Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study.

Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

Health-related quality of life in multiple system atrophy and progressive supranuclear palsy.

OBJECTIVE: Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), known as atypical parkinsonian syndromes (APS), are neurodegenerative disorders with severe disability and decreased life expectancy. Little is known about the health-related quality of life (HrQoL) and its determinants in patients with those disorders. The objective of our cross-sectional study was to evaluate the HrQoL in patients with APS and to identify the determinants of HrQoL. METHODS: A total of 101 consecutive patients with MSA (n = 54) and PSP (n = 47) were recruited in four German neurological centers. Disease severity was assessed using the Hoehn and Yahr stages and the Unified MSA Rating Scale. The HrQoL was evaluated using the EuroQol instrument (EQ-5D and EQ-VAS). Independent determinants of HrQoL were identified in multiple regression analyses. RESULTS: The mean EQ-VAS score was 52% lower than that reported for the general population (36.9 ± 18.3 vs. 77.4 ± 19.0). Of the study participants, 63% reported severe problems in at least one dimension of the EQ-5D. Cerebellar dysfunction was associated with a more considerable reduction of HrQoL. Independent determinants of reduced HrQoL were female gender, <12 years of education, disease severity, a decreased number of persons in the household and depression. CONCLUSIONS: The HrQoL in MSA and PSP is considerably reduced. While therapeutic options in the treatment of motor symptoms remain restricted, greater attention should be paid to the treatment of depression, which was identified among independent determinants of HrQoL. Independent determinants of HrQoL should be considered when developing healthcare programs aimed at improving the HrQoL in APS.