# Early Cognitive Impairment as a function of Alzheimer's Disease and Trauma

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2024 · —

## Abstract

Risk for dementia, including late-onset Alzheimer’s disease (AD) and vascular dementia, is
determined by a complex mix of environmental, health, and genetic factors. Veterans have
higher rates of vascular problems, PTSD, combat trauma, and traumatic brain injuries, which
have all been linked to increased rates of age-related cognitive impairment and dementia.
Further, studies have indicated that these Veteran-relevant exposures may interact with AD
genetics to further increase the risk of cognitive decline. This application represents an
outgrowth of a project examining dementia and combat related gene by environment (GxE)
interactions in the Million Veteran Program (MVP), one of the world’s largest electronic-medical
record (EMR) linked biobanks. The original 2-year MVP Gamma project (MVP015) generated
working definitions of mild cognitive impairment (MCI), AD, and all-cause dementia from the VA
EMR. These were examined for association with combat exposure, head injury, and PTSD in
aging Veterans. We found evidence that head injury, combat, PTSD symptomatology, and AD
genetic risk variants were all associated with self-reported cognitive difficulties and MCI in
Veterans as young as 45-55, and with AD and related dementias in those age 65+. We
additionally identified GxE interactions between candidate variants in several genes and
combat/head injury on MCI and AD risk. In this application, we propose expanding on the initial
study, by 1) performing a genome wide association study (GWAS) of Dementia cases and
controls in multiple ancestry groups as well as examining the performance of GWAS-based
genetic risk scores in African American and Hispanic MVP participants, 2) performing
multivariate GxE analyses examining a range of Veteran relevant health exposures, 3) Further
developing and validating dementia diagnoses in MVP for genetic analyses including a machine
learning based method of identification of Dementia cases. This project will expand on our
continuing work and increase our knowledge of the impact of Veteran specific environmental
exposures and their interactions with AD genes on risk for AD and dementia.

## Key facts

- **NIH application ID:** 10765602
- **Project number:** 5I01BX005749-02
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** MARK W LOGUE
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765602

## Citation

> US National Institutes of Health, RePORTER application 10765602, Early Cognitive Impairment as a function of Alzheimer's Disease and Trauma (5I01BX005749-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10765602. Licensed CC0.

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