Aging, Exercise
Conditions
Keywords
Exercise, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Aging
Brief summary
The purpose of this research study is to test whether differing levels of physical fitness affects patterns of motor dexterity and brain activity that have been shown to differ due to aging. Testing will take place at the Atlanta VA Medical Center and at Emory University. Participants will be healthy adults within the target age range of 60-85 for the study. The study will require multiple visits over 15 months. There will be about 64 people volunteering for this study.
Detailed description
The U.S. Census reports over 14 million U.S. Veterans (\>63%) are beyond mid-life (\>55 years). Declines in upper extremity motor performance respective of strength and dexterity are well documented within this age cohort). Recent cross-sectional research has discovered that aging related motor deficits may be influenced by a loss of interhemispheric inhibition (IHI) between primary motor cortices. However, this loss may not be an inevitable consequence of aging. Work from previous VA OAA Predoctoral and CDA-1 awards have shown that aerobic fitness may serve to mitigate losses in interhemispheric inhibition assessed by both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS). That is, individuals who are aerobically fit show higher levels of IHI and improved dexterity and reaction times. In light of new evidence from the investigators' lab's recent cross-sectional studies, physical activity over the long term (at least 2-5 years) may serve to alter levels of IHI and improve motor performance in the upper extremity. Aerobic exercise may provide a mechanism (reduced loss of interhemispheric inhibition) that could serve to improve motor function, but the neural mechanism responsible for such effects remains unclear. Previous investigations of interhemispheric communication and exercise have been limited by nature of inquiry, as cross-sectional research cannot measure changes over time in participants. As such, it is currently unknown how exercise may directly affect levels of interhemispheric communication and motor performance. Behavioral interventions (motor strength and coordination) have been shown to be effective in improving upper extremity motor performance in older adults, however the duration of these gains appear to be short-lived. After as little as a few weeks of detraining, motor strength and coordination in the upper extremity rapidly begins to return to pre-intervention levels. Evidence from exercise interventions assessing gait and locomotion have shown that exercise programs over a longer term (\>6 months) are associated with improved proprioception, fewer falls and better balance. However, the comparison of outcomes of upper extremity function in elderly adults respective of exercise duration remains largely unexplored. In addition to comparing the effects of short-term exercise (3 months) versus behavioral training (3 months) on upper extremity function, the current proposal will evaluate if a longer-term (6 months) exercise program can maintain or enhance upper extremity function and associated levels of interhemispheric inhibition. The current study proposes the next logical step in my line of research and directly investigates the effects of exercise in an intervention with sedentary older Veterans (50-80 years), a group most likely to exhibit aging-related motor deficits. The investigators propose to enroll 40 Veterans into an upper extremity dexterity improvement program involving behavioral and exercise components. The behavioral intervention is a muscle coordination training previously shown to improve unimanual motor performance in older adults. The exercise intervention is a supervised group cycling regimen. The figure below shows the study design. Interhemispheric communication will be assessed with fMRI, and TMS.
Interventions
BEHAVIORALStretching Exercise Intervention
A. Light stretching and balance exercises under supervised trainer. 3 times per week for 20-45 minutes. HR will be targeted to be under 50% of age-related maximum.
BEHAVIORALAerobic Exercise Intervention
Supervised weekly exercise. 3 bouts of 45 minutes weekly on a cycle ergometer. HR will be kept at 75% of age-related maximum.
