Longstanding disease-free survival in idiopathic REM sleep behavior disorder: Is neurodegeneration inevitable?

Studies estimate that >80% of patients with idiopathic REM sleep behavior disorder (iRBD) eventually develop parkinsonism or dementia. However, a small group remains disease-free for long periods, raising the question of whether they truly have prodromal disease. We selected subjects with iRBD who were diagnosed at least 10 years previously, and were still disease free (longstanding iRBD) (n = 11). We compared them to 'early converters' (n = 27) defined as those who phenoconverted to parkinsonism or dementia within 4 years after diagnosis, and to age- and sex-matched healthy controls (n = 68). We compared the frequency and progression of numerous markers of prodromal synucleinopathy between groups, and assessed likelihood of meeting prodromal Parkinson's disease criteria. After at least 10 years follow-up, almost all longstanding iRBD subjects showed multiple features of neurodegeneration, and 9/11 met criteria for prodromal PD. Evolution of markers was slower than early-converters, with an annual increase in prodromal PD probability of 3.9 ± 3.2% in longstanding iRBD compared to 12.4 ± 7.8% for early-convertors (p-value = 0.002). However, subjects with longstanding iRBD at their last visit had similar prodromal measures as the baseline evaluation of the early-convertors, with similarly-abnormal UPDRS scores, quantitative motor tests, cognition and autonomic symptoms and signs. Although phenoconversion rates can differ dramatically between patients, almost all individuals with iRBD in our cohort appear to have underlying neurodegeneration. •Although the majority of patients with idiopathic REM sleep behavior disorder undergo phenoconversion, there remain long survivors.•Patients’ clinical signs and prodromal neurodegenerative markers are still progressing after >10 years of follow up.•Based on their progression pattern, most longstanding iRBD subjects are still undergoing neurodegeneration.