Glycemia and Cognitive Function in Metabolic Syndrome and Coronary Heart Disease

OBJECTIVE: Higher hemoglobin A(1c) (HbA(1c)) is associated with lower cognitive function in type 2 diabetes. To determine whether associations persist at lower levels of dysglycemia in patients who have established cardiovascular disease, cognitive performance was assessed in the Targeting INflammation Using SAL-salate in CardioVascular Disease (TINSAL-CVD) trial. METHODS: The age-adjusted relationships between HbA(1c) and cognitive performance measured by the Mini-Mental State Examination, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency were assessed in 226 men with metabolic syndrome and established stable coronary artery disease. RESULTS: Of the participants, 61.5% had normoglycemia, 20.8% had impaired fasting glucose, and 17.7% had type 2 diabetes. HbA(1c) was associated with cognitive function tests of Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency (all P < .02), but not the Mini-Mental State Examination. In an age-adjusted model, a 1% (11 mmol/mol) higher HbA(1c) value was associated with a 5.9 lower Digit Symbol Substitution Test score (95% confidence interval [CI], -9.58 to -2.21; P < .0001); a 2.44 lower Rey Auditory Verbal Learning Test score (95% CI, -4.00 to -0.87; P < .0001); a 15.6 higher Trail Making Test score (95% CI, 5.73 to 25.6; P < .0001); and a 3.71 lower Categorical Verbal Fluency score (95% CI, -6.41 to -1.01; P < .02). In a multivariate model adjusting for age, education, and cardiovascular covariates, HbA(1c) remained associated with cognitive function tests of Rey Auditory Verbal Learning Test (R-2 = 0.27, P < .0001), Trail Making Test (R-2 = 0.18, P < .0001), and Categorical Verbal Fluency (R-2 = 0.20, P < .0001), although association with the Digit Symbol Substitution Test was reduced. CONCLUSIONS: Higher HbA(1c) is associated with lower cognitive function performance scores across multiple domain tests in men with metabolic syndrome and coronary artery disease. Future studies may demonstrate whether glucose lowering within the normative range improves cognitive health. (c) 2015 Elsevier Inc. All rights reserved.