Proximity to residential and workplace pesticides application and the risk of progression of Parkinson's diseases in Central California

BACKGROUND: Pesticide exposure has consistently been associated with Parkinson's disease (PD) onset. Yet, fewer epidemiologic studies have examined whether pesticides influence PD motor and non-motor symptom progression. OBJECTIVES: Using a geographic information system tool that integrates agricultural pesticide use reports and land use records to derive ambient exposures at residences and workplaces, we assessed associations between specific pesticides previously related to PD onset with PD symptom progression in two PD patient cohorts living in agricultural regions of California. METHODS: We calculated the pounds of pesticide applied agriculturally near each participant's residential or occupational addresses from 1974 to the year of PD diagnosis, using a geographic information system tool that links the California Pesticide Use Reports database to land use data. We examined 53 pesticides selected a priori as they have previously been associated with PD onset. We longitudinally followed two PD patient cohorts (PEG1 N = 242, PEG2 N = 259) for an average of 5.0 years (SD ± 3.5) and 2.7 years (SD ± 1.6) respectively and assessed PD symptoms using the movement disorder specialist-administered Unified Parkinson's disease Rating Scale part III (UPDRS), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Weighted time-to-event regression models were implemented to estimate effects. RESULTS: Ten agricultural pesticides, including copper sulfate (pentahydrate), 2-methyl-4-chlorophenoxyacetic acid (MCPA) dimethylamine salt, tribufos, sodium cacodylate, methamidophos, ethephon, propargite, bromoxynil octanoate, monosodium methanearsonate (MSMA), and dicamba, were associated with faster symptom progression. Among these pesticides, residential or workplace proximity to higher amounts of copper sulfate (pentahydrate) and MCPA (dimethylamine salt) was associated with all three progression endpoints (copper sulfate: HRs = 1.22-1.36, 95 % CIs = 1.03-1.73; MCPA: HRs = 1.27-1.35, 95 % CIs = 1.02-1.70). CONCLUSIONS: Our findings suggest that pesticide exposure may not only be relevant for PD onset but also PD progression phenotypes. We have implicated ten specific pesticide active ingredients in faster PD motor and non-motor decline.