Trial Outcomes & Findings for Exercise Effects on Brain Health and Learning From Minutes to Months (NCT NCT03114150)

Last Updated: 2025-08-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

122 participants

Primary outcome timeframe

Baseline, 24-weeks

Results posted on

2025-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	Moderate Intensity Aerobic Exercise First, Then Light Intensity Aerobic Exercise Crossover of Moderate Intensity Aerobic exercise condition followed by Light Intensity Aerobic Exercise for Acute exercise manipulation	Light Intensity Aerobic Exercise First, Then Moderate Intensity Aerobic Exercise Crossover of Light Intensity Aerobic exercise condition followed by Moderate Intensity Aerobic Exercise for Acute exercise manipulation	Cardiorespiratory Fitness Training Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness
Crossover: One Week STARTED	58	64	0	0
Crossover: One Week COMPLETED	58	61	0	0
Crossover: One Week NOT COMPLETED	0	3	0	0
Randomized Trial: 24 Weeks STARTED	0	0	60	56
Randomized Trial: 24 Weeks COMPLETED	0	0	55	52
Randomized Trial: 24 Weeks NOT COMPLETED	0	0	5	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Exercise Effects on Brain Health and Learning From Minutes to Months

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cardiorespiratory Fitness Training n=60 Participants Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training n=56 Participants Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness	Total n=116 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 6 • n=5 Participants	63.4 years STANDARD_DEVIATION 5 • n=7 Participants	63.3 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	35 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	57 Participants n=5 Participants	52 Participants n=7 Participants	109 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants	56 participants n=7 Participants	116 participants n=5 Participants
Cardiorespiratory fitness (VO2 max as ml/kg/min)	20.1 VO2 max (ml/kg/min) STANDARD_DEVIATION 5.2 • n=5 Participants	21.1 VO2 max (ml/kg/min) STANDARD_DEVIATION 5.8 • n=7 Participants	20.6 VO2 max (ml/kg/min) STANDARD_DEVIATION 5.5 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 24-weeks

Population: Participants with both pre- and post-intervention measurements.

Outcome measures

Outcome measures
Measure	Cardiorespiratory Fitness Training n=48 Participants Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training n=45 Participants Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness
Change in Hippocampal-dependent Learning	-.00369 learning rate (proportion correct/trial) Standard Deviation .03	.00404 learning rate (proportion correct/trial) Standard Deviation .04

SECONDARY outcome

Timeframe: Baseline, 30 minutes

Population: Before randomization in the parallel assignment intervention study, all participants completed an acute exercise manipulation that had a repeated measures, within-subject cross-over design for exposure to exercise intensity. Participants completed this acute exercise manipulation before randomization so participants are not yet in their chronic intervention arm. The N for each arm therefore corresponds to the n that was exposed to each of the acute exercise conditions.

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.

Outcome measures

Outcome measures
Measure	Cardiorespiratory Fitness Training n=118 Participants Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training n=122 Participants Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness
Change in Hippocampal-cortical Functional Connectivity	.001 functional connectivity (correlation) Standard Error .005	-.005 functional connectivity (correlation) Standard Error .005

SECONDARY outcome

Timeframe: Baseline, 24-weeks

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.

Outcome measures

Outcome measures
Measure	Cardiorespiratory Fitness Training n=50 Participants Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training n=48 Participants Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness
Change in Hippocampal-cortical Functional Connectivity	-.007 functional connectivity (correlation) Standard Deviation .07	-.005 functional connectivity (correlation) Standard Deviation .06

SECONDARY outcome

Timeframe: Baseline, 24-weeks

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.

Outcome measures

Outcome measures
Measure	Cardiorespiratory Fitness Training n=48 Participants Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training n=44 Participants Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness
Change in Cardiorespiratory Fitness	2.33 ml/kg/min Standard Deviation 2.26	.53 ml/kg/min Standard Deviation 2.40

Adverse Events

Moderate Intensity Aerobic Exercise

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Light Intensity Aerobic Exercise

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cardiorespiratory Fitness Training

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Functional Fitness Training

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Moderate Intensity Aerobic Exercise n=119 participants at risk Crossover condition of Moderate Intensity Aerobic Exercise preceding Light Intensity Aerobic Exercise for acute exercise manipulation	Light Intensity Aerobic Exercise n=122 participants at risk Crossover condition of Light Intensity Aerobic Exercise preceding Moderate Intensity Aerobic Exercise for acute exercise manipulation	Cardiorespiratory Fitness Training n=60 participants at risk Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down). Cardiorespiratory fitness training: Physical exercise of moderate intensity designed to improve cardiorespiratory fitness	Functional Fitness Training n=56 participants at risk Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups. Functional fitness training: Physical exercise of light intensity designed to improve functional fitness
Musculoskeletal and connective tissue disorders Pain (knee, joint, hip)	0.00% 0/119 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	0.00% 0/122 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	26.7% 16/60 • Number of events 16 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	8.9% 5/56 • Number of events 5 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.
Cardiac disorders Heart abnormality at peak at fitness test	0.00% 0/119 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	0.00% 0/122 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	6.7% 4/60 • Number of events 4 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	3.6% 2/56 • Number of events 2 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.
Nervous system disorders Incidental finding in MRI	0.00% 0/119 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	0.00% 0/122 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	0.00% 0/60 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	1.8% 1/56 • Number of events 1 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.
Infections and infestations Positive for COVID-19	0.00% 0/119 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	0.00% 0/122 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	3.3% 2/60 • Number of events 2 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.	0.00% 0/56 • The duration of enrollment for all participant, which includes from the time they signed informed consent until completion of their last post-intervention assessment. Typically this was 8 months.

Additional Information

Dr. Michelle Voss, Study Principal Investigator

The University of Iowa

Phone: 319-335-2057

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place