BEHAVIORALSelf Monitoring
6 month self-monitored training phase during which time participants will exercise according to prescribed regimen (cycling)
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
A. Light stretching and balance exercises under supervised trainer. 3 times per week for 20-45 minutes. HR will be targeted to be under 50% of age-related maximum. B. Interval aerobic cycling under supervised trainer. 3 times per week for 20-45 minutes. HR will be targeted between 50-85% of age-related maximum. C. 6 month self-monitored training phase during which time participants will exercise using a take home bike ergometer
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Living persons between 60 and 85 years of age
Exclusion criteria
* unmanaged diabetes * participants completing vigorous exercise per week * participants whose profession requires vigorous physical labor * contraindication to magnetic resonance imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Silent Period Duration After Balance Exercise | 24 and 48 weeks | Comparison of Home based training effects on TMS measures of silent period duration as compared to facility based exercise programs. |
| Comparison of Cardiovascular Efficiency for Aerobic Exercise First Group After Home-based Intervention | 24 and 48 weeks | Comparison of home based aerobic exercise intervention to assessments made after completion of crossover intervention in Participants receiving aerobic condition first. VO2peak estimation completed using the YMCA protocol investigating overall volume of oxygen consumption as a function of heart rate during work loads. Estimated VO2 peak values are in ml/kg(min). |
| Comparison of Cardiovascular Efficiency for Balance Exercise First Group After Home-based Intervention | 24 and 48 weeks | VO2peak estimation completed using the YMCA protocol investigating overall volume of oxygen consumption as a function of heart rate during work loads. |
| Comparison of Silent Period Duration After Aerobic Exercise | Baseline, 12 weeks, 24 weeks | Comparison of silent period duration at 24 weeks compared to baseline |
| Estimate Cardiovascular Efficiency After Aerobic Exercise | Baseline, 12 weeks, 24 weeks | Estimate of Volume of oxygen consumption (VO2peak) using YMCA protocol for cardiovascular assessment. |
| Estimate of Cardiovascular Efficiency After Balance Training | Baseline, 12 weeks, 24 weeks | Estimated VO2peak using YMCA cycle test completed over nine to twelve minutes. |
| Silent Period Duration After Exercise Cycling Program | Baseline, 12 weeks, 24 weeks | Duration of ipsilateral silent period from Transcranial magnetic stimulation measured in milliseconds |
| Silent Period Duration for Balance Group | Baseline, 12 weeks, 24 weeks | Ipsilateral silent period duration as assessed by TMS |
| fMRI Interhemispheric Inhibition Improvement After Aerobic Exercise | Baseline to 24 Weeks with cross-over | Participants who exercise will evidence larger increases in interhemispheric inhibition as assessed by functional magnetic resonance measured by a z-normalized area under curve of right primary motor cortex. The area under the curve is an estimate of the fMRI hemodynamic response impulse response function. A higher number of AUC indicates less interhemispheric inhibition. In contrast, a lower number in this analysis indicates higher interhemispheric inhibition. |
| fMRI Interhemispheric Inhibition Improvement After Balance Training | Baseline, 12 weeks, 24 weeks | Area under the curve of fMRI measures of right motor cortex BOLD profile will remain similar to pre measurements. The BOLD profile is the z-normalized area under the curve value of the fMRI impulse response function. A higher number indicates less interhemispheric inhibition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target Heart Rate Zone After Aerobic Exercise First | 24 and 48 weeks | Targeted Heart Rate Zone among participants compared among short term exercise groups |
| Heart Rate Workload After Home Based Intervention | 24 and 48 weeks | Measured heart rate after home based intervention Technical implementation at the facility level prevented acquisition of these metrics until late in the project. |
| Target Heart Rate Zone for Balance First Participants | 24 and 48 weeks | Heart rate in aerobic target zone is measured in percentage of time in at least 50% of participants heart rate reserve. |
Countries
United States
Participant flow
Recruitment details
Community-dwelling individuals were recruited for participation using approved flyer and advertising materials. All participants gave voluntary written consent prior to participation. After consenting, participants were randomly assigned to one of two 12-week exercise interventions involving a followed by cross-over to the other intervention.
Participants by arm
| Arm | Count |
|---|---|
| Exercise Interventions for Crossover Design This study was a cross-over design with two groups to which participants were randomized. Group one received a 12-week Aerobic exercise intervention and then crossed over into a balance exercise intervention. Group two received the balance intervention for 12 weeks and then crossed over into the aerobic exercise intervention. All completing participants then engaged in a home based exercise program during which they were instructed to exercise thrice weekly over 24 weeks. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Crossover Exercise Interventions | Withdrawal by Subject | 2 | 2 |
| Home Based Exercise Program | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Exercise Interventions for Crossover Design |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 25 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 69.05 years STANDARD_DEVIATION 5.98 |
| Cardiovascular Efficiency | 25.25 ml/kg(min) STANDARD_DEVIATION 9.74 |
| FMRI of Right Motor Cortex | 1.85 area under curve STANDARD_DEVIATION 1.2 |
| Ipsilateral Silent Period | 22.39 milliseconds STANDARD_DEVIATION 4.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 16 |
| other Total, other adverse events | 0 / 17 | 0 / 16 |
| serious Total, serious adverse events | 0 / 17 | 0 / 16 |
Outcome results
Primary
Comparison of Cardiovascular Efficiency for Aerobic Exercise First Group After Home-based Intervention
Comparison of home based aerobic exercise intervention to assessments made after completion of crossover intervention in Participants receiving aerobic condition first. VO2peak estimation completed using the YMCA protocol investigating overall volume of oxygen consumption as a function of heart rate during work loads. Estimated VO2 peak values are in ml/kg(min).
Time frame: 24 and 48 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Comparison of Cardiovascular Efficiency for Aerobic Exercise First Group After Home-based Intervention | Within one week of completing 24 week intervention | 25.25 ml/kg(min) | Standard Deviation 12.25 |
| Experimental: Aerobic First | Comparison of Cardiovascular Efficiency for Aerobic Exercise First Group After Home-based Intervention | Within one week of completing 48 Week Intervention | 21.2 ml/kg(min) | Standard Deviation 9.88 |
p-value: 0.01t-test, 2 sided
Primary
Comparison of Cardiovascular Efficiency for Balance Exercise First Group After Home-based Intervention
VO2peak estimation completed using the YMCA protocol investigating overall volume of oxygen consumption as a function of heart rate during work loads.
