# ENIGMA World Aging Center

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $696,496

## Abstract

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.

## Key facts

- **NIH application ID:** 10119038
- **Project number:** 1R01AG058854-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** PAUL M THOMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $696,496
- **Award type:** 1
- **Project period:** 2021-01-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119038

## Citation

> US National Institutes of Health, RePORTER application 10119038, ENIGMA World Aging Center (1R01AG058854-01A1). Retrieved via AI Analytics 2026-06-07 from https://api.ai-analytics.org/grant/nih/10119038. Licensed CC0.

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