Long-term cognitive trajectories in isolated REM sleep behavior disorder: effects of sex and longstanding disease duration

Gradual cognitive decline in attention/working memory and memory may represent a natural course of neurodegeneration in men with iRBD, without necessarily indicating imminent phenoconversion. Women with iRBD appeared to show greater resilience to cognitive decline compared to men. Statement of Significance Cognitive impairment is common in isolated REM sleep behavior disorder (iRBD) and is considered a potential marker of phenoconversion to overt neurodegenerative disorders, such as Parkinson's disease or dementia with Lewy bodies. This study, overcoming prior limitations of short follow-up and small samples, provides long-term data demonstrating a gradual decline in attention/working memory and memory domains among people with iRBD. It also reveals sex-specific vulnerability, with men showing more pronounced decline than women, and confirms that even people with longstanding iRBD experience cognitive deterioration over time. These findings highlight the need for sex-specific approaches when monitoring cognitive progression in iRBD, and future studies should map distinct cognitive-decline trajectories to subsequent phenoconversion risk and clarify the mechanisms underlying the observed sex differences.