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Background and Objectives  Owing to the lack of long-term observations or comprehensive adjustment for confounding factors, reliable conclusions regarding long-term effects of exercise and regular physical activity in Parkinson disease (PD) have yet to be drawn. Here, using data from the Parkinson's Progression Markers Initiative study that includes longitudinal and comprehensive evaluations of many clinical parameters, we examined the long-term effects of regular physical activity and exercise habits on the course of PD.    Methods  In this retrospective, observational cohort study, we primarily used the multivariate linear mixed-effects models to analyze the interaction effects of their regular physical activity and moderate to vigorous exercise levels, measured with the Physical Activity Scale for the Elderly questionnaire, on the progression of clinical parameters, after adjusting for age, sex, levodopa equivalent dose, and disease duration. We also calculated bootstrapping 95% confidence intervals (CIs) and conducted sensitivity analyses using the multiple imputation method and subgroup analyses using propensity score matching to match for all baseline background factors.    Results  Two hundred thirty-seven patients with early PD (median [interquartile range] age, 63.0 [56.0–70.0] years, male 69.2%, follow-up duration 5.0 [4.0–6.0] years) were included. Regular physical activity and moderate to vigorous exercise levels at baseline did not significantly affect the subsequent clinical progression of PD. However, average regular overall physical activity levels over time were significantly associated with slower deterioration of postural and gait stability (standardized fixed-effects coefficients of the interaction term [β interaction ] = −0.10 [95% CI −0.14 to −0.06]), activities of daily living (β interaction  = 0.08 [95% CI 0.04–0.12]), and processing speed (β interaction  = 0.05 [95% CI 0.03–0.08]) in patients with PD. Moderate to vigorous exercise levels were preferentially associated with slower decline of postural and gait stability (β interaction  = −0.09 [95% CI −0.13 to −0.05]), and work-related activity levels were primarily associated with slower deterioration of processing speed (β interaction  = 0.07 [95% CI 0.04–0.09]). Multiple imputation and propensity score matching confirmed the robustness of our results.    Discussion  In the long term, the maintenance of high regular physical activity levels and exercise habits was robustly associated with better clinical course of PD, with each type of physical activity having different effects.    Trial Registration Information   ClinicalTrials.gov  Identifier:  NCT01176565 .    Classification of Evidence  This study provides Class II evidence that sustained increase in overall regular physical activity levels in patients with early PD was associated with slower decline of several clinical parameters.

Long-term Effect of Regular Physical Activity and Exercise Habits in Patients With Early Parkinson Disease