Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes.

Objective: Type 2 diabetes is associated with cognitive dysfunction, but the mechanisms are unknown. We assessed the relationships of biomarkers of oxidation, endothelial function and inflammation with cognition in participants of the CAROLINA trial (CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes). Methods: Baseline circulating biomarkers of oxidation (8-iso-prostaglandin F2 alpha), endothelial function (asymmetric dimethylarginine, endothelin-1) and inflammation (C-reactive protein, interleukin-6, tumour necrosis factor-alpha), based on linear regression, were related to cognition on five domains, as measured with an automated battery. Results: In 37 patients (mean age 66.7 +/- 8.7 years, median HbA1c 6.9%/52 mmol/mol), 8-iso-prostaglandin F2 alpha was associated with reduced mental flexibility and attention (standardised regression coefficients -0.47, -0.34), whereas asymmetric dimethylarginine was associated with reduced psychomotor speed and attention (standardised regression coefficients -0.39, -0.34). No significant associations were observed between biomarkers of inflammation and cognition. Conclusion: Elevated biomarkers of oxidation and endothelial function are associated and may play a role in reduced psychomotor speed, mental flexibility and attention in type 2 diabetes.