Linking the cerebellum posterior lobules atrophy to multiple system atrophy cognitive impairment

Cognitive impairments in multiple system atrophy (MSA) are linked to cerebellar dysfunction, but the role of specific posterior cerebellar lobules in domain-specific deficits remains unclear.

Structural MRI and cognitive assessments were conducted in 108 MSA patients (61 MSA-C, 47 MSA-P) and 53 healthy controls. Cerebellar gray matter (GM) volumes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT). Multivariate regression models tested associations between posterior lobule volumes and cognitive domain scores.

MSA patients showed significant GM atrophy in cerebellar subregions VI-VIII compared to controls, with greater reductions in MSA-C than MSA-P. Cognitive deficits were observed in visuospatial function, executive abilities, attention, and working memory across the cohort. Regression analyses revealed distinct patterns: In the overall MSA group, Crus II atrophy predicted visuospatial impairment, while Lobule VIIIa atrophy explained executive dysfunction. In MSA-C, Crus II atrophy remained a significant predictor of visuospatial deficits, but no cerebellar-predictive relationships emerged in MSA-P.

Distinct posterior cerebellar subregions contribute differentially to cognitive profiles in MSA. These findings highlight the role of cerebellar dysfunction in the pathophysiology of cognitive impairment across MSA subtypes.