Neuroimaging Study of Exercise and Memory Function (EMF)

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

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.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Behavioral: Aerobic Exercise; Behavioral: Non-Aerobic Exercise

• Study Type: Interventional
• Enrollment (Actual): 190
• 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: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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:

  1. learning disability
  2. neurological disorders or conditions (movement disorder, history of head trauma or stroke, epilepsy, etc.)
  3. 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:

  1. heart (e.g. heart attack, arrhythmias, etc.)
  2. circulatory (e.g. uncontrolled hypertension, high cholesterol, etc.)
  3. respiratory conditions (e.g., asthma or lung conditions, such as chronic obstructive pulmonary disease, acute bronchitis, acute common cold, lung cancer, pneumonia, etc.)
  4. current musculoskeletal impairments (e.g. leg claudication, fractures, hemiplegia, chronic joint pain, arthritis, osteoporosis, not able to walk comfortably without assistance, etc.)
  5. diagnosis of electrolyte disorder or abnormality
  6. 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

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
Active Comparator: Healthy Sedentary Young Adults; Participants 18-35 years of age will be randomized to either aerobic or non-aerobic exercise training.	Behavioral: Aerobic Exercise; 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.; Other Names: Endurance Training; Behavioral: Non-Aerobic Exercise; 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.; Other Names: Strength, balance, stretching
Experimental: Healthy Sedentary Older Adults; Participants 55-85 years of age will be randomized to either aerobic or non-aerobic exercise training.	Behavioral: Aerobic Exercise; 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.; Other Names: Endurance Training; Behavioral: Non-Aerobic Exercise; 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.; Other Names: Strength, balance, stretching

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood cortisol levels	Cortisol levels will be obtained from the blood sample drawn during baseline and follow-up.	5 min each at Visits 4 and 43
Anthropometric measurements	Anthropometric measurements include height, weight, and body mass index. Percent body fat will also be estimated.	10 minutes each during Visits 2 and 41
Blood serum levels of other neurotrophins	The blood draw will be used for other neurotrophins related to exercise and cognition.	5 min each at Visit 4 and 43
Neuropsychological test performance	Baseline-to-follow-up change in performance of the Wechsler Adult Intelligence Scale-IV subtests	15-30 minutes each at Visits 4 and 43

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: National Institute on Aging (NIA)
• 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.
• Nauer RK, Dunne MF, Stern CE, Storer TW, Schon K. Improving fitness increases dentate gyrus/CA3 volume in the hippocampal head and enhances memory in young adults. Hippocampus. 2020 May;30(5):488-504. doi: 10.1002/hipo.23166. Epub 2019 Oct 7.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2018
• Last Update Submitted That Met QC Criteria: April 23, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Exercise; Magnetic Resonance Imaging; Memory; Hippocampus; Cognition; Brain; Walking; Resistance Training; Neuroimaging; Learning; Hydrocortisone; Physical Fitness; Brain-Derived Neurotrophic Factor; Brain Mapping; Nerve Growth Factors; Physical Endurance
• Other Study ID Numbers: H-32635; R00AG036845 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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