Dietary advanced glycation end products (AGEs) and brain health

Background: The Western diet contains high amounts of dietary advanced glycation end products (AGEs), which have been found to promote insulin resistance, various micro- and macro-vascular diabetic complications, inflammation, oxidative stress, and endothelial dysfunction. In the brain, this endothelial dysfunction may lead to reduced cognition in adults with insulin resistance and T2DM. Methods: This cross-sectional study evaluated the relationship between AGEs in diet and plasma (dietary AGEs, plasma N-carboxymethyllysine (CML), and plasma methylgloxal (MG)), inflammatory and endothelial markers, and resting hippocampal blood flow (rHBF) in 13 healthy controls, 17 insulin resistant and 11 participants with Type 2 Diabetes Mellitus (T2DM). Data were collected using validated methods, including dietary assessment (Block Food Frequency Questionnaire and Mt. Sinai AGE questionnaire), arterial spin labeled MRI (ASL-MRI), and endothelial and inflammatory marker assays. All statistical analyses were adjusted for age, smoking, energy intake, and antioxidant intake. Results: Plasma AGEs significantly correlated to dietary AGEs (CML, r = 0.317, P = 0.063; MG, r = 0.421, P = 0.012). Plasma CML significantly predicted rHBF (β = -0.43, 95% CI: -204.14, -28). The relationship between CML, MG, and rHBF illustrated the presence of an interaction by levels of glucose control. AGEs in diet and plasma were not significantly associated with inflammation, as measured by endothelial markers vascular cell adhesion molecule (VCAM-1) and vascular endothelial growth factor (VEGF), and inflammatory markers tumor necrosis factor alpha (TNF-α) (P > 0.05). Lastly, results from a Sobel mediation analysis did not indicate mediation by inflammation on the relationship between AGEs and rHBF (P > 0.05) Conclusion: In agreement with the current literature, dietary AGEs are correlated to plasma AGEs. Plasma AGEs may predict decline in resting hippocampal blood blow (rHBF), an indication of progression to hippocampal impairment. Moreover, potentially AGE-induced decline in rHBF may be stratified by levels of glucose control, with healthy persons illustrating greater robustness in preservation of rHBF compared to persons with insulin resistance and T2DM. With further confirmation from larger experimental studies, following a low-AGE diet may be beneficial for brain health.