Background

Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.

Objectives

Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.

Methods

We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case.

Results

In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7).

Conclusions

PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.

Pesticides have been associated with Parkinson’s disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We examined whether such practices modified the pesticide-PD association. The Farming and Movement Evaluation Study is a case-control study nested within the Agricultural Health Study, a cohort of pesticide applicators (mostly farmers) and their spouses. Use of pesticides, protective gloves, and hygiene practices were determined from structured interviews of 69 neurologist-confirmed cases and 237 matched controls. We considered interactions of glove use and hygiene with ever-use of all pesticides with sufficient exposed cases in each category of glove use (permethrin, trifluralin, rotenone, and paraquat). 61% of respondents used gloves more than half the time and 87% used 2 or more hygiene practices. Both permethrin and paraquat were associated with PD among people who did not wear protective gloves (permethrin odds ratio (OR) 4.3 [95% confidence interval (CI) 1.2, 15.6], paraquat OR 3.9 [95% CI 1.3, 11.7]), but not among people who did (permethrin OR 0.8 [95% CI 0.3, 2.4], paraquat OR 1.3 [95% CI 0.5, 3.9]; permethrin interaction p = 0.05, paraquat interaction p = 0.15). Rotenone was associated with PD regardless of glove use, although the association was stronger among those not using gloves. Trifluralin was associated with PD among people with <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]), but not among people with =2 practices (OR 0.6 [95% CI 0.3, 1.3], interaction p=0.03). Hygiene did not modify the association of the other pesticides with PD. All of the commonly used agricultural pesticides studied here were associated with PD after accounting for the modifying effects of protective gloves and/or hygiene practices. PD risk associated with pesticides might be reduced by the use of protective gloves and improved workplace hygiene.