Biomarkers and risk factors for prodromal Parkinson's disease and its progression

帕金森病前驱期及其进展的生物标志物和危险因素

• 批准号: 10594036
• 负责人: ALBERTO ASCHERIO
• 金额: $ 47.7万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594036
• 关键词: 2019-nCoV; Address; Adrenergic beta-Antagonists; Adult; Agonist; Antigens; Appearance; Biological; Biological Markers; Brain; COVID-19; COVID-19 impact; Caffeine; Carnitine; Clinical; Constipation; Data; Diagnosis; Dietary Practices; Disease Progression; Early Intervention; Early identification; Event; Flavonoids; Follow-Up Studies; Food; Funding; Future; Genetic Complementation Test; Goals; Health Professional; Heterogeneity; Individual; Intervention; Investigation; Knowledge; Life; Life Style; Lipids; Machine Learning; Medical History; Metabolism; Monitor; Motor; Movement Disorders; National Institute of Neurological Disorders and Stroke; Natural History; Nerve Degeneration; Nurses' Health Study; Nutrient; Parkinson Disease; Parkinsonian Disorders; Participant; Patients; Pharmaceutical Preparations; Phase; Physical activity; Play; Population; Positioning Attribute; Prevention trial; Probability; REM Sleep Behavior Disorder; Recommendation; Research; Resources; Risk Factors; Role; Sampling; Sebum; Smoking; Societies; Source; Sphingolipids; Subgroup; Surveys; Testing; Time; Training; Volatilization; Woman; algorithm training; case control; cohort; design; dietary; disability; disorder risk; experience; follow-up; hyposmia; insight; men; metabolome; modifiable risk; novel; novel marker; prediction algorithm; prevent; prospective; recruit; screening; sex; virtual

PROJECT SUMMARY The highest priority recommended by NINDS for clinical Parkinson’s research is to define “the features and natural history of prodromal Parkinson disease (PPD), including the events that underlie phenoconversion to clinically manifest PD, and biomarkers or other determinants of prodromal subtypes with the goal of providing sufficient rationale to initiate proof-of-concept prevention trials....” We are in a privileged position to address this priority by leveraging 25 years of research on PD in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), large cohorts of women and men recruited in mid-adult life and followed prospectively for over 30 years. In 2012, we screened the active participants in these cohorts for probable REM sleep behavior disorder (pRBD) and constipation, and selected a sub-cohort enriched for these features for further investigation (the ProPD cohort). This sub-cohort included 20,455 individuals who have so far completed two olfactory tests and two comprehensive mailed surveys of non-motor and early motor features of PPD, and have been actively followed until 2018. We are now proposing to extend the longitudinal follow-up of this unique cohort and its source population to monitor the progression of prodromal features and phenoconversion to clinically manifest PD (“phenoconversion”, for brevity), thus providing important insights on the course of PPD and fill the gap between current knowledge and what we need to know for implementing prevention trials. Further, as part of the proposed project, we will examine the impact of covid-19 on PPD and its progression and collect new biological samples to evaluate the sebum volatilome and metabolome, novel promising and non-invasive biomarkers that could play an important role in the early identification of PPD. The Aims of the study include: i) to obtain an in-depth descriptive characterization of PPD and its heterogeneity; ii) to identify risk factors for PPD progression and phenoconversion; iii) to assess the impact of SARS-Cov2/covid-19 on features of prodromal PD and phenoconversion; and iv) to evaluate the relationship between the sebum volatilome and metabolome with prodromal features and manifest PD (sebum samples will be collected from individuals with high probability of PPD, manifest PD, and matched controls). A unique and virtually irreproducible strength of the proposed study are the data prospectively collected since mid-adult life (men were 40 to 65 at recruitment, women 30 to 55) on lifestyle and medical history, including risk factors for PD and several features associated with PPD. If funded, the proposed study stands to lead to groundbreaking discoveries and create an invaluable resource that will offer numerous opportunities for further in-depth investigations on PPD and its determinants. Most importantly, the information generated by the proposed investigation will be pivotal to assess the feasibility of prevention trials and inform their design.

项目摘要 NINDS 建议的帕金森病临床研究的最高优先级是 定义“前驱帕金森病 (PPD) 的特征和自然史，包括事件 是表型转变为临床表现 PD 的基础，以及生物标志物或其他决定因素 前驱亚型，目的是提供足够的理由来启动概念验证预防 试验......”我们处于有利地位，可以利用 25 年的研究来解决这一优先事项 护士健康研究 (NHS) 和卫生专业人员随访研究 (HPFS) 中的 PD，大型 招募了中年时期的女性和男性队列，并进行了 30 多年的前瞻性随访。 2012 年，我们对这些队列中的活跃参与者进行了可能的快速眼动睡眠行为障碍筛查 （pRBD）和便秘，并选择了一个富含这些特征的子队列进行进一步研究 （ProPD 队列）该子队列包括 20,455 名迄今为止已完成两项任务的人。 嗅觉测试和两次针对 PPD 的非运动和早期运动特征的综合邮寄调查， 并一直积极随访至2018年。我们现在建议延长纵向随访 对这个独特的队列及其来源人群进行监测，以监测前驱特征的进展， 表型转化为临床表现的 PD（简称“表型转化”），从而提供了重要的 对 PPD 过程的见解并填补当前知识与我们需要了解的知识之间的差距 此外，作为拟议项目的一部分，我们将检查其影响。 covid-19对PPD及其进展的影响并收集新的生物样本来评估皮脂 挥发性和代谢组学，新型有前景和非侵入性生物标志物，可以发挥重要作用 在 PPD 早期识别中的作用 该研究的目的包括： i) 获得深入的描述性信息。 PPD 的特征及其异质性； ii) 确定 PPD 进展的危险因素； 表型转化；iii) 评估 SARS-Cov2/covid-19 对前驱 PD 特征的影响； 表型转化；和 iv) 评估皮脂挥发组和代谢组之间的关系 具有前驱症状和明显的 PD（皮脂样本将从具有高 PPD 的概率、明显的 PD 和匹配的对照）。 拟议研究的数据是自中年以来前瞻性收集的数据（男性年龄为 40 至 65 岁） 招募，女性 30 至 55 岁）的生活方式和病史，包括 PD 的危险因素和一些 如果获得资助，拟议的研究将带来突破性的结果。 发现并创造了宝贵的资源，将为进一步深入研究提供大量机会 对 PPD 及其决定因素的调查最重要的是，由 PPD 生成的信息。 拟议的调查对于评估预防试验的可行性并为其设计提供信息至关重要。