Can Nicotine be Used Medicinally in Parkinson's Disease?

Claire Thiriez; Gabriel Villafane; Frédérique Grapin; Gilles Fenelon; Philippe Remy; Pierre Cesaro

Disclosures

Expert Rev Clin Pharmacol. 2011;4(4):429-436. 

In This Article

Epidemiology

Physicians working on PD have found nicotine of particular interest since it has been shown that there was less PD among smokers. It was firstly noticed in 1959[6] and more than 50 epidemiological studies have confirmed this observation.[2,4] Some suggested that this association could be due either to a selective mortality of smokers[7] (as PD affects more middle-aged and elderly people), to the disease affecting smoking habits or to a reporting bias. However, a case–control study[8] with 350 PD patients and 350 matched controls showed a relative risk of 0.52, with an intermediate risk for people who had quit. Furthermore, huge prospective cohort studies[9,10] brought even more credibility to the hypothesis of a protective role of smoking in PD. A pooled analysis confirmed the negative association between PD and smoking that was more pronounced for current smokers than for former ones;[11] it also showed that there was a dose–response, with the ratio decreasing when the pack-years increase, and that other forms of tobacco also had this effect. Even passive smoking seems to be less frequent in PD than in controls.[12] Duration of smoking also seems to be more important than intensity.[13] A study in twin pairs in which at least one twin had PD found the same negative correlation: the twins without PD smoked significantly more than their brothers, even when smoking dose was calculated only until 10 years before PD onset;[14] this argued against a genetic and behavioral hypothesis, as a link between genetical propensity to smoke and susceptibility to PD. A recent review on nicotine addiction suggested a potential interaction between multiple small-effect alleles and the environment.[15]

The risk of developing PD in a cohort was 27% lower when both parents were smokers;[16] but when the research was restricted to never-smokers, the correlation was no longer seen. The effect of parental smoking on susceptibility of PD was probably due to the higher proportion of smokers in offspring when parents smoke.

As a study showed that this negative correlation was not found in the elderly,[17] the hypothesis was that smoking could delay the onset of PD. However, age at onset seemed to be the same in both populations of smokers and nonsmokers.[17,18] In addition, a study found no significant differences in progression of Parkinsonism, cognitive impairment and mood between smoking and nonsmoking PD patients.[19]

The demonstration that there is a negative correlation between smoking and PD is of great interest as it may point to potential protective strategies for PD. However, there are numerous components in cigarette smoke that may contribute to this apparent neuroprotective effect. Interestingly, evidence using Parkinsonian animal models suggest that the nicotine in tobacco may play a role. Long-term studies in PD patients are now required to address this issue.

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