Parkinson disease and smoking revisited：Ease of quitting is an early sign of the disease

[[abstract]]Objective: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being “neuroprotective,” we analyzed information about ease of quitting and nicotine substitute use. Methods: For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders. Results: Fewer patients with PD than controls ever established a smoking habit. Among former smokers, those with greater difficulty quitting or using nicotine substitutes were less likely to develop PD, with the risk being lowest among those reporting “extremely difficult to quit” compared with “easy to quit.” Nicotine substitute usage was strongly associated with quitting difficulty and duration of smoking, i.e., most strongly among current smokers, followed by former smokers who had used nicotine substitutes, and less strongly among former smokers who never used substitutes. Conclusions: Our data support the notion that patients with PD are able to quit smoking more easily than controls. These findings are compatible with a decreased responsiveness to nicotine during the prodromal phase of PD. We propose that ease of smoking cessation is an aspect of premanifest PD similar to olfactory dysfunction, REM sleep disorders, or constipation and suggests that the apparent “neuroprotective” effect of smoking observed in epidemiologic studies is due to reverse causation