The Many Faces of REM Sleep Behavior Disorder. Providing Evidence for a New Lexicon

Background: People with idiopathic/isolated REM sleep behavior disorder (iRBD) are highly heterogeneous, showing mild motor, cognitive, and dysautonomia symptoms. The aim of this study is to unveil the clinical heterogeneity of iRBD with a specific reference to overlapping features with prodromal Parkinson's disease (pPD) and prodromal dementia with Lewy bodies (pDLB) labels. Methods: People with a polysomnography-confirmed diagnosis of iRBD were enrolled and followed over time. At baseline, pPD and pDLB criteria were assessed. Results: Among the 285 iRBD people (68.2 ± 7.6 years, 81% males), due to additional signs or symptoms, 49.8% fulfilled pPD criteria only, 5.6% pDLB criteria only, and 14.4% subjects fulfilled both pPD and pDLB criteria. Conversely, about one third of iRBD people (30.2%) did not meet either pPD or pDLB criteria. At follow-up (40.6 ± 43.6 months), 28.8% subjects phenoconverted, developing PD (56.1%), DLB (39%), or multiple system atrophy (4.9%). Subjects with iRBD fulfilling either pPD or pDLB criteria, or both, have an increased risk of phenoconversion (adjusted hazard ratio, aHR 2.34, 95% confidence interval, CI 1.24-4.41). On the opposite, subjects not fulfilling prodromal criteria have a significantly reduced short-term phenoconversion likelihood (aHR 0.43, 95% CI 0.23-0.81). Notably, pPD and pDLB criteria did not predict PD and DLB diagnoses, respectively. Conclusions: People with iRBD are highly heterogeneous, and the presence of other concomitant signs and symptoms is frequent, leading to faster phenoconversion. Thus, the terms idiopathic and isolated may be poorly appropriate and possibly even confounding. These results pave the way to a more appropriate new lexicon for people with RBD.