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Cerebellar Atrophy Modulates Freezing of Gait in Multiple System Atrophy Through Cognitive Dysfunction
Huaguang Yang1, Liang Li1, Zhi Wen1
1Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, China.
CNS Neuroscience & Therapeutics
|July 27, 2026
Summary
Cerebellar atrophy, particularly in Crus II, is linked to freezing of gait (FOG) severity in multiple system atrophy (MSA). Cognitive deficits in executive function and attention mediate this relationship, suggesting cerebellar biomarkers for FOG.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Cerebellar atrophy is common in multiple system atrophy (MSA) and linked to cognitive impairment.
- The role of cognitive dysfunction in causing freezing of gait (FOG) in MSA patients is not well understood.
Purpose of the Study:
- To determine if cognitive deficits mediate the association between cerebellar atrophy and FOG in MSA patients.
- To explore the relationship between specific cerebellar lobule volumes, cognitive domains, and FOG severity.
Main Methods:
- Assessed cognitive function in 106 MSA patients (58 with FOG, 48 without) using neuropsychological tests.
- Utilized MRI scans with FreeSurfer and SUIT for cerebellar lobule segmentation.
- Employed multivariate linear regression and mediation analyses to link cerebellar volumes, cognition, and FOG scores (N-FOGQ).
Main Results:
- MSA patients with FOG showed deficits in executive function, visuospatial ability, attention, working memory, language, and delayed recall.
- Significant global cerebellar and lobule I-X gray matter atrophy was observed in MSA-FOG patients.
- Crus II atrophy independently predicted higher FOG severity, with executive function and attention deficits mediating this link.
Conclusions:
- Reduced Crus II volume may be associated with FOG severity via impaired executive function and attention.
- Cerebellar atrophy, specifically in Crus II, could serve as a potential biomarker for FOG in MSA.
- Cognitive assessment may help elucidate the mechanisms underlying FOG in MSA.
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