Cigarette Smoking Exacerbates Chronic Alcohol‐Induced Brain Damage: A Preliminary Metabolite Imaging Study

Abstract

Background: Cigarette smoking is common among alcohol‐dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol‐induced brain injury and neurocognition. Methods: Twenty‐four 1‐week‐abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light‐drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short–echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status. Results: Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N‐acetylaspartate (NAA) and frontal choline‐containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four‐group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1‐week‐abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory. Conclusions: These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol‐induced neuronal injury and cell membrane damage in the frontal lobes of RAs and has independent adverse effects on neuronal viability and cell membranes in the midbrain and on cell membranes of the cerebellar vermis. Higher smoking levels are associated with metabolite concentrations in select subcortical structures. Greater consideration of the potential effects of comorbid cigarette smoking on alcohol‐induced brain damage and other diseases affecting the central nervous system is warranted.