Rapid eye movement sleep behavior disorder as a biomarker for neurodegeneration: the past 10 years

Since its original description, idiopathic rapid eye movement sleep behavior disorder (RBD) has become a well-established risk factor for neurodegenerative disease. Studies from sleep centers have found that at least 40-65% of patients with idiopathic RBD will develop a defined neurodegenerative phenotype over 10 years. This elevated risk of neurodegeneration has been recently confirmed in a population-based study of probable RBD. When a defined syndrome develops, it is almost always a 'synucleinopathy' (Parkinson's disease, Dementia with Lewy Bodies or multiple system atrophy). Often, manifestations of parkinsonism and cognitive impairment overlap. The ability of RBD to predict disease has major implications for development of neuroprotective therapy. First, RBD is a prodromal marker with a disease risk sufficiently high for design of neuroprotective trials. Second, study of idiopathic RBD allows prospective testing of other predictive markers of neurodegeneration. Third, it allows an unprecedented direct examination of the evolution of prodromal disease into defined neurodegenerative syndromes. This review summarizes what is known about the risk of neurodegeneration in idiopathic RBD, the utility of prodromal/predictive markers in synuclein-mediated neurodegeneration, and the evolution of motor and non-motor markers in prodromal stages.