# The Impact of Early and Later-life Stress on Later-life Cognition and Plasma Biomarkers of Alzheimer's Disease and Related Dementias

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT
By 2050, the estimated cost of Alzheimer’s disease and related dementias (ADRD) in the US is estimated at 1.6
trillion dollars. Thus, it is crucial to understand the factors contributing to the development of ADRD to identify
strategies for prevention or intervention. Stress is a multidimensional construct that can occur at various points
across the life course (early and later-life), either accumulating gradually over time or manifesting suddenly with
an immediate impact. Although stress has been associated with the risk of cardiovascular disease, there is
limited research on the potential association between stress and the risk of cognitive decline and ADRD, or on
biomarkers of ADRD pathology. Moreover, few studies have assessed sex differences even though both stress
and ADRD differ by sex. In this proposal, stress will be defined as occurring across the life-course as well as an
individual's perception of psychological stress. The overarching goal of this proposal is to examine the
associations of early and later-life stress on later-life cognition and plasma biomarkers of ADRD
pathology including Abeta 40 [Aβ40], Abeta 42 [Aβ42], Glial Fibrillary Acidic Protein [GFAP], and Neurofilament
light [NfL], phosphorylated tau181 (p-tau181), and phosphorylated tau217 (p-tau217), and whether associations
are modified by sex. To examine these associations, we will cross-sectionally examine the relationship between
life course stress and cognition (Aim 1) or plasma biomarkers of ADRD pathology (Aim 2). We will also assess
whether sex modifies the association. Moreover, we will examine these associations among participants
without dementia, recruited into the Wake Forest Alzheimer’s Disease Research Center (ADRC). The ADRC
consists of community-dwelling individuals, who are clinically well-characterized, have completed seven different
stress questionnaires, and provided a blood sample. The applicant will receive training in advanced methods in
epidemiology, biostatistics, sex differences, and how life course stress impacts health. Additionally, they will also
develop an understanding of ADRD clinical diagnosis and cognitive outcomes, while acquiring the necessary
skills to interpret plasma ADRD biomarkers – all of which are essential for achieving the proposed aims.
Mentorship will be provided by a multidisciplinary team of researchers and physicians at Wake Forest University
School of Medicine. The team will provide the applicant with feedback regarding project implementation, data
collection and analysis, and manuscript preparation. The proposed aims have the potential to provide essential
insight into the impact of life course stress on later-life cognition and by understanding which measures of stress
influence ADRD markers. Future interventions can be targeted towards those at highest risk.

## Key facts

- **NIH application ID:** 10902537
- **Project number:** 1F31AG087696-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jillian Lee
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902537

## Citation

> US National Institutes of Health, RePORTER application 10902537, The Impact of Early and Later-life Stress on Later-life Cognition and Plasma Biomarkers of Alzheimer's Disease and Related Dementias (1F31AG087696-01). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10902537. Licensed CC0.

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