Glycemia and cognitive function in metabolic syndrome and coronary heart disease

Abstract

Objective: Higher hemoglobin A1c (HbA1c) 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 SALsalate in CardioVascular Disease (TINSAL-CVD) trial.

Methods: The age-adjusted relationships between HbA1c 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. HbA1c 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 HbA1c 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, HbA1c 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 HbA1c 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.

Keywords: Cardiovascular disease; Cognitive function; Glycemia; Hemoglobin A(1c).

Conflict of interest statement

Conflict of interest: None

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1. Association of Glycemia with Measures of Cognitive Function

Figure 1A: Mini-Mental State Exam Figure 1B: Digit Symbol Substitution Test Figure 1C: Rey Auditory Verbal Learning Test Figure 1D: Trail Making Test B Figure 1E: Categorical Verbal Fluency Figure 1 displays in the full study cohort population scatterplots showing correlation, fitted regression, and 95% confidence intervals relating Hemoglobin A1c and cognitive function tests [A] Displays the fit plot for regression of Mini-mental state examination (MMSE) and Hemoglobin A1c (HbA1c). There is no association between HbA1c and Mini-Mental State Examination score (P=0.07). [B] Displays the fit plot regression for Digit Symbol Substitution Test (DSST) and HbA1c. The average DSST score of a patient changes by β̂ =−7.79 units for each unit change in HbA1c (r=−0.27, P<0.0001), [C] Displays the fit plot for regression of Rey Auditory Verbal Learning Test (RAVLT) and HbA1c. The average RAVLT score of a patient changes by β̂= −3.44 units for each unit change in HbA1c (r=−0.27, P <0.0001). [D] Displays the fit plot for regression of Trail Making B and HbA1c, The average Trail Making B score of a patient changes by β̂=20.6 units for each unit change in HbA1c (r=0.27, P<0.0001) and [E] Displays the fit plot for regression of Categorical Verbal Fluency (CVF) and HbA1c. The average CVF score of a patient changes by β̂= −3.82 units for each unit change in HbA1c (r=−0.19, P=0.0042). To convert HbA1c: HbA1c(%) = [0.09148 * HbA1c (mmol/mol)] + 2.152.

Figure 1. Association of Glycemia with Measures of Cognitive Function

Figure 1A: Mini-Mental State Exam Figure 1B: Digit Symbol Substitution Test Figure 1C: Rey Auditory Verbal Learning Test Figure 1D: Trail Making Test B Figure 1E: Categorical Verbal Fluency Figure 1 displays in the full study cohort population scatterplots showing correlation, fitted regression, and 95% confidence intervals relating Hemoglobin A1c and cognitive function tests [A] Displays the fit plot for regression of Mini-mental state examination (MMSE) and Hemoglobin A1c (HbA1c). There is no association between HbA1c and Mini-Mental State Examination score (P=0.07). [B] Displays the fit plot regression for Digit Symbol Substitution Test (DSST) and HbA1c. The average DSST score of a patient changes by β̂ =−7.79 units for each unit change in HbA1c (r=−0.27, P<0.0001), [C] Displays the fit plot for regression of Rey Auditory Verbal Learning Test (RAVLT) and HbA1c. The average RAVLT score of a patient changes by β̂= −3.44 units for each unit change in HbA1c (r=−0.27, P <0.0001). [D] Displays the fit plot for regression of Trail Making B and HbA1c, The average Trail Making B score of a patient changes by β̂=20.6 units for each unit change in HbA1c (r=0.27, P<0.0001) and [E] Displays the fit plot for regression of Categorical Verbal Fluency (CVF) and HbA1c. The average CVF score of a patient changes by β̂= −3.82 units for each unit change in HbA1c (r=−0.19, P=0.0042). To convert HbA1c: HbA1c(%) = [0.09148 * HbA1c (mmol/mol)] + 2.152.

Figure 1. Association of Glycemia with Measures of Cognitive Function

Figure 1A: Mini-Mental State Exam Figure 1B: Digit Symbol Substitution Test Figure 1C: Rey Auditory Verbal Learning Test Figure 1D: Trail Making Test B Figure 1E: Categorical Verbal Fluency Figure 1 displays in the full study cohort population scatterplots showing correlation, fitted regression, and 95% confidence intervals relating Hemoglobin A1c and cognitive function tests [A] Displays the fit plot for regression of Mini-mental state examination (MMSE) and Hemoglobin A1c (HbA1c). There is no association between HbA1c and Mini-Mental State Examination score (P=0.07). [B] Displays the fit plot regression for Digit Symbol Substitution Test (DSST) and HbA1c. The average DSST score of a patient changes by β̂ =−7.79 units for each unit change in HbA1c (r=−0.27, P<0.0001), [C] Displays the fit plot for regression of Rey Auditory Verbal Learning Test (RAVLT) and HbA1c. The average RAVLT score of a patient changes by β̂= −3.44 units for each unit change in HbA1c (r=−0.27, P <0.0001). [D] Displays the fit plot for regression of Trail Making B and HbA1c, The average Trail Making B score of a patient changes by β̂=20.6 units for each unit change in HbA1c (r=0.27, P<0.0001) and [E] Displays the fit plot for regression of Categorical Verbal Fluency (CVF) and HbA1c. The average CVF score of a patient changes by β̂= −3.82 units for each unit change in HbA1c (r=−0.19, P=0.0042). To convert HbA1c: HbA1c(%) = [0.09148 * HbA1c (mmol/mol)] + 2.152.

Figure 1. Association of Glycemia with Measures of Cognitive Function

Figure 1A: Mini-Mental State Exam Figure 1B: Digit Symbol Substitution Test Figure 1C: Rey Auditory Verbal Learning Test Figure 1D: Trail Making Test B Figure 1E: Categorical Verbal Fluency Figure 1 displays in the full study cohort population scatterplots showing correlation, fitted regression, and 95% confidence intervals relating Hemoglobin A1c and cognitive function tests [A] Displays the fit plot for regression of Mini-mental state examination (MMSE) and Hemoglobin A1c (HbA1c). There is no association between HbA1c and Mini-Mental State Examination score (P=0.07). [B] Displays the fit plot regression for Digit Symbol Substitution Test (DSST) and HbA1c. The average DSST score of a patient changes by β̂ =−7.79 units for each unit change in HbA1c (r=−0.27, P<0.0001), [C] Displays the fit plot for regression of Rey Auditory Verbal Learning Test (RAVLT) and HbA1c. The average RAVLT score of a patient changes by β̂= −3.44 units for each unit change in HbA1c (r=−0.27, P <0.0001). [D] Displays the fit plot for regression of Trail Making B and HbA1c, The average Trail Making B score of a patient changes by β̂=20.6 units for each unit change in HbA1c (r=0.27, P<0.0001) and [E] Displays the fit plot for regression of Categorical Verbal Fluency (CVF) and HbA1c. The average CVF score of a patient changes by β̂= −3.82 units for each unit change in HbA1c (r=−0.19, P=0.0042). To convert HbA1c: HbA1c(%) = [0.09148 * HbA1c (mmol/mol)] + 2.152.

Figure 1. Association of Glycemia with Measures of Cognitive Function

Figure 1A: Mini-Mental State Exam Figure 1B: Digit Symbol Substitution Test Figure 1C: Rey Auditory Verbal Learning Test Figure 1D: Trail Making Test B Figure 1E: Categorical Verbal Fluency Figure 1 displays in the full study cohort population scatterplots showing correlation, fitted regression, and 95% confidence intervals relating Hemoglobin A1c