REM sleep behavior disorder as a shared motor phenotype: A multidimensional clinical study

REM sleep behavior disorder (RBD) is increasingly recognized as a heterogeneous condition that may arise in different etiological contexts, including an isolated form that is often a prodromal synucleinopathy, antidepressant exposure, and RBD occurring in the context of clinically diagnosed tau-spectrum neurodegenerative syndromes. The aim of this study was to compare clinical, cognitive, neuroimaging, and polysomnographic features of isolated RBD (iRBD), antidepressant-associated RBD (iatroRBD), and tauopathy-associated RBD (tauRBD) associated with Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, or frontotemporal dementia, within a single cohort.

We conducted a retrospective analysis of patients with polysomnographically confirmed RBD evaluated at a tertiary sleep center, excluding individuals with established synucleinopathies. Patients were classified as iRBD (n = 26), iatroRBD (n = 16), or tauRBD (n = 6) based on the current criteria. Demographics, non-motor symptoms, Mini-Mental State Examination (MMSE) scores, neuroimaging reports, and detailed polysomnographic parameters were compared using non-parametric statistics and effect sizes.

Age, age at onset, and disease duration did not differ across groups. Sex distribution showed a significant male predominance in iRBD, with a more balanced distribution in iatroRBD and tauRBD. Cognitive performance differed markedly, with tauRBD patients showing significantly lower MMSE scores than both iRBD and iatroRBD, whereas cognition was largely preserved in the latter groups. Non-motor symptoms, including hyposmia and depressive symptoms, showed limited discriminatory value. Polysomnography revealed selective differences in REM sleep architecture, including reduced REM sleep percentage in tauRBD and prolonged REM sleep latency in iatroRBD, while REM atonia, limb movements, and respiratory parameters were broadly similar.

RBD appears to be a shared motor phenotype that can arise in different etiological contexts. In this cohort, cognitive status, sex distribution, and selected REM sleep features were the most informative contextual markers, whereas history-derived non-motor features available in this retrospective dataset (hyposmia and depressive symptoms) and routine PSG metrics showed limited discrimination.