# Gene-environment Interplay Among Modifiable Factors for AD/ADRD: Risk and Resilience Across the Lifespan

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2024 · $798,110

## Abstract

Project Summary/Abstract
The proposed project will leverage 16 twin samples from the Interplay of Genes and Environments across
Studies (IGEMS) Consortium, and incorporate four additional samples, to clarify which modifiable risk factors
may be most influential in increasing risk for Alzheimer’s disease and related dementias (AD/ADRD) and at
which developmental stages their risks are greatest. The overarching goal of this project is to apply twin
models to strengthen or refute causal hypotheses and test gene-environment interplay among modifiable
factors for AD/ADRD, considering risk and resilience profiles within and across developmental periods of the
lifespan. Given the aging of the populations worldwide, AD/ADRD are expected to show substantial increases
over the next few decades, making the proposed study especially timely. We focus on modifiable risk factors in
the hope that clarifying the mechanisms and timing of their effects may help to guide prevention and
intervention to reduce AD/ADRD. Many of our genetically- and environmentally-informed samples include
longitudinal data and polygenic scores (PGS). Drawing from samples in Sweden, Denmark, Australia, and the
United States, we will (a) create multi-dimensional risk scores for early life contexts and (b) evaluate PGSs for
neurodevelopmental disorders and educational attainment in addition to PGSs for Alzheimer’s disease (AD),
AD resilience, and modifiable factors. We will leverage within-between models of twins and siblings of
exposures and genetic risk to test causal hypotheses that control for confounding, and explore gene-
environment (GE) interplay of modifiable risk factors for AD/ADRD and qualities of resilience to address our
aims: (SA1) evaluate mid- and late life physical health and health behavior factors that alter AD/ADRD risk;
(SA2) evaluate midlife and late life socioemotional factors that alter AD/ADRD risk; and (SA3) examine how
early life risks work together with midlife and late life health and socioemotional factors to influence AD/ADRD
risk while also incorporating GE interplay. The proposed research study will extend the life course model of
AD/ADRD by implementing a systems-level approach, guided by the NIH disparities framework, to investigate
key environmental factors that contribute to social inequities, including multiple early life adversities and risk
factors and measuring them at different times. Indeed, we will evaluate how mid- and late life risk act in
combination with early life risks and genetics to create differential profiles of AD/ADRD risk across sex,
cohorts, and countries. Our novel approach of leveraging both twin and genomic data will provide converging
evidence to inform clinical and policy recommendations with regard to the genetic interplay among risk and
protective factors that create differential vulnerabilities for AD/ADRD. The IGEMS Consortium is uniquely
positioned to advance the study aims using powerful approaches, rich phenotypes, hig...

## Key facts

- **NIH application ID:** 10985828
- **Project number:** 1R01AG089666-01
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Jenae M. Neiderhiser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $798,110
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985828

## Citation

> US National Institutes of Health, RePORTER application 10985828, Gene-environment Interplay Among Modifiable Factors for AD/ADRD: Risk and Resilience Across the Lifespan (1R01AG089666-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10985828. Licensed CC0.

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