Effects of Exercise Intervention on Aging-related Motor Decline

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Exercise Intervention on Aging-related Motor Decline (AGING)

Conditions
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Aging, Exercise

Intervention / Treatment
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* Behavioral: Stretching Exercise Intervention
* Behavioral: Aerobic Exercise Intervention
* Behavioral: Self Monitoring


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stretching Exercise Intervention<br>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. | Behavioral: Stretching Exercise Intervention<br>* 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.<br>|
| Experimental: Aerobic Exercise Intervention<br>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. | Behavioral: Aerobic Exercise Intervention<br>* Supervised weekly exercise. 3 bouts of 45 minutes weekly on a cycle ergometer. HR will be kept at 75% of age-related maximum.<br>|
| Experimental: Self Monitoring Intervention<br>C. 6 month self-monitored training phase during which time participants will exercise using a take home bike ergometer. | Behavioral: Self Monitoring<br>* 6 month self-monitored training phase during which time participants will exercise according to prescribed regimen (cycling)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate Cardiovascular Efficiency After Aerobic Exercise | Estimate of Volume of oxygen consumption (VO2peak) using YMCA protocol for cardiovascular assessment. | Baseline, 12 weeks, 24 weeks | 
| Estimate of Cardiovascular Efficiency After Balance Training | Estimated VO2peak using YMCA cycle test completed over nine to twelve minutes. | Baseline, 12 weeks, 24 weeks | 
| Silent Period Duration After Exercise Cycling Program | Duration of ipsilateral silent period from Transcranial magnetic stimulation measured in milliseconds | Baseline, 12 weeks, 24 weeks | 
| Silent Period Duration for Balance Group | Ipsilateral silent period duration as assessed by TMS | Baseline, 12 weeks, 24 weeks | 
| 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. | Baseline to 24 Weeks with cross-over | 
| 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. | Baseline, 12 weeks, 24 weeks | 
| 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). | 24 and 48 weeks | 
| 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. | 24 and 48 weeks | 
| Comparison of Silent Period Duration After Aerobic Exercise | Comparison of silent period duration at 24 weeks compared to baseline | Baseline, 12 weeks, 24 weeks | 
| 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. | 24 and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 and 48 weeks | 
| Target Heart Rate Zone After Aerobic Exercise First | Targeted Heart Rate Zone among participants compared among short term exercise groups | 24 and 48 weeks | 
| 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. | 24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Aging