# Blood Biomarkers as Surrogate Endpoints of Treatment Responses to Aerobic Exercise and/or Cognitive Training in Amnestic Mild Cognitive Impairment

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $480,197

## Abstract

Project Summary
Alzheimer’s disease (AD) is an epidemic with tremendous public health impacts, and cannot be prevented or
cured. Randomized controlled trials (RCTs) for AD prevention often use clinical endpoints that take years to
manifest (e.g., incident AD) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance
imaging [MRI] or cerebrospinal fluid biomarkers). Blood biomarkers represent a clinically applicable alternative
surrogate endpoint for RCTs that would be both cost-effective and minimally invasive. Significant evidence
supports blood biomarkers as prognostic indicators of cognitive decline and risk of AD in epidemiological
studies, but little is known about their value as surrogate endpoints for treatment responses in AD prevention.
The long-term goal of our research is to establish blood biomarkers that can be used to personalize AD
prevention and treatment. The objective of this study is to investigate blood neuropathological and neurotrophic
biomarkers as surrogate endpoints for treatment responses to 3 interventions in older adults with amnestic mild
cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise; cognitive training; and combined
aerobic exercise and cognitive training (ACT). We chose these biomarkers for their unique mechanistic
associations with cerebral amyloidosis, neurodegeneration and neurogenesis. Our central hypothesis is that
blood biomarkers change differently as a result of these 3 interventions and predict cognitive responses to
these interventions. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2×2
factorial Phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and
MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n=128). The ACT Trial will
randomize older adults with aMCI equally to 1 of 4 groups (aerobic exercise, cognitive training, ACT, and
attention control) for 6 months and then follow them for another 12 months. Cognition will be assessed at
baseline, 3, 6, 12, and 18 months, and AD-signature cortical thickness and hippocampal volume will be
assessed by MRI at baseline, 6, 12, and 18 months. In this ancillary blood biomarker study, we will enroll 120
ACT Trial participants and measure blood biomarkers at baseline, 3, 6, 12, and 18 months. The specific aims
are: (1) Determine the effects of interventions on blood biomarkers over 6 months in aMCI; (2) Evaluate blood
biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months in aMCI;
and (3; exploratory) Examine the correspondence between changes in blood and MRI biomarkers in response
to interventions over 18 months in aMCI. We have established the feasibility of enrollment, retention, and blood
collections in an ancillary blood biomarker study in our ongoing RCT of aerobic exercise effects in AD. By
examining the synergistic effects of ACT on blood biomarkers and the potential of ...

## Key facts

- **NIH application ID:** 10190758
- **Project number:** 5R01AG059654-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Danni Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $480,197
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190758

## Citation

> US National Institutes of Health, RePORTER application 10190758, Blood Biomarkers as Surrogate Endpoints of Treatment Responses to Aerobic Exercise and/or Cognitive Training in Amnestic Mild Cognitive Impairment (5R01AG059654-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10190758. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*