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：
10471960
负责人：
Kathleen Lombard Poston
金额：
$ 63.49万
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/10471960
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 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 Persons 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 translational goal 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.

抽象的帕金森氏病（PD）是一种毁灭性的进行性神经退行性脑疾病，没有已知的治愈方法。该疾病遭受了全球1000万人的困扰 - 仅在美国，约有150万人，新病例约50k -60k 每年诊断。风险因素或干预措施极难评估，因为我们缺乏客观的指标 PD如何影响大脑。大脑成像的庞大可用性导致了几个有前途的指标大脑的量规PD进展 - 巴萨神经节和运动皮层的结构变化，异常通过扩散MRI（DMRI）观察到的神经连通性，以及大脑功能同步的破坏区域，请参阅静止状态功能性MRI（fMRI）。尽管有这些发现，影响疾病严重程度的因素很难发现，因为大多数对PD扫描<100例患者的成像研究。大多数PD研究是在从美国和欧洲孤立的人群，限制了全球的普遍性。影响PD进展的因素很难验证，导致可重复性的危机。回应NIH的呼吁进行更多可重复的研究，在这里，我们发起了Enigma的全球帕金森氏倡议。谜最近发表了最大的精神分裂症，躁郁症，严重抑郁症，癫痫和自闭症谱系的神经影像学研究紊乱。通过Enigma的全球协调，高功率的财团方法，我们计划克服小型研究的危机，功率差和可重复性。汇总解剖，扩散和静止状态功能来自21个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：疾病如何影响大脑的结构，神经连通性和功能同步？哪些成像生物标志物追踪疾病进展并一贯预测临床结果？ PD的遗传风险基因座有助于预测大脑的下降吗？什么PD 亚型或簇可以想象吗？结合来自2,307例患者和1,264个对照的多模式数据，我们将在PD中彻底评估预测因子和脑生物标志物。我们的目标是：（1）评估和排名全球PD的结构，扩散和静止状态功能性MRI生物标志物；（2）评估添加的多基因风险评分（PR）在预测PD脑生物标志物中的值；（3）预测未来的功能机器学习，多模式成像和基因组学的PD下降。我们将使用遗传数据和来自PD患者的基线临床变量和我们队列中的健康对照，以构建预测运动障碍协会合并分数的年度变化率的模型帕金森氏病评级量表II和III。我们将对下降的最佳预测指标进行评估，并评估如何强大的他们在国际上。通过更好地建模患者结局的差异，我们的多模式预测模型将通过对Burnen疾病的生物标志物进行排名并确定它们的环境来增强PD临床试验的能力可靠，准确且可行。