Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

Study Overview
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Brief Summary
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The rate of obesity in the United States is high and is a risk factor for concurrent cognitive impairment and, in late life, dementias such as Alzheimer's disease. In order to prevent or reduce cognitive impairment, the mechanism underlying the link between obesity and cognitive impairment must be understood. The current study aims to provide preliminary data on whether brain inflammation occurs in obesity and relates to cognitive deficits using magnetic resonance neuroimaging and cognitive testing. It is hypothesized that obese individuals will have greater brain inflammation and lower cognitive function compared to normal-weight individuals. Further, it is predicted that brain inflammation will relate to cognitive function and plasma indicators of inflammation in obese individuals.

Detailed Description
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Initially, normal-weight or obese potential participants are screened by a phone interview that assesses medical history. Obtainment of informed consent and further screening occurs on the day of the study visit. Participants then undergo a 2 hour oral glucose tolerance test (OGTT) including blood draws for metabolic and inflammatory marker levels in plasma. Lunch is then provided. Participants are then administered 30 minute computer-based cognitive testing from the NIH Toolbox Cognition Battery. After cognitive testing, participants undergo 1.5 hour magnetic resonance imaging (MRI) that includes structural, diffusion tensor, and functional MR imaging.

Official Title
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Neuroinflammation in Obesity

Conditions
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Obesity

Intervention / Treatment
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* Procedure: Oral glucose tolerance test
* Behavioral: Cognitive testing
* Procedure: Magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-obese (body mass index = 18 - 25 kg/m^2) or Obese (body mass index ≥ 30 kg/m^2 Any race or ethnicity Native English speaker Exclusion Criteria: Past or current diabetes Current psychotropic medication use Past or current neurological illness Past or current substance or alcohol misuse Past or current mental illness Current binge eating disorder Magnetic resonance imaging contraindications Pregnancy Currently lactating Tobacco use within past month Over 350 lb

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: This study employed a single group model in which participants with obesity and participants with normal-weight underwent magnetic resonance imaging, blood draws and cognitive assessment.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normal-weight<br>Participants who have a body mass index within the normal-weight category. | Procedure: Oral glucose tolerance test<br>* After 8 hours fasting overnight, an intravenous catheter is placed in the arm or hand for blood draws. Participants drink 75 grams of an oral glucose drink after baseline blood samples are drawn. More blood draws occur at 10, 20, 30, 60 and 120 min post-glucose drink.<br>Behavioral: Cognitive testing<br>* For approximately 40 minutes, participants are assessed for cognitive function using computer-based tests available from the NIH Toolbox Cognitive Battery (Weintraub et al., 2013), including attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall.<br>Procedure: Magnetic resonance imaging<br>* Magnetic resonance imaging (MRI) scans will be performed in a 3 Tesla MRI scanner over 1.5 hours. Participants will be asked to lay down flat on their backs and to try to stay still throughout the MRI scan. The participant will wear MRI-safe headphones to block out noise due to the MRI scans. Participant comfort will be verbally checked on throughout the scan and the participant will be provided with a 'squeeze ball' to signal the MRI technician that they want to get out of the scanner immediately.<br>|
| Active Comparator: Obese<br>Participants who have a body mass index within the obese category. | Procedure: Oral glucose tolerance test<br>* After 8 hours fasting overnight, an intravenous catheter is placed in the arm or hand for blood draws. Participants drink 75 grams of an oral glucose drink after baseline blood samples are drawn. More blood draws occur at 10, 20, 30, 60 and 120 min post-glucose drink.<br>Behavioral: Cognitive testing<br>* For approximately 40 minutes, participants are assessed for cognitive function using computer-based tests available from the NIH Toolbox Cognitive Battery (Weintraub et al., 2013), including attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall.<br>Procedure: Magnetic resonance imaging<br>* Magnetic resonance imaging (MRI) scans will be performed in a 3 Tesla MRI scanner over 1.5 hours. Participants will be asked to lay down flat on their backs and to try to stay still throughout the MRI scan. The participant will wear MRI-safe headphones to block out noise due to the MRI scans. Participant comfort will be verbally checked on throughout the scan and the participant will be provided with a 'squeeze ball' to signal the MRI technician that they want to get out of the scanner immediately.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Inflammation Metrics in Obese and Normal-weight Individuals as Measured by Magnetic Resonance Image-based Diffusion Basis Spectrum Imaging (DBSI) | Diffusion Basis Spectrum Imaging (Cross and Song, 2017) is a computational method that will be applied to diffusion tensor images of the brain to estimate putative inflammation-related markers including cellularity and edema in obese and normal-weight individuals. DBSI metrics are quantitative but unitless. Cellularity and edema fractions of the total diffusion signal (including axial, radial, restricted (cellularity) and hindered (edema)) will be estimated in brain white matter tracts. | 1.5 hours at the end of one (up to) 8 hour study day that includes all outcome measures | 
| Cognitive Function in Obese and Normal-weight Individuals as Measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery and DBSI Putative Neuroinflammation Metrics | Cognitive performance including fluid and crystallized cognition composite T-scores from computer-based NIH Cognitive Toolbox assessments (Weintraub et al., 2013) will be assessed in obese and normal-weight individuals. These T-scores will include scores from tasks that assess attention and executive functioning, episodic memory, working memory, language, processing speed, and immediate recall (see NIH Toolbox Cognitive Battery website). T-scores are corrected for socioeconomic status and their distribution has a mean of 50 and a standard deviation of 10. Higher T-scores indicate better cognitive function. T-scores will be correlated with DBSI-assessed neuroinflammation metrics including restricted fraction (DBSI RF, putative cellularity) and hindered fraction (DBSI HF, putative vasogenic edema) in brain white matter tracts. | 40 minutes during one (up to) 8 hour study day that includes all outcome measures; after OGTT and prior to MRI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Inflammation, Cognitive impairment, Neuroimaging, Magnetic resonance imaging