ENIGMA World Aging Center

ENIGMA世界老龄化中心

• 批准号: 10328963
• 负责人: PAUL M THOMPSON
• 金额: $ 64.96万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10328963
• 关键词: Address; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Atrophic; Biological; Blood; Brain; Capital; Chronology; Clinical; Clinical Data; Cost of Illness; Country; Cytosine; DNA; Data; Data Collection; Data Set; Dementia; Diffusion; Diffusion Magnetic Resonance Imaging; Educational Status; Epigenetic Process; Functional Magnetic Resonance Imaging; Funding; Genetic; Genetic Carriers; Genetic Risk; Genetic study; Genome; Genomics; Goals; Grant; Guanine; Haplotypes; Health Priorities; Hippocampus (Brain); Image; Infrastructure; Institution; International; Libraries; Life; Longevity; Magnetic Resonance Imaging; Maps; Measures; Mental disorders; Methods; Nature; Nerve Degeneration; Nomograms; Pattern; Persons; Pilot Projects; Population; Population Heterogeneity; Problem Solving; Proxy; Publications; Publishing; Pythons; Reproducibility; Research; Rest; Risk; Risk Factors; Role; Science; Site; Structure; Testing; Tissues; Variant; Weight; Woman; Work; age related; aged; aging brain; base; brain magnetic resonance imaging; brain tissue; brain tract; cerebral atrophy; clinical predictors; cognitive performance; cohort; cost; disorder risk; economic cost; epigenetic marker; epigenome; epigenome-wide association studies; epigenomics; executive function; fluorodeoxyglucose positron emission tomography; functional decline; genome wide methylation; genome-wide; genomic locus; global health; hazard; human old age (65+); imaging genetics; indexing; inorganic phosphate; longitudinal analysis; machine learning algorithm; men; mortality; multimodality; nervous system disorder; neural tract; neuroimaging; neuroimaging marker; novel; physical conditioning; polygenic risk score; processing speed; prototype; sex

ABSTRACT One in three seniors dies with Alzheimer’s disease (AD) or another dementia - diseases that cost the nation $259 billion, to rise to $1.1 trillion by 2050 (Alzheimer’s Association, 2017). Despite the vast personal and economic cost of these diseases, two major barriers stall efforts to discover key biological mechanisms that influence brain aging. First, the sheer cost of data collection means that most national initiatives have limited power to detect factors that affect brain aging. Even in datasets of N=1,000+ people (e.g., ADNI) – the power to discover modulators of brain aging is limited and may not generalize worldwide. Second, with the crisis of reproducibility, we do not always know if a finding will replicate; and if not, if this is due to true population heterogeneity or problems with methods. ENIGMA offers a coordinated global approach to solve these problems. ENIGMA’s World Aging Center is a global brain aging study that builds on our vast and highly productive ENIGMA consortium - a global network of 340 institutions in 45 countries. ENIGMA published the largest-ever genetic studies of the brain (Nature 2017; Science 2020), and the largest neuroimaging studies of 5 major psychiatric disorders. ENIGMA’s World Aging Center is a concerted global effort to pool all available data, methods, expertise and capital infrastructure to discover factors that affect brain aging. Our long-term goal is to identify personalized biological predictors of brain structural and functional decline and assess how they generalize globally. We have 4 aims: Aim 1: ENIGMA-Lifespan. Develop Lifespan Charts for Brain and Neural Tract Aging in 20,000 people. We will create charts showing how MRI brain measures change throughout life in 20,000 people, aged 1-92. We will compute a composite brain aging score, ‘Brain Age’, from available MRI, DTI, rsFMRI data, that measures how much the brain deviates from expected values, for a person’s age and sex. Aim 2: ENIGMA-Epigenetics. Relate genome-wide methylation levels to brain metrics in 10,000+ people, to discover epigenetic markers of accelerated brain aging. We discovered 2 epigenetic loci promoting brain aging in pilot studies. We will compute a “epigenetic clock” and test if it predicts brain metrics better than simple biological age. Aim 3: ENIGMA-Plasticity. Discover genomic loci that promote or mitigate brain tissue loss, in > 37 worldwide cohorts with longitudinal MRI. Aim 4: ENIGMA-Alzheimer’s Disease (New Aim). Meta-analyze the role of APOE, AD polygenic risk, and a new risk score for accelerated atrophy on neuroimaging biomarkers in aging and AD, including amyloid and FDG PET. These aims seek to analyze worldwide imaging, epigenetic, and clinical data with harmonized methods. We aim to create new aging “clocks” and reveal targetable risk factors and modifiers of brain aging in the genome and epigenome, test how and when they shift AD biomarkers, and test their generalizability worldwide.

摘要