Parkinson disease and smoking revisited

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. Neurology ® 2014;83:1396-1402 GLOSSARY CI 5 confidence interval; GWAS 5 genome-wide association study; OR 5 odds ratio; PD 5 Parkinson disease.According to epidemiologic studies, patients with Parkinson disease (PD) are less likely to smoke.1-3 Also, those who smoke for longer are at lower risk while lengthening time since quitting increases PD risk, causing some to argue that smoking may protect against PD and even prompting nicotine PD prevention trials. 4 While this is counterintuitive given the otherwise adverse health effects of smoking, common biases including confounding, selection, or measurement error do not explain this finding. Alternatively, the possibility exists that biological mechanisms responsible for PD result in smoking avoidance or the ability to quit smoking more easily among those at risk of developing PD. That is, individuals who develop PD may not experience the positive reinforcement from, and possibly the addictive response to, nicotine many years before motor symptom development, and thus are able to quit more easily than smokers who never develop PD. This distinction is important because smoking may either provide leads for treatment/prevention of PD or be plainly no more than an early marker of insidious PD onset. To explore this, we examined difficulty quitting and use of nicotine substitutes in relation to PD risk in the Danish PASIDA (Parkinson...

Linking Smoking, Coffee, Urate, and Parkinson’s Disease – A Role for Gut Microbiota?

“…Reduced inflammation and gut permeability combined with a decrease in Enterobacteriaceae abundance after smoke exposure fits to the co-occurrence of Escherichia coli invasion, mucosal inflammation, and permeability increase reported in PD [16,52]. Even the abovementioned hypothesis of the inverse association of smoking and PD being explained by certain personality traits or loss of nicotine reward is not in contradiction with an involvement of gut microbiota [11,12]. The gut microbiome influences reward seeking behavior and could therefore influence the propensity to smoke [56].…”

“…It is still unclear whether these molecules are solely responsible for the observed risk reduction. Challenging common interpretations related to neuroprotection, a recent study suggested that the reduced risk of PD in smokers could instead be explained by reverse causation in terms of a greater ease of smoking cessation in the prodromal phase of PD related to the loss of nicotinic rewards [11]. More generally it has been speculated that personality traits associated with PD, in particular low sensation seeking, could be the cause for reduced cigarette smoking and caffeine consumption in subjects later diagnosed with PD [12].…”

Vagotomy and subsequent risk of Parkinson's disease

“…A potential protective effect of smoking has been suggested, 3 but this association has recently been questioned. 4 There are also suggestions of a protective effect of coffee and nonsteroidal anti-inflammatory drugs and increased risk with pesticide exposure. 3,5 The "dual hit" hypothesis for PD development posits that a neurotropic pathogen enters the brain by a nasal and/or gastric route by axonal transport through the vagal nerve.…”

Cancers Preceding Parkinson’s Disease after Adjustment for Bias in a Danish Population-Based Case-Control Study

“…Study details have been described elsewhere [20,29]. Patients over 35 years of age were identified from the Danish National Hospital Register files between 1996 and 2009 at 10 major neurological departments with a PD diagnosis (ICD-10 code: G20) assigned by at least 1 neurologist.…”

“…This still gives no explanation why cancers that are not related to smoking -with a few exceptions -seem also to be under-represented among PD patients. Also, we recently suggested that quitting smoking is an early prodromal symptom signifying a loss of nicotine responsiveness that sets in years before motor symptoms and a PD diagnosis [20]. Similarly, there are other lifestyle-related or biologic factors such as physical activity levels or oestrogen status among women that have previously been associated with the developing PD [21,22] and also affecting cancer risk [23][24][25][26] which may confound PD cancer associations.…”