# Exercise to improve hippocampal connectivity and learning in older adults

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $707,022

## Abstract

Project Summary
Given the rising proportion of older adults and the progressive cognitive decline with aging, there is a
pressing need for therapeutics that remediate age-related cognitive decline. Animal models robustly
support that endurance exercise protects brain areas vulnerable to aging such as the hippocampus and
that these benefits lead to better learning. In contrast, there are mixed findings from human studies on
the cognitive benefits of exercise with healthy older adults. This contrast indicates we still do not
understand how exercise could change the course of cognitive decline in aging adults. However, no
human studies have comprehensively tested exercise effects on cognition in older adults with learning
tasks inspired from basic exercise neuroscience. Our objective in the proposed research is to fill this
translational gap by determining if exercise improves the same kinds of learning in older adults that have
been shown to improve in animal models by improving hippocampal function. This will bring us closer to
our long-term goal of determining how exercise protects the brain from adverse effects of aging in order
to develop interventions that minimize age-related cognitive decline. Our overall hypothesis is that
exercise improves learning when it increases functional hippocampal-cortical communication that
otherwise declines with aging. We will test this in a sample of healthy older adults by determining if
increases in functional hippocampal-cortical connectivity from moderate intensity exercise improve
learning on an array of tasks that require the hippocampus for acquisition of new relational memories but
not in tasks that do not require the hippocampus to learn such as motor or response learning. We further
pursue mechanistic insight on the direct effects of exercise by determining if individual differences in the
rapid effects of moderate intensity exercise on hippocampal-cortical connectivity predict training-related
change in connectivity and learning, and by determining if training-related changes in cardiorespiratory
fitness are a critical factor. Our results will be significant because early prevention has the biggest impact
and determining how exercise counteracts mechanisms of cognitive aging leads to understanding how
such plasticity is possible and informs prevention strategies. The proposed work is innovative because
we test how exercise affects cognition by bringing together conceptually advanced measures of
hippocampal-dependent learning and memory processes with novel conceptualizations for how to
capture the physiological changes induced by exercise that change hippocampal-cortical connectivity.
Because hippocampal connectivity deteriorates with Alzheimer's, results could also lead to an
understanding of the mechanisms by which exercise reduces risk of this devastating and costly disease.

## Key facts

- **NIH application ID:** 9902292
- **Project number:** 5R01AG055500-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** MICHELLE WEBB VOSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $707,022
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902292

## Citation

> US National Institutes of Health, RePORTER application 9902292, Exercise to improve hippocampal connectivity and learning in older adults (5R01AG055500-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9902292. Licensed CC0.

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