R01AG058854

Enigma World Aging Center - 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 an "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.

University Of Southern California

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

California United States

State-Wide

Secondary Analyses of Existing Cohorts, Data Sets and Stored Biospecimens to Address Clinical Aging Research Questions (R01) (PA-17-088)

Amendment Since initial award the total obligations have increased 377% from $696,496 to $3,319,630.