Physical Activity and Motor and Cognitive Progression in Parkinson Disease: A Longitudinal Cohort Study

Evidence for the effect of physical activity on disease progression in Parkinson disease (PD) remains limited. We aimed to examine whether physical activity is associated with the rate of motor and cognitive progression in PD and to identify specific components of physical activity underlying these associations.

In this longitudinal cohort study, we analyzed data from individuals with mild-to-moderate PD enrolled in the Cincinnati Cohort Biomarker Program between January 2019 and February 2025. Physical activity was assessed using standardized interviews and quantified as total physical activity time (TPT), total physical activity volume (TPV), and vigorous physical activity time (VPT). Longitudinal associations between physical activity and annual changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS-III; higher is worse) and Montreal Cognitive Assessment (MoCA; higher is better) scores were assessed using linear mixed-effects models adjusted for demographic and disease-related covariates. We compared predicted severity trajectories across tertiles of TPT and used residualized analyses to evaluate the independent effects of activity intensity and timing.

A total of 294 individuals with PD (mean age, 66.4 years; 33.0% female) were included, with up to 5 years of follow-up for MoCA and 7 years for MDS-UPDRS-III. Higher TPT, TPV, and VPT were each associated with slower cognitive decline and motor progression. The annual MoCA change was -0.478, -0.090, and -0.007 points in the low, mid, and high TPT tertiles, respectively, with corresponding annual MDS-UPDRS-III changes of 0.143, -0.225, and -0.783. Compared with the lowest tertile, the highest tertile showed slower cognitive (β = 0.470; 95% CI 0.203-0.737; p < 0.001) and motor (β = -0.926; 95% CI -1.835 to -0.017; p = 0.048) progression. In residualized analyses, recent physical activity remained associated with longitudinal changes in both MoCA and MDS-UPDRS-III scores after accounting for previous 10-year physical activity, whereas vigorous physical activity was no longer associated with outcomes after adjustment for total physical activity time.

Higher levels of physical activity were associated with slower cognitive and motor progression in PD. The beneficial associations of moderate-to-vigorous physical activity may be related to activity duration and ongoing engagement. Limitations include the observational design, self-reported physical activity, and potential selection bias.