Alcohol-induced brain damage associated with genetic variations

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Matsushita S1, Matsui T2, Higuchi S1

1 National Hospital Organization Kurihama Medical and Addiction Center, Kanagawa, Japan

2 Oouchi Hospital, Tokyo, Japan


Although cognitive decline is common in patients with alcohol use disorder (AUD), brain damage associated with symptomatic differences and genetic variations in MRI scans have not been fully explored in patients with AUD. We examined a large population of consecutively recruited Japanese men with AUD, classified into two groups: Korsakoff amnestic syndrome group (KS) and cognitively normal patients with AUD (ALN) and compared with age-matched control group. We conducted voxel-based morphometry (VBM) analyses of gray matter and statistical parametric mapping (SPM) to compare brain damage among these groups. The VBM showed that the affected brain regions were larger in the KS group than in the ALN group. The affected regions included the frontal lobe and cerebellum in both groups. In the KS group the insular, limbic, and thalamic regions showed distinct or graded brain atrophy, with enlargement of the third ventricle.

Furthermore, to clarify the effect of genetic variations of aldehyde dehydrogenase-2 (ALDH2) gene on the brain, comparisons were made between AUD patients with the ALDH2*2/*1 genotype and those with the ALDH2*1/*1 genotype. VBM analysis revealed that hippocampal and parahippocampal atrophy was more severe in the ALDH2*2/*1 group than in the ALDH2*1/*1 group suggesting that alcohol and acetaldehyde cause brain damage differently.

In conclusion, cognitive decline in patients with AUD appears to be associated with the interruption of complex limbic-diencephalic circuits and may result from subclinical Wernicke’s encephalopathy as a common disease entity, and alterations in alcohol metabolism by the ALDH2*2 allele may promote hippocampal and parahippocampal atrophy in AUD patients.