Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

NCT04116229 | Completed Results DMC

• 2 other identifiers: 201805053P30DK020579
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Keywords

Obesity; Inflammation; Cognitive impairment; Neuroimaging; Magnetic resonance imaging

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Normal-weight

ACTIVE COMPARATOR

Participants who have a body mass index within the normal-weight category.

Procedure: Oral glucose tolerance test; Behavioral: Cognitive testing; Procedure: Magnetic resonance imaging

Obese

ACTIVE COMPARATOR

Participants who have a body mass index within the obese category.

Procedure: Oral glucose tolerance test; Behavioral: Cognitive testing; Procedure: Magnetic resonance imaging

Interventions

Oral glucose tolerance test PROCEDURE

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.

Normal-weight; Obese

Cognitive testing BEHAVIORAL

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.

Normal-weight; Obese

Magnetic resonance imaging PROCEDURE

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.

Normal-weight; Obese

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Weintraub S, Dikmen SS, Heaton RK, Tulsky DS, Zelazo PD, Bauer PJ, Carlozzi NE, Slotkin J, Blitz D, Wallner-Allen K, Fox NA, Beaumont JL, Mungas D, Nowinski CJ, Richler J, Deocampo JA, Anderson JE, Manly JJ, Borosh B, Havlik R, Conway K, Edwards E, Freund L, King JW, Moy C, Witt E, Gershon RC. Cognition assessment using the NIH Toolbox. Neurology. 2013 Mar 12;80(11 Suppl 3):S54-64. doi: 10.1212/WNL.0b013e3182872ded.

  PMID: 23479546 BACKGROUND

• Cross AH, Song SK. "A new imaging modality to non-invasively assess multiple sclerosis pathology". J Neuroimmunol. 2017 Mar 15;304:81-85. doi: 10.1016/j.jneuroim.2016.10.002. Epub 2016 Oct 8.

  PMID: 27773433 BACKGROUND

• Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes. 2001 Jan;50(1):150-8. doi: 10.2337/diabetes.50.1.150.

  PMID: 11147781 BACKGROUND

Related Links

• NIH Toolbox Cognitive Battery description

MeSH Terms

Conditions

Obesity; Inflammation; Cognitive Dysfunction

Interventions

Glucose Tolerance Test; Neuropsychological Tests; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Psychological Tests; Behavioral Disciplines and Activities; Spectrum Analysis; Chemistry Techniques, Analytical

Limitations and Caveats

An early anticipated enrollment table specified a total of 8 individuals. Due to necessary change in study methods, we were able to increase the anticipated enrollment to 20 individuals. 20 individuals were enrolled but 5 met exclusion criteria during further screening (after signing informed consent) and one could not be scheduled due to scheduling conflicts (but they had signed the consent form). In total, we had complete datasets from 14 enrolled individuals.

Results Point of Contact

• Title: Sarah Eisenstein, Associate Professor in Psychiatry
• Organization: Washington University School of Medicine

seisens@wustl.edu

3143627107

Study Officials

• Tamara Hershey, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Neuroimaging data was processed using automated methods blind to group membership. Blood samples were analyzed by laboratory personnel blind to group membership.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 4, 2019
• Study Start: March 19, 2019
• Primary Completion: October 30, 2020
• Study Completion: October 30, 2020
• Last Updated: March 10, 2023
• Results First Posted: October 19, 2022

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data is available immediately as of August 15, 2022 for 5 years.
• Access Criteria: Upon reasonable request

Locations

US (1)