# Vanderbilt Memory & Aging Project

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $3,787,834

## Abstract

PROJECT SUMMARY
As the population ages, Alzheimer's disease and dementia are becoming a public health crisis. In our initial
cycle, the Vanderbilt Memory & Aging Project was established to examine cardiovascular function in relation to
structural neuroimaging changes and cognition. We also tested whether associations were more prominent in
clinically symptomatic individuals. We successfully enrolled several hundred participants age 60 and older, our
data successfully supported multiple training grant opportunities (e.g., National Research Service Awards,
Career Development Awards), and we published numerous papers. Our results suggest subclinical
cardiovascular changes relate to worse cognition, white matter changes, and cerebral atrophy, especially in the
hippocampus and other cortical regions primarily affected in Alzheimer's disease. Evidence to date supports
our central hypothesis that well-established homeostatic mechanisms designed to protect cerebral blood
supply become less effective with age, altering the integrity of cerebral hemodynamics, and lowering the
threshold for neurodegenerative and cognitive changes. Interestingly, our preliminary associations between
subclinical cardiovascular integrity and cerebral hemodynamics are stronger among carriers of the
apolipoprotein E ε4 (APOE-ε4) allele, an Alzheimer's disease genetic risk factor. Furthermore, findings are
more prominent in cognitively unimpaired participants, suggesting subtle cardiac hemodynamic changes may
act as an underrecognized precipitating contributor of neurodegeneration and corresponding cognitive decline,
distinct from the exacerbating effects of overt cerebrovascular disease. In the next cycle, we propose to better
characterize underlying mechanisms linking early cardiac hemodynamic changes to abnormal brain aging in
cognitively unimpaired participants, and test whether APOE-ε4 moderates the effect of vascular damage on
brain health. We will follow the existing cohort and supplement it with enrollment of several hundred cognitively
unimpaired participants to increase statistical power for more comprehensive analyses. The new participants
will complete serial longitudinal assessments with identical procedures plus lumbar puncture for cerebrospinal
fluid acquisition. Innovative translational efforts leveraging sophisticated neuroimaging and molecular
biomarkers are critical to better detect early, asymptomatic cardiac hemodynamic changes, which may be
more influential in initiating downstream cerebrovascular and neurodegenerative processes than previously
recognized.

## Key facts

- **NIH application ID:** 10183086
- **Project number:** 5R01AG034962-09
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** ANGELA L. JEFFERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,787,834
- **Award type:** 5
- **Project period:** 2011-03-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183086

## Citation

> US National Institutes of Health, RePORTER application 10183086, Vanderbilt Memory & Aging Project (5R01AG034962-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10183086. Licensed CC0.

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