特发性REM睡眠行为障碍(iRBD)是帕金森病的一个强有力的早期征兆,路易体痴呆症,和多系统萎缩。这为直接观察前驱神经退行性状态提供了前所未有的机会,并可能干预神经保护疗法。为了将来的神经保护试验,准确估计表型转化率和确定表型转化的潜在预测因子至关重要。这项研究评估了iRBD的大型多中心队列中神经退行性疾病的风险和神经退行性疾病的预测因素。我们结合了来自国际RBD研究组24个中心的前瞻性随访数据。在基线,多导睡眠检查证实为iRBD但没有帕金森病或痴呆的患者进行睡眠,电机,认知,自主和特殊感官测试。然后对患者进行前瞻性随访,在此期间评估痴呆和帕金森病的风险.使用Kaplan-Meier分析估计痴呆和帕金森病的风险。用Cox比例风险分析评估表型转化的预测因子,调整年龄,性别,和中心。使用时间至事件分析计算疾病改善试验的样本量估计值。总的来说,1280名患者被招募。平均年龄为66.3±8.4,男性占82.5%。平均随访时间为4.6年(范围=1-19年)。从iRBD到明显的神经退行性综合征的总转化率为每年6.3%,在12年的随访后,73.5%的人转化。异常定量运动测试显着增加了表型转化率[危险比(HR)=3.16],客观运动检查(HR=3.03),嗅觉赤字(HR=2.62),轻度认知障碍(HR=1.91-2.37),勃起功能障碍(HR=2.13),运动症状(HR=2.11),异常DAT扫描(HR=1.98),色觉异常(HR=1.69),便秘(HR=1.67),REM失速损失(HR=1.54),和年龄(HR=1.54)。性别没有显著的预测价值,白天嗜睡,失眠,不宁腿综合征,睡眠呼吸暂停,泌尿功能障碍,直立症状,抑郁症,焦虑,或黑质超声的高回声性。在预测标志物中,转换为原发性痴呆和帕金森病患者在基线时只有认知变量不同.确定性神经保护试验的样本量估计为每臂142至366名患者。这项大型多中心研究记录了从iRBD到明显的神经退行性综合征的高表型转化率。我们的发现提供了对前驱标志物的相对预测值的估计,可用于对患者进行神经保护试验。
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.