Smoking is associated with lower brain volume and cognitive differences: A large population analysis based on the UK Biobank

The evidence about the association of smoking with both brain structure and cognitive functions remains inconsistent. Using structural magnetic resonance imaging from the UK Biobank (n = 33,293), we examined the relationships between smoking status, dosage, and abstinence with total and 166 regional brain gray matter volumes (GMV). The relationships between the smoking parameters with cognitive function, and whether this relationship was mediated by brain structure, were then investigated. Smoking was associated with lower total and regional GMV, with the extent depending on the frequency of smoking and on whether smoking had ceased: active regular smokers had the lowest GMV (Cohen's d = - 0.362), and former light smokers had a slightly smaller GMV (Cohen's d = - 0.060). The smaller GMV in smokers was most evident in the thalamus. Higher lifetime exposure (i.e., pack-years) was associated with lower total GMV (beta = - 311.84, p = 8.35 x 10-36). In those who ceased smoking, the duration of abstinence was associated with a larger total GMV (beta = 139.57, p = 2.36 x 10- 08). It was further found that reduced cognitive function was associated with smoker parameters and that the associations were partially mediated by brain structure. This is the largest scale investigation we know of smoking and brain structure, and these results are likely to be robust. The findings are of associations between brain structure and smoking, and in the future, it will be important to assess whether brain structure influences smoking status, or whether smoking influences brain structure, or both.