7T magnetic resonance imaging-based investigation of the correlation between mammillary body structure and cognitive impairment in patients with spinocerebellar ataxia type 3

TL;DR

This study uses 7T MRI to show that structural changes in the mammillary bodies and related brain structures are linked to cognitive impairment in patients with spinocerebellar ataxia type 3.

Contribution

The study is the first to use 7T MRI to investigate Papez circuit structures in SCA3 and their association with cognitive decline.

Findings

SCA3 patients had reduced volumes in mammillary bodies, mammillothalamic tract, and post-commissural fornix compared to healthy controls.

Cognitive impairment in SCA3 was associated with smaller left-side volumes of the mammillary bodies, mammillothalamic tract, and post-commissural fornix.

Cognitive function was positively correlated with these structures, while motor function was negatively correlated.

Abstract

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).

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.

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.

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.

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