Abstract Introduction REM sleep behavior disorder (RBD) is classically considered a prodromal marker of α-synucleinopathies, yet it also occurs in association with other neurological disorders and with antidepressant use. Whether these forms represent clinically and biologically distinct entities remains insufficiently explored. This study aimed to compare multidimensional clinical profiles of idiopathic, antidepressant-associated, and tauopathy-associated RBD. Methods We retrospectively reviewed clinical and video-polysomnographic data of patients hospitalized between 2018 and 2023 with polysomnography-confirmed RBD, excluding individuals with Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy. Patients were classified as idiopathic RBD (iRBD), antidepressant-associated RBD, or tauopathy-associated RBD. Demographic variables, disease duration, sleep-related comorbidities, cognitive status (including Mini-Mental State Examination), depressive symptoms, and neuroimaging findings (vascular damage and cerebral atrophy) were compared across groups using non-parametric statistics. Results Eighty-four patients were included (iRBD n = 45; antidepressant-associated RBD n = 27; tauopathy-associated RBD n = 12). Age at diagnosis did not differ between groups. Male predominance and longer disease duration characterized iRBD. Sleep-related comorbidities, including obstructive sleep apnea and periodic leg movements, were similarly prevalent across groups. Tauopathy-associated RBD showed a markedly higher prevalence of cognitive impairment or dementia, significantly lower MMSE scores, and more frequent and severe cerebral atrophy. Depressive symptoms were most prevalent in antidepressant-associated RBD, whereas vascular neuroimaging findings did not differ among groups. Conclusion RBD encompasses etiologically distinct clinical profiles. Stratification by underlying context reveals meaningful differences in cognitive, psychiatric, and neuroimaging features, with important implications for diagnosis, risk assessment, and clinical management. Support (if any) No specific external funding was received.
Lanza et al. (Fri,) studied this question.