Posterior cerebellar degeneration associates with executive dysfunction in multiple system atrophy: a voxel-based and atlas-based morphometric study

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Background: Executive dysfunction is frequently observed in multiple system atrophy (MSA), yet its neuroanatomical substrates remain incompletely characterized. Emerging evidence suggests that the cerebellum contributes to higher cognitive functions beyond motor control. Objective: To investigate structural cerebellar alterations associated with executive dysfunction in patients with MSA using complementary voxel-based and atlas-based morphometric analyses. Methods: In this case-control study, 27 patients with clinically established MSA and 19 age-matched healthy controls underwent 3D T1-weighted MRI. Voxel-based morphometry and subsequent atlas-based cerebellar volumetry were performed to identify regional brain volume differences between groups, adjusting for age, sex, total intracranial volume, and MSA clinical subtype (MSA-P vs. MSA-C). Executive function was assessed with the Frontal Assessment Battery (FAB). Partial correlations between regional cerebellar volumes and FAB scores were examined within the MSA group. Results: Compared with healthy controls, patients with MSA showed significant gray matter volume reductions in the bilateral putamen and cerebellar cortex, as well as white matter reductions extending from the brainstem to the middle cerebellar peduncles. Atlas-based analyses demonstrated reduced normalized volumes in bilateral cerebellar white matter and left vermian VIIIA, whereas larger volumes were observed in bilateral vermian Crus II and left lobule IV. Within the MSA group, FAB scores showed nominal positive associations with left VIIIB, bilateral VIIIA, and right vermis IX volumes, without surviving multiple-comparison correction. Conclusions: Posterior cerebellar degeneration may be related to executive dysfunction in MSA. These exploratory findings warrant validation in larger longitudinal studies with detailed cognitive and motor assessments.

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