Combined Exercise Trial

Study Overview
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Brief Summary
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The number of older Americans will double in the next 4 decades to nearly 90 million, placing an unprecedented financial and resource burden on the health care system. Exercise has clear and demonstrable physical benefits, but a more precise understanding of how exercise supports cognitive function is essential. Demonstrating definitively that exercise as recommended by public health entities has benefits for cognition would have enormous public health implications, encourage the public to adapt more active lifestyles, and stimulate the development of effective exercise delivery programs.

Detailed Description
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Older adults often experience physical decline that can be directly ameliorated by physical activity and exercise. Evidence is building that exercise prevents cognitive decline or delays the onset of debilitating dementia (e.g. Alzheimer's disease) yet, the optimal dose and combination of exercise modalities for promoting brain health, however, remains unknown and essentially untested. The long-term research goal of this project is to develop and test strategies to support successful aging and prevent Alzheimer's disease. The study will enroll 280 individuals, age 65 to 80 years without cognitive impairment, into a 26-week exercise intervention to test the combined and independent effects of aerobic and resistance training on cognition, brain structure, and physical function. The project will also explore underlying biological mechanisms that may link exercise with brain health. Participants will be randomized into 1 of 4 groups: flexibility, toning and balance (control), aerobic exercise training, progressive resistance training, or combined aerobic and resistance training. All intervention groups represent the most common modalities of exercise and directly reflect the public health recommendations for aerobic and resistance training. Exercise training will occur in a community setting through the network of Greater Kansas City Young Men's Christian Association. It is hypothesized that 26 weeks of exercise will improve 1) cognitive performance, 2) regional brain volume, 3) cardiorespiratory fitness and strength 4) biomarkers. This will be the largest study to assess the combined and independent effects of the two most recommended forms of exercise. Demonstrating specific exercise effects on cognitive function and brain health in older adults would have enormous public health implications. The study's results will also impact public health policy and education by providing evidence towards the specific or synergistic effects of aerobic and resistance training on cognition and brain structure. Encouraging the public to adapt more active lifestyles and stimulate the development of effective exercise delivery programs to enhance initiation and maintenance of physical activity interventions is key to increasing the number of quality years of life for America's aging population.

Official Title
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Differential Effects of Exercise Modality on Cognition and Brain in Older Adults

Conditions
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Healthy Aging

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65-80 yrs (inclusive at time of consent). Conversant English speaking and reading ability. Medical clearance by a health care provider. Reliable means of transportation. Telephone Interview of Cognitive Status score > 25 and adjudication of normal cognition based on cognitive test data by a study medical monitor. Exclusion Criteria: Intention to move out of the area or travel for more than 4 weeks in the next year. Use of an assistive device for ambulation. Joint pain severe enough to prevent taking walks in community, lifting objects over your head due to pain or restriction of movement, or that is worsened by increasing physical activity. Any MRI contraindications or refusal to attempt MRI. Treatment for alcohol or substance abuse in the last 2 years. Treatment for cancer (other than non-metastatic, localized cancer) in the last 2 years. Currently taking insulin. Diagnosis of heart disease, heart failure, heart attack, or heart surgery or chest pain with effort in the last 2 years. Untreated atrial fibrillation, valve replacements, angioplasty or stent placement in the last 2 years regardless of physician clearance. History of major psychiatric illness including schizophrenia (not including general anxiety disorder or depression), multiple sclerosis, Parkinson's, Dementia, mild cognitive impairment, brain injury (traumatic or clinically evident Stroke), or similar, likely to negatively impact cognitive testing. Head injury with loss of consciousness for more than a few minutes. Change in blood pressure medication in the last 2 months. Considered Active or engaging in a progressive resistance training 2 or more times a week. reported condition likely to compromise ability to safely perform exercise as determined by study medical monitor (e.g. chronic obstructive pulmonary disease, Lupus, end stage renal disease, etc.)

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Participants will be randomized to 1 of 4 study arms. Intervention arm include: core and fusion control condition; 150 minutes of endurance training (ET) only; 2 days a week of progressive weight training (WT) only; 150 minutes of ET and 2 days a week of WT. Participants exercise according to allocation for 1 year.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Core and Fusion Training<br>150 minutes/week of Core and Fusion exercise, a mix of low impact toning, strengthening, flexibility and balance exercises. | Behavioral: Exercise<br>* Standard public health exercise recommendations<br>* Other names: Weight Training, Aerobic Exercise, Progressive Resistance Exercise, Cross Training;|
| Active Comparator: Endurance Training<br>Moderate-intensity endurance training such as brisk walking, 150 minutes/week over 3-5 days. Progression based on a set schedule. In addition 0-2 days of Core and Fusion control exercise will also be recommended. | Behavioral: Exercise<br>* Standard public health exercise recommendations<br>* Other names: Weight Training, Aerobic Exercise, Progressive Resistance Exercise, Cross Training;|
| Active Comparator: Weight Training<br>Progressive resistance training 2 days/week, non-consecutive, of 2 sets (10 - 15 repetitions) of 10 exercises ( 75 minutes/week). Progression based on repetition completion and 1-repetition maximum. In addition 3 days of Core and Fusion control exercise will also be recommended. | Behavioral: Exercise<br>* Standard public health exercise recommendations<br>* Other names: Weight Training, Aerobic Exercise, Progressive Resistance Exercise, Cross Training;|
| Active Comparator: Combined Endurance and Weight Training<br>Moderate-intensity endurance training such as brisk walking, 150 minutes/week over 3-5 days. Progression based on a set schedule. Progressive resistance training 2 days/week, non-consecutive, of 2 sets (10 - 15 repetitions) of 10 exercises ( 75 minutes/week). Progression based on repetition completion and 1-repetition maximum. | Behavioral: Exercise<br>* Standard public health exercise recommendations<br>* Other names: Weight Training, Aerobic Exercise, Progressive Resistance Exercise, Cross Training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Cognition | Assessing change in cognitive function from baseline to 12 months. The 6 month measure is being used to assess the trajectory of the change. A comprehensive neuropsychological battery will be used that assesses a global cognition score derived from domains of cognition (e.g. Executive Function, Visuospatial Processing, Episodic Memory, Processing Speed). We will use a second order confirmatory factor analysis (CFA) to estimate the factor loadings between the observed indicators and the first order factors and between the first and second order factors. The CFA will use baseline data to avoid any potential intervention related biases. The primary outcome will be constructed by summing the weighted average (by the estimated first and second order loadings) of the standardized observed scores across the cognitive tests. | Baseline, 6 months, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal volume | Volume of bilateral hippocampus in milliliters | Baseline, 12 months | 
| Peak oxygen consumption | Peak volume of oxygen used in in milliliters per kilogram of body mass per minute during a graded maximal exercise test | Baseline, 12 months | 
| 1-Repetition Maximum | The maximum amount of mass that can be lifted one time (summed leg press and chest press) | Baseline, 12 months |