Rapid eye movement sleep behavior disorder as a model of early neurodegeneration: challenges for research and clinical diagnosis
Year: 2026
Type: review
Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) has evolved from a descriptive parasomnia to a clinically informative model for studying early neurodegenerative processes, particularly within the spectrum of α-synucleinopathies. Defined by the loss of REM sleep atonia and the emergence of dream enactment behaviors, RBD reflects dysfunction of brainstem circuits that normally suppress motor output during dreaming. Longitudinal evidence indicates that many individuals with isolated RBD eventually develop neurodegenerative disease, most commonly Parkinson's disease, dementia with Lewy bodies, or, less frequently, multiple system atrophy, positioning RBD among the most specific clinical markers of prodromal synucleinopathy currently recognized. Mechanistic studies suggest that RBD arises from instability within distributed REM sleep regulatory networks involving dopaminergic, noradrenergic, serotonergic, and cholinergic systems. This network dysfunction may precede classic motor and cognitive symptoms and can be accompanied by early abnormalities in neurophysiology, imaging, cognition, olfaction, autonomic function, and molecular biomarkers. These findings support a model in which RBD may represent one of the earliest clinically accessible manifestations of a multisystem neurodegenerative process, although anatomical origin, propagation patterns, and phenoconversion trajectories vary across patients. Despite these advances, clinical management remains largely symptomatic, and key challenges persist in diagnosis, risk stratification, prognostic counselling, and therapeutic development. A broader clinical framework is therefore needed, in which RBD is not viewed solely as an isolated sleep disorder but also as a potential marker of early neurodegeneration in appropriately characterized patients. Integrating polysomnography with multimodal biomarkers and network-based models of disease may refine risk stratification and support the development of targeted interventions at earlier stages of neurodegenerative disease.
Source: Frontiers in Aging Neuroscience
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223117640