Dietary and Circulating Advanced Glycation End Products in Relation to Inflammation and Cognitive Function in Healthy...

Background: Advanced glycation end products (AGEs) may link diet, systemic inflammation, and cognitive function; however, evidence in healthy young adults is limited. Objective: This study aimed to examine the associations of dietary AGE (dAGE) intake, circulating AGE-RAGE biomarkers, inflammation, and oxidant-antioxidant markers with cognitive performance. Methods: This cross-sectional study included healthy young adults aged 19-26 years. dAGE intake was estimated using a food-frequency questionnaire (FFQ) and a three-day food record (3D-FR). Serum AGEs (sAGEs), soluble RAGE (sRAGE), interleukin-6, tumour necrosis factor-alpha (TNF-α), malondialdehyde, catalase, superoxide dismutase, and glutathione were measured. Cognitive performance was assessed using Digit Span Forward, Backward, and Total scores and Stroop Interference. Separate multivariable linear regression models were adjusted for age, sex, body mass index, and Beck Depression Inventory-II scores, with Benjamini-Hochberg false-discovery-rate correction. Covariate-adjusted partial least squares structural equation modelling (PLS-SEM) examined the prespecified sAGE-sRAGE-inflammation pathways. Results: In the correlation analyses, dAGE intake estimated using the FFQ and 3D-FR was not significantly associated with sAGE concentrations (p > 0.05). In the separate regression models, higher sAGEs (β = -0.36, 95% CI -0.54 to -0.16) and TNF-α (β = -0.33, 95% CI -0.53 to -0.13) were associated with poorer Digit Span Backward performance after false-discovery-rate correction. No other cognitive associations remained significant. In PLS-SEM, sAGEs were positively associated with sRAGE (β = 0.505, p < 0.001), and sRAGE was positively associated with inflammation (β = 0.601, p < 0.001). Greater inflammation was associated with poorer Digit Span Backward performance (β = -0.398, 95% CI -0.697 to -0.110, p = 0.009), whereas the direct sRAGE-Digit Span Backward path was not significant. An indirect inverse association between sRAGE and Digit Span Backward through inflammation was supported (β = -0.239, 95% bootstrap CI -0.457 to -0.057). Conclusions: In conclusion, higher circulating sAGEs and TNF-α concentrations were associated with poorer working-memory performance, particularly on Digit Span Backward, in healthy young adults, whereas estimated dAGE intake showed no significant associations with cognitive performance. Longitudinal studies with larger samples are needed to establish temporality and confirm the significance of these associations.