Advances in the Understanding of REM Sleep Behavior Disorder as a Biomarker for Neurodegenerative Diseases

REM sleep behavior disorder (RBD) is a well-established prodromal marker of α-synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Over 80% of individuals with isolated RBD (iRBD) eventually phenoconvert to a neurodegenerative disease, making it a valuable target for early diagnosis and intervention. This review highlights advances in the epidemiology, pathophysiology, and clinical features of RBD, and synthesizes evidence from longitudinal studies linking iRBD to phenoconversion risk. Emerging biomarkers—including neurophysiologic, neuroimaging, fluid, tissue, autonomic, cognitive, and genetic markers —enhance risk stratification, track disease progression and provide insight into disease mechanisms. Neuroanatomical and molecular insights support RBD as an early manifestation of synuclein pathology. With growing global research networks and a long prodromal window, iRBD represents an ideal population for neuroprotective trials. Standardization of diagnostic criteria and integration of multimodal biomarkers will be essential to advancing early detection and disease-modifying strategies in α-synucleinopathies.