Cognition and Neuroplasticity Sedentary Adults After 8 Weeks of Aerobic Exercise

Study Overview
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Brief Summary
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The overall goal of the proposed study is to evaluate the effects of an 8-week aerobic exercise program on cognition and determine the relationship between cognitive improvements and Transcranial Magnetic Stimulation (TMS) neuroplasticity. The investigators will also explore the effect modification of BDNF levels and BDNF allelic status, and APOE4 status on cognitive response after exercise.

Detailed Description
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The investigators will quantify cognitive improvements following moderate to high intensity aerobic exercise intervention (participant will choose between treadmill, elliptical or stationary bike). Each participant will engage in 60 minute daily sessions delivered 3 times/week for 8 consecutive weeks (a total of 24 sessions). The investigators will determine the relationship between cognitive improvements and TMS neuroplasticity. The cognitive domains explored will be: 1) Visuomotor processing speed and cognitive flexibility/task switching; 2) Response inhibition, mental flexibility, and attentional control; 3) Attention and working memory; 4) List Learning and Memory; and 5) Semantic Verbal Fluency. The investigators will also explore the effect modification of BDNF levels and BDNF allelic status, and APOE4 status on cognitive response after exercise.

Official Title
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Assessing Cognitive Improvements, Brain Neuroplasticity and the Role of Genetic Factors After Aerobic Exercise in Sedentary Adults

Conditions
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Sedentary Behavior

Intervention / Treatment
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* Behavioral: Aerobic Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 55years no clinically detectable cognitive impairment (MoCA score ≥ 24 and Clinical Dementia Rating (CDR) score of 0) low activity level (individuals who do not engage in regular exercise, or currently exercise once a week or less) primary language is English Exclusion Criteria: any unstable medical condition (i.e.: uncontrolled hypertension or uncontrolled diabetes) medical contraindication to physical exercise contraindication to TMS Neuroplasticity testing, as per the TMS Safety Guidelines. History of fainting spells of unknown or undetermined etiology that might constitute seizures History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG or family history of treatment resistant epilepsy Any current history of a psychiatric illness No medication is an absolute exclusion from TMS. Medications will be reviewed by the Principal Investigator and a decision about inclusion will be made based on the following: The subject's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other Central Nervous System (CNS) active drugs. The published TMS guidelines review medications to be considered with TMS. Any metal in the brain, skull or elsewhere unless approved by the responsible MD Any medical devices (i.e. Cardiac pacemaker, deep brain stimulator, medication infusion pump, cochlear implant, vagal nerve stimulator) Intracranial lesion Substance abuse or dependence within the past six months Pregnant women Vulnerable populations such as prisoner's People unable to consent themselves Subjects who, in the Investigator's opinion might not be suitable for the study

Ages Eligible for Study
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Minimum Age: 55 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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: The intervention group will perform 4-weeks of moderate intensity exercise followed by 4-weeks of high intensity aerobic exercise.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise group<br>Each participant will engage in 60 minute daily sessions delivered 3 times/week for 8 consecutive weeks (a total of 24 sessions). | Behavioral: Aerobic Exercise<br>* Participants will be fitted with a heart rate monitor and will be instructed to walk (or trot) to maintain 55-64% of maximal heart rate (determined by exercise test) for the first 4-weeks of exercise or to maintain 65-90% of maximal heart rate (determined by exercise test) for the second 4-weeks of exercise during each session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TMS Plasticity Measures | An index of the duration of the Theta-Burst Stimulation (TBS) induced modulation of corticospinal excitability (the time-point at which the normalized mean Motor Evoked Potential (MEP) amplitude returns to baseline values) will be defined for each participant. | baseline and after 8 weeks of exercise | 
| Change in Cognitive Performance | Cognitive performance will be assessed using a neuropsychological test battery in executive function, processing speed, learning, and language. | baseline and after 8 weeks of exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in BDNF Levels | Blood samples will be collected for BDNF levels. | baseline and after 8 weeks of exercise | 
| Change in Aerobic Capacity (Cardiovascular Fitness) | A maximal treadmill test will be performed to determine maximal oxygen uptake (VO2) as a measure of aerobic capacity. | baseline and after 8 weeks of exercise | 
| Allelic Status BDNF | Genetic testing will be performed to assess for brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. | baseline | 
| Allelic Status APOE | Genetic testing will be performed to assess for the presence of apolipoprotein-E (APOE) e4 allele. | baseline |