Characterizing progressive cortical thinning in multiple system atrophy: a longitudinal MRI study

Longitudinal cortical involvement in Multiple System Atrophy (MSA) remains poorly investigated, as the disease is classically characterized by infratentorial and striatal atrophy. In this study, we characterized the longitudinal progression of cortical thinning in MSA, together with subcortical atrophy, using MRI. We studied 36 clinically diagnosed patients (25 cerebellar, 11 Parkinsonian variant) who underwent T1-weighted MRI at baseline and follow-up (median 0.96 years; interquartile range 0.20). Images were processed with state-of-the-art neuroimaging tools. Longitudinal changes in cortical thickness were assessed using linear mixed-effects models within anatomical (Desikan-Killiany) and functional (Schaefer) cortical parcellations, while volumetric changes were evaluated in subcortical and infratentorial regions using the same statistical framework. Patients exhibited progressive cortical thinning affecting motor, frontal, cingulate and insular regions, with involvement of functional networks including the somatomotor, default mode, frontoparietal and salience/ventral attentional networks (all Bonferroni-corrected, p ≤ 0.001). Over the 1-year time span, subcortical and infratentorial regions, including the pons, putamen, cerebellar gray and white matter, showed significant volume loss (Bonferroni-corrected, p ≤ 0.001) and these changes were more marked than the observed cortical thinning. No significant associations were observed between regions showing thinning over time and disease severity or duration. Our results provide a comprehensive longitudinal characterization of distributed cortical thinning, consistent with the view of MSA as a multisystem disorder extending beyond the infratentorial and subcortical degeneration.