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. 2016 Jun;53:35-44.
doi: 10.1016/j.alcohol.2016.04.002. Epub 2016 Apr 30.

The Effects of Chronic Smoking on the Pathology of Alcohol-Related Brain Damage

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Free PMC article

The Effects of Chronic Smoking on the Pathology of Alcohol-Related Brain Damage

A N McCorkindale et al. Alcohol. .
Free PMC article

Abstract

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.

Keywords: Alcohol; Brain atrophy; Human postmortem brain; Neuron density; Smoking.

Figures

Fig. 1
Fig. 1. Parcellation of white matter
A medial view of the left hemisphere shows approximate boundaries of WM regions of interest (ROI) explored in the study. A = posterior WM, B = middle WM, C = posterior frontal WM, D = prefrontal WM, and E = temporal WM.
Fig. 2
Fig. 2. Point-counting technique
A transparent counting grid is overlaid across a typical coronal section image of the right hemisphere. Individual crosses are then counted within the various white and grey matter regions. The boundaries between regions of the frontal lobe have been manually drawn (in red).
Fig. 3
Fig. 3. Lifetime smoking and alcohol use and brain atrophy
Scatter plots show the Pearson correlations between cigarette smoking pack-years and (A) total white matter (WM) and (B) total gray matter (GM) volumes, and the correlations between lifetime alcohol consumption and (C) total WM and (D) total GM volumes. Plots generated in JMP® Pro 9.0.0.

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