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Oxidative stress and endothelial dysfunction are associated with reduced cognition

Diab Vasc Dis Res. 2019 Nov;16(6):577-581. Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes. Groeneveld ON1, van den Berg E1,2, Johansen OE3, Schnaidt S4, Hermansson K5, Zinman B6, Espeland MA7, Biessels GJ1. Author information 1 Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. 2 Department of Neurology, Erasmus MC – University Medical Center, Rotterdam, The Netherlands. 3 Therapeutic Area Cardiometabolism, Boehringer Ingelheim, Asker, Norway. 4 Global Biostatistics and Data Sciences, Boehringer Ingelheim, Ingelheim am Rhein, Germany. 5 Clinical Operations, Boehringer Ingelheim AB, Stockholm, Sweden. 6 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. 7 Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA. Abstract 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. KEYWORDS: Type 2 diabetes; circulating biomarkers; cognitive dysfunction; endothelial dysfunction; oxidative stress Full-Text

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