BackgroundMitochondrial 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.ObjectivesOur goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.MethodsWe 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.ResultsIn 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).ConclusionsPD 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.

Findings indicate that infrequent bowel movements are associated with an elevated risk of future PD. Further study is needed to determine whether constipation is part of early PD processes or is a marker of susceptibility or environmental factors that may cause PD.

Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.

Context: Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention.Objective: To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. Design, Setting, and Participants: We conducted the first ever pooled analysis of PD combining individuallevel data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age-and sex-matched risk sets. Main Outcome Measure: Incident PD.Results: We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (Ͼ75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. Conclusions: Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.

Previous studies based on limited exposure assessment have suggested that Parkinson's disease (PD) is associated with pesticide exposure. The authors used data obtained from licensed private pesticide applicators and spouses participating in the Agricultural Health Study to evaluate the relation of self-reported PD to pesticide exposure. Cohort members, who were enrolled in 1993-1997, provided detailed information on lifetime pesticide use. At follow-up in 1999-2003, 68% of the cohort was interviewed. Cases were defined as participants who reported physician-diagnosed PD at enrollment (prevalent cases, n = 83) or follow-up (incident cases, n = 78). Cases were compared with cohort members who did not report PD (n = 79,557 at enrollment and n = 55,931 at follow-up). Incident PD was associated with cumulative days of pesticide use at enrollment (for highest quartile vs. lowest, odds ratio (OR) = 2.3, 95% confidence interval: 1.2, 4.5; p-trend = 0.009), with personally applying pesticides more than half the time (OR = 1.9, 95% confidence interval: 0.7, 4.7), and with some specific pesticides (ORs > or = 1.4). Prevalent PD was not associated with overall pesticide use. This study suggests that exposure to certain pesticides may increase PD risk. Findings for specific chemicals may provide fruitful leads for further investigation.