Predictors of Neurodegeneration in Idiopathic REM sleep behavior disorder: a multicenter cohort study (CCI.003)

Objective: To define neurodegenerative disease risk and predictors of neurodegeneration in a large multicenter cohort of idiopathic REM sleep behavior disorder(RBD). Background: Idiopathic RBD is the strongest known predictor for Parkinson’s disease, dementiawith Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromalneurodegenerative states and to intervene with neuroprotective therapy. For neuroprotective trials, it is essential to accurately estimate neurodegeneration risk and identify predictors of decline. Design/Methods: We combined prospective follow-up data from 21 centers of the International RBD study group. We included patients with polysomnographic-proven RBD, without neurodegenerative disease at baseline, with at least 1 annual prospective follow-up. Each center assessed sleep, motor, cognitive, autonomic and special sensory tests at baseline. We assessed risk of dementia and parkinsonism conversion with Kaplan-Meier analysis. Predictors of conversion were assessed with Cox proportional hazards analysis. Results: 1130 patients from 21 centers were recruited. Mean age was 68.1, 82% were male, and mean follow-up duration was 4.1 years (range=1–19). Depending upon analysis method, the conversion rate to dementia/parkinsonism was 12–18% at 3 years, 24–36% at 5 years, and 51–63% at 10 years. Disease conversion risk was significantly increased with abnormal olfaction(HR=2.6,p Conclusions: This large multicenter study confirms the high rate of conversion from idiopathic RBD to neurodegenerative disease. We established the predictive value of numerous prodromalmarkers, which can be used to stratify patients for neuroprotective trials. Study Supported by: Canadian Institute of Health Research, Fonds de la Recherche Sante Quebec Disclosure: Dr. Postuma hasreceived personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biotie, Roche/Prothena, Teva Neurosciences, Jazz Pharmaceuticals, Novartis Canada, Theranexus, GE HealthCare, . Dr. Iranzo has nothingto disclose. Dr. Hu has nothingto disclose. Dr. Manni has nothingto disclose. Dr. Oertel hasreceived personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Adamas, Desitin, Mundipharma, Novartis, Prothena,UCB. Dr. Oertel hasreceived compensation for serving on the Board of Directors of BiogenIdec , Medigene, Merck Darmstadt, Roche. Dr. Oertel hasreceived research support from Novartis Pharma Germany. Dr. Boeve hasreceived research support from GE Heathcare and Axovant. Dr. Hogl has nothingto disclose. Dr. Arnulf has nothingto disclose. Dr. Arnaldi has nothingto disclose. Dr. Cochen hasreceived personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with LVL medicla, Orkyn, Eole sante and SOS oxygen. Dr. Mollenhauer has nothingto disclose. Dr. Puligheddu has nothingto disclose. Dr. Sonka has nothingto disclose. Dr. Jung has nothingto disclose. Dr. Videnovic hasreceived personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Acorda, and Wilsons Therapeutics. Dr. Provini hasreceived personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Fidia and VandaPharmaceutical. Dr. Dauvilliers has nothingto disclose. Dr. Lewis has nothingto disclose. Dr. Heidbreder has nothingto disclose. Dr. Kunz hasreceived personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Durable, Actelion, Medice. Dr. Pavlova has nothingto disclose. Dr. Montplaisir has nothingto disclose. Dr. Dawson has nothingto disclose. Dr. Pelletier has nothingto disclose. Dr. Gagnon has nothingto disclose. Dr. Santamaria has nothingto disclose. Dr. Barber has nothingto disclose. Dr. Terzaghi has nothingto disclose. Dr. Janzen has nothingto disclose. Dr. St. Louis has nothingto disclose. Dr. Stefani has nothingto disclose. Dr. Nobili has nothingto disclose. Dr. Sixel-Doring has nothingto disclose. Dr. Dusek has nothingto disclose. Dr. Cortelli has nothingto disclose. Dr. Martens has nothingto disclose. Dr. Latreille has nothingto disclose. Dr. Gaig has nothingto disclose. Dr. Trenkwalder has nothingto disclose. Dr. Mahlknecht has nothingto disclose. Dr. Holzknecht has nothingto disclose.