# Antioxidant Imaging Marker of Investigating Gains in Neurocognition in an Intervention Trial of Exercise (AIM-IGNITE)

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $667,736

## Abstract

PROJECT SUMMARY / ABSTRACT
 The absence of effective methods for treating age-relate cognitive decline presents a significant public
health problem, considering its ubiquity with unprecedented increases in the aging population. Recently,
lifestyle choices, particularly exercise, have been noted as potential effective strategies for maintaining and
enhancing brain health and cognitive function in older adults. However, the public and scientific community is
yet to reach agreements on the conclusive benefits of exercise on the brain. Currently a Phase III clinical
trial: IGNITE (Investigating Gains in Neurocognition in an Intervention Trial of Exercise) is ongoing to address
the ambiguity in influences of exercise on brain health and cognitive function in older adults. We propose an
ancillary study to determine the impact of exercise on antioxidant status in the brain of participants drawn
from IGNITE, in which clinical, imaging, genetic, molecular and physiological measures will be acquired. We
will determine the association of antioxidant status with cognitive function and brain health as well as the
impact of genetic and molecular risk factors of Alzheimer's disease (AD) on these relationships.
 Our long-term goal is 1) to identify the underlying mechanisms of improved brain health and cognitive
performance associated with behavioral interventions and/or new targeted therapies in older adults, and 2) to
offer novel possibilities for directly monitoring the impact of these emergent treatment options through new
quantitative, non-invasive neuroimaging indices of brain health in aging, AD and AD-related diseases. Our
overall hypothesis is that exercise enhances cerebral antioxidant defenses to fight against oxidative stress in
the aging brain by increasing the levels of glutathione (GSH), which leads to improved brain health and
cognitive function. GSH is a key component of the cerebral antioxidant system, which is consumed to protect
cells against oxidative damage resulting in lower GSH levels in brain tissue.
 Our preliminary data suggest that brain GSH is related with the cognitive performance of older adults in
multiple domains, lowered in aging and AD, and increases after exercise interventions. The Specific Aims
are: (1) to determine the influence of exercise intervention on the brain antioxidant status in the aging brain,
(2) to determine the mediating relationship between the brain antioxidant status and exercise-associated
improvements in cognitive function and brain health, and (3) to examine modulating effects of
genetic/molecular markers of Alzheimer's disease on changes in brain antioxidant status after exercise
intervention. The expected outcome of this project is 1) the identification of a major mechanism, oxidative
stress, underlying the beneficial effects of exercise on cognitive function and brain health seen in older adults,
2) the identification of a mechanism-based neuroimaging marker reflecting neuromodulating effects of
exerc...

## Key facts

- **NIH application ID:** 10076750
- **Project number:** 5R01AG060050-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Phil Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $667,736
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076750

## Citation

> US National Institutes of Health, RePORTER application 10076750, Antioxidant Imaging Marker of Investigating Gains in Neurocognition in an Intervention Trial of Exercise (AIM-IGNITE) (5R01AG060050-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076750. Licensed CC0.

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