Daily steps are a predictor of, but perhaps not a modifiable risk factor for Parkinson's Disease: findings from the UK Biobank.

Importance: Higher physical activity levels have been suggested as a potential modifiable risk factor for lowering the risk of incident Parkinson's disease (PD). This study uses objective measures of physical activity to investigate the role of reverse causation in the observed association. Objective: To investigate the association between accelerometer-derived daily step count and incident PD, and to assess the impact of reverse causation on this association. Design: This prospective cohort study involved a follow-up period with a median duration of 7.9 years, with participants who wore wrist-worn accelerometers for up to 7 days. Setting: The study was conducted within the UK Biobank, a large, population-based cohort. Participants: The analysis included 94,696 participants aged 43-78 years (56% female) from the UK Biobank who provided valid accelerometer data and did not have prevalent PD. Exposure: Daily step counts were derived using machine learning models to determine the median daily step count over the monitoring period. Main Outcomes and Measures: The primary outcome was incident PD, identified through hospital admission and death records. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between daily step count and incident PD, with adjustments for various covariates and evaluation of reverse causation by splitting follow-up periods. Results: During a median follow-up of 7.9 years (IQR: 7.4-8.4), 407 incident PD cases were identified. An inverse linear association was observed between daily step count and incident PD. Participants in the highest quintile of daily steps (>12,369 steps) had an HR of 0.41 (95% CI 0.31-0.54) compared to the lowest quintile (<6,276 steps; HR 1.00; 95% CI 0.84-1.19). A per 1,000 step increase was associated with an HR of 0.92 (95% CI 0.89-0.94). However, after excluding the first six years of follow-up, the association was not significant (HR 0.96, 95% CI 0.92-1.01). Conclusions and Relevance: The observed association between higher daily step count and lower incident PD is likely influenced by reverse causation, suggesting changes in physical activity levels occur years before PD diagnosis. While step counts may serve as a predictor for PD, they may not represent a modifiable risk factor. Further research with extended follow-up periods is warranted to better understand this relationship and account for reverse causation.