Pathophysiology of REM sleep behaviour disorder

Abstract REM sleep behaviour disorder (RBD) is a parasomnia characterised by loss of muscle atonia and dream enactment behaviour during REM sleep. RBD is recognised as a significant prodromal marker of α-synucleinopathies, but characterising 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 postmortem 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.