Rotenone, paraquat, and Parkinson's disease

Abstract

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.

Figure 1

Screening process of cases and controls. We identified 170 suspect cases and 644 potential controls and screened 156 (92%) and 542 (84%) of these, respectively. We conducted study evaluations in 137 (88%) of eligible suspect cases (including four initially identified as potential controls who self-reported PD at screening) and 383 (71%) of eligible potential controls. Suspect cases were evaluated in home visits or from medical records, matched controls in home visits. Final diagnoses in suspect cases were PD (115), essential tremor/other tremor disorder (12), no neurologic diagnosis (5), dystonia (2), multiple system atrophy (2), and atypical parkinsonism not fulfilling any diagnostic criterion (1). The latter three cases were subsequently termed “atypical parkinsonism.”