# Exercise for Brain Health with Increased Genetic Risk for Alzheimer's Disease

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $753,911

## Abstract

Project Summary
This competitive revision of our currently funded clinical trial (AG057552, Exercise for Brain Health with
Increased Genetic Risk for Alzheimer's Disease) aims to elucidate the vascular mechanisms whereby exercise
training protects brain structure and brain function and improves cognition, of which very little is known. We
will focus on cognitively intact older adults who carry the apolipoprotein-E epsilon4 (APOE-ε4) allele, a
candidate gene for late-onset Alzheimer's disease (AD), as well as vascular disease. There is evidence that
compromised cerebral perfusion is associated with cognitive decline and progression along the AD continuum.
We have recently shown that 12 weeks of exercise training increased CBF in the anterior cingulate cortex in
healthy older adults. Moreover, recent studies have shown that AD patients have lower levels of CACs, which
may be leading to endothelial dysfunction. It is unknown, however, if CAC levels are lower in cognitively intact
APOE-ε4 allele carriers, or if exercise may bolster vascular function through enhanced CAC function.
Understanding the mechanisms underlying perfusion deficits that may precede/contribute to cognitive impairments is
an important next step in understanding the progression and prevention of AD. Our novel approach with this
revision is to determine is whether exercise protects the neural networks of cognitively healthy APOE-ε4 allele
carriers by bolstering CACs and promoting responsive endothelial function. Our primary aims for the current
revision application build on our preliminary data and published work showing that exercise training in older
adults: 1) increases circulating angiogenic cells (CACs) and endothelial progenitor cells (EPCs) that promote
vessel growth and capillarization and protect cardiometabolic health; and 2) improves vascular function in
peripheral arteries and carotid artery. The key unanswered questions we will address are: 1) do the exercise
training-induced effects on vascular function in older adults differ among cognitively intact APOE-ε4 allele
carriers and non-carriers; and 2) are the exercise-induced effects on vascular function in older adults related to
changes in MRI indices of brain function, brain structure, and/or changes in cognition? The hub of our single
site parent study is the University of Maryland College Park, where we partner with local retirement
communities and fitness centers. This competitive revision application leverages two recent hires by the
Department of Kinesiology, Dr. Steven Prior and Dr. Sushant Ranadive, both of whom are experts in the fields
exercise physiology and human vascular function. Dr. Prior's work focuses on identifying cellular mechanisms
of vascular health in older adults induced by exercise and physical activity, including factors that promote
angiogenesis and new capillary growth in muscle. Dr. Ranadive is an expert in studying vascular function in
older adults, including neurovascular control mechanis...

## Key facts

- **NIH application ID:** 10052083
- **Project number:** 3R01AG057552-04S1A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** JEROME CARSON SMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $753,911
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052083

## Citation

> US National Institutes of Health, RePORTER application 10052083, Exercise for Brain Health with Increased Genetic Risk for Alzheimer's Disease (3R01AG057552-04S1A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052083. Licensed CC0.

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