66) had triple the risk of developing PD compared with those who scored highest.

After adjusting for nighttime sleep disturbances and duration, the risk of developing PD among participants who scored in the lowest quartile compared with the highest exhibited similarly heightened risk (OR for amplitude, = 2.40; 95% CI, 1.15-5.00; OR for mesor, 2.76; 95% CI, 1.35-5.67; OR for robustness, 2.33; 95% CI, 1.07-5.07). No significant association was observed between acrophase and risk of PD.

Although the neurocognitive effects of PD are not reversible, Leng highlights the potential of circadian problems as risk factors for neurodegeneration prior to traditional symptoms. “We may be able to use that information for early detection and diagnosis, or we might be able to intervene in ways that prevent development of neurodegenerative loss of function," concluded Leng.

Reference

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. Published online June 15, 2020. doi:10.1001/jamaneurol.2020.1623