Re-investigating the effects of chronic smoking on the pathology of alcohol-related human brain damage.

Both pathological and neuroimaging studies have shown that chronic alcohol abuse causes generalized white matter, but limited gray matter, volume loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals. However, a recent pathological study, employing a manual technique to determine regional volumes, found no significant effects of smoking on either global or selected regional gray matter volumes in smokers or smoking alcoholics. Here a high-resolution computerized method was employed in the same cohort to evaluate four regions where neuroimaging studies have found atrophy in smokers and alcoholics: insula, thalamus, prefrontal cortex, and anterior cingulate cortex. Brain images from 44 cases comprising 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics were quantified. No significant differences between the groups were found, although the alcoholic groups tended to have smaller volumes in most regions. Furthermore, there were no smoking or interactive effects, and no correlation between gray matter volumes and either tobacco pack-years or lifetime alcohol consumption. These results do not support the hypotheses that tobacco smoking causes gray matter loss or that smoking potentiates gray matter atrophy in chronic alcoholics.

The effects of chronic smoking on the pathology of alcohol-related brain damage.

Both pathological and neuroimaging studies demonstrate that chronic alcohol abuse causes brain atrophy with widespread white matter loss limited gray matter loss. Recent neuroimaging studies suggest that tobacco smoking also causes brain atrophy in both alcoholics and neurologically normal individuals; however, this has not been confirmed pathologically. In this study, the effects of smoking and the potential additive effects of concomitant alcohol and tobacco consumption were investigated in autopsied human brains. A total of 44 cases and controls were divided into four groups: 16 non-smoking controls, nine smoking controls, eight non-smoking alcoholics, and 11 smoking alcoholics. The volumes of 26 gray and white matter regions were measured using an established point-counting technique. The results showed trends for widespread white matter loss in alcoholics (p < 0.007) but no effect on gray matter regions. In contrast, smoking alone had no effect on brain atrophy and the combination of smoking and alcohol showed no additional effect. Neuronal density was analyzed as a more sensitive assay of gray matter integrity. Similar to the volumetric analysis, there was a reduction in neurons (29%) in the prefrontal cortex of alcoholics, albeit this was only a trend when adjusted for potential confounders (p < 0.06). There were no smoking or combinatorial effects on neuronal density in any of the three regions examined. These results do not support the hypothesis that smoking exacerbates alcohol-related brain damage. The trends here support previous studies that alcohol-related brain damage is characterized by focal neuronal loss and generalized white matter atrophy. These disparate effects suggest that two different pathogenic mechanisms may be operating in the alcoholic brain. Future studies using ultrastructural or molecular techniques will be required to determine if smoking has more subtle effects on the brain and how chronic alcohol consumption leads to widespread white matter loss.