# Physical Activity and Dementia: Mechanisms of Action

> **NIH NIH R35** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $882,583

## Abstract

Abstract
Exercise is one of the most promising methods for positively influencing neurocognitive function in late
adulthood. Yet, despite this recognition, several major knowledge gaps preclude the ability to broadly prescribe
exercise to prevent or treat cognitive impairment. This R35 proposal includes a series of innovative and
potentially groundbreaking studies that will contribute to major advancements in the field of exercise and brain
health. The studies that we describe in this proposal would be led by several highly promising junior scientists
with the support of an experienced and dedicated mentorship team. The conceptual and scientific framework
for the hypotheses described in this proposal orbit around three major challenges facing the field of exercise
and cognitive aging: (1) We have a poor understanding of the mechanisms by which exercise influences
cognitive function in late adulthood, (2) We have a poor understanding of the factors that moderate, or explain
individual variation in, the response to exercise, and (3) We do not understand the factors that predict long-
term adoption of exercise behavior and how to reduce barriers and enhance incentives for individuals who find
it challenging to continue to exercise. Despite the clear benefits of an active lifestyle, most people fail to meet
public health recommendations for exercise. The more we know about the factors that predict and enhance
long-term adoption of exercise, the more we will know about whether exercise influences incidence of
Alzheimer’s Disease and best practices for prescribing and maintaining exercise for the prevention and
treatment of cognitive impairment. We propose to conduct secondary analysis of banked data from two
rigorous and well-controlled supervised exercise randomized clinical trials (RCTs) and to conduct a 3-year
follow-up of >570 participants from both of these RCTs of exercise to assess cognitive, cardiorespiratory
fitness, and physical activity levels. In particular, we propose to examine whether exercise-induced changes in
cardiometabolic and sleep measures mediate exercise-derived benefits to cognitive and brain outcomes. We
will also target moderators of exercise including APOE genotype and racial disparities to better characterize
which individual difference variables influence the magnitude of effects of exercise on brain health. Finally, we
propose a discovery aim that would leverage our rich measurement of participants at the genetic,
physiological, brain, cognitive, and socioemotional levels to perform predictive modeling to forecast long-term
adoption of exercise (or barriers prohibiting long-term adoption). In short, this research proposal describes a
broad and ambitious line of work that will produce groundbreaking and innovative studies to address significant
gaps in our understanding of exercise and brain health in late adulthood. The aims target several major
AD/ADRD milestones identified by NIH and will position junior scientists in ...

## Key facts

- **NIH application ID:** 10208017
- **Project number:** 1R35AG072307-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Kirk I Erickson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $882,583
- **Award type:** 1
- **Project period:** 2021-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208017

## Citation

> US National Institutes of Health, RePORTER application 10208017, Physical Activity and Dementia: Mechanisms of Action (1R35AG072307-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10208017. Licensed CC0.

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