Pathophysiology of REM sleep behaviour disorder
Nita E Alpin1, Kristijan D Jovanoski1, Pietro-Luca Ratti1,2
1Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, United Kingdom.
Abstract:
REM sleep behaviour disorder (RBD) is a parasomnia characterized by loss of muscle atonia and dream enactment behaviour during REM sleep. RBD is recognized as a significant prodromal marker of α-synucleinopathies, but characterizing its unique neuropathological features is challenging due to reliance on individual case reports. Additionally, RBD is not a terminal illness, and data generalisability is limited by the high co-occurrence of α-synucleinopathies. In this review, we discuss the mechanisms responsible for altered REM sleep regulation in RBD, incorporating evidence from human post-mortem histological analyses, structural and functional neuroimaging data on patients with RBD, and pharmacological studies. We explore the risks, biomarkers, and mechanisms of phenoconversion from RBD to α-synucleinopathies, drawing on data from large longitudinal patient cohorts, and we consider disease remission. Lastly, we propose several promising directions for future studies.
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