Temporal relationship between cigarette smoking and risk of Parkinson disease

Abstract
Objective: To characterize further the relationship between smoking history and Parkinson disease (PD) risk by considering temporal and qualitative features of smoking exposure, including duration, average intensity, and recentness, as well as the relative importance of smoking during different periods of life. Methods: We prospectively assessed incident PD from 1992 to 2001 among 79,977 women and 63,348 men participating in the Cancer Prevention Study II Nutrition Cohort, according to their cigarette smoking status and lifetime smoking histories. Results: During follow-up, 413 participants had definite or probable PD confirmed by their treating neurologists or medical record review. Compared with never smokers, former smokers had a relative risk (RR) of 0.78 (95% CI 0.64 to 0.95) and current smokers had an RR of 0.27 (95% CI 0.13 to 0.56). On average, participants with more years smoked, more cigarettes per day, older age at quitting smoking, and fewer years since quitting smoking had lower PD risk. The relative risks and trends did not vary significantly by sex. The cumulative incidence of PD was lowest among participants who quit smoking at later ages. A 30% to 60% decreased risk of PD was apparent for smoking as early as 15 to 24 years before symptom onset, but not for smoking 25 or more years before onset. Conclusions: The lower risk of Parkinson disease among current and former smokers varied with smoking duration, intensity, and recentness. The dependence of this association on the timing of smoking during life is consistent with a biologic effect.