Proton Magnetic Resonance Spectroscopy (1H-MRS)-Based Neurometabolite Levels and Cognitive Function in Relation to Visceral Obesity and Non-Alcoholic Fatty Liver Disease (P14-019-19)

Intra-abdominal adiposity in the viscera and liver, compared to total adiposity, carries a higher metabolic risk, and it varies substantially by sex and race. We examined the association of neurometabolites and cognitive function with visceral obesity and non-alcoholic fatty liver disease (NAFLD) in multiethnic older adults. The Multiethnic Cohort Brain-Gut-Adiposity Study included 100 participants aged 61–77 years, who were recruited into balanced strata by sex, ancestry (Japanese, Native Hawaiian or white) and body mass index (BMI) levels (range: 18.0–44.9 kg/m²). We measured the concentration of key brain metabolites in the frontal and parietal gray matter (GM) and frontal white matter using ¹H-MRS and assessed cognitive function using the Modified Mini-Mental State (3MS) and the NIH Toolbox (NIHTB) tests. Mean neurometabolite levels and cognition scores were compared by visceral obesity (visceral fat area at L1-L5 > 150 cm²) and NAFLD (liver fat >5.0%) status determined by abdominal MR imaging, while adjusting for age, sex, race, education, dual energy X-ray absorptiometry-based total adiposity and other confounders. The prevalence of visceral obesity was 52%, NAFLD 32%, and both conditions 27%. Participants with visceral obesity had higher adjusted mean levels of total glutamate [11.6 (11.3, 12.0) vs. 10.8 (10.4, 11.2) mM/kg; P = 0.01] and myo-inositol [5.2 (5.0, 5.4) vs. 4.7 (4.6, 4.9) mM/kg; P = 0.004] in the parietal GM but had similar levels of total choline, total creatine and N-acetylaspartate. NAFLD status was not significantly associated with the levels of neurometabolites. No significant interaction was detected between the two conditions: participants with either condition compared to those with neither showed a trend toward higher levels of myo-inositol [5.2 (4.9, 5.5) vs. 4.8 (4.5, 5.0) mM/kg; P = 0.07]. Further, participants with NAFLD scored lower for crystallized cognition for language [113 (110, 117) vs. 118 (116, 120); P = 0.02], in particular for reading ability [113 (109, 117) vs. 119 (117, 123); P = 0.03]. Results of this comprehensive, pilot imaging study suggest that, regardless of total adiposity and race/ethnicity, high visceral adiposity is associated with elevated concentrations of inflammatory neurometabolites, and NAFLD is associated with reduced language abilities. National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute).