Background and ObjectivesPrevious cohort studies reported that a single measure of physical activity (PA) assessed at baseline was associated with lower Parkinson disease (PD) incidence, but a meta-analysis suggested that this association was restricted to men. Because of the long prodromal phase of the disease, reverse causation could not be excluded as a potential explanation. Our objective was to study the association between time-varying PA and PD in women using lagged analyses to address the potential for reverse causation and to compare PA trajectories in patients before diagnosis and matched controls.MethodsWe used data from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (1990-2018), a cohort study of women affiliated with a national health insurance plan for persons working in education. PA was self-reported in 6 questionnaires over the follow-up. As questions changed across questionnaires, we created a time-varying latent PA (LPA) variable using latent process mixed models. PD was ascertained using a multistep validation process based on medical records or a validated algorithm based on drug claims. We set up a nested case-control study to examine differences in LPA trajectories using multivariable linear mixed models with a retrospective timescale. Cox proportional hazards models with age as the timescale and adjusted for confounders were used to estimate the association between time-varying LPA and PD incidence. Our main analysis used a 10-year lag to account for reverse causation; sensitivity analyses used 5-, 15-, and 20-year lags.ResultsAnalyses of trajectories (1,196 cases and 23,879 controls) showed that LPA was significantly lower in cases than in controls throughout the follow-up, including 29 years before diagnosis; the difference between cases and controls started to increase ∼10 years before diagnosis (p interaction = 0.003). In our main survival analysis, of 95,354 women free of PD in 2000, 1,074 women developed PD over a mean follow-up of 17.2 years. PD incidence decreased with increasing LPA (p trend = 0.001), with 25% lower incidence in those in the highest quartile compared with the lowest (adjusted hazard ratio 0.75, 95% CI 0.63-0.89). Using longer lags yielded similar conclusions.DiscussionHigher PA level is associated with lower PD incidence in women, not explained by reverse causation. These results are important for planning interventions for PD prevention.