Alcohol, smoking, and brain structure: common or substance specific associations

Abstract

Alcohol use and smoking are common substance-use behaviors with well-established negative health effects, including decreased brain health. We examined whether alcohol use and smoking were associated with the same neuroimaging-derived brain measures. We further explored whether the effects of alcohol use and smoking on the brain were additive or interactive. We leveraged a cohort of 36,309 participants with neuroimaging data from the UK Biobank. We used linear regression to determine the association between 354 neuroimaging-derived brain measures and alcohol use defined as drinks per week, pack years of smoking, and drinks per week × pack years smoking interaction. To assess whether the brain associations with alcohol are broadly similar or different from the associations with smoking, we calculated the correlation between z-scores of association for drinks per week and pack years smoking. Results indicated overall moderate positive correlation in the associations across measures representing brain structure, magnetic susceptibility, and white matter tract microstructure, indicating greater similarity than difference in the brain measures associated with alcohol use and smoking. The only evidence of an interaction between drinks per week and pack years smoking was seen in measures representing magnetic susceptibility in subcortical structures. The effects of alcohol use and smoking on brain health appeared to be additive rather than multiplicative for all other brain measures studied. 97% (224/230) of associations with alcohol and 100% (167/167) of the associations with smoking that surpassed a p value threshold are in a direction that can be interpreted to reflect reduced brain health. Our results underscore the similarity of the adverse associations between use of these substances and neuroimaging derived brain measures.

Figure 1.. Scatter plots of correlation between z-score of association with alcohol vs smoking for brain measures.

Scatter plots to visualize the correlation (Pearson’s product moment correlation, r) between the z-score (beta / se) of association with alcohol (drinks per week) and the z-score of association with smoking (pack years) for each IDP. Dashed grey line represents p = 0.01. Model equation: scaled IDP ~ scaled drinks per week + scaled pack years + scaled drinks per week * scaled pack years + covariates.

Figure 2.. Negative log p value of the interaction term in 354 IDPs

We employed a plot of the negative log of p-values to identify IDPs across all brain measures in which the interaction term reaches any of several levels of statistical significance. We do not find an interaction with p < 0.01 in total brain volume, total grey matter volume, or total white matter volume. IDPs representing magnetic susceptibility from T2* in subcortical structures form a peak.

Figure 3.. Comparison of the relationship between pack years and brain difference in total brain volume vs. left caudate magnetic susceptibility

A) Plot of total brain volume (mm³, normalized) by pack year, stratified by drinks per week. We do not see any evidence of an interaction in which drinks per week affects the association with pack years. B) Plot of magnetic susceptibility in the left caudate (normalized units) by pack year, stratified by drinks per week. In this structure we see evidence of an interaction in which the slope of the relationship with pack years differs depending on drinks per week.