Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity

Objective: Obesity has been related to later-life dementia. Serum glucose levels and insulin resistance are known to influence cognition in individuals with diabetes. This study aimed to evaluate memory function in middle-aged individuals with obesity in association with glucose metabolism and brain iron content. Methods: This was a cross-sectional case-control study including 121 participants aged 27.2 to 66.6 years (56 without obesity, 65 with obesity) stratified according to sex and menopausal status. Insulin sensitivity, body composition, brain iron content, and memory function were evaluated by euglycemic hyperinsulinemic clamp, dual-energy x-ray absorptiometry, magnetic resonance relaxometry (R2*), and California Verbal Learning Test, respectively. Results: Women with obesity, but not men, had lower scores in some California Verbal Learning Tests in association with metabolic parameters and increased brain iron content compared with controls. Fasting plasma glucose, glycated hemoglobin (HbA1c; within normal range), and R2* were negatively associated with memory scores, whereas insulin sensitivity showed positive associations. Remarkably, only HbA1c levels and R2* in the right inferior fronto-orbital region remained significant after controlling for age, sex, education, and BMI. Conclusions: Impairments in memory function in middle-aged women with obesity are associated with HbA1c levels and brain iron content independently of insulin sensitivity. These results may have implications in the design of therapeutic strategies in women with obesity.