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

NCT03313895 | Completed DMC

• 1 other identifier: STUDY00001135
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Mild Cognitive Impairment

Keywords

Alzheimer's disease; exercise; cognitive training; imaging

Outcome Measures

Primary Outcomes (6)

• Executive function

  EXAMINER

  Change from baseline to 3, 6, 12, and 18 months

• Episodic memory

  RAVLT and BVMTR

  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

• 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

Study Arms (4)

Cycling Only

ACTIVE COMPARATOR

Moderate-intensity cycling, 3 times a week for 6 months, supervised by an exercise specialist

Behavioral: Cycling Only

Cognitive Training Only

ACTIVE COMPARATOR

Computerized cognitive training, 3 times a week for 6 months, supervised by a specialist

Behavioral: Cognitive Training Only

ACT

EXPERIMENTAL

Moderate-intensity cycling followed by computerized cognitive training, 3 times a week for 6 months, supervised by a specialist

Behavioral: Aerobic & Cognitive Training (ACT)

Stretching and Mental Stimulation Activities

SHAM COMPARATOR

Stretching and mental stimulation activities, 3 times a week for 6 months, supervised by a specialist

Behavioral: Stretching and Mental Stimulating Activities

Interventions

Aerobic & Cognitive Training (ACT) BEHAVIORAL

ACT stands for combined aerobic exercise and cognitive training.

ACT

Cycling Only BEHAVIORAL

Cycling on a recumbent stationary cycle

Cycling Only

Cognitive Training Only BEHAVIORAL

Engage in cognitive training on a computer

Cognitive Training Only

Stretching and Mental Stimulating Activities BEHAVIORAL

Stretching exercises and mental stimulating activities on a computer

Stretching and Mental Stimulation Activities

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arizona State University: lead
• University of Rochester: collaborator
• Mayo Clinic: collaborator
• University of St Thomas: collaborator
• University of Minnesota: collaborator

Study Sites (4)

Arizona State University

Phoenix, Arizona, 85004, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (4)

• Derboghossian G, Pituch K, Anthony M, Salisbury D, Lin FV, Yu F. Relationships among cardiorespiratory fitness, brain age, and neurodegeneration in older adults with amnestic mild cognitive impairment. J Alzheimers Dis. 2025 Jun;105(3):945-954. doi: 10.1177/13872877251333613. Epub 2025 Apr 22.

  PMID: 40262108 DERIVED

• Salisbury DL, Lin FV, Yu F. Testing the iMplementation Framework fOr behavioral and LIfestyLe interventions in AlZheimer's DiseasE (MOBILIZE) via the ACT randomized controlled trial. Sci Rep. 2025 Feb 13;15(1):5341. doi: 10.1038/s41598-025-88890-9.

  PMID: 39948366 DERIVED

• 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.

  PMID: 31907024 DERIVED

• 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.

  PMID: 30577848 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Motor Activity

Interventions

Cognitive Training

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Behavior

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Fang Yu, PhD

  Arizona State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: October 18, 2017
• Study Start: July 5, 2018
• Primary Completion: July 17, 2024
• Study Completion: July 17, 2024
• Last Updated: April 25, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)