The ACT Trial: Effects of Combined Aerobic Exercise and Cognitive Training in MCI

Study Overview
=================
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).

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).

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

Conditions
-----------------
Mild Cognitive Impairment

Intervention / Treatment
-----------------
* Behavioral: ACT
* Behavioral: Cycling Only
* Behavioral: Cognitive Training Only
* Behavioral: Stretching and Mental Stimulating Activities


Participation Criteria
=================
Eligibility Criteria
-----------------
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, and 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), and Abnormal MRI findings.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition | Change in the composite measures of executive function and episodic memory | Change from baseline to 3, 6, 12, and 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AD-signature cortical thickness | measured by the Magnetic Resonance Imaging (MRI) | Change from baseline to 6, 12, and 18 months | 
| Functional connectivity | measured by functional MRI | Change from baseline to 6, 12, and 18 months | 
| Aerobic fitness | measured by the symptom-limited peak cycle-ergometer test | Change from baseline to 3, 6, 12, and 18 months | 
| Conversion to Alzheimer's diseae | Change in memory, global cognition, and instrumental activities of daily living will be assessed to make a clinical decision if a participant has progressed from MCI to AD | Change in clinical status from MCI to AD at 6, 12, and 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cognitive impairment, Alzheimer's disease, exercise, cognitive training, imaging