After reading our recent post, “How to quit smoking, and a challenge to currently-standard individualistic theories in social science,” Gur Huberman writes:
You may be aware that the incidence of Parkinson (PD) is lower in the smoking population than in the general population, and that negative relation is stronger for the heavier & longer duration smokers.
The reason for that is unknown. Some neurologists conjecture that there’s something in smoked tobacco which causes some immunity from PD. Other conjecture that whatever causes PD also helps people quit or avoid smoking. For instance, a neurologist told me that Dopamine (the material whose deficit causes PD) is associated with addiction not only to smoking but also to coffee drinking.
Your blog post made me think of a study that will try to distinguish between the two explanations for the negative relation between smoking and PD. Such a study will exploit variations (e.g., in geography & time) between the incidence of smoking and that of PD.
It will take a good deal of leg work to get the relevant data, and a good deal of brain work to set up a convincing statistical design. It will also be very satisfying to see convincing results one way or the other. More than satisfying, such a study could help develop medications to treat or prevent PD.
If this project makes sense perhaps you can bring it to the attention of relevant scholars.
OK, here it is. We’ll see if anyone wants to pick this one up.
I have some skepticism about Gur’s second hypothesis, that “whatever causes PD also helps people quit or avoid smoking.” I say this only because, from my perspective, and as discussed in the above-linked post, the decision to smoke seems like much more of a social attribute than an individual decision. But, sure, I could see how there could be correlations.
In any case, it’s an interesting statistical question as well as an important issue in medicine and public health, so worth thinking about.
What is the difference between a “social attribute” and an “individual decision?” All individual decisions are made in the context of the social milieu, moderated by individual predispositions. Isn’t Gur’s question just one of interactions between social milieu (“variations…in geography and time”) and individual predispositions (assumed relatively fixed by evolution). The predispositions include both predispositions to smoke and to get PD. The changes in social milieu (which by themselves ought to be PD-independent) help identify the effect of the two predispositions and then allow estimation of a pure smoking effect.
Isn’t this easy, you have countries with higher and lower rates of smoking, just chart smoking rate and incidence of parkenson disease. Quick googling, Chile has one of the highest rates of smoking, and totally average incidence of Parkinsons. I’d check some more countries to be sure but looks people attracked to smoking are less likely to get pk.
This won’t answer the question, you can prove all kinds of things that aren’t true if you do this. You can google “ecological fallacy” and find articles and examples that illustrate the problem.
This seems similar to the birthweight paradox and obesity paradox, where counterintuitive protective health effects were found from maternal smoking during pregnancy and obesity, respectively. However, these observed effects have been proposed to be due to collider stratification bias, when stratifying on an effect shared between two variables induces a spurious statistical relationship. Much better explainers can be found here: https://pubmed.ncbi.nlm.nih.gov/19689488/
https://pubmed.ncbi.nlm.nih.gov/25867852/
Or another way to think of this: generally, incidence of Parkinson’s increases with age (particularly 65+). But we know also smoking is associated with numerous health issues that can impact one’s likelihood of even making it to 65 — heart disease, stroke, diabetes, emphysema, etc. I would find it believable that, at a population level, smokers are more likely to die of other issues before they get to an age at which they would be diagnosed with Parkinson’s. Or smoking-related health issues are more pressing that they mask or supersede symptoms indicative of PD. Nonsmokers might be more likely to get a PD diagnosis just because they don’t have these other competing health issues.
Not sure if this is the right path for this particular paradox, but definitely an interesting question!
Case-control studies (some of them good) have also reported the inverse association of smoking with Parkinson’s. Would these findings address your concern?
I’m probably being dense, but assuming you’re more likely to get PD the older you are, and knowing that smoking kills you sooner, does that not qualitatively explain why smokers would have less PD on average? They even observe that heavier smokers (who die even sooner) have less PD!
Of course you’d need to analyze this quantitatively as well.
Another one would be that COPD and other not-immediately lethal effects of smoking hide the symptoms of PD. So what you have is not less PD, but fewer PD diagnoses. It seems diagnosing PD is a bit of a bear, so it’s actually quite reasonable that smoking effects would block PD diagnosis.
Mendelian randomization is the obvious tool here. There are fairly good PGSes for both nicotine/tobacco and PD, and biobanks might have adequate sample sizes.
In addition to the “not living long enough to get Parkinson’s” hypothesis, there’s also the “get Parkinson’s too severe to smoke a cigarette” hypothesis.
There are a lot of possible pathways to explain this association. For instance, smokers tend to have a lower BMI, and obesity tends to lead to more senescence of dopaminergic neurons. Dopamine deficiency produces Parkinson’s. It would be interesting to see the effects of GLP-1 drugs that do lead to weight loss on Parkinson’s. My point is that correlations between a clinical risk and some behavioral factors are apt to be very complex and hard to tease out. If you start some smoking/Parkinson’s trial, the natural ebb and flow of influenza A infections might smear out your results.
I should add that about twenty-twenty five years ago it was recognized that smoking lowered the severity of ulcerative colitis. There were several randomized trials of nicotine (including nicotine enemas) that did not show benefit. This line of investigation appears to be abandoned.
Transdermal nicotine does seem to help keep patients in remission, however. There’s a Cochrane review about this (McGrath et al, 2010).
Ah, the old “smoking gene”. Wasn’t this Fisher’s idea about smoking and cancer?