Isolated REM sleep behavior disorder (iRBD) is strongly associated with synucleinopathies. Previous iRBD cohort studies have primarily focused on older (>50 years), male-predominant cohorts. Risk of phenoconversion in women and younger adults remains unclear. The study aimed to determine clinical features associated with conversion to a defined neurodegenerative disorder in women and men with iRBD. One hundred eighty-six women and 186 men with iRBD were matched by polysomnography month. Baseline clinical variables and subsequent neurodegenerative outcomes were abstracted by chart review. Kaplan-Meier curves assessed conversion rates. Cox proportional hazards modeling evaluated factors associated with phenoconversion risk. Age at iRBD diagnosis was younger in women compared with men (54.9 vs 62.5 years, p < 0.01). Forty-eight patients (12.9%), including 18 women (9.7%) and 30 men (16.1%), phenoconverted during a median follow-up of 6.0 years. Conversion rates were lower in antidepressant users and patients with chronic pain or psychiatric comorbidity while rates were higher in those with vascular comorbidity. Only age at diagnosis (HR 1.09, 95% CI 1.06-1.13) was associated with phenoconversion after adjusting for RBD symptom duration; sex; antidepressant use; and psychiatric, chronic pain, and vascular comorbidities. Age at diagnosis was independently associated with phenoconversion risk in women and men with iRBD.
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