Exercise Effects on Brain Health and Learning From Minutes to Months

Michelle W. Voss122 enrolled

Overview

Given the accelerating growth of older adults worldwide and the decline in cognitive function with aging, therapeutics that remediate age-related cognitive decline are needed more than ever. The proposed research seeks to better understand and enhance the detection of exercise effects on hippocampal network function and learning and memory, which decline with aging and Alzheimer's. Success would lead to new ways to detect benefits of exercise on cognitive aging and would lead to mechanistic insight on how such plasticity is possible while also informing prevention strategies.

Animal models robustly support that exercise protects brain areas vulnerable to aging such as the hippocampus and that these benefits lead to better learning. In contrast, there are mixed findings from human studies on the cognitive benefits of exercise with healthy older adults. This contrast indicates there is still a lack of understanding for how exercise could change the course of cognitive decline in aging adults. However, no human studies have comprehensively tested exercise effects on cognition in older adults with learning tasks inspired from basic exercise neuroscience. The objective in the proposed research is to fill this translational gap by determining if different types of exercise improve the same kinds of learning in older adults that have been shown to improve in animal models by improving hippocampal function. This will bring the investigators closer to a long-term goal of determining how exercise protects the brain from adverse effects of aging in order to develop interventions that minimize age-related cognitive decline. The overall hypothesis is that exercise improves learning when it increases functional hippocampal-cortical communication that otherwise declines with aging. The investigators will test this in a sample of healthy older adults by determining if increases in functional hippocampal-cortical connectivity from exercise training improve learning on an array of tasks that require the hippocampus for acquisition of new relational memories compared to conditions of the same tasks that should not require the hippocampus for learning and memory.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Conditions

Sedentary Lifestyle

Interventions

Cardiorespiratory fitness trainingBEHAVIORAL

Physical exercise of moderate intensity designed to improve cardiorespiratory fitness

Functional fitness trainingBEHAVIORAL

Physical exercise of light intensity designed to improve functional fitness

Eligibility

Sex: ALLMin age: 55 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Eligible to participate in an aerobic exercise intervention based on the Physical Activity Readiness Questionnaire, and corrected vision of 20/40. * Approval from a physician that monitored electrocardiography (ECG) response during a maximal aerobic fitness test that is part of the second study visit described below. * Exercising less than 60 minutes a week for the past calendar year Exclusion Criteria: * Not between the ages of 55 and 80 years old * Not fluent in English * Score \< 20 (out of 30) on the Montreal Cognitive Assessment (MoCA) * Inability to comply with experimental instructions * Qualify as "high risk" for acute cardiovascular event by the published standards of the American College of Sports Medicine * Previous diagnosis of neurological, metabolic, or psychiatric condition, and no previous brain injury associated with loss of consciousness * Inability to complete an MRI

Locations (1)

University of Iowa

Iowa City, Iowa, United States

Outcomes

Primary Outcomes

Change in Hippocampal-dependent Learning

Learning rate on constructs that have been examined in animal models including context acquisition, episodic associations, and spatial navigation. The primary outcome is reported for the spatial navigation task that is associated with hippocampal structure and function, which is learning in the wayfinding condition. We report change in slope for wayfinding learning trials. The slope is computed based on the proportion of items correctly recalled on a map, over four learning trials. For each trial, proportion correct can range from 0 to 1, and a higher number represents faster learning, which is better.

Time frame: Baseline, 24-weeks

Secondary Outcomes

Change in Hippocampal-cortical Functional Connectivity

The change in strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system.

Time frame: Baseline, 30 minutes

Change in Hippocampal-cortical Functional Connectivity

The change in strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system.

Time frame: Baseline, 24-weeks

Change in Cardiorespiratory Fitness

Cardiorespiratory fitness will be measured during a maximal exercise test. Oxygen uptake (VO2) will be measured from expired air samples taken at 30 second intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion. Change in maximal VO2 is reported for descriptive results.

Time frame: Baseline, 24-weeks

Data from ClinicalTrials.gov

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