Project: Predicting Phenoconversion

摘要：NAPS2项目--预测表型转化 快速眼动(REM)睡眠行为障碍RBD是一种肌肉瘫痪的情况 伴随着快速眼动睡眠的睡眠丢失，导致反复的做梦行为。RBD发生在 大约40%的帕金森病患者，75%的DLB患者和80%的MSA患者。特发性/孤立性RBD(即没有 已知的相关神经退行性疾病)发生在50岁以上人口的1%。具有里程碑意义的研究已经 建议80%患有这种形式的RBD的人实际上患有前驱综合征核素病，而6%-10% 每年都会表观转化为PD、DLB或MSA。因此，RBD代表着一个前所未有的机会 直接详细研究PD、DLB和MSA的早期阶段。认识到及早干预的重要性， 关注美国神经退行性疾病的主要联邦机构提出了高度优先的建议 建议研究并核病的临床前和前驱症状，为临床做准备 审判。北美前驱综合征核素病联合会，阶段2(NAPS2)代表 扩大和延伸了最初的国家行动方案联盟的努力，重点是2018年开始的成果文件。在……里面 NAPS2,300多名患有RBD的参与者以及部分匹配的对照将在 全面和标准化的方式，由RBD参与者进行纵向临床、血液和 脑脊液、多导睡眠图和神经影像检查。这些数据、样本和扫描将被收集， 在核心中处理和分析，以提供关键变量，以便在 项目，重点是预测表观转化。因此，该项目将寻求解决许多 与RBD和神经保护临床试验规划有关的关键科学问题，包括：1) 确定临床测量、PSG和生物体液生物标志物的异常程度和分布 在大量RBD患者中；2)确定从RBD到显性RBD的转换率 联核病，并定义表型转化的预测生物标志物；3)跟踪临床变化 开发共核病进展生物标记物的措施和生物标记物，以及4)结合 表型转化、预测性生物标记物和进展生物标记物，以根据 RBD神经保护临床试验的不同患者选择标准和主要结果。

ABSTRACT: NAPS2 PROJECT – PREDICTING PHENOCONVERSION Rapid eye movement (REM) sleep behavior disorder RBD is a condition in which the muscular paralysis that accompanies REM sleep is lost, resulting in recurrent dream enactment behavior. RBD occurs in approximately 40% of patients with PD, 75% of DLB, and 80% of MSA. Idiopathic/Isolated RBD (i.e. without a known associated neurodegenerative disease) occurs in 1% of the population over 50. Landmark studies have suggested that >80% of individuals with this form of RBD in fact have prodromal synucleinopathy, and 6-10% will phenoconvert to PD, DLB, or MSA each year. RBD therefore represents an unprecedented opportunity to directly study early stages of PD, DLB and MSA in detail. Recognizing the importance of early intervention, the key federal agencies focused on neurodegenerative disease in the US have proposed high priority recommendations to study the preclinical and prodromal aspects of synucleinopathies to prepare for clinical trials. The North American Prodromal Synucleinopathy Consortium, Stage 2 (NAPS2) represents expanded and extended efforts of the original NAPS Consortium focused on RBD which began in 2018. In NAPS2, over 300 participants with RBD along with a subset of matched controls will be evaluated in a comprehensive and standardized manner, with the RBD participants undergoing longitudinal clinical, blood and CSF, polysomnographic, and neuroimaging studies. These data, samples and scans will be collected, processed and analyzed in the Cores to provide key variables for conducting hypothesis-driven analyses in the Project, with the focus on Predicting Phenoconversion. This project will therefore seek to address many critical scientific issues pertaining to RBD and neuroprotective clinical trial planning, including the following: 1) determining the degree and distribution of abnormalities in clinical measures, PSG and biofluid biomarkers among a large cohort of persons with RBD; 2) determining the conversion rate from RBD to an overt synucleinopathy, and to define predictive biomarkers of phenoconversion; 3) tracking change on clinical measures and biomarkers to develop progression biomarkers of synucleinopathy, and 4) combining data on phenoconversion, predictive biomarkers, and progression biomarkers to estimate sample size according to different patient selection criteria and primary outcomes for neuroprotective clinical trials in RBD.