Rapid Eye Movement Sleep Behavior Disorder as a Prodromal Manifestation of Alpha-Synucleinopathies

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia in which patients physically act out their dreams due to loss of the normal muscle paralysis that occurs during REM sleep.It is now recognized that isolated RBD (iRBD) is strongly associated with future development of α-synuclein-related neurodegenerative diseases, including Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).It is seen that most patients with polysomnography-confirmed iRBD eventually develop a clinically defined synucleinopathy, often after a long symptom-free interval.This long prodromal phase makes iRBD a unique clinical model for studying the earliest stages of neurodegeneration, before the onset of clear motor or cognitive disability.α-synuclein pathology frequently begins in the lower brainstem and autonomic nervous system, affecting REM sleep regulatory circuits early in the disease process.As pathology spreads, dopaminergic, cholinergic, and cortical systems become involved, leading to the gradual emergence of motor, autonomic, and cognitive symptoms.As a result, many individuals with iRBD exhibit subtle non-motor features such as hyposmia, constipation, orthostatic hypotension, anxiety, and mild cognitive changes years before a formal neurological diagnosis is made.Recent advances have improved the ability to identify patients at the highest risk of near-term phenoconversion.Quantitative measures of REM sleep without atonia, dopamine transporter imaging, autonomic testing, and emerging molecular biomarkers, including α-synuclein seed amplification assays, have shown promise in risk stratification.In addition, cognitive changes may occur earlier than previously recognized, particularly in patients with iRBD who also demonstrate hyposmia or dopaminergic dysfunction.Management of RBD remains largely symptomatic and focuses on injury prevention and sleep stabilization.While clonazepam and melatonin remain first-line therapies, alternative treatments including sodium oxybate, serotonergic agents, cannabinoids, and modulation of the gut-brain axis through probiotic supplementation have also been explored.This narrative review summarizes current knowledge regarding the clinical features, mechanisms, biomarkers, and management of RBD as a prodromal manifestation of α-synucleinopathies, with emphasis on its importance for early diagnosis and future disease-modifying research.