Cognition and Magnetic Resonance Imaging of Brain Inflamm... | NCT04116229

ID	Type	Description	Link
P30DK020579	U.S. NIH Grant/Contract		View source

Cognition and Magnetic Resonance Imaging of Brain Inflamm... | NCT04116229 | Trialant

Sponsor/Collaborators Module

Name	Class
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	NIH

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

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

Contacts/Locations Module

Name	Affiliation	Role
Tamara Hershey, PhD	Washington University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Washington University School of Medicine		St Louis	Missouri	63110	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23479546	Background	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.
27773433	Background

Label	URL
NIH Toolbox Cognitive Battery description	View source

Arm/Group Information

ID	Title	Description
FG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
FG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00010 subjects FG00110 subjects
COMPLETED		FG0008 subjects FG0016 subjects
NOT COMPLETED		FG0002 subjects FG0014 subjects

Type	Comment	Reasons
Met exclusion criteria during screeneing on day of study visit.		FG0002 subjects FG0013 subjects
Scheduling not possible.		FG0000 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Data from 8 individuals with normal-weight and 6 individuals with obesity were included in baseline analyses. Five individuals were enrolled in the study but their data was not collected due to meeting exclusion criteria. One individual was enrolled but could not be scheduled for the study and therefore did not contribute data.

Posted

Mean

Standard Deviation

unitless

1.5 hours at the end of one (up to) 8 hour study day that includes all outcome measures

ID	Title	Description

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Sarah Eisenstein, Associate Professor in Psychiatry	Washington University School of Medicine	3143627107		seisens@wustl.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 25, 2020	Jul 14, 2022	Prot_SAP_000.pdf

Condition Browse Module

ID	Term
D009765	Obesity
D007249	Inflammation
D060825	Cognitive Dysfunction

ID	Term
D050177	Overweight
D044343	Overnutrition
D009748	Nutrition Disorders
D009750	Nutritional and Metabolic Diseases

Intervention Browse Module

ID	Term
D005951	Glucose Tolerance Test
D009483	Neuropsychological Tests
D009682	Magnetic Resonance Spectroscopy

ID	Term
D001774	Blood Chemical Analysis
D019963	Clinical Chemistry Tests
D019411	Clinical Laboratory Techniques
D019937	Diagnostic Techniques and Procedures

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Black, non-Hispanic

Title	Measurements
	BG0001 BG0012 BG0023

White, non-Hispanic

Title	Measurements
	BG0006 BG0014 BG00210

Asian, non-Hispanic

Title	Measurements
	BG0001 BG0010 BG0021

Homeostatic measure of insulin resistance (HOMA-IR)

Homeostatic model for insulin resistance, where greater HOMA-IR indicates greater insulin resistance.

Mean

Standard Deviation

unitless

Title

Denominators

Categories

Title	Measurements
	BG0001.21± 0.79 BG0013.47± 2.56 BG0022.18± 2.05

Fasting plasma monocyte chemoattractant protein-1 (MCP-1)

Pro-inflammatory marker

Mean

Standard Deviation

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG000140.9± 37.0 BG001160.3± 40.1 BG002149.2± 38.2

OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Title

Denominators

Categories

DBSI restricted fraction (cellularity)

Title	Measurements
	OG000.0468± .0024 OG001.0492± .0034

DBSI hindered fraction (vasogenic edema)

Title	Measurements
	OG000.176± .013 OG001.186± .014

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study.	Independent-Samples Median Test		0.28	a priori threshold: p < 0.05	Median Difference (Final Values)	0.05			2-Sided								Equivalence	Alternative hypothesis: people with normal-weight BMI have lower DBSI restricted fraction, or putative cellularity, than people with obesity. Null hypothesis: DBSI restricted fraction, or putative cellularity, is not different between normal-weight and obese groups.
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study.	Independent-Samples Median Test		0.03	a priori threshold: p < 0.05	Median Difference (Final Values)	0.18			2-Sided								Equivalence	Alternative hypothesis: people with normal-weight BMI have lower DBSI hindered fraction, or putative vasogenic edema, than people with obesity. Null hypothesis: DBSI hindered fraction, or putative vasogenic edema, is not different between normal-weight and obese groups.

Primary

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.

Two individuals in the normal-weight group were not native English speakers and their cognitive data is not included. A complete set of fluid cognition measures was not collected from one normal-weight participant and their fluid cognition data is not included.

Posted

Mean

Standard Deviation

T-score

40 minutes during one (up to) 8 hour study day that includes all outcome measures; after OGTT and prior to MRI

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0006 OG0016

Title

Denominators

Categories

Crystallized Cognition

- ParticipantsOG0006
- ParticipantsOG0016

Title	Measurements
	OG00060.3± 6.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.01	a priori threshold: p < 0.05	Slope	-0.69			2-Sided								Other	Alternative hypothesis: Worse crystallized cognitive function will relate to greater putative vasogenic edema (DBSI HF) in white matter tracts. Null hypothesis: Crystallized cogntive function is not related to DBSI HF.

Post-Hoc

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals.

Fasting plasma insulin, a measure of insulin resistance in which higher levels may reflect greater effort to maintain glucose homeostasis, was measured by radioimmunoassay. Normal fasting plasma insulin levels are < 25 uU/mL.

Posted

Mean

Standard Deviation

uU/mL

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0005.28± 3.73 OG00115.62± 10.82

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		>0.46	a priori threshold: p < 0.05	Slope	-0.18			2-Sided								Other	Alternative hypothesis: higher levels of insulin, a pro-inflammatory marker, will relate to higher levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: Insulin levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals.

Fasting plasma leptin, a hormone related to adipose tissue mass such that higher levels reflect greater adipose tissue mass, was measured by radioimmunoassay.

For body mass index (BMI) in normal-weight (18.5-24.9 kg/m^2), leptin reference range = 1.8-24.2 ug/L in females and 0.2-7.7 in males. For BMI in individuals with obesity, leptin reference range = 10.6-141 in females and 3.2-135 in males.

Posted

Mean

Standard Deviation

ug/L

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG00019.9± 13.4 OG001110± 49.7

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.62	a priori threshold: p < 0.05	Slope	0.15			2-Sided								Other	Alternative hypothesis: higher levels of leptin, a pro-inflammatory marker and "satiety" hormone, will relate to higher levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: Leptin levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals.

Fasting plasma ghrelin, a hormone related to hunger in which higher levels may signal the stomach is empty and it is time to eat, was measured by radioimmunoassay.

Plasma ghrelin levels tend to be lower in people with obesity. There is no established normal range for fasting plasma ghrelin levels as assessed by radioimmunoassay.

Posted

Mean

Standard Deviation

pg/mL

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0001498.5± 568.6 OG001914.8± 261.7

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.53	a priori threshold: p < 0.05	Slope	0.19			2-Sided								Other	Alternative hypothesis: higher levels of ghrelin, an anti-inflammatory marker and "hunger" hormone, will relate to lower levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: Ghrelin levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Metabolic Markers in Plasma and Relationships With DBSI Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals.

Homeostatic measure of insulin resistance (HOMA-IR) where higher scores indicate greater insulin resistance, or diminished maintenance of glucose homeostasis by insulin. HOMA-IR was calculated according to the formula: fasting insulin (uU/L) * fasting glucose (nmol/L)/22.5

A HOMA-IR score >2.5 indicates insulin resistance.

Posted

Mean

Standard Deviation

HOMA-IR score

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0001.21± 0.79 OG0013.47± 2.56

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.53	a priori threshold: p < 0.05	Slope	-0.19			2-Sided								Other	Alternative hypothesis: greater HOMA-IR, where higher HOMA-IR indicates greater insulin resistance, will relate to higher levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: HOMA-IR levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals

Fasting plasma interleukin (IL)-10, an anti-inflammatory cytokine important for immune response. IL-10 was measured using high-sensitive enzyme-linked immuno-absorbent assay (ELISA). Normal reference ranges for IL-10 have not been established and better or worse levels depend on disease state.

Posted

Mean

Standard Deviation

pg/mL

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0001.85± 1.38 OG0011.97± 0.75

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.09	a priori threshold: p < 0.05	Slope	0.5			2-Sided								Other	Alternative hypothesis: higher levels of IL-10, an anti-inflammatory marker, will relate to lower levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: IL-10 levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals

Fasting plasma adiponectin, an anti-inflammatory cytokine important for immune response. Adiponectin was measured using radioimmunoassay. Normal reference ranges for adiponectin is 2.5-21.1 ug/mL. Lower levels of adiponectin tend to be associated with worse metabolic health and higher body mass index.

Posted

Mean

Standard Deviation

ug/mL

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG00011.3± 5.6 OG00110.8± 4.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.19	a priori threshold: p < 0.05	Slope	0.38			2-Sided								Other	Alternative hypothesis: higher levels of adiponectin, an anti-inflammatory marker, will relate to lower levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: Adiponectin levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals

Fasting plasma tumor necrosis factor (TNF)-alpha, a pro-inflammatory cytokine important for systemic inflammation. TNF-alpha was measured using high-sensitive enzyme-linked immuno-absorbent assay (ELISA). Normal TNF-alpha levels range from non-detectable to 8.1 pg/mL and tend to be higher in people with obesity compared to normal-weight.

Posted

Mean

Standard Deviation

pg/mL

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0000.69± 0.16 OG0010.84± 0.16

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.90	a priori threshold: p < 0.05	Slope	-0.05			2-Sided								Other	Alternative hypothesis: higher levels of TNF-alpha, a pro-inflammatory marker, will relate to higher levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: TNF-alpha levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals

Fasting plasma monocyte chemoreactant protein (MCP)-1, a pro-inflammatory chemokine important for immune response and inflammation. MCP-1 was measured using enzyme-linked immuno-absorbent assay (ELISA). Normal reference ranges for MCP-1 have not been established but higher levels tend to be associated with higher body mass index.

Posted

Mean

Standard Deviation

pg/mL

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG000140.9± 37 OG001160.3± 40.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.26	a priori threshold: p < 0.05	Slope	0.34			2-Sided								Other	Alternative hypothesis: higher levels of MCP-1, a pro-inflammatory marker, will relate to higher levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: MCP-1 levels will not be related to DBSI RF in white matter tracts after controlling for BMI.

Post-Hoc

Peripheral Inflammation as Measured by Plasma Assays and Relationships With DBSI Putative Neuroinflammation Metrics in White Matter Tracts in Obese and Normal-weight Individuals

Fasting plasma high-sensitive C-reactive protein (CRP), where higher levels may reflect greater low-grade inflammation. High-sensitive CRP was measured using high-sensitive CRP turbidimetry assay. Higher high-sensitive CRP levels may reflect greater risk for cardiovascular disease. Normal range for hs-CRP is usually below 1 mg/L.

Posted

Mean

Standard Deviation

mg/L

Baseline

ID	Title	Description
OG000	Normal-weight	Participants who have a body mass index within the normal-weight category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.
OG001	Obese	Participants who have a body mass index within the obese category. Oral glucose tolerance test: 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. Cognitive testing: 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. Magnetic resonance imaging: 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.

Units	Counts
Participants	OG0008 OG0016

Title

Denominators

Categories

Title	Measurements
	OG0001± 0.8 OG0014.8± 3.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This is a pilot study with a small sample. Power to detect significant results is therefore low in the current study. Analyses performed across normal-weight and obese groups.	Regression, Linear		0.54	a priori threshold: p < 0.05	Slope	0.19			2-Sided								Other	Alternative hypothesis: higher levels of CRP, a pro-inflammatory marker, will relate to higher levels of putative neuroinflammation in white matter tracts as measured by DBSI restricted fraction after controlling for BMI. Null hypothesis: CRP levels will not be related to DBSI RF in white matter tracts after controlling for BMI.