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Although pesticide exposure has been linked to worse motor symptoms in Parkinson's disease (PD), its associations with non-motor burden and with post-diagnostic progression rate remain unclear. We analyzed two large longitudinal cohorts, PPMI Online (n = 7190) and Fox Insight (n = 2298), using linear mixed-effects models and Cox regression, with supportive triangulation in an EHR cohort. In PPMI Online, pesticide exposure was associated with higher MDS-UPDRS Part II scores (β = 1.97, 95% CI 1.34-2.60), lower PDAQ-15 scores (β = -2.40, 95% CI -3.23 to -1.57), and greater anxiety, daytime sleepiness, and sleep disturbance. Motor and cognition-related estimates were directionally similar in Fox Insight. Time interaction estimates showed no consistent exposure-related differences. Primary Cox models indicated earlier motor milestones in both cohorts and earlier sleepiness and anxiety milestones in the PPMI Online cohort. Co-exposure to more pesticide classes was associated with worse motor function in both cohorts. TriNetX also showed elevated risks across five ICD-coded symptom domains (RRs 1.44-1.87), although these findings should be interpreted cautiously because the outcomes were defined differently. Further longitudinal studies using harmonised exposure assessments and repeated multidomain measures are needed to clarify the relationship between pesticide exposure and symptom trajectories after PD diagnosis.
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