Acute Exercise on Brain Insulin Sensitivity

Study Overview
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Brief Summary
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Dementia is a leading cause of death in the United States among aging adults. Brain insulin resistance has emerged as a pathologic factor affecting memory, executive function as well as systemic glucose control. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. However, there is limited data available on how exercise impacts brain insulin resistance in aging. This study will test the effect of acute exercise on brain insulin sensitivity in middle-aged to older adults. The study will also examine cognition and cardiometabolic health in relation to brain insulin sensitivity.

Detailed Description
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Obesity, hypertension, high blood glucose (e.g. prediabetes/type 2 diabetes), and physical inactivity is thought to worsen brain insulin resistance and reduce cerebral blood flow. This suggests lifestyle approaches may be necessary to counteract declines in brain health. Regular aerobic exercise decreases Alzheimer's Disease (AD) risk, in part, through changes in brain structure and function. Moreover, exercise-related structural changes in the brain, namely increased hippocampal volume, is linked to improved memory. However, there is limited data available on how exercise impacts brain insulin resistance in aging. It is also unclear if one bout of exercise may help improve brain insulin responses to insulin before fitness gains or weight loss in people at risk for dementia, type 2 diabetes and cardiovascular disease. Because single bouts of exercise are established to improve metabolic and vascular insulin sensitivity in people with obesity, the investigators anticipate exercise to raise brain insulin sensitivity in relation to cognition and cardiometabolic health.

Official Title
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Impact of Acute Exercise on Brain Insulin Sensitivity in Middle-aged to Older Adults

Conditions
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Aging, Obesity, Insulin Resistance, Cognition, Cardiovascular Disease Risk

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >40 and <80 years old. Has a body mass index >25 and <45 kg/m2. Physical Activity (<150 min of moderate/high intensity exercise per week) Exclusion Criteria: Subjects who have not been weight stable (>2 kg weight change in past 3 months) Subjects who are smokers or who have quit smoking <1 years ago Subjects with abnormal estimated glomerular filtration rate (eGFR). Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects Hypertensive (>160/100 mmHg) Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures or impact subject safety. Pregnant (as evidenced by positive urine pregnancy test) or nursing women Subjects with contraindications to participation in an exercise Current Pregnancy Currently taking active weight suppression medication (e.g. phentermine, orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine) Subjects currently taking medications that affect heart rate and rhythm (i.e. Ca++ channel blockers, nitrates, alpha- or beta-blockers). Known contraindications for MRI imaging

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Individuals will perform both rest and exercise conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Rest<br>Individuals will rest for about 1 hour in the seated position to mimic time exercising. | |
| Experimental: Exercise<br>Individuals will exercise for at medium to hard intensity for 1 hour. | Behavioral: Exercise<br>* Exercise will be walking/jogging at a medium to hard intensity for 1 hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain insulin sensitivity | MRI arterial spin labeling, cerebral blood flow | Change from baseline to exercise; about 1 week apart | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition | NIH Toolbox Cognitive Battery | Change from baseline to exercise; about 1 week apart | 
| Blood Glucose | Blood draw via oxidase method | Change from baseline to exercise; about 1 week apart | 
| Blood Free Fatty Acids | Blood draw via colorimetric assays | Change from baseline to exercise; about 1 week apart | 
| Carbohydrate Use | Indirect Calorimetry | Change from baseline to exercise; about 1 week apart | 
| Systolic and Diastolic Blood Pressure | Cuff around arm | Change from baseline to exercise; about 1 week apart | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise