Depressive Symptoms: A Sign of Phenoconversion in Patients with Isolated REM Sleep Behavior Disorder

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Abstract 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 HADS assessments, we examined clinical correlates 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 clinically significant depressive symptoms (HADS-D > 7), associated with apathy, daytime sleepiness, and hallucinations. Both apathy and depressive symptoms worsened over time, with apathy increasing earlier and depression only after five years. Each additional point in HADS-D score was associated with a 30% increase in the hazard of phenoconversion (HR: 1.30, p = 0.020), specifically to Parkinson's disease (HR: 1.57, p = 0.013) but not to dementia with Lewy bodies. These findings support depressive symptoms as a meaningful marker of neurodegeneration in iRBD.

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