Effects of Change in Insulin Resistance and Systemic Inflammation on Brain Structure and Function

Study Overview
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Brief Summary
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Obesity is associated with alterations in brain structure and cognitive impairment and is a risk factor for Alzheimer's disease and vascular dementia. The mechanisms underlying obesity related decline in cognitive function are not fully understood. The long-term goal of this project is to understand how obesity affects cognitive function, with the aim to develop new ways to prevent and treat obesity related cognitive decline

Detailed Description
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A growing body of evidence suggests that obesity is associated with alterations in brain structure and cognitive impairment. Mid-life obesity is a risk factor for Alzheimer's disease and vascular dementia. The mechanisms underlying obesity related decline in cognitive function are not fully understood. The long-term goal of this research is to identify how obesity, insulin resistance (IR), and their treatment impact brain structure and function. The investigators propose that IR and obesity related inflammation are two modifiable factors that affect neuronal integrity and lead to cognitive dysfunction. In this proposal, investigators will test two hypotheses: 1) among obese patients planning to undergo bariatric surgery (specifically vertical sleeve gastrectomy), baseline IR and systemic and brain markers of inflammation will inversely correlate with performance on cognitive testing and correlate with abnormalities in brain structure and 2) following bariatric surgery subjects who experience the greatest reduction in IR and obesity related inflammation will have the greatest improvement in cognitive function and brain structure. To address these hypotheses, investigators will use a comprehensive battery of tests to evaluate cognition and state of the art magnetic resonance imaging (MRI) techniques to assess brain structure and neurochemistry before and six months after bariatric surgery.

Official Title
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Effects of Change in Insulin Resistance and Systemic Inflammation After Bariatric Surgery on Brain Neurochemistry, Neuroinflammation and Cognitive Function

Conditions
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Obesity, Bariatric Surgery Candidate

Intervention / Treatment
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* Procedure: bariatric surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese Group Undergoing VSG-type bariatric surgery BMI > 30 Current weight less than 400 lbs Non-Obese Group Age 30-50 BMI < 25 Exclusion Criteria: Both Groups History of type 1 or type 2 diabetes History of stroke History of epilepsy History of Neurosurgical procedures Past or current history of severe psychiatric illness Pass or current history of alcohol or substance abuse Absence of metallic substances in body or ability to remove before imaging procedure History of claustrophobia or known inability to tolerate MRI Inability to consent

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 50 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Obese<br>Obese individuals undergoing bariatric surgery | Procedure: bariatric surgery<br>* Obese patients will undergo brain imaging, neurocognitive function testing and measurement of insulin resistance and inflammatory markers pre- and post bariatric surgery<br>|
| controls<br>matched non-obese controls | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change insulin resistance and inflammatory markers | Change in insulin resistance and blood inflammatory markers from baseline (before surgery) and at 6 months post surgery | at baseline (before surgery) and 6 months post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in neurocognitive function testing | changes in neurocognitive function testing from baseline (before surgery) and at 6 months post surgery | at baseline (before surgery) and 6 months post surgery |