‘Neuroprotective’ effects of smoking disputed

Oct 22 2014

By Eleanor McDermid, Senior medwireNews Reporter

The apparent neuroprotective effect of smoking may simply be because ease of quitting smoking is a marker of prodromal Parkinson’s disease (PD), say researchers.

Their findings from 1808 PD patients and 1876 matched controls, identified in Danish registries, indicate that former smokers who struggled to quit smoking had a lower risk of PD than those who found it easy to give up.

Patients with PD have reduced numbers of nicotinic acetylcholine receptors in the brain, which may result in them experiencing less reward from nicotine use and finding it easier to quit smoking, explain editorialists Linda Hershey (University of Oklahoma Health Sciences Center, Oklahoma City, USA) and Joel Perlmutter (Washington University, St. Louis, Missouri, USA).

“All of the past smoke about PD may have been a misinterpretation of the data”, they observe.

They stress that neurologists should not recommend smoking as a means to delay or prevent PD and that development of nicotine-based PD therapy may not be justified, given that the “rationale may be faulty.”

In the current study, PD patients were more frequently never-smokers than controls, at 50.3% versus 35.6%. They were also significantly less likely to have high alcohol and caffeine consumption.

Among former smokers (41.5% of patients; 44.4% of controls), those who reported finding it “extremely difficult” to quit smoking were 31% less likely to have PD than those who found it easy. This association was independent of age, age at first motor symptom, gender, education, caffeine and alcohol consumption, degree of urbanisation and family history of PD.

Former smokers who used nicotine substitutes to help them quit were a significant 46% less likely to have PD than those who did not. Nicotine substitutes were 9.6 times more likely to have been used by people who found it extremely difficult to quit than those who found it easy.

“Ease of quitting results in fewer current smokers and a lower number of pack–years smoked among patients with PD and may explain previous epidemiologic findings without the need to invoke a ‘protective’ role of smoking or nicotine”, say Beate Ritz (University of California at Los Angeles School of Public Health, USA) and study co-authors.

The researchers also did bias analyses that showed there would need to be “implausibly strong uncontrolled confounding” to generate an apparent protective effect of smoking on PD risk, indicating that reverse causality is the more likely explanation.

They conclude that ease of quitting smoking is a prodromal marker, similar to constipation and loss of smell, for which there are “very long latency periods and large relative risks for PD”.

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