The Combined Aerobic Exercise and Cognitive Training (ACT) Trial: The ACT Trial

Efficacy and Mechanisms of Combined Aerobic Exercise and Cognitive Training (ACT) in MCI

This multi-site clinical trial occurs at the University of Minnesota and University of Rochester. It tests the efficacy and additive/synergistic effects of an ACT intervention on cognition and relevant mechanisms (aerobic fitness, Alzheimer's disease [AD] signature cortical thickness, and default mode network [DMN]) in older adults with amnestic MCI (aMCI).

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: Cycling Only; Behavioral: Cognitive Training Only; Behavioral: Stretching and Mental Stimulating Activities; Behavioral: Aerobic & Cognitive Training (ACT)

Detailed Description

Because almost all drug trials for Alzheimer's disease (AD) have failed, developing non-pharmacological interventions with strong potential to prevent or delay the onset of AD in high-risk populations (e.g., those with mild cognitive impairment [MCI]) is critically important. Aerobic exercise and cognitive training are 2 promising interventions for preventing AD. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective neural function intensively. Hence, combined Aerobic exercise and Cognitive Training (ACT) may very well have an additive or synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested ACT's effects, and those studies have reported discrepant findings, largely due to varying ACT programs. 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).

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Arizona State University
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A clinical diagnosis of MCI
• Community-dwelling
• Age 65 years and older
• English-speaking
• Adequate visual acuity
• Verified exercise safety by medical provider
• Stable on drugs affecting cognitive and psychological status
• Verified MRI safety
• Capacity to consent

Exclusion Criteria:

• Geriatric Depression Scale < 5
• Resting heart rate (HR) ≤50 due to arrhythmia or ≥100 beats/min
• Neurological (e.g., dementia, head trauma), psychiatric (e.g., bipolar, schizophrenia, or depression), or substance dependency (alcohol or chemical dependency) in the past 5 years that are the main contributor to MCI
• Contraindications to exercise, e.g. unstable angina, recent surgery
• New symptoms or diseases that have not been evaluated by a health care provider
• Current enrollment in another intervention study related to cognitive improvement (reduce confounding effects on outcomes)
• Abnormal MRI findings

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cycling Only; Moderate-intensity cycling, 3 times a week for 6 months, supervised by an exercise specialist	Behavioral: Cycling Only; Cycling on a recumbent stationary cycle
Active Comparator: Cognitive Training Only; Computerized cognitive training, 3 times a week for 6 months, supervised by a specialist	Behavioral: Cognitive Training Only; Engage in cognitive training on a computer
Experimental: ACT; Moderate-intensity cycling followed by computerized cognitive training, 3 times a week for 6 months, supervised by a specialist	Behavioral: Aerobic & Cognitive Training (ACT); ACT stands for combined aerobic exercise and cognitive training.
Sham Comparator: Stretching and Mental Stimulation Activities; Stretching and mental stimulation activities, 3 times a week for 6 months, supervised by a specialist	Behavioral: Stretching and Mental Stimulating Activities; Stretching exercises and mental stimulating activities on a computer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Executive function	EXAMINER	Change from baseline to 3, 6, 12, and 18 months
AD-signature cortical thickness	Magnetic Resonance Imaging (MRI)	Change from baseline to 6, 12, and 18 months
Episodic memory	RAVLT and BVMTR	Change from baseline to 3, 6, 12, and 18 months
Functional connectivity in DMN	Functional MRI for Default Mode Network	Change from baseline to 6, 12, and 18 months
Aerobic fitness	VO2peak from symptom-limited peak cycle-ergometer test, and 10-m Incremental Shuttle Walk Test	Change from baseline to 3, 6, 12, and 18 months
Conversion to Alzheimer's disease	Clinical adjudication of Alzheimer's disease dementia	Change from baseline to 6, 12, and 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AD-signature cortical thickness	Magnetic Resonance Imaging (MRI)	Change from baseline to 6, 12, and 18 months
Functional connectivity	Functional MRI for Default Mode Network	Change from baseline to 6, 12, and 18 months
Aerobic fitness	VO2peak from symptom-limited peak cycle-ergometer test	Change from baseline to 3, 6, 12, and 18 months
Conversion to Alzheimer's diseae	Clinical adjudication of Alzheimer's disease dementia	Change from baseline to 6, 12, and 18 months

Collaborators and Investigators

• Sponsor: Arizona State University
• Collaborators: Mayo Clinic; University of Minnesota; University of Rochester; University of St Thomas
• Investigators: Principal Investigator: Fang Yu, PhD, Arizona State University

Publications and helpful links

General Publications

• Li D, Mielke MM, Bell WR, Reilly C, Zhang L, Lin FV, Yu F. Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial). Trials. 2020 Jan 6;21(1):19. doi: 10.1186/s13063-019-3798-1.
• Yu F, Lin FV, Salisbury DL, Shah KN, Chow L, Vock D, Nelson NW, Porsteinsson AP, Jack C Jr. Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial. Trials. 2018 Dec 22;19(1):700. doi: 10.1186/s13063-018-3054-0.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2018
• Primary Completion (Actual): July 17, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 13, 2017
• First Posted (Actual): October 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: imaging; exercise; Alzheimer's disease; cognitive training
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: STUDY00001135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No