Rapid eye movement sleep behavior disorder as a model of early neurodegeneration: challenges for research and clinical diagnosis
- 1Department of Physiology, Faculty of Medicine, Laboratory of Regenerative Medicine, National Autonomous University of Mexico, Mexico City, Mexico
- 2División de Neurociencias Clínica, Instituto Nacional de Rehabilitación, Mexico City, Mexico
- 3Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
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.
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BibTeX
@article{guerracrespo2026rapid,
title = {{Rapid eye movement sleep behavior disorder as a model of early neurodegeneration: challenges for research and clinical diagnosis}},
author = {Magdalena Guerra-Crespo and Emmanuel Ortega-Robles and Oscar Arias-Carrión},
journal = {Frontiers in Aging Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnagi.2026.1961735},
url = {https://doi.org/10.3389/fnagi.2026.1961735},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Rapid eye movement sleep behavior disorder as a model of early neurodegeneration: challenges for research and clinical diagnosis
AU - Magdalena Guerra-Crespo
AU - Emmanuel Ortega-Robles
AU - Oscar Arias-Carrión
PY - 2026
DA - 2026/10/21
JO - Frontiers in Aging Neuroscience
DO - 10.3389/fnagi.2026.1961735
UR - https://doi.org/10.3389/fnagi.2026.1961735
AB - 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.
SN - 1663-4365
ER -