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
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