# Impact of Combat Exposure on Structural and Functional Brain Connectivity and Risk forAlzheimer's Disease in Aging Veterans

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2022 · —

## Abstract

Military service in young adulthood is typically accompanied by a variety of combat exposures
that are known to increase the risk for cognitive impairment and Alzheimer’s disease (AD) in
later life (e.g. hypertension, diabetes, hypercholesterolemia, and body mass index). Although
the significant healthcare and societal costs of combat exposure are well documented, it is
possible that these primary young adulthood exposures additionally promote later life secondary
conditions that are only now being uncovered. Identification of factors that contribute to
advanced risk for diseases of aging in older Veterans provides the opportunity to test and
initiate treatments that may slow progression of these conditions. Additionally, these data could
be used to inform care for the younger, current generation of veterans, including the initiation of
lifestyle and medical changes that may ameliorate progression of conditions that promote later
life cognitive and behavioral conditions. It is possible that combat-exposure in young adulthood
initiates a trajectory of ‘unhealthy aging’ with progressive elevation in biological risk that
promotes aging-related neural ‘disconnection’ of structural and functional brain networks.
However, limited work to date has been performed linking young adulthood combat exposure to
alterations in neural structure and function in older Veterans. Additionally, whether combat-
exposure in young adulthood is related to the accumulation of late life biomarker hallmarks of
AD, known as the amyloid, tau, neurodegeneration (A-T-N) framework, is currently unknown.
Thus, intermediary mechanisms linking young adulthood combat exposure to late life risk must
be examined. In the large Translational Research Center for TBI and Stress Disorders
(TRACTS) cohort study, we find that younger Veterans with combat exposures and symptoms
additionally 1) have elevations in systemic biological risk; 2) show alterations in critical brain
network circuitry such as amygdala and default mode network (DMN); and 3) show accelerated
aging trends in structural connectivity and white matter microstructure. We aim to conceptually
link these findings in the proposed work. We propose that late life risk is conferred first through
elevation in systemic health conditions starting in young adulthood (i.e. ‘cumulative biological
risk’) that lead to damage to critical brain connections. Combined effects of cumulative biological
risk accelerate the deterioration of structural and functional brain networks that support higher
cognitive function, including memory systems and/or compensatory systems that provide
cognitive reserve in the face of AD pathology. We will test a model of combat-associated
amygdala network dysregulation promoting systemic health risk in young adulthood. This
cumulative biological risk in turn contributes to neural and cognitive deterioration that is
pronounced in older Veterans. This work will elucidate mechanisms that contribute to elevated
risk f...

## Key facts

- **NIH application ID:** 10364388
- **Project number:** 1I01CX002312-01A1
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** DAVID H SALAT
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364388

## Citation

> US National Institutes of Health, RePORTER application 10364388, Impact of Combat Exposure on Structural and Functional Brain Connectivity and Risk forAlzheimer's Disease in Aging Veterans (1I01CX002312-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364388. Licensed CC0.

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