Neuroimaging Study of Exercise and Memory Function

Study Overview
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Brief Summary
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The investigators are examining the effects of exercise and cardiovascular fitness on cognitive processes, brain function, and the amount of several proteins in the blood. These proteins include a hormone called cortisol, also known as the stress hormone, and a growth factor called brain-derived neurotrophic factor (BDNF). The stress hormone cortisol is produced by the adrenal glands. Stress, exercise, obesity, and other factors may influence cortisol levels. BDNF is a protein that promotes the health of nerve cells in the brain and in the body. It plays a role in the growth, maturation, and maintenance of these cells. The amount of this protein in blood samples is therefore an indicator of healthy nerve cell function. Here, the investigators are investigating if exercise improves brain function by changing BDNF levels. Participation in this research study will take approximately 4 months. During this time, participants will make four initial study visits. The first visit is for informed consent and screening, the second and third visits are for baseline fitness testing, and the fourth visit is for a blood draw, cognitive testing, and a functional Magnetic Resonance Imaging (fMRI) exam. Functional MRI is a brain imaging technique that uses a magnetic field to take pictures of the brain while a person performs a given task. It will take up to approximately three weeks to complete these initial four study visits. Following the four initial study visits, the exercise-training program will begin. Participants will be randomized to one of two training programs: an aerobic exercise program and a non-aerobic exercise program consisting of strengthening, balance and stretching exercises. The exercise training program will last 12 weeks. There will be three one-hour exercise sessions per week. After completion of the exercise-training program, participants will attend three follow-up study visits. The first two follow-up visits are for fitness testing. The third and final follow-up visit is for a blood draw, cognitive testing, and an MRI exam.

Official Title
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Aerobic Exercise, Neurotrophins, and fMRI of Hippocampal Function and Structure

Conditions
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Aging

Intervention / Treatment
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* Behavioral: Aerobic Exercise
* Behavioral: Non-Aerobic Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking Age between 18-35 years or between 55-85 years Sedentary status (physically inactive) Generally healthy Native-English speaker Exclusion Criteria: Diagnosis of severe anemia Past or present condition that affect cognitive functioning: learning disability neurological disorders or conditions (movement disorder, history of head trauma or stroke, epilepsy, etc.) psychiatric disorders or conditions (depression, anxiety disorder, etc.) Poor vision that cannot be corrected with glasses or contact lenses Presence of an infection Diagnosis of kidney failure Diagnosis of liver disease Diagnosis of thyrotoxicosis/hyperthyroidism Diagnosis of cancer Past or present conditions that are counter indicators for participation in cardio-respiratory fitness assessment and physical exercise: heart (e.g. heart attack, arrhythmias, etc.) circulatory (e.g. uncontrolled hypertension, high cholesterol, etc.) respiratory conditions (e.g., asthma or lung conditions, such as chronic obstructive pulmonary disease, acute bronchitis, acute common cold, lung cancer, pneumonia, etc.) current musculoskeletal impairments (e.g. leg claudication, fractures, hemiplegia, chronic joint pain, arthritis, osteoporosis, not able to walk comfortably without assistance, etc.) diagnosis of electrolyte disorder or abnormality presence of diabetes mellitus Claustrophobia (fear of small, encloses spaces) Female subjects: breast-feeding or potentially pregnant Obesity Eating disorder Compulsive exercising Ferro-magnetic metal in or on the body that cannot be removed (e.g. pacemaker, defibrillator, permanent tattoo or eyeliner with metallic specks) Prescription medication or other drugs that are cardio-active Prescription medication or other drugs that are psycho-active Drug abuse or alcohol misuse Regularly exercising Unavailable for the approximately 4-month duration of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Sedentary Young Adults<br>Participants 18-35 years of age will be randomized to either aerobic or non-aerobic exercise training. | Behavioral: Aerobic Exercise<br>* The goal of the aerobic exercise training is to increase aerobic endurance. Walking on treadmill at moderate intensity with grade adjusted. Exercise tailored to individual ability level.<br>* Other names: Endurance Training;Behavioral: Non-Aerobic Exercise<br>* The goal of this training is to improve overall muscle strength, balance and flexibility. Participants will do strength, balance and stretching exercises. Exercises tailored to individual ability level.<br>* Other names: Strength, balance, stretching;|
| Experimental: Healthy Sedentary Older Adults<br>Participants 55-85 years of age will be randomized to either aerobic or non-aerobic exercise training. | Behavioral: Aerobic Exercise<br>* The goal of the aerobic exercise training is to increase aerobic endurance. Walking on treadmill at moderate intensity with grade adjusted. Exercise tailored to individual ability level.<br>* Other names: Endurance Training;Behavioral: Non-Aerobic Exercise<br>* The goal of this training is to improve overall muscle strength, balance and flexibility. Participants will do strength, balance and stretching exercises. Exercises tailored to individual ability level.<br>* Other names: Strength, balance, stretching;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI | Measurement of brain activity during task performance and measurement of change in regional brain volumes. | 1.5 to 2 hours each at Visits 4 and 43 | 
| Serum BDNF level | Fasting blood draw on same day of MRI to measure change in serum BDNF from baseline to follow-up | 5 minutes each at Visits 4 and 43 | 
| Memory test performance | Participants will perform recognition memory tests during and after functional MRI. Measurements include baseline-to-follow-up change in reaction times and accuracy. | 1.5 to 2 hours each at Visits 4 and 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aerobic capacity and muscle strength | Participants will perform two treadmill tests and several muscle strength tests to estimate baseline-to-follow-up change in aerobic capacity, measure change in time on treadmill, and determine change in muscle strength. | 80 min each at Visits 2, 3, 41 and 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain, Brain-Derived Neurotrophic Factor, Brain Mapping, Cognition, Exercise, Hippocampus, Hydrocortisone, Learning, Memory, Magnetic Resonance Imaging, Nerve Growth Factors, Neuroimaging, Physical Endurance, Physical Fitness, Resistance Training, Walking