Update on Rapid-Eye-Movement Sleep Behavior Disorder (RBD): Focus on Its Strong Association with α-Synucleinopathies

Abstract

REM sleep behavior disorder (RBD) is a parasomnia in which the customary generalized skeletal muscle atonia of REM sleep, “REM-atonia”, is compromised, allowing for the injurious acting-out of dreams. RBD can be idiopathic/isolated (iRBD) or symptomatic of neurological disorders, and can be triggered by most antidepressants. RBD mainly affects middle-aged and older adults, and is strongly linked with alpha-synucleinopathies, mainly Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). iRBD is now known to be the earliest and strongest predictor of future PD/DLB, which has stimulated a major international clinical and basic science research effort to enroll iRBD patients for upcoming neuroprotective/disease-modifying trials and to identify the most promising interventions to test in these cohorts. This review will provide the latest pertinent information on the rapidly expanding field of RBD. The methods included a PubMed literature search that included PubCrawlers, which utilizes the NCBI (National Center for Biotechnology Information) E-utils tools for publication retrieval, using the keywords “REM sleep behavior disorder” and “RBD”. The results yielded the latest updates on iRBD as prodromal PD/DLB, with the most promising biomarkers for phenoconversion provided, along with a presentation of three clinical research consortiums that are systematically gathering patients in preparation for enrollment in upcoming clinical trials: (i) The International RBD Study Group; (ii) The North American Prodromal Synucleinopathy (NAPS and NAPS2) Consortium; and (iii) The FARPRESTO Italian multicenter RBD research consortium. In addition, updates on the Parasomnia Overlap Disorder (RBD + NREM parasomnia) and on narcolepsy-RBD are provided, along with new epidemiologic data, the latest RBD management guidelines, and updates on animal models of RBD. Emerging areas of critical RBD research are also highlighted. In conclusion, RBD is a notable example of clinical and translational neuroscience research.