Association of Circadian Abnormalities in Older Adults With an Increased Risk of Developing Parkinson Disease

This cohort study assesses the association between rest-activity rhythm and risk of incident Parkinson disease and explores whether this association is independent of nighttime sleep disturbances in community-dwelling older men. Question Are circadian abnormalities in older adults associated with an increased risk of developing Parkinson disease over time? Findings In this longitudinal study of 2930 community-dwelling older men without Parkinson disease at baseline, the risk of incident Parkinson disease increased significantly with decreasing circadian amplitude, mesor, or robustness. Participants in the lowest quartile for these measures had approximately 3 times the risk of developing Parkinson disease compared with those in the highest quartile. Meaning Circadian rhythm disruption in elderly individuals may represent an important prodromal feature for Parkinson disease, and future studies should test whether circadian disruption could also be a risk factor for Parkinson disease and whether strategies to improve circadian function affect the risk of Parkinson disease. Importance Disruption in circadian activity rhythms is very common in older adults, particularly among those with neurodegenerative diseases, including Parkinson disease (PD). However, whether circadian disruption could be a prodrome for PD is unclear. Objective To determine the association between rest-activity rhythm (RAR) and risk of incident PD and to explore whether this association is independent of nighttime sleep disturbances. Design, Setting, and Participants The ancillary sleep study of the longitudinal cohort Osteoporotic Fractures in Men Study (MrOS) was conducted from December 1, 2003, to March 31, 2005. Of the 3135 community-dwelling men enrolled in the MrOS sleep study, 3049 had technically adequate RAR data; of these, 119 were excluded for having prevalent PD or missing incident data, leaving 2930 men without PD at baseline. Data were analyzed from February 1 through August 31, 2019. Exposures Twenty four-hour RAR parameters (amplitude, mesor, robustness, and acrophase) generated by wrist actigraphy-extended cosinor analysis. Main Outcomes and Measures Incident PD based on physician diagnosis. Multivariable logistic regression was used to determine the association between quartiles of RAR parameters and risk of incident PD. Results Among the 2930 men included in the analysis (mean [SD] age, 76.3 [5.5] years), 78 (2.7%) developed PD during 11 years of follow-up. After accounting for all covariates, the risk of PD increased with decreasing circadian amplitude (strength of the rhythm) (odds ratio [OR] per 1-SD decrease, 1.77; 95% CI, 1.30-2.41), mesor (mean level of activity) (OR per 1-SD decrease, 1.64; 95% CI, 1.22-2.21), or robustness (how closely activity follows a cosine 24-hour pattern) (OR per 1-SD decrease, 1.54; 95% CI, 1.14-2.07) (P < .005 for trend). Those in the lowest quartile of amplitude, mesor, or robustness had approximately 3 times the risk of developing PD compared with those in the highest quartile of amplitude (OR, 3.11; 95% CI, 1.54-6.29), mesor (OR, 3.04; 95% CI, 1.54-6.01), and robustness (OR, 2.65; 95% CI, 1.24-5.66). The association remained after further adjustment for nighttime sleep disturbances and duration in the lowest compared with the highest quartile (OR for amplitude, 3.56 [95% CI, 1.68-7.56]; OR for mesor, 3.24 [95% CI, 1.52-6.92]; and OR for robustness, 3.34 [95% CI, 1.45-7.67]). These associations were somewhat attenuated, but the pattern remained similar after excluding PD cases developed within 2 years after baseline in the lowest compared with the highest quartile (OR for amplitude, 2.40 [95% CI, 1.15-5.00]; OR for mesor, 2.76 [95% CI, 1.35-5.67]; and OR for robustness, 2.33 [95% CI, 1.07-5.07]). Acrophase was not significantly associated with risk of PD. Conclusions and Relevance In this cohort study, reduced circadian rhythmicity was associated with an increased risk of incident PD, suggesting it may represent an important prodromal feature for PD. Future studies are needed to determine whether circadian disruption could also be a risk factor for PD and whether strategies to improve circadian function affect the risk of PD.