Onno N Groeneveld1, Esther van den Berg1,2, Odd Erik Johansen3, Sven Schnaidt4, Karin Hermansson5, Bernard Zinman6, Mark A Espeland7, Geert Jan Biessels1. 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.
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.
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