# Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training in MCI_The ACT Trial COVID Admin Sup

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2023 · $405,487

## Abstract

Brief Summary of Protocol (5,000 characters max)
The purpose of this single-blinded, 2×2 factorial Phase II randomized controlled trial (RCT) is to test the
efficacy and additive/synergistic effects of a 6-month combined cycling and speed of processing (SOP) training
intervention on cognition and relevant mechanisms (aerobic fitness, AD signature cortical thickness, and
functional connectivity in the default mode network [DMN]) in older adults with amnestic MCI (aMCI). Our
preliminary studies have shown that enhanced aerobic fitness is associated with better cognition and resting-
state functional connectivity in the DMN in AD, and ~20 hours of SOP training improves executive function and
maintains functional connectivity in the DMN in aMCI. This RCT will randomize 128 participants equally to 4
arms: ACT, cycling only, SOP training only, or attention control for 6 months, and then follow them for another
12 months. Cognition and aerobic fitness will be assessed at baseline, 3, 6, 12, and 18 months; AD signature
cortical thickness and functional connectivity in the DMN at baseline, 6, 12, and 18 months; AD conversion at
3, 6, 12, and 18 months. The specific aims are to: Aim I. Determine the efficacy and additive/synergistic effects
of ACT on cognition over 6 months. H1: ACT will have the greatest effects on executive function and episodic
memory compared with other groups. Aim II. Examine the underlying mechanisms of ACT over 6 months. H2a:
ACT will have the greatest effects on AD signature cortical thickness, functional connectivity in the DMN, and
aerobic fitness compared with other groups. H2b: Changes in the mechanistic measures are related to
cognitive changes. H2c: Changes in AD signature cortical thickness and DMN mediate aerobic fitness' effects
on cognition. Aim III (exploratory). Calculate the long-term effect sizes of ACT on cognition and clinical and
pathological AD conversion to inform future Phase III RCTs. Analysis will use intention-to-treat and linear
mixed-effect modeling. This trial will be the first to test the synergistic effects on cognition and mechanisms
(relevant to AD-associated neurodegeneration) of a uniquely conceptualized and rigorously designed ACT in
older adults with aMCI. It will advance AD prevention research by providing precise effect-size estimates of the
ACT intervention. Our long-term goal is to delay AD onset and slow AD progression.

## Key facts

- **NIH application ID:** 10747055
- **Project number:** 3R01AG055469-05S1
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Feng Vankee Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $405,487
- **Award type:** 3
- **Project period:** 2021-04-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747055

## Citation

> US National Institutes of Health, RePORTER application 10747055, Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training in MCI_The ACT Trial COVID Admin Sup (3R01AG055469-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10747055. Licensed CC0.

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