Depressive symptoms increase during follow-up and are associated with phenoconversion in isolated REM sleep behavior disorder

Depressive symptoms are common in synucleinopathies, emerging during prodromal stages such as isolated REM sleep behavior disorder (iRBD), yet their association with phenoconversion remains unclear. Among 167 patients with iRBD from the FranceRBD cohort with at least two yearly Hospital Anxiety and Depression Scale (HADS) assessments, we examined the clinical correlates and longitudinal trajectory of depressive symptoms and their association with phenoconversion using linear regression and joint models for longitudinal and survival data. At first assessment, 13% of patients had depressive symptoms (HADS-D > 7), which were associated with apathy, daytime sleepiness, and abnormal visual perception. HADS-D scores progressively increased over time, with a later increase than that observed for apathy. Each additional point in HADS-D score was associated with a 27% higher hazard of phenoconversion (HR 1.27, p < 0.05). These findings suggest that depressive symptoms evolve dynamically across the prodromal phase of synucleinopathies and are associated with phenoconversion, supporting their longitudinal assessment in iRBD.