Objective:

To investigate ethnoracial disparities in grey matter (GM) atrophy in multiple sclerosis (MS), and the contribution of white matter lesions and consequent structural disconnectivity.

Background:

Significant ethnoracial disparities were highlighted in different MS outcomes. GM atrophy is a chief correlate of physical disability and cognitive decline in MS.

Design/Methods:

This retrospective study included 297 people with MS (PwMS) divided into 3 self-identified age- and sex-matched groups: 82 Non-Hispanic Black (BA), 117 Non-Hispanic White (WA), 98 Hispanic (HA) PwMS. Included subjects underwent clinical evaluation and magnetic resonance imaging at an academic MS center. We assessed GM atrophy using univariate (voxel-based morphometry) and multivariate (source-based morphometry) techniques, as well as white matter hyperintense lesion burden and distribution. Lesion distributions were used to estimate the consequent structural disconnectivity patterns. Mediation analyses explored the relationships between ethnoracial groups, white matter lesions, structural disconnectivity, and grey matter atrophy.

Results:

The groups did not show significant differences in disease duration (P=0.4), disability severity (P=0.3), clinical phenotype (P=0.2), or disease-modifying therapy (P=0.4). BA and HA exhibited greater global grey matter atrophy compared to WA (P=0.02), particularly in temporal, precuneus, occipital, and cingulate GM. Lesion burden was significantly higher in BA and HA compared to WA (P<0.001), and structural disconnectivity was most prominent in hippocampal, cingulate, precuneus, and deep grey matter regions. Mediation analyses showed that lesion load significantly mediated group differences in global GM atrophy (Percent mediated=52.4%), while structural disconnectivity mediated group differences notably in deep grey matter, insular, and cingulate regions.

Conclusions:

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.