Dietary and Circulating Advanced Glycation End Products in Relation to Inflammation and Cognitive Function in Healthy Young Adults
Higher levels of circulating AGEs and inflammation markers were linked to poorer cognitive performance in young adults, but dietary AGEs intake did not show a significant effect.
Where it sits
this study against the rest of the glutathione (gsh) corpusSummary and findings
This study examined the associations of dietary advanced glycation end products (dAGEs) intake, circulating AGE–RAGE biomarkers, inflammation, and oxidant–antioxidant markers with cognitive performance in healthy young adults aged 19–26 years. The study found that higher serum AGEs and TNF-α were associated with poorer cognitive performance on the Digit Span Backward task. No significant associations were found with dAGEs intake.
Abstract
Background: Advanced glycation end products (AGEs) may link diet, systemic inflammation, and cognitive function; however, evidence in healthy young adults is limited. Objective: To examine the associations of dietary AGEs (dAGEs) 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. dAGEs intake was estimated independently 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 depressive symptoms, with Benjamini–Hochberg false-discovery-rate correction. Covariate-adjusted partial least squares structural equation modelling (PLS-SEM) examined the prespecified AGE–RAGE–inflammation pathways. Results: Neither FFQ-derived nor 3D-FR-derived dAGEs intake was associated with serum AGEs. 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: Circulating AGE–RAGE-related and inflammatory activity, rather than estimated dAGEs intake, was associated with selected aspects of cognitive performance in healthy young adults. Longitudinal studies with larger samples are needed to establish temporality and confirm the significance of these associations.
Background
This study addresses the relationship between dietary advanced glycation end products (AGEs), inflammation, and cognitive function in healthy young adults. Previous research has suggested that AGEs may contribute to systemic inflammation and cognitive decline, but evidence in this demographic is limited. Understanding these associations could provide insights into dietary impacts on cognitive health.
Methods
This cross-sectional study included healthy young adults aged 19–26 years. Dietary AGEs intake was estimated using a food-frequency questionnaire and a three-day food record. Serum biomarkers including AGEs, soluble RAGE, interleukin-6, TNF-α, and others were measured. Cognitive performance was assessed using Digit Span tests and Stroop Interference, with multivariable linear regression models applied to adjust for confounding variables.
Results
The primary finding indicated that higher serum AGEs (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 performance on the Digit Span Backward task. Other cognitive associations were not significant after correction for multiple comparisons. The analysis also revealed significant positive associations between sAGEs and sRAGE, as well as between sRAGE and inflammation.
Interpretation
These findings suggest that circulating AGE–RAGE-related biomarkers and inflammation may influence cognitive performance, rather than dietary AGEs intake. While the statistical significance of the associations is noted, the clinical relevance may be limited due to the small effect sizes. The study's cross-sectional design and small sample size also restrict the ability to draw definitive conclusions about causality.
Key findings
- Higher sAGEs (β = −0.36, 95% CI −0.54 to −0.16) associated with poorer Digit Span Backward performance.
- Higher TNF-α (β = −0.33, 95% CI −0.53 to −0.13) associated with poorer Digit Span Backward performance.
- sAGEs positively associated with sRAGE (β = 0.505, p < 0.001).
- sRAGE positively associated with inflammation (β = 0.601, p < 0.001).
- Greater inflammation associated with poorer Digit Span Backward performance (β = −0.398, 95% CI −0.697 to −0.110, p = 0.009).
- Indirect inverse association between sRAGE and Digit Span Backward through inflammation (β = −0.239, 95% bootstrap CI −0.457 to −0.057).
Limitations
- cross-sectional design limits causal inference
- small sample size
- self-reported dietary intake may introduce bias
- no longitudinal data to establish temporality