ENIGMA Parkinson’s Initiative: A Global Initiative for Parkinson’s Disease

ENIGMA 帕金森病倡议：针对帕金森病的全球倡议

基本信息

批准号：
10209632
负责人：
Kathleen Lombard Poston
金额：
$ 67.6万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10209632
关键词：
Affect Africa Age of Onset Amygdaloid structure Anatomy Anterior Area Asia Atrophic Attenuated Austria Basal Ganglia Belgium Biological Markers Bipolar Disorder Bradykinesia Brain Brain Diseases Brain imaging Brazil China Clinical Clinical Trials Cognitive Cognitive deficits Collaborations Corpus Callosum Corpus striatum structure Corticospinal Tracts Country Data Data Pooling Data Set Data Sources Development Diagnosis Diffusion Diffusion Magnetic Resonance Imaging Dimensions Disease Disease Progression Environmental Risk Factor Epilepsy Europe Foundations Functional Magnetic Resonance Imaging Future Gait Genetic Genetic Predisposition to Disease Genetic Risk Genomics Goals Head Image Impaired cognition Impulsivity Individual International Intervention Investigation Italy Japan Lead Learning Least-Squares Analysis Letters Machine Learning Major Depressive Disorder Measures Mental Depression Modeling Motor Motor Cortex Movement Movement Disorder Society Unified Parkinson&apos s Disease Rating Scale Multimodal Imaging Nerve Degeneration Netherlands Neurodegenerative Disorders New Zealand North America Oceania Parkinson Disease Pathway interactions Patient-Focused Outcomes Patients Pattern Pharmaceutical Preparations Phenotype Posture Predictive Factor Protocols documentation Publishing Reproducibility Research Rest Risk Risk Factors Russia Sample Size Scanning Schizophrenia Severities Severity of illness Source South Africa South America Structure Structure of inferior temporal gyrus Susceptibility Gene Switzerland Symptoms Taiwan Testing Thalamic structure Thick Treatment Efficacy Tremor United States National Institutes of Health autism spectrum disorder biobank biological sex burden of illness cholinergic cognitive impairment in Parkinson&apos s cohort design disease diagnosis disorder risk disorder subtype diverse data economic cost functional decline genetic risk factor imaging biomarker imaging genetics imaging study improved indexing magnetic resonance imaging biomarker multimodal data multimodality neuroimaging neuropsychiatry personalized medicine polygenic risk score predict clinical outcome predictive modeling putamen rate of change relating to nervous system response risk variant shape analysis simulation thalamocortical tract treatment response uptake white matter

项目摘要

ABSTRACT Parkinson’s disease (PD) is a devastating, progressive neurodegenerative brain disease, with no known cure. The disease afflicts 10 million people worldwide - ~1.5 million in the U.S. alone, and ~50k-60k new cases are diagnosed annually. Risk factors or interventions are extremely hard to evaluate as we lack objective metrics of how PD affects the brain. The vast global availability of brain imaging has led to several promising metrics to gauge PD progression in the brain - structural changes in the basal ganglia and motor cortex, abnormalities in neural connectivity seen with diffusion MRI (dMRI), and disruptions of the brain’s functional synchrony across regions, seen with resting state functional MRI (fMRI). Despite these findings, factors that affect disease severity are difficult to discover, as most imaging studies of PD scan <100 patients. Most PD research is conducted in isolated cohorts from the US and Europe, limiting worldwide generalizability. Factors that affect PD progression are hard to verify, leading to a crisis of reproducibility. Responding to NIH’s call for more reproducible studies, here we launch ENIGMA’s Worldwide Parkinson’s Initiative. ENIGMA recently published the largest neuroimaging studies of schizophrenia, bipolar disorder, major depression, epilepsy, and autism spectrum disorder. With ENIGMA’s globally coordinated, highly powered consortium approach, we plan to overcome the crisis of small studies with poor power and reproducibility. Pooling anatomic, diffusion and resting state functional MRI metrics from 21 deeply assessed international cohorts - from the US, Brazil, Taiwan, New Zealand, the Netherlands, Italy, Switzerland, South Africa, China, and Russia - we ask: How does the illness affect the brain's structure, neural connectivity, and functional synchrony? What imaging biomarkers track disease progression and consistently predict clinical outcomes? Do genetic risk loci for PD help predict brain decline? What PD subtypes, or clusters, can imaging identify? Combining multimodal data from 2,307 patients and 1,264 controls, we will thoroughly evaluate predictors and brain biomarkers in PD. Our aims are to: (1) Evaluate and rank structural, diffusion, and resting state functional MRI biomarkers of PD worldwide; (2) Evaluate the added value of polygenic risk scores (PRS) in predicting PD brain biomarkers; (3) Predict future functional decline in PD with machine learning, multi-modal imaging and genomics. We will use genetic data and baseline clinical variables from PD patients and healthy controls across our cohorts to construct an ensemble of models to predict the annual rate of change in combined scores from the Movement Disorder Society—Unified Parkinson's Disease Rating Scale parts II and III. We will rank the best predictors of decline, and assess how robust they are internationally. By better modeling variance in patient outcomes, our multimodal predictive model will empower PD clinical trials by ranking biomarkers of disease burden and determining the contexts where they are reliable, accurate, and feasible to use.

抽象的帕金森病 (PD) 是一种毁灭性的、进行性神经退行性脑部疾病，目前尚无已知的治愈方法。全球有 1000 万人受到这种疾病的影响，仅在美国就有约 150 万人患病，新增病例约 5 万至 6 万例每年诊断出的风险因素或干预措施非常难以评估，因为我们缺乏客观的衡量标准。脑成像在全球范围内的广泛应用已经产生了一些有希望的指标测量大脑中的 PD 进展 - 基底神经节和运动皮层的结构变化、异常通过扩散 MRI (dMRI) 观察到的神经连接，以及大脑功能同步的中断尽管有这些发现，但影响疾病严重程度的因素仍然存在。很难发现，因为大多数 PD 扫描的影像学研究都在 <100 名患者中进行。来自美国和欧洲的孤立队列，限制了影响帕金森病进展的因素在全球范围内的普遍性。难以验证，导致可重复性危机响应 NIH 的呼吁，进行更多可重复的研究，我们在此推出 ENIGMA 的全球帕金森氏症计划 ENIGMA 最近发布了最大的一项计划。精神分裂症、双向情感障碍、重度抑郁症、癫痫和自闭症谱系的神经影像学研究通过 ENIGMA 的全球协调、强大的联盟方法，我们计划克服这一问题。汇集解剖学、扩散和静息状态功能的小型研究的危机。来自 21 个经过深入评估的国际队列的 MRI 指标——来自美国、巴西、台湾、新西兰、荷兰、意大利、瑞士、南非、中国和俄罗斯——我们问：这种疾病如何影响大脑的结构、神经连接和功能同步性有哪些成像生物标志物可以追踪疾病进展？并持续预测临床结果？PD 的遗传风险位点有助于预测大脑衰退吗？结合 2,307 名患者和 1,264 名对照者的多模态数据，影像可以识别亚型或簇吗？我们将彻底评估 PD 的预测因素和大脑生物标志物。我们的目标是：(1) 评估和排名。（2）评估全球PD的结构、扩散和静息态功能MRI生物标志物；（3）预测多基因风险评分（PRS）在预测PD大脑生物标志物中的未来功能价值；我们将利用遗传数据和基因组学来减少帕金森病的发生。来自我们队列中的 PD 患者和健康对照的基线临床变量，以构建一个集合预测运动障碍协会综合评分年变化率的模型——统一帕金森病评定量表第二部分和第三部分我们将对衰退的最佳预测因素进行排名，并评估如何进行。通过更好地对患者结果的差异进行建模，我们的多模式预测模型是稳健的。将通过对疾病负担的生物标志物进行排名并确定它们的背景来增强PD临床试验的能力可靠、准确且易于使用。