1145 Longitudinal Association Between Circadian Activity Rhythms And Risk Of Incident Parkinson’s Disease In Older Men

Abstract

Abstract Introduction Disruption in circadian activity rhythms are very common in older adults, particularly among those with neurodegenerative diseases. However, the longitudinal association between circadian disruption and subsequent risk of developing neurodegenerative diseases, including Parkinson’s disease (PD), is unclear. Methods We examined rest-activity rhythms in 2930 community-dwelling older men (mean age 76.3 ± 5.5 years) without PD and followed them for incident PD over the next 11 years. 24-h rest-activity rhythm parameters (amplitude, mesor, robustness, acrophase) were generated by wrist actigraphy-extended cosinor analysis. Incident PD cases were identified based on physician-diagnosed PD between 2005 and 2016. Logistic regression was used to determine the association between quartiles of rest-activity parameters and risk of incident PD. Results 78 (2.7%) men developed PD during 11 years of follow-up. The risk of PD increased with decreasing circadian amplitude (strength of the rhythm), mesor (mean level of activity) or robustness (how closely activity follows a cosine 24h pattern); p for trend across quartiles <0.05. After accounting for demographics, clinic site, education, depressive symptoms, body mass index, physical activity, benzodiazepine use, alcohol, caffeine, smoking, comorbidities and baseline cognition, those in the lowest quartile of amplitude, mesor or robustness had approximately three times the risk of developing PD compared to those in the highest quartile of amplitude [ORs (95% CI)= 3.11 (1.54-6.29)], mesor [3.04 (1.54-6.01)] and robustness [2.65 (1.24-5.66)]. The association remained after further adjustment for nighttime sleep disturbances and sleep duration. These associations were somewhat attenuated, but the pattern remained similar after excluding PD cases developed within 2 years after baseline. Acrophase was not significantly associated with risk of PD. Conclusion Older men with reduced circadian rhythmicity had an increased risk of incident PD over 11 years. Circadian disruption in the elderly may represent an important prodrome or risk factor for PD. Randomized trials should evaluate whether strategies to improve circadian function impact risk of PD. Support This work was supported by the NIA, NIAMS, NCATS, NIH Roadmap for Medical Research and the NHLBI under the grant numbers: U01AG027810, U01AG042124, U01AG042139, U01AG042140, U01AG042143, U01AG042145, U01AG042168, U01AR066160, UL1TR000128, R01HL071194, R01HL070848, R01HL070847, R01HL070842, R01HL070841, R01HL070837, R01HL070838, and R01HL070839.