Sleep · 2026
Long-term cognitive trajectories in isolated REM sleep behavior disorder: effects of sex and longstanding disease duration.
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Hong Jung Kyung, Han Ji Won, Kim Jong-Min, Ahn Soyeon, Yoon In-Young
Аннотация
STUDY OBJECTIVES: The long-term trajectory of cognitive changes in isolated REM sleep behavior disorder (iRBD) remains unclear. Increasing evidence suggests potential heterogeneity in disease progression.
METHODS: People who maintained an iRBD diagnosis without phenoconversion for at least 5 years were included in this study. Cognitive changes over time were assessed using linear mixed models. Subgroup analyses were conducted for men and women separately, and for people with longstanding iRBD.
RESULTS: A total of 318 neuropsychological assessments from 162 people with iRBD (28% women) were analyzed. The mean age at diagnosis was 65.6 years, with an average follow-up duration of 7.7 years. Significant linear declines were observed across attention/working memory and memory domains, with notable decreases in Digit Symbol ($\beta$= -0.084, 95% confidence intervals [CI] -0.102 to -0.066), the Stroop color-naming test ($\beta$= -0.054, 95% CI -0.074 to -0.054), and Word List Recall ($\beta$= -0.054, 95% CI -0.078 to -0.030) as representative examples. In the longstanding-iRBD subgroup (n = 33) and among men, cognitive decline patterns largely mirrored those observed in the full cohort, with significant declines in attention/working memory and memory. In contrast, women exhibited a more restricted decline, limited to digit span forward ($\beta$= -0.055, 95% CI -0.102 to -0.008) and digit symbol ($\beta$= -0.082, 95% CI -0.121 to -0.043).
CONCLUSIONS: 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.
METHODS: People who maintained an iRBD diagnosis without phenoconversion for at least 5 years were included in this study. Cognitive changes over time were assessed using linear mixed models. Subgroup analyses were conducted for men and women separately, and for people with longstanding iRBD.
RESULTS: A total of 318 neuropsychological assessments from 162 people with iRBD (28% women) were analyzed. The mean age at diagnosis was 65.6 years, with an average follow-up duration of 7.7 years. Significant linear declines were observed across attention/working memory and memory domains, with notable decreases in Digit Symbol ($\beta$= -0.084, 95% confidence intervals [CI] -0.102 to -0.066), the Stroop color-naming test ($\beta$= -0.054, 95% CI -0.074 to -0.054), and Word List Recall ($\beta$= -0.054, 95% CI -0.078 to -0.030) as representative examples. In the longstanding-iRBD subgroup (n = 33) and among men, cognitive decline patterns largely mirrored those observed in the full cohort, with significant declines in attention/working memory and memory. In contrast, women exhibited a more restricted decline, limited to digit span forward ($\beta$= -0.055, 95% CI -0.102 to -0.008) and digit symbol ($\beta$= -0.082, 95% CI -0.121 to -0.043).
CONCLUSIONS: 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.