REM sleep behavior disorder: from dreams to neurodegeneration

Abstract

REM sleep behavior disorder is a unique parasomnia characterized by dream enactment behavior during REM sleep. Unless triggered by pharmacologic agents such as antidepressants, it is generally related to damage of pontomedullary brainstem structures. Idiopathic REM sleep behavior disorder (RBD) is a well-established risk factor for neurodegenerative disease. Prospective studies have estimated that at least 40-65% of patients with idiopathic RBD will eventually develop a defined neurodegenerative phenotype, almost always a 'synucleinopathy' (Parkinson's disease, Lewy Body dementia or multiple system atrophy). In most cases, patients appear to develop a syndrome with overlapping features of both Parkinson's disease and Lewy body dementia. The interval between RBD onset and disease onset averages 10-15 years, suggesting a promisingly large window for intervention into preclinical disease stages. The ability of RBD to predict disease has major implications for design and development of neuroprotective therapy, and testing of other predictive markers of synuclein-mediated neurodegeneration. Recent studies in idiopathic RBD patients have demonstrated that olfaction, color vision, severity of REM atonia loss, transcranial ultrasound of the substantia nigra, and dopaminergic neuroimaging can predict development of neurodegenerative disease.