Volumetric and Cortical Thickness Alterations in Alcohol Dependence: Evidence of Accelerated Brain Aging and Clinical Correlations

Abstract

Background: Chronic alcohol dependence is associated with structural brain changes that resemble premature aging, particularly in frontal, parietal, and subcortical regions. This study examined brain volume, cortical thickness, and brain-predicted age in individuals with alcohol dependence and assessed associations with clinical symptoms. Methods: Thirty-one alcohol-dependent patients (mean age = 37.8 +/- 7.3 years) and 26 age-matched healthy controls (mean age = 35.0 +/- 8.5 years) underwent high-resolution T1-weighted MRI scanning. Brain structural analyses, including regional volumetry and cortical thickness estimation, were conducted using the validated volBrain platform. The system also provided individualized brain-predicted age estimates via its machine learning-based Brain Structure Ages (BSA) pipeline. Clinical assessments included the Michigan Alcoholism Screening Test (MATT), Penn Alcohol Craving Scale (PENN), Beck Depression and Anxiety Inventories (BDI-II, BAI), and detailed alcohol use history. Results: Alcohol-dependent participants showed significant reductions in total white matter, right frontal lobe, inferior frontal gyrus, bilateral postcentral gyri, and left superior occipital gyrus volumes (p < 0.05), along with widespread cortical thinning. Brain-predicted age was on average 11.5 years greater in patients than in controls (p < 0.001), especially in white matter and basal ganglia structures. Higher MATT scores correlated with reduced right precentral gyrus and left caudate volumes. PENN scores were positively associated with occipital volumes; however, this association weakened after controlling for age. Depression was linked to reduced frontal pole and increased amygdala volume, while anxiety was associated with smaller orbitofrontal and angular gyrus volumes. Conclusions: Alcohol dependence is marked by diffuse brain atrophy and accelerated brain aging. Structural alterations correspond to addiction severity, craving, and mood symptoms, highlighting brain-predicted age as a potential biomarker of cumulative alcohol-related neurodegeneration.