# Longitudinal Investigation of Cardiorespiratory Fitness and AD Biomarkers in an At-Risk Cohort

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $190,081

## Abstract

PROJECT SUMMARY/ABSTRACT
Currently-available drug treatments for Alzheimer's disease (AD) are not curative. Furthermore, findings from
clinical trials testing novel disease-modifying therapeutics have been disappointing. Accordingly, the urgency of
alternative approaches for halting the global crisis posed by AD cannot be overstated. Although data from
cohort and epidemiological studies have long suggested a strong link between physical activity and dementia
due to AD, the question of whether physical activity modulates the underlying pathophysiology of AD has only
recently begun receiving attention. While the emerging evidence appears overall supportive of such a role for
physical activity, several critical knowledge gaps persist. First, past studies have been largely cross-sectional.
This leaves unresolved the possibility that observed effects simply reflect reverse causation. Second, “physical
activity” has been assessed via a variety of approaches including self-report, activity trackers, and maximal
graded exercise testing, leading to conflicting findings. Third, because past research has primarily been done
in elderly persons, little is known about the potential influence of physical activity on AD risk in midlife, when
most AD-related changes begin. Lastly, there is need for a better understanding of the mechanisms by which
physical activity exerts its salutary effects. To address these gaps in knowledge (1) we focus this project on
cardiorespiratory fitness (CRF), which constitutes the physiological nexus for *habitual* physical activity, (2)
we employ a longitudinal design, which would allow us rigorously exclude the possibility of reverse causation,
(3) we study a cohort of late-middle-aged adults who are, in principle, potentially only at the inceptive stages of
AD, and (4) we investigate vascular and glucoregulatory function as viable transducers of the link between
CRF and AD pathophysiology. Importantly, because the participants targeted for this study are being followed
longitudinally through the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's
Disease Research Center, we will be uniquely positioned in the long term to elucidate the impact of midlife
CRF on clinical endpoints of mild cognitive impairment and dementia. In sum, the multimodal and integrative
study proposed here stands to provide critical insights into CRF as a potentially viable therapeutic for altering
disease trajectory in the early stages of AD, prior to pervasive neurodegeneration, thereby delaying the
emergence of clinical symptoms.

## Key facts

- **NIH application ID:** 10082736
- **Project number:** 3R01AG062167-02S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Ozioma C Okonkwo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,081
- **Award type:** 3
- **Project period:** 2019-01-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082736

## Citation

> US National Institutes of Health, RePORTER application 10082736, Longitudinal Investigation of Cardiorespiratory Fitness and AD Biomarkers in an At-Risk Cohort (3R01AG062167-02S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10082736. Licensed CC0.

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