# Contributions of stress reactivity to risk of Alzheimer's disease and related dementia's in a community-based cohort

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $822,597

## Abstract

Racial/ethnic minority adults are at higher risk for Alzheimer's disease and related dementias
(ADRD). Moreover, minority adults are not only exposed to more intense and frequent stressful
situations in their daily lives but they also have fewer resources to manage these situations in
healthy ways. Limited resources among these adults may lead to impaired physiologic stress
responses (i.e., stress reactivity), specifically dysregulation of the sympathetic nervous system
and the hypothalamic-pituitary-adrenocortical (HPA) axis. Our understanding of the impact of
stress reactivity on ADRD risk comes from animal studies and experiments in humans using
controlled, laboratory stressors. This is a major limitation because laboratory stressors cannot
capture the variety, severity, or duration of stressors that individuals face in their daily lives.
Thus, there remains a need to more rigorously evaluate relationships of stress reactivity with
ADRD risk in natural settings. We propose to fill this critical gap in the literature by adding more
personalized and objective indicators of stress and stress reactivity to a longstanding
community-based cohort, the Multi-Ethnic Study of Atherosclerosis (MESA). We will use existing
gene expression data to calculate a molecular marker of the physiologic response to chronic
exposure to adversity. We will also collect repeated measurements of stressful experiences,
negative affect (emotions), and heart rate in order to develop participant-specific markers of
affective and autonomic stress reactivity, respectively. Our overall goal is to use these
measures to examine associations of the body's response to stressful experiences with risk of
ADRD in a natural setting. We will leverage existing and ongoing repeated assessments of
cognitive function as well as ongoing assessments of neuroimaging biomarkers of both vascular
and AD pathology including cerebral blood flow (CBF), white matter hyperintensities, Aβ
deposition, and gray matter volume loss. Our proposed study will allow us to begin to
disentangle the pathways through which stress exposure and stress reactivity impact vascular
dementia pathology and/or AD positivity. Findings will inform stress management interventions
and precision medicine initiatives designed to prevent ADRD and/or slow its progression.

## Key facts

- **NIH application ID:** 10895482
- **Project number:** 5R01AG067557-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kiarri N Kershaw
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $822,597
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895482

## Citation

> US National Institutes of Health, RePORTER application 10895482, Contributions of stress reactivity to risk of Alzheimer's disease and related dementia's in a community-based cohort (5R01AG067557-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10895482. Licensed CC0.

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