The Entorhinal Cortex and Aerobic Exercise in Aging

Not Applicable

Terminated

Conditions: Aging

Interventions: Behavioral: Cardiovascular endurance
Behavioral: Strength, balance, and flexibility

Registration Number: NCT02775760

Lead Sponsor: Boston University

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 29

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cardiovascular endurance	Cardiovascular endurance	Participants will undergo cardiovascular endurance training. The trainer-supervised endurance training will involve walking on a treadmill at moderate intensity
Strength, balance, and flexibility	Strength, balance, and flexibility	Participants will undergo Strength, balance, and flexibility training.

Primary Outcome Measures

Name	Time	Method
Functional MRI - Post-intervention Right Subiculum	4 months	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.
Cognitive Test Performance: Virtual Navigation	4 months	Participants will perform a virtual navigation test during functional MRI. Measurements include baseline-to-follow-up change in test performance.
Functional MRI - Right Subiculum	0 months-baseline (pre-intervention)	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.
Cognitive Test Performance: Spatial Memory	4 months	Participants will perform a spatial memory test during functional MRI. Measurements include baseline-to-follow-up change test performance.
Structural MRI - Post-intervention Right Dentate Gyrus Head	4 months	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.
Structural MRI - Right Dentate Gyrus Head	0 months-baseline (pre-intervention)	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.

Secondary Outcome Measures

Name	Time	Method
Muscle Strength	4 months	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.
Aerobic Capacity	4 months	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.