Exercise Effects on Brain Health and Learning From Minutes to Months

Study Overview
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Brief Summary
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Given the accelerating growth of older adults worldwide and the decline in cognitive function with aging, therapeutics that remediate age-related cognitive decline are needed more than ever. The proposed research seeks to better understand and enhance the detection of exercise effects on hippocampal network function and learning and memory, which decline with aging and Alzheimer's. Success would lead to new ways to detect benefits of exercise on cognitive aging and would lead to mechanistic insight on how such plasticity is possible while also informing prevention strategies.

Detailed Description
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Animal models robustly support that exercise protects brain areas vulnerable to aging such as the hippocampus and that these benefits lead to better learning. In contrast, there are mixed findings from human studies on the cognitive benefits of exercise with healthy older adults. This contrast indicates there is still a lack of understanding for how exercise could change the course of cognitive decline in aging adults. However, no human studies have comprehensively tested exercise effects on cognition in older adults with learning tasks inspired from basic exercise neuroscience. The objective in the proposed research is to fill this translational gap by determining if different types of exercise improve the same kinds of learning in older adults that have been shown to improve in animal models by improving hippocampal function. This will bring the investigators closer to a long-term goal of determining how exercise protects the brain from adverse effects of aging in order to develop interventions that minimize age-related cognitive decline. The overall hypothesis is that exercise improves learning when it increases functional hippocampal-cortical communication that otherwise declines with aging. The investigators will test this in a sample of healthy older adults by determining if increases in functional hippocampal-cortical connectivity from exercise training improve learning on an array of tasks that require the hippocampus for acquisition of new relational memories compared to conditions of the same tasks that should not require the hippocampus for learning and memory.

Official Title
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Exercise to Improve Hippocampal Connectivity and Learning in Older Adults

Conditions
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Sedentary Lifestyle

Intervention / Treatment
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* Behavioral: Cardiorespiratory fitness training
* Behavioral: Functional fitness training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible to participate in an aerobic exercise intervention based on the Physical Activity Readiness Questionnaire, and corrected vision of 20/40. Approval from a physician that monitored electrocardiography (ECG) response during a maximal aerobic fitness test that is part of the second study visit described below. Exercising less than 60 minutes a week for the past calendar year Exclusion Criteria: Not between the ages of 55 and 80 years old Not fluent in English Score < 20 (out of 30) on the Montreal Cognitive Assessment (MoCA) Inability to comply with experimental instructions Qualify as high risk for acute cardiovascular event by the published standards of the American College of Sports Medicine Previous diagnosis of neurological, metabolic, or psychiatric condition, and no previous brain injury associated with loss of consciousness Inability to complete an MRI

Ages Eligible for Study
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Minimum Age: 55 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiorespiratory fitness training<br>Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). | Behavioral: Cardiorespiratory fitness training<br>* Physical exercise of moderate intensity designed to improve cardiorespiratory fitness<br>|
| Active Comparator: Functional fitness training<br>Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. | Behavioral: Functional fitness training<br>* Physical exercise of light intensity designed to improve functional fitness<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hippocampal-dependent learning | Learning rate on constructs that have been examined in animal models including context acquisition, episodic associations, and spatial navigation. | Baseline, 24-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hippocampal-cortical functional connectivity | The strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system. | Baseline, 30 minutes | 
| Change in hippocampal-cortical functional connectivity | The strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system. | Baseline, 24-weeks | 
| Change in cardiorespiratory fitness | Cardiorespiratory fitness will be measured during a maximal exercise test. Oxygen uptake (VO2) will be measured from expired air samples taken at 30 second intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion. | Baseline, 24-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aging, physical activity, learning and memory, exercise, brain