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 significantly worse performance in emotion attribution tasks than females (42.8 ± 8.5 vs 53.1 ± 5.7, p = 0.029). Over time, both sexes showed slightly worsening cognitive performance, with males demonstrating deficits in verbal fluency, visual memory recall, and emotion attribution (p < 0.05). 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.