Time frame: 24 and 48 weeks
Population: Participants completed both exercise interventions but completed Balance training prior to engaging in aerobic exercise training.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Comparison of Cardiovascular Efficiency for Balance Exercise First Group After Home-based Intervention | Within one week of completing 24 week intervention | 25.5 ml/kg(min) | Standard Deviation 12.8 |
| Experimental: Aerobic First | Comparison of Cardiovascular Efficiency for Balance Exercise First Group After Home-based Intervention | Within one week of completing 48 Week Intervention | 20.8 ml/kg(min) | Standard Deviation 12.2 |
p-value: 0.5t-test, 2 sided
Primary
Comparison of Silent Period Duration After Aerobic Exercise
Comparison of silent period duration at 24 weeks compared to baseline
Time frame: Baseline, 12 weeks, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Comparison of Silent Period Duration After Aerobic Exercise | Pre | 20.58 milliseconds | Standard Deviation 7.5 |
| Experimental: Aerobic First | Comparison of Silent Period Duration After Aerobic Exercise | 12-Weeks | 26.2 milliseconds | Standard Deviation 7.5 |
| Experimental: Aerobic First | Comparison of Silent Period Duration After Aerobic Exercise | 24-week post-cross | 27.5 milliseconds | Standard Deviation 7.4 |
p-value: 0.6t-test, 2 sided
Primary
Comparison of Silent Period Duration After Balance Exercise
Comparison of Home based training effects on TMS measures of silent period duration as compared to facility based exercise programs.
Time frame: 24 and 48 weeks
Population: Participants completing balance training then crossing over into aerobic exercise were then tested for effects of facility based treatments against home exercise.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Comparison of Silent Period Duration After Balance Exercise | Within one week of completing 24 week intervention | 26.54 milliseconds | Standard Deviation 8.4 |
| Experimental: Aerobic First | Comparison of Silent Period Duration After Balance Exercise | Within one week of completing 48 Week Intervention | 21.6 milliseconds | Standard Deviation 9.3 |
p-value: 0.4t-test, 2 sided
Primary
Estimate Cardiovascular Efficiency After Aerobic Exercise
Estimate of Volume of oxygen consumption (VO2peak) using YMCA protocol for cardiovascular assessment.
Time frame: Baseline, 12 weeks, 24 weeks
Population: Estimated VO2 peak values in ml/kg(min)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Estimate Cardiovascular Efficiency After Aerobic Exercise | Baseline | 24.01 ml/kg(min) | Standard Deviation 9.29 |
| Experimental: Aerobic First | Estimate Cardiovascular Efficiency After Aerobic Exercise | 12-Week post | 31.2 ml/kg(min) | Standard Deviation 8.6 |
| Experimental: Aerobic First | Estimate Cardiovascular Efficiency After Aerobic Exercise | 24-week post-cross | 32.3 ml/kg(min) | Standard Deviation 6.8 |
p-value: 0.001ANCOVA
Primary
Estimate of Cardiovascular Efficiency After Balance Training
Estimated VO2peak using YMCA cycle test completed over nine to twelve minutes.
Time frame: Baseline, 12 weeks, 24 weeks
Population: Sedentary older adults who engaged in less than 45 minutes of regular exercise per week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Estimate of Cardiovascular Efficiency After Balance Training | Pre | 22.83 ml/kg(min) | Standard Deviation 7.35 |
| Experimental: Aerobic First | Estimate of Cardiovascular Efficiency After Balance Training | 12-Weeks | 24.72 ml/kg(min) | Standard Deviation 9.36 |
| Experimental: Aerobic First | Estimate of Cardiovascular Efficiency After Balance Training | 24-week post-cross | 23.58 ml/kg(min) | Standard Deviation 8.25 |
Comparison: To account for sequence carryover, we employed analysis of covariance inclusive of sequence by period covariates against treatment effects.p-value: 0.8ANCOVA
Primary
fMRI Interhemispheric Inhibition Improvement After Aerobic Exercise
Participants who exercise will evidence larger increases in interhemispheric inhibition as assessed by functional magnetic resonance measured by a z-normalized area under curve of right primary motor cortex. The area under the curve is an estimate of the fMRI hemodynamic response impulse response function. A higher number of AUC indicates less interhemispheric inhibition. In contrast, a lower number in this analysis indicates higher interhemispheric inhibition.
Time frame: Baseline to 24 Weeks with cross-over
Population: Analysis of area under curve of right primary motor cortical area
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | fMRI Interhemispheric Inhibition Improvement After Aerobic Exercise | Pre | 1.5 Z-transformed impulse response function | Standard Deviation 1.2 |
| Experimental: Aerobic First | fMRI Interhemispheric Inhibition Improvement After Aerobic Exercise | 12 week intervention | .58 Z-transformed impulse response function | Standard Deviation 0.98 |
| Experimental: Aerobic First | fMRI Interhemispheric Inhibition Improvement After Aerobic Exercise | 24 week post-crossover | .58 Z-transformed impulse response function | Standard Deviation 0.98 |
p-value: 0.01t-test, 2 sided
Primary
fMRI Interhemispheric Inhibition Improvement After Balance Training
Area under the curve of fMRI measures of right motor cortex BOLD profile will remain similar to pre measurements. The BOLD profile is the z-normalized area under the curve value of the fMRI impulse response function. A higher number indicates less interhemispheric inhibition.
Time frame: Baseline, 12 weeks, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | fMRI Interhemispheric Inhibition Improvement After Balance Training | Pre | 1.49 Z-transformed impulse response function | Standard Deviation 0.88 |
| Experimental: Aerobic First | fMRI Interhemispheric Inhibition Improvement After Balance Training | 12-Weeks | .62 Z-transformed impulse response function | Standard Deviation 0.52 |
| Experimental: Aerobic First | fMRI Interhemispheric Inhibition Improvement After Balance Training | 24-week post-cross | .62 Z-transformed impulse response function | Standard Deviation 0.52 |
p-value: 0.01t-test, 2 sided
Primary
Silent Period Duration After Exercise Cycling Program
Duration of ipsilateral silent period from Transcranial magnetic stimulation measured in milliseconds
Time frame: Baseline, 12 weeks, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Silent Period Duration After Exercise Cycling Program | 12-Week post | 26.2 milliseconds | Standard Deviation 7.5 |
| Experimental: Aerobic First | Silent Period Duration After Exercise Cycling Program | 24-week post-cross | 27.5 milliseconds | Standard Deviation 7.4 |
| Experimental: Aerobic First | Silent Period Duration After Exercise Cycling Program | Baseline | 22 milliseconds | Standard Deviation 7.8 |
p-value: 0.05ANCOVA
Primary
Silent Period Duration for Balance Group
Ipsilateral silent period duration as assessed by TMS
Time frame: Baseline, 12 weeks, 24 weeks
Population: Sedentary older adults engaging in less than 45 minutes of total activity per week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Silent Period Duration for Balance Group | Pre | 23 milliseconds | Standard Deviation 8.9 |
| Experimental: Aerobic First | Silent Period Duration for Balance Group | 12-Weeks | 21.2 milliseconds | Standard Deviation 5.1 |
| Experimental: Aerobic First | Silent Period Duration for Balance Group | 24-week post-cross | 26.2 milliseconds | Standard Deviation 8.1 |
p-value: 0.05ANCOVA
Secondary
Heart Rate Workload After Home Based Intervention
Measured heart rate after home based intervention Technical implementation at the facility level prevented acquisition of these metrics until late in the project.
Time frame: 24 and 48 weeks
Population: Participants completing home based interventions compared to facility based interventions - measured in time in aerobic zone.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Heart Rate Workload After Home Based Intervention | Within one week of completing 24 week intervention | 78 percentage of time | Standard Deviation 18 |
| Experimental: Aerobic First | Heart Rate Workload After Home Based Intervention | Within one week of completing 48 Week Intervention | 48 percentage of time | Standard Deviation 30 |
p-value: 0.01t-test, 2 sided
Secondary
Target Heart Rate Zone After Aerobic Exercise First
Targeted Heart Rate Zone among participants compared among short term exercise groups
Time frame: 24 and 48 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Target Heart Rate Zone After Aerobic Exercise First | Within one week of completing 24 week intervention | 93.7 percentage of time | Standard Deviation 10.1 |
| Experimental: Aerobic First | Target Heart Rate Zone After Aerobic Exercise First | Within one week of completing 48 Week Intervention | 70.6 percentage of time | Standard Deviation 22.5 |
p-value: 0.25t-test, 2 sided
Secondary
Target Heart Rate Zone for Balance First Participants
Heart rate in aerobic target zone is measured in percentage of time in at least 50% of participants heart rate reserve.
Time frame: 24 and 48 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Experimental: Aerobic First | Target Heart Rate Zone for Balance First Participants | Within one week of completing 24 week intervention | 58.4 percentage of time | Standard Deviation 34.6 |
| Experimental: Aerobic First | Target Heart Rate Zone for Balance First Participants | Within one week of completing 48 Week Intervention | 88.5 percentage of time | Standard Deviation 14.7 |
p-value: 0.05t-test, 2 sided