Alzheimer's Co‐Pathology Burden on Basal Forebrain Atrophy and Cognitive Impairment in Dementia with Lewy Bodies: A Cross‐Sectional Pilot Study

Objective Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease (AD), with significant pathological overlap between the two conditions. However, the impact of Alzheimer's co‐pathology on basal forebrain (BF) atrophy and its relationship with neurodegeneration and cognitive decline in patients with DLB remains underexplored. Methods Forty patients with DLB and 14 healthy controls (HCs) were included from the Centre for Neurodegenerative Diseases, University of Bari. Participants underwent neuropsychological evaluations, 3T magnetic resonance imaging (MRI) scans, and Alzheimer's biomarkers assessment. Patients with DLB were grouped by AD co‐pathology using in vivo biomarkers. BF and hippocampal volumes and mean cortical thickness values were analyzed using analysis of covariance (ANCOVA), adjusted for age, sex, and total intracranial volume. Mediation analyses were conducted to examine the indirect effects of Alzheimer's pathology and BF atrophy on neurodegeneration (hippocampal volume and cortical thickness) and cognitive function (Mini‐Mental State Examination [MMSE]). Results Patients with DLB exhibited significant BF atrophy compared with HCs ( p < 0.001). AD co‐pathology was associated with greater BF atrophy ( p = 0.046) and reduced mean cortical thickness ( p = 0.025). Significant correlations were found between BF volume and the pTAU 181 /Aβ 1−42 ratio ( p = 0.009) and between BF volume and MMSE scores ( p = 0.016). Mediation analysis revealed that BF atrophy mediated the relationship between the pTau/Aβ42 ratio and neurodegeneration, and that the BF has a direct association with cognitive impairment. Interpretation AD co‐pathology in DLB exacerbates BF atrophy, correlating with cognitive decline. These results emphasize the need to consider AD co‐pathology in evaluating neurodegeneration in DLB, suggesting future studies should explore targeted interventions to address this pathological overlap. ANN NEUROL 2026