Dose Response Study of Aerobic Exercise in Older Adults

Study Overview
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Brief Summary
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This is a randomized, 26-week study of supervised exercise assessing three doses of exercise in sedentary individuals 65 years of age and over with age-related cognitive changes. A total of 100 subjects (n=25 in each of four groups) will be randomized to a non-aerobic control group, 75 minutes, 150 minutes, or 225 minutes a week of moderate intensity aerobic exercise spread over 3 to 5 days a week for 26 weeks. These exercise doses represent 50%, 100%, or 150% of the recommended exercise dose. Participants will be directly supervised during all exercise sessions for the first two months after which direct supervision will occur during at least one session a week. This is intended to provide increased flexibility while also maintaining direct contact with the participant to enhance adherence. Aerobic fitness, physical function, and cognition will be assessed at baseline and 26 weeks to examine the dose-response relationships.

Official Title
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Dose Response Study of Exercise for Age-related Cognitive Changes

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Behavioral: Nonexercise control group
* Behavioral: Aerobic Exercise Group 1
* Behavioral: Aerobic Exercise Group 2
* Behavioral: Aerobic Exercise Group 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Age 65 years or older Underactive or sedentary based on the Telephone Assessment of Physical Activity Community dwelling with a caregiver willing to accompany the participant to visits to the screening evaluation. The caregiver must visit with the subject more than five times a week. Nondemented: Clinical Dementia Rating (CDR) 0 Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments Stable doses of medications for at least 30 days prior to screening. Likely to participate in all scheduled evaluations and complete the exercise program over 52 weeks Exclusion Criteria: Dementia CDR > 0 Current clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to Diagnostic Statistical Manual (DSM)-IV criteria or Geriatric Depression score of 5 or greater. Significant psychiatric symptoms (e.g., hallucinations) that could impair the completion of the study Current clinically-significant systemic illness likely to result in deterioration of the patient's condition or affect the patient's safety during the study History of clinically-evident stroke Clinically-significant infection within the last 30 days Myocardial infarction or symptoms of coronary artery disease (e.g., angina) in the last two-years. Uncontrolled hypertension within the last 6 months History of cancer within the last 5 years (except non-metastatic basal or squamous cell carcinoma) History of drug or alcohol abuse as defined by DSM-IV criteria within the last 2 years Insulin-dependent diabetes mellitus Significant pain or musculoskeletal disorder that would prohibit participation in an exercise program

Ages Eligible for Study
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Minimum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nonexercise control group<br> | Behavioral: Nonexercise control group<br>* Participants randomized to the nonexercise control group will be asked to maintain their current level of physical activity during the 26-week active study period. They will perform outcome assessments and receive the same telephone checks as the exercise group at baseline, 26 and 52 weeks. The purpose of including a non-exercise control group is to allow adequate comparisons with the low, medium and high exercise dose groups on changes in cognitive and physiologic outcome measures.<br>|
| Experimental: Aerobic Exercise Group 1<br> | Behavioral: Aerobic Exercise Group 1<br>* The 50% group will perform 75 minutes a week of moderate intensity exercise spread over 3 days.<br>|
| Experimental: Aerobic Exercise Group 2<br> | Behavioral: Aerobic Exercise Group 2<br>* The 100% group will perform 150 minutes a week of exercise over 3 - 5 days<br>|
| Experimental: Aerobic Exercise Group 3<br> | Behavioral: Aerobic Exercise Group 3<br>* The 150% group will perform 225 minutes a week of exercise over 4 - 5 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visuospatial Processing | Visuospatial Processing is a latent derived variable derived estimated mean.The reported latent means for this trial are created from the well-known neuropsychological tests: Block Design, Stroop Color Reading, Digit Symbol Substitution and Trailmaking Test A. Latent variables cannot be measured directly but are derived from a theory-driven confirmatory factor analysis in a structural equation model framework. The latent scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores. Positive number indicate improved performance. Negative numbers indicate worsening performance. | 26 weeks | 
| Change in Maximal Oxygen Consumption | Maximal Oxygen consumption (VO2 max) is the standard, quantitative measure of aerobic fitness. The physiologic range of scores is approximately 3.5 milliliters of oxygen per kilogram of body weight per minute (ml/kg/min) to approximately 90 (ml/kg/min). Higher numbers indicate greater fitness and positive change indicates increasing fitness. Lower number indicate worse fitness | 26 weeks | 
| Change in Physical Performance Test | The Physical Performance Test is a 9-item measure of physical function. The range of scores is 0-34. Higher numbers indicate better physical function. Positive change indicates improving function. Negative change indicates decreasing function. | 26 Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal Memory | Verbal Memory is a latent derived variable derived estimated mean. The reported latent means for this trial are created from the well-known neuropsychological tests: Logical Memory, Delayed Logical Memory, Selective Reminding Task - Free Recall Total, Boston Naming Test. Latent variables cannot be measured directly but are derived from a theory-driven confirmatory factor analysis in a structural equation model framework. The latent scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores. Positive number indicate improved performance.Negative numbers indicate worsening performance. | 26 weeks | 
| Simple Attention | Simple Attention is a latent derived variable derived estimated mean. The reported latent means for this trial are created from the well-known neuropsychological tests: Digit span Forward and Backward, Letter Numbers Sequencing. Latent variables cannot be measured directly but are derived from a theory-driven confirmatory factor analysis in a structural equation model framework. The latent scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores. Positive number indicate improved performance. Negative numbers indicate worsening performance. | 26 Weeks | 
| Set Maintenance & Shifting | Set Maintenance and Switching is a latent derived variable derived estimated mean. The reported latent means for this trial are created from the well-known neuropsychological tests: DKEFS Card Sort, Animal and Vegetable Category Fluency. Latent variables cannot be measured directly but are derived from a theory-driven confirmatory factor analysis in a structural equation model framework. The latent scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores. Positive number indicate improved performance. Negative numbers indicate worsening performance. | 26 Weeks | 
| Reasoning | Reasoning is a latent derived variable derived estimated mean. The reported latent means for this trial are created from the well-known neuropsychological tests:Letter and Word Inductive Reasoning, Matrix Reasoning. Latent variables cannot be measured directly but are derived from a theory-driven confirmatory factor analysis in a structural equation model framework. The latent scores are centered around a mean of 0 and standardized so each value represents a fraction of the standard deviation. There are no limits to the scores. Positive number indicate improved performance. Negative numbers indicate worsening performance. | 26 Weeks |