0305 Degraded Fractal Activity Regulation and Incident Parkinsonism in Community-Based Older Adults

Healthy physiological systems exhibit fractal regulation, generating similar fluctuation patterns in physiological outputs across different time scales from seconds to hours. Evidence indicates a mechanistic link between fractal regulation and sleep/circadian control, and both degraded with aging and in diseases. It is accepted that sleep and circadian disturbances are common non-motor symptoms of Parkinson’s disease (PD). We tested whether degraded fractal regulation is associated with incident Parkinsonism. We examined 810 older adults (620 females; age: 80.4±7.2 [SD], range 59.4-98.9) in the Rush Memory and Aging Project who were free from any parkinsonian signs at baseline and had undergone annual motor tests for assessment of 4 parkinsonian signs (i.e., bradykinesia, gait, rigidity, and tremor) for up to 13 years. Parkinsonism was rendered if ≥2 parkinsonian signs presented. Motor activity was monitored on the wrist continuously for up to 10 days at baseline. Detrended fluctuation analysis was performed to obtain a metric α that quantifies fractal temporal correlations of motor activity at time scales ~0.1-1.5h. A Cox proportional hazards model was performed to examine the association of α with incident Parkinsonism. Parkinsonism was observed in 332 subjects (~41%) after 3.9±2.8 [SD] years on average from baseline. Older age (hazard ratio [HR]=1.07, p<0.0001) and less education (HR=1.07, p=0.002) but not sex (p=0.6) were associated with a higher risk of Parkinsonism. After controlled for age, sex, and education, 1-SD decrease in α (0.06) was also associated with increased risk for Parkinsonism with an HR of 1.22 (95% CI: 1.09-1.37, p=0.001). The effect is equivalent to that of being ~2.9 years older. The association remained after further adjusting for actigraphy-derived sleep and/or circadian metrics (i.e., sleep fragmentation and interdaily stability). Degraded fractal regulation was associated with increased PD risk. Even though previous studies have well documented the mechanistic link between fractal regulation and sleep/circadian control, the effect of fractal degradation on PD risk appears to be independent from sleep/circadian control. This work was supported by NIH grants R01AG048108, RF1AG059867, R01AG017917, and R01NS078009.