Abstract
OBJECTIVE: To investigate ethnoracial disparities in gray matter (GM) atrophy, the contribution of white matter lesions and consequent structural disconnectivity among patients with multiple sclerosis (MS). METHODS: This retrospective study included 297 patients with MS (pwMS), 98 Hispanic/Latinx (H-MS), 82 non-Hispanic Black (B-MS), and 117 non-Hispanic White (W-MS). GM atrophy was assessed using univariate, voxel-based morphometry, and multivariate techniques, source-based morphometry. Structural disconnectivity secondary to white matter lesions was evaluated using the network modification tool. Mediation analyses explored relationships between ethnoracial groups, white matter lesions, structural disconnectivity, and gray matter atrophy. RESULTS: B-MS and H-MS generally exhibited greater gray matter atrophy compared to W-MS, particularly in temporal, parahippocampal, precuneus, and cuneus GM. Structural disconnectivity differences were most prominent in the hippocampal, cingulate, precuneus, and deep gray matter regions. Mediation analyses revealed that lesion load significantly mediated group differences in global GM atrophy (percent mediated = 52.4%), while structural disconnectivity mediated some differences in specific gray matter components, notably in deep gray matter, insular, and anterior cingulate regions. INTERPRETATION: Significant ethnoracial disparities exist in GM atrophy and its patterns among diverse MS patients, partially mediated by white matter lesions and consequent structural disconnectivity. These findings underscore the importance of considering ethnoracial factors in MS research and clinical practice, potentially informing personalized treatment strategies and emphasizing the need for diverse representation in clinical trials.