The Entorhinal Cortex and Aerobic Exercise in Aging (ECE)

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.

Study Overview

• Status: Terminated
• Conditions: Aging
• Intervention / Treatment: Behavioral: Cardiovascular endurance; Behavioral: Strength, balance, and flexibility

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body composition measurement	Measurement of lean body mass with bio-electrical impedance analysis (BIA) to estimate baseline-to-follow-up change in lean body mass.	12 weeks
Neuropsychological test score: spatial reasoning	Participants will perform several neuropsychological tests of spatial reasoning to measure baseline-to-follow-up change in spatial reasoning ability. A composite score will be calculated.	12 weeks
Neuropsychological test score: spatial cognition	Participants will perform several neuropsychological tests of spatial cognition to measure baseline-to-follow-up change in spatial cognition. A composite score will be calculated.	12 weeks
Neuropsychological test score: verbal memory	Participants will perform a neuropsychological test of verbal memory to measure baseline-to-follow-up change in verbal memory.	12 weeks
Neuropsychological test score: visuospatial memory	Participants will perform a neuropsychological test of visuospatial memory to measure baseline-to-follow-up change in memory.	12 weeks
Neuropsychological test score: executive function	Participants will perform a neuropsychological test of executive function to measure baseline-to-follow-up change in executive function.	12 weeks

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: National Institute on Aging (NIA); Brigham and Women's Hospital; Georgia Institute of Technology
• Investigators: Principal Investigator: Karin Schon, PhD, Boston University

Publications and helpful links

General Publications

• Kern KL, Storer TW, Schon K. Cardiorespiratory fitness, hippocampal subfield volumes, and mnemonic discrimination task performance in aging. Hum Brain Mapp. 2021 Mar;42(4):871-892. doi: 10.1002/hbm.25259. Epub 2020 Dec 16.

Helpful Links

• Brain Plasticity and Neuroimaging Laboratory at Boston University

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2018
• Primary Completion (Actual): February 9, 2021
• Study Completion (Actual): February 9, 2021

Study Registration Dates

• First Submitted: May 11, 2016
• First Submitted That Met QC Criteria: May 15, 2016
• First Posted (Estimate): May 18, 2016

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: memory; physical activity; magnetic resonance imaging; exercise; cognition; functional neuroimaging; exercise test; learning; body composition; walking; brain; executive function; resistance training; attention; physical fitness; neuropsychological tests; hippocampus; muscle stretching exercises; physical endurance; spatial navigation; brain mapping; entorhinal cortex
• Other Study ID Numbers: H-34579; R21AG049968 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No