Cognitive performance deteriorates with drinking. However, the neural basis of cognitive deficits in alcohol use disorder (AUD) is still incompletely understood. Here we examined the relationship between overall drinking, brain structural alterations and cognitive deficits in AUD. A total of 40 middle-aged AUD males and 40 healthy controls (HC) underwent high-resolution anatomical imaging scans, and the data were analyzed using voxel-based morphometry, support vector machine (SVM) classification and mediation analysis. The AUD patients demonstrated reduced gray matter (GM) volumes that included left amygdala, thalamus, hippocampus, precentral gyrus, cerebellum, calcarine, right supplementary motor area and bilateral superior temporal gyri (voxel-wise p < 0.05, FWE corrected). The SVM results could distinguish AUD from HC with satisfactory classification results (0.8275). GM volumes in the bilateral cerebellum and thalamus, left anterior medial temporal lobe, left nucleus ambiguus + parahippocampus gyrus, left fusiform gyrus, left lingual gyrus, left hippocampus, and right nucleus accumbens had positive correlations with the Montreal Cognitive Assessment (MoCA) scores. Further mediation analysis showed that left cerebellum crus 1 partially mediated the relationship between overall drinking and MoCA scores (standardized beta coefficient = −0.0973, SE = 0.0002, 95% CI = (−0.0006, 0.0000)). Our findings showed widespread GM atrophies and many of these atrophies also mirrored cognitive deficits and were robustly distinguishable. Critically, the left cerebellum crus 1 partially mediated the relationship betweem overall drinking and MoCA scores, suggesting a pathway by which alcohol abuse impairs cognition and accelerates brain ageing in middle-aged AUD males.

饮酒会导致认知能力下降。然而，酒精使用障碍 (AUD) 认知缺陷的神经基础仍未完全了解。在这里，我们检查了整体饮酒、大脑结构改变和 AUD 认知缺陷之间的关系。共有 40 名中年 AUD 男性和 40 名健康对照者 (HC) 接受了高分辨率解剖成像扫描，并使用基于体素的形态计量学、支持向量机 (SVM) 分类和中介分析对数据进行了分析。AUD 患者表现出灰质 (GM) 体积减少，包括左侧杏仁核、丘脑、海马、中央前回、小脑、距突、右侧辅助运动区和双侧颞上回（体素水平p < 0.05，FWE 校正）。SVM 结果可以将 AUD 与 HC 区分开来，分类结果令人满意（0.8275）。双侧小脑和丘脑、左侧前内侧颞叶、左侧模糊核+海马旁回、左侧梭状回、左侧舌回、左侧海马和右侧伏隔核的GM体积与蒙特利尔认知评估（MoCA）评分呈正相关。进一步的中介分析表明，左小脑小腿 1 部分介导了整体饮酒与 MoCA 评分之间的关​​系（标准化 β 系数 = -0.0973，SE = 0.0002，95% CI = (-0.0006, 0.0000)）。我们的研究结果显示广泛的 GM 萎缩，其中许多萎缩也反映了认知缺陷，并且具有很强的可区分性。至关重要的是，