Sex Differences in Spinocerebellar Ataxia Type 1: Clinical Presentation and Progression

Background: Spinocerebellar ataxia type 1 (SCA1) is characterised by motor and cognitive symptoms. Sex-specific differences in disease presentation and progression remain poorly understood. This study investigates the role of sex in clinical-demographic and motor/cognitive outcomes in SCA1. Methods: This single-centre, longitudinal observational cohort study was conducted at the University Hospital of Ferrara between 2021 and 2024. Consecutively, genetically confirmed SCA1 patients were evaluated at baseline and after 24±6 months. Assessments included comprehensive neuropsychological testing and auditory event-related potentials (aERPs). Motor function was evaluated using the Scale for Assessment and Rating of Ataxia (SARA). Results: Sixteen SCA1 patients (9 males, seven females) were evaluated at baseline, with 10 patients (5 males, five females) completing follow-up. Even if most cognitive functions were preserved in both sexes at baseline, males showed worse performance in emotion attribution tasks than females (42.8 ± 8.5 vs. 53.1 ± 5.7, r = 0.63). Over time, both sexes showed slightly worsening cognitive performance, although not statistically significant, with males demonstrating deficits in verbal fluency (p = 0.036) and emotion attribution (p = 0.048). In the same group, motor impairment worsened at follow-up, though not significantly. aERPs revealed no differences between sexes at follow-up. Conclusion: Sex may influence cognitive outcomes in SCA1, with male patients showing greater vulnerability to cognitive decline. aERPs did not show significant modifications. These findings highlight the importance of considering sex-specific approaches in the clinical management of SCA1 patients and the higher values of a comprehensive neuropsychological assessment compared to the neurophysiological approach with aERPs to reach these slight changes over time. Clinical trial number: Not applicable.