# Examining multiple etiologies underlying white matter disease in aging adults

> **NIH NIH F30** · VANDERBILT UNIVERSITY · 2020 · $30,229

## Abstract

PROJECT SUMMARY
Cerebral white matter changes are common in aging adults and contribute to adverse clinical consequences.
Vascular disease, specifically arterial stiffness, is thought to be the most prevalent etiology underlying white
matter disease. Arterial stiffness may lead to hypoxia in downstream tissue, leaving the deep white matter
tracts that lack collateral blood supply especially vulnerable. However, mounting evidence has implicated AD
pathology, including amyloid-β (Aβ) and hyperphosphorylated tau (ptau), as important contributors to white
matter disease. These pathologies may contribute to white matter damage in tracts overlapping with regions of
Aβ and ptau deposition, such as the frontal lobe, temporal lobe, and hippocampus. Given the strong evidence
suggesting vascular disease and AD pathology interact to hasten clinical progression, it is possible that these
pathologies exert overlapping effects on particularly vulnerable white matter tracts, accelerating cognitive
decline. The proposed research will examine age-related arterial stiffness and in vivo molecular biomarkers of
AD pathology in relation to longitudinal decline in white matter microstructure (assessed on diffusion tensor
imaging) over a 5-year follow-up period. Analyses will examine associations between the integrity in white
matter tracts identified as especially vulnerable to each pathology and cognitive decline. The proposed
research will leverage the rich resources of the Vanderbilt Memory & Alzheimer’s Center, Vanderbilt University
Institute of Imaging Science, Vanderbilt Translational Clinical Cardiovascular Research Group, Vanderbilt
Advanced Computing Center for Research and Education, and Vanderbilt Brain Institute. The research will be
guided by an interdisciplinary mentorship team, including experts in geriatric neuropsychology, AD, cerebral
small vessel disease, magnetic resonance imaging, statistical analysis, clinical management of abnormal
cognitive aging, and AD molecular biomarkers. The parallel training plan will facilitate the candidate’s
acquisition of the necessary knowledge and skills to study the etiologies of white matter disease in abnormal
cognitive aging and propel her into a successful career as an independent physician scientist. Understanding
the etiology of age-related white matter changes, especially the vulnerability of specific tracts and
corresponding clinical consequences, would provide critical information regarding the neurobiology underlying
cognitive decline. Findings will offer more comprehensive information regarding how white matter disease
integrates into AD pathogenesis.

## Key facts

- **NIH application ID:** 10014557
- **Project number:** 5F30AG064847-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Elizabeth E Moore
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,229
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10014557

## Citation

> US National Institutes of Health, RePORTER application 10014557, Examining multiple etiologies underlying white matter disease in aging adults (5F30AG064847-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10014557. Licensed CC0.

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