Effects of a Bicycling Intervention on Cognitive Skills and Cardiovascular Health

Study Overview
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Brief Summary
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Although exercise is known to delay cognitive decline and decrease our risk of Alzheimer's Disease, there is a lack of understanding of how exercise protects the aging brain. The proposed research takes a novel approach to this problem by testing the concept that there are acute, direct effects of exercise in the same brain regions that are affected by chronic exercise training. If the investigators are successful, the acute paradigm will allow us to determine the critical exercise parameters that modulate brain function in humans using only a single exercise dose.

Detailed Description
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Given the rising proportion of older adults worldwide and the progressive decline in brain function with advancing age, there is a pressing need to develop novel interventions that protect the aging brain. The predominant approach for implementing exercise training to improve brain function is to increase cardiovascular fitness. However, there is mixed empirical support for the effectiveness of this approach. Further, there are also acute effects of exercise within one hour of the cessation of a single exercise session. These effects occur before adaptations related to fitness could occur and animal studies have shown they occur in the same brain regions that benefit from longer-term exercise training. Therefore, the investigators propose the acute paradigm is a tool to probe this early, direct response from exercise in order to determine how best to maximize the long-term benefit of exercise training on the aging brain. This presents a critical need to determine the mechanistic relation between acute and long-term effects of exercise on the aging brain. Our long-term goal is to determine how exercise protects the brain from the adverse effects of aging. In turn, our specific objective in this R21 proposal is to support or refute the concept that a single session of exercise produces acute increases in functional synchrony of clinically relevant brain networks that are related to accrued exercise-training effects in the same brain systems. Our central hypothesis is that the effects of moderate intensity exercise will increase the functional synchrony of the hippocampus with the Default Mode Network, and the Prefrontal Cortex with the Fronto-Executive Network, in the same fashion as a 12-week moderate intensity exercise training program. This hypothesis is based on data showing acute effects of exercise on factors related to neuronal plasticity and excitability in the same brain regions that show long-term effects of exercise in animals. The contribution of the proposed research is significant because it will determine the extent to which the acute exercise paradigm can provide insight into how regular exercise protects the brain from adverse effects of aging. The proposed research is innovative because for the first time the investigators will examine the overlapping neural systems and outcomes associated with acute and chronic exercise in the same individuals. Overall, success in this project will enable future research to study how varying exercise parameters such as mode or intensity affect exercise-induced change in brain function and the timecourse of these effects, as well as the neurobiological mechanisms associated with the direct effects of exercise on the aging brain.

Official Title
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Effects of a Bicycling Intervention on Cognitive Skills and Cardiovascular Health

Conditions
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Sedentary Lifestyle

Intervention / Treatment
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* Behavioral: Cycling


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. Because our older adult sample is over the age of 40, we will also require completion of a detailed health history questionnaire and further eligibility for the exercise intervention will be determined following 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. Exclusion Criteria: Not between the ages of 60 and 80 years old Not fluent in English Score < 26 (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 Left-handed 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: 60 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Steady state moderate intensity cycling<br>Moderate intensity exercise training will be a 12-week supervised cycling program, 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 moderate intensity cycling and 30 minutes passive cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, we will add 6 minutes of moderate intensity cycling per session, 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: Cycling<br>* The experimental group will complete a 3 month exercise program that includes working up to cycling at a moderate intensity for 50 minutes/session 3 times a week. The comparison group will complete a 3-month exercise program that includes intermittent cycling (alternating between passive and moderate intensity) for 50 minutes/session 3 times a week. Both groups will exercise in our laboratory at Spence Labs, and will be supervised by an exercise trainer that is trained in working with elderly and special populations.<br>* Other names: Exercise;|
| Active Comparator: Intermittent cycling<br>The intermittent cycling group will come to the exercise lab for the same duration and frequency each week and complete primarily passive cycling such that a motor in the stationary bicycle moves the pedals for them. To maintain interest in this intervention, we will include short bouts of moderate intensity activity. The short bouts of moderate intensity cycling will be designed to be ineffective for substantially increasing cardiorespiratory fitness over the course of the intervention. | Behavioral: Cycling<br>* The experimental group will complete a 3 month exercise program that includes working up to cycling at a moderate intensity for 50 minutes/session 3 times a week. The comparison group will complete a 3-month exercise program that includes intermittent cycling (alternating between passive and moderate intensity) for 50 minutes/session 3 times a week. Both groups will exercise in our laboratory at Spence Labs, and will be supervised by an exercise trainer that is trained in working with elderly and special populations.<br>* Other names: Exercise;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional brain network integrity: the strength of the correlation between fluctuating functional magnetic resonance imaging (fMRI) signal in different brain regions of the Default Mode Network (DMN) and the Executive Control Network (ECN) at rest | Resting state brain networks known to be vulnerable to decline with normal aging | Change from baseline functional network integrity at 12-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor learning rate | Learning rate parameter expressing rate of reaction time speeding in an alternating serial reaction time task (ASRTT) | Change from baseline learning rate at 12-weeks | 
| Explicit paired associates learning rate | Learning rate parameter expressing rate of improvement in accuracy in a paired associates learning task | Change from baseline learning rate at 12-weeks | 
| Executive function composite measure | Composite score from performance (speed and accuracy) on four executive function tasks, including Trails A and B, Go/No-Go dual task, a modified flanker task, and a non-verbal working memory n-back task | Change from baseline executive function performance at 12-weeks | 
| Cardiovascular fitness measured as Vo2 max from a cycle ergometer test | The ability of the heart and lungs to supply oxygen to working muscle tissues and the ability of the muscles to use oxygen to produce energy for movement | Change from baseline fitness at 12-weeks | 

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