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


To determine whether greater physical activity could modify the negative association of APOE 4 with longitudinal cognitive changes in early Parkinson disease (PD) and to uncover the disease-specific mechanism for explaining such benefits of physical activity.


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 4 allele on the longitudinal changes in MoCA scores and striatal DAT activities.


A total of 173 patients with early PD (age 63.3 ± 10.0 years, 27% APOE 4 carriers) were included. The APOE 4 allele showed a steeper rate of cognitive decline than the non–APOE 4 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 4 such that higher physical activity was related to slower APOE 4-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 4 allele regarding the change in striatal DAT activities.


Increased physical activity attenuated APOE 4-related vulnerability to early cognitive decline in patients with PD. This protective effect did not appear to be mediated by striatal dopaminergic function.

Trial Registration Information Identifier: NCT01141023.

Classification of Evidence

This study provides Class II evidence that increased physical activity was associated with decreased APOE 4-related early cognitive decline in patients with PD.

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