Cognition and Magnetic Resonance Imaging of Brain Inflammation in Obesity

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.

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

Population: 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.

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.

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

Population: 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.

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline

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.

Time frame: Baseline