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 F2α), endothelial function (asymmetric dimethylarginine, endothelin-1) and inflammation (C-reactive protein, interleukin-6, tumour necrosis factor-α), 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 F2α 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.