Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study
Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study
复制标题
DOI：
10.1093/brain/awz030
复制
发表时间：
2019-03-01
期刊：
影响因子：
14.5
通讯作者：
Pelletier, Amelie
中科院分区：
文献类型：
--
作者：
Postuma, Ronald B.;Iranzo, Alex;Pelletier, Amelie
特发性快速眼动睡眠行为障碍（iRBD）是帕金森病、路易体痴呆和多系统萎缩的有力早期体征。这为直接观察前驱期神经退行性状态提供了前所未有的机会，并可能通过神经保护性治疗进行干预。对于未来的神经保护试验，准确估计表型转换率并确定表型转换的潜在预测因子至关重要。本研究在iRBD的大型多中心队列中评估了神经退行性疾病的风险和神经退行性病变的预测因素。我们综合了国际RBD研究组24个中心的前瞻性随访数据。在基线时，经多导睡眠描记术证实的无帕金森症或痴呆的iRBD患者接受了睡眠、运动、认知、自主神经和特殊感觉测试。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。采用Kaplan-Meier分析评估痴呆和帕金森病的风险。表型转换的预测因素采用考克斯比例风险分析进行评估，并根据年龄、性别和研究中心进行调整。使用至事件发生时间分析计算疾病改善试验的样本量估计值。总共招募了1280名患者。平均年龄为66.3 ± 8.4岁，82.5%为男性。平均随访4.6年（范围= 1-19年）。从iRBD到明显神经退行性综合征的总体转换率为每年6.3%，12年随访后73.5%转换。定量运动试验异常[风险比（HR）= 3.16]、客观运动检查异常（HR = 3.16）和运动功能异常（HR = 3.16）均显著增加了表型转化率。（HR = 3.03），嗅觉障碍（HR = 2.62），轻度认知功能障碍（HR = 1.912.37），勃起功能障碍（HR = 2.13），运动症状（HR = 2.11），DAT扫描异常（HR = 1.98）、色觉异常（HR = 1.69）、便秘（HR = 1.67）、REM弛缓丧失（HR = 1.54）和年龄（HR = 1.54）。性别、日间嗜睡、失眠、不宁腿综合征、睡眠呼吸暂停、排尿功能障碍、直立性症状、抑郁、焦虑或黑质超声强回声性无显著预测价值。在预测标志物中，只有认知变量在转换为原发性痴呆与帕金森综合征的患者之间存在基线差异。确定性神经保护试验的样本量估计为每组142至366例患者。这项大型多中心研究记录了iRBD向明显神经退行性综合征的高表型转化率。我们的研究结果提供了前驱标志物的相对预测价值的估计，可用于对神经保护试验的患者进行分层。
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 pheno-conversion 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 = 1.912.37), 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.