0791 Cognitive and Motor Wobbling in Isolated RBD: A Multicentric Study by the International RBD Study Group (IRBDSG)

Abstract Introduction Patients with isolated RBD (iRBD) often develop motor and non-motor signs/symptoms before phenoconversion to overt alpha-synucleinopathy. These may wobble for a long time, making the timing of phenoconversion difficult. Although such patients may be called prodromal PD, DLB or MSA, they do not yet fulfil diagnostic criteria for a neurodegenerative disorder. This study aimed at defining and characterizing the clinically fluctuating transition phases from iRBD to possible overt alpha-synucleinopathy. Methods IRBDSG centers included patients with >3-year follow-up, who underwent ≥3 assessments at intervals ≥6months apart. A wobble event was defined as an improvement at least once in ≥1 of the following: MDS-UPDRS III (≥4 points); MoCA (≥4 points)/MMSE (≥3 points)/MCI reverting to normal; orthostatic hypotension reverting to normal. PD, DLB or MSA criteria could not be fulfilled at any timepoint. Results 87 iRBD wobblers (17.2% female) from 15 centres (Europe, Canada, USA, Australia, Asia) were included. Mean age at iRBD diagnosis was 65.3±7.2y, with a time from diagnosis to first wobble event of 4.9±4.3y. At baseline the MDS-UPDRS-III was 3.7±3.6 and MoCA 23.7±3.2 (MCI 26.1%). At baseline, 13.0% presented OH, 55.6% cardiovascular disease, 29.6% psychiatric disorder, and 12.0% diabetes mellitus. 50.0% of the patients were taking symptomatic treatment for RBD. 41 patients (48%) were classified as pure cognitive (C) wobblers, 22 (25%) as pure motor (M) wobblers, 19 (22%) as both cognitive and motor (C+M) wobblers. Age at RBD diagnosis, sex, time from diagnosis to first wobble event, presence of MCI, OH, comorbidities, and use of RBD symptomatic treatment did not differ among groups. At baseline, the MDS-UPDRS-III score was higher in the M wobblers and in the C+M wobblers, compared to the C wobblers. The MoCA score was lower in the C wobblers and in the C+M wobblers, compared to the M wobblers. Conclusion In iRBD, cognitive and motor symptoms can wobble over time, making the diagnosis of phenoconversion difficult. Wobbling is yet unreported in iRBD and presents important clinical and research implications: if these measures are selected as outcomes in neuroprotective trials, wobbling could be misinterpreted as treatment efficacy. Further observations of wobblers are necessary to determine their final outcomes. Support (if any) None