Background: Spinocerebellar ataxia type 3 (SCA3) is a hereditary disease characterized by cerebellar atrophy and motor dysfunction. Patients also exhibit non-ataxic symptoms such as cognitive impairment. While prior neuroimaging studies have identified multiple cognition-associated brain regions in SCA3 patients, research on Papez circuit structural damage (e.g., mammillary bodies (MBs)) remains sparse. Advancements in 7T magnetic resonance imaging (MRI) technology have enabled scanning and quantitative analysis of structures such as the MBs within the Papez circuit. In this study, we investigated the relationship between cognitive impairment in patients with SCA3 and structural changes in the three Papez circuit structures: the MBs, the mammillothalamic tract (MTT), and the post-commissural fornix (PF).
Methods: This cross-sectional study included 46 SCA3 patients and 48 healthy controls undergoing 7T MRI and neuropsychological assessments. Using manual delineation and a deep learning model, we extracted the MB, MTT, and PF volumes from participants. Subsequently, we statistically analyzed the quantitative data.
Results: SCA3 patients exhibited reduced MB, PF, and MTT volumes compared with those of the healthy controls. The MB, left MTT, and left PF volumes were significantly lower in cognitive impairment than in cognitive preserved. Cognitive function in SCA3 patients was positively correlated with the MB, left MTT, and left PF, whereas motor function was negatively correlated with the MB and left PF.
Conclusion: Decreased cognitive and memory function in SCA3 patients is associated with MB, MTT, and PF alterations and is more pronounced on the left side. Motor dysfunction may be correlated with cognitive impairment development.
Keywords: 7T MRI; Papez circuit; cognitive impairment; mammillary body; spinocerebellar ataxia.
© The Author(s) 2025. Published by Oxford University Press on behalf of West China School of Medicine/West China Hospital (WCSM/WCH) of Sichuan University.