Physical activity mediates the association between striatal dopamine transporter availability and cognition in Parkinson's disease

Objective: Associations between cognition and nigrostriatal dopaminergic deficits in Parkinson's disease have been documented in the literature, but are incompletely understood. Here we studied the extent to which physical activity mediates the relationship between striatal dopamine transporter availability and global cognition among patients with Parkinson's disease. Methods: Data from 174 patients from a multi-center study were analyzed using regression-based mediation analysis. Striatal dopamine transporter binding ratio (SBR), Physical Activity Scale for Elderly (PASE), and Montreal Cognitive Assessment (MoCA) were used to evaluate patients' dopamine transporter availability (DAT), physical activity, and global cognition respectively at the time of testing. Confidence intervals (CI) of 95% were established using a bootstrapping approach to test the statistical significance of the direct, indirect (i.e., mediation), and total effects of the mediation model. Results: As hypothesized, the positive mediating effect of physical activity in the association between DAT and global cognition was significant, while adjusting for age (95% CI [0.0030, 0.3942]). Specifically, higher SBRs were positively associated with PASE scores, which in turn, were positively associated with MoCA scores. Secondary analyses revealed a similar positive mediation effect of physical activity for DAT in the caudate and putamen separately (95% CI [0.0377, 0.4231] and [0.0211, 1.1000], respectively). Conclusion We report that the relationship of dopamine transporter availability with global cognition in Parkinson's disease is mediated by physical activity. Pending further research for specific recommendations, interventions to increase physical activity as tolerated should be considered in patients with Parkinson's disease.