Association of Physical Activity and APOE Genotype With Longitudinal Cognitive Change in Early Parkinson Disease

Objective: To determine whether greater physical activity could modify the negative association of APOE ϵ4 with longitudinal cognitive changes in early Parkinson disease (PD) and to uncover the disease-specific mechanism for explaining such benefits of physical activity. Methods: We used data from the Parkinson's Progression Markers Initiative cohort. Because self-reported physical activity, measured by the Physical Activity Scale of the Elderly, was initiated at 2 years after enrollment, this longitudinal analysis was based on assessments performed at years 2, 3, and 4. Cognitive function was measured annually with the Montreal Cognitive Assessment (MoCA). Dopamine transporter (DAT) imaging was performed at years 2 and 4. We assessed the interactive associations between physical activity and the APOE ϵ4 allele on the longitudinal changes in MoCA scores and striatal DAT activities. Results: A total of 173 patients with early PD (age 63.3 ± 10.0 years, 27% APOE ϵ4 carriers) were included. The APOE ϵ4 allele showed a steeper rate of cognitive decline than the non-APOE ϵ4 allele (estimate -1.33, 95% confidence interval [CI] -2.12 to -0.47, p = 0.002). However, there was a significant interaction between physical activity and APOE ϵ4 such that higher physical activity was related to slower APOE ϵ4-related cognitive decline (estimate 0.007, 95% CI 0.003-0.011, p = 0.001). No significant interaction was found between physical activity and the APOE ϵ4 allele regarding the change in striatal DAT activities. Conclusion: Increased physical activity attenuated APOE ϵ4-related vulnerability to early cognitive decline in patients with PD. This protective effect did not appear to be mediated by striatal dopaminergic function.