The Entorhinal Cortex and Aerobic Exercise in Aging

Study Overview
=================
Brief Summary
-----------------
The overall goal of this study is to examine how regular exercise affects brain function, spatial memory, and virtual navigation. Participation in this research study will take approximately 4 months.

Detailed Description
-----------------
The investigators are examining the effects of exercise and cardiovascular fitness on cognitive processes. Specifically, the investigators are examining if exercise improves brain function in a brain area known as the entorhinal cortex. Together with the hippocampus this brain area is important for memory formation and spatial navigation. Participation in this research study will take approximately 4 months. During this time, participants will make three initial study visits. The first visit is for informed consent and screening, the second visit is for baseline fitness testing, and the third visit is for cognitive testing and a functional MRI exam. Functional MRI is a brain imaging technique that uses a magnetic field to take pictures of the brain while a person performs a cognitive task. It will take up to approximately three weeks to complete these initial three study visits. Following the three initial study visits, the exercise-training program will begin. Participants will be randomized to one of two training programs: a cardiovascular endurance-training program (aerobic exercise) and a strength, balance, and flexibility training program (non-aerobic exercise). 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 two follow-up study visits. The first follow-up visit is for fitness testing. The second follow-up visit is for cognitive testing and an MRI exam.

Official Title
-----------------
The Entorhinal Cortex and Aerobic Exercise in Aging

Conditions
-----------------
Aging

Intervention / Treatment
-----------------
* Behavioral: Cardiovascular endurance
* Behavioral: Strength, balance, and flexibility


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 60-80 years Physical inactivity/sedentary status (The American College of Sports Medicine defines a sedentary lifestyle as a lifestyle in which a person is not participating in at least 30 minutes of moderate intensity physical activity on at least three days per week for at least three months.) Generally healthy Living in the greater Boston area Fluent in English (must have attended elementary school and higher in English) Non-smoking Exclusion Criteria: Poor vision that cannot be corrected with glasses or contact lenses Presence of an acute infection Diagnosis of kidney failure Diagnosis of liver disease Diagnosis of thyrotoxicosis/hyperthyroidism Diagnosis of cancer Diagnosis of severe anemia Past or present conditions that affect cognitive functioning: learning disability neurological disorders or conditions (movement disorder, history of head trauma or stroke, epilepsy, etc.) psychiatric disorders or conditions within last 5 years (depression, anxiety disorder, etc.) Severe stress Evidence of cognitive impairment (e.g. dementia) Claustrophobia (fear of small, enclosed spaces) Obesity Past or present conditions that are counter indicators for participation in cardio-respiratory fitness assessment and physical exercise: heart conditions (e.g. heart attack, arrhythmias, etc.) circulatory conditions (e.g. uncontrolled hypertension, leg claudication, 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. 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 Prescription medication or other drugs that treat heart, lung, or circulatory conditions (e.g. beta blockers, bronchodilators, etc.) Prescription medication or other drugs that affect chemicals in the brain (e.g. antidepressants, anxiolytics, etc.) Drug abuse or alcohol misuse Metal in or on the body that cannot be removed (e.g. pacemaker, defibrillator, metal implant that is ferrous) Some known abnormal MRI findings (case by case basis) Regularly exercising Unavailable for the approx. 4-month duration of the study

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiovascular endurance<br>Participants will undergo cardiovascular endurance training. The trainer-supervised endurance training will involve walking on a treadmill at moderate intensity | Behavioral: Cardiovascular endurance<br>* Physical exercise at the Boston University Fitness and Recreation Center<br>|
| Active Comparator: Strength, balance, and flexibility<br>Participants will undergo Strength, balance, and flexibility training. | Behavioral: Strength, balance, and flexibility<br>* Physical exercise at the Boston University Fitness and Recreation Center<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional MRI - Right Subiculum | The fMRI is measuring blood oxygenation levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. This measurement was obtained while participants were performing a virtual navigation task in the MRI scanner. Data reported for fMRI is in beta-weight for navigation greater control contrast of BOLD images. The beta-weight is a standardized regression coefficient. Higher beta-weights mean greater activation and lower beta-weights mean less activation in specific brain regions being monitored. Negative beta-weights mean lower activation for the navigation condition than for the control condition, positive beta-weights mean greater activation for the navigation condition than for the control condition. | 0 months-baseline (pre-intervention) | 
| Structural MRI - Right Dentate Gyrus Head | Measurement of regional brain volumes in the medial temporal lobes to assess change in regional brain volumes. Reported outcome measure is volume of the right anterior (i.e., head) dentate gyrus, a hippocampal subfield known to show plasticity in response to exercise in animal models. The hippocampus is part of the medial temporal lobes. | 0 months-baseline (pre-intervention) | 
| Cognitive Test Performance: Spatial Memory | Participants will perform a spatial memory test during functional MRI. Measurements include baseline-to-follow-up change test performance. | 4 months | 
| Cognitive Test Performance: Virtual Navigation | Participants will perform a virtual navigation test during functional MRI. Measurements include baseline-to-follow-up change in test performance. | 4 months | 
| Functional MRI - Post-intervention Right Subiculum | The fMRI is measuring blood oxygenation levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. This measurement was obtained while participants were performing a virtual navigation task in the MRI scanner. Data reported for fMRI is in beta-weight for navigation greater control contrast of BOLD images. The beta-weight is a standardized regression coefficient. Higher beta-weights mean greater activation and lower beta-weights mean less activation in specific brain regions being monitored. Negative beta-weights mean lower activation for the navigation condition than for the control condition, positive beta-weights mean greater activation for the navigation condition than for the control condition. | 4 months | 
| Structural MRI - Post-intervention Right Dentate Gyrus Head | Measurement of regional brain volumes in the medial temporal lobes to assess change in regional brain volumes. Reported outcome measure is volume of the right anterior (i.e., head) dentate gyrus, a hippocampal subfield known to show plasticity in response to exercise in animal models. The hippocampus is part of the medial temporal lobes. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aerobic Capacity | Participants will perform a treadmill test to estimate baseline-to-follow-up change in aerobic capacity. Aerobic capacity is the maximum amount of oxygen (O2;(expressed in volume: VO2) a person can utilize during strenuous exercise. This maximum volume of oxygen is known as VO2max or aerobic capacity. For this study, we measured heart rate during the treadmill test and estimated VO2max from heart rate, thus we estimated VO2max rather than measured oxygen and carbondioxyde in the breath while exercising. VO2max is expressed in milliliters per kilogram of body weight per minute (ml/kg/min). We calculated percentage change from baseline to post-intervention. | 4 months | 
| Muscle Strength | Participants will perform several muscle strength tests to estimate baseline-to-follow-up change in muscle strength. Percentage change in chess press weight lifted is reported in results. | 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
walking, brain, brain mapping, cognition, exercise, physical activity, hippocampus, entorhinal cortex, spatial navigation, learning, memory, magnetic resonance imaging, functional neuroimaging, physical endurance, physical fitness, resistance training, muscle stretching exercises, exercise test, neuropsychological tests, executive function, attention, body composition