Sex differences in clinical and prognostic trajectories in patients with idiopathic REM sleep behavior disorder: Insights from the FARPRESTO cohort

Introduction There are conflicting findings regarding the influence of sex on idiopathic REM sleep behavior disorder (iRBD) in terms of prevalence and associated clinical characteristics. This study, conducted as part of the Italian multicenter longitudinal FARPRESTO project, aims to explore sex-related differences in the age of onset, iRBD diagnosis, and phenoconversion, as well as in cognitive and non-motor features and the occurrence of RBD-related injuries among male and female patients with iRBD.Methods The FARPRESTO study included 536 iRBD patients recruited from 13 Italian centers. This analysis assessed the age at iRBD diagnosis, diagnostic delay, motor and non-motor symptoms, global cognitive performance, conversion rates to neurodegenerative disorders, and the prevalence of RBD-related injuries at the time of iRBD diagnosis, stratified by sex.Results Female patients were older at iRBD diagnosis compared to males (males: 67.8 years, IQR 62.5-72.6; females: 69.8 years, IQR 65.1-74.8; p = 0.003). Compared to male patients, female patients exhibited a higher prevalence of orthostatic hypotension (27.9% vs. 16.2%; p = 0.019), depression (43.9% vs. 26.6%; p = 0.010), and hallucinations (43.9% vs. 26.6%; p = 0.010) at iRBD diagnosis. Additionally, self-directed injuries were significantly more frequent in females compared to males at the first visit (71% vs. 53.2%; p = 0.034). No significant differences were observed in the phenoconversion rate between sexes.Conclusion Although research on sex-related differences in iRBD remains limited, this study highlights the importance of understanding sex-specific characteristics. As diagnostic and therapeutic approaches evolve, incorporating these differences will be essential for tailoring clinical strategies and improving patient outcomes.