Association between lifetime cigarette smoking and lewy body accumulation

Abstract

Cigarette smoking has been associated repeatedly in observational studies with decreased risk of Parkinson's disease (PD), but its relationship to the risk of dementia or Alzheimer's disease (AD) is inconsistent. All of these studies have used clinical diagnoses of disease. We tested the hypothesis that lifetime cigarette use might be associated with reduced risk of neuropathologic changes of Lewy-related pathology (LRP) in multiple brain regions or with reduced risk of consensus neuropathologic changes of AD in a prospective community-based study of brain aging and dementia, the Adult Changes in Thought (ACT) study. We observed that heavy lifetime cigarette smoking (>50 pack years) was associated with significantly reduced relative risk (RR) for LRP, but not AD-type pathologic changes, after correcting for selection bias, and with significantly reduced frequency of LRP in the substantia nigra. These findings are the first of which we are aware to associate reduced LRP in human brain with any exposure, and substantiate observational studies that have associated cigarette smoking with reduced risk of PD. Although cigarette smoking is too toxic to suggest as a treatment, if confirmed, these findings may guide future therapeutic strategies that attempt to suppress LRP in human brain by other means.

Figure 1

Cubic spline estimate and associated pointwise 95% confidence bounds of the association between the probability of Lewy‐related pathology (LRP) and smoking pack years. Observed pack years of smoking by LRP status is indicated below (absence of LRP) and above (presence of LRP) the plot. For ease of visualization, eight subjects with >85.5 pack years of smoking, all of whom were without LRP, are omitted from the plot (but not from estimation of the smoothed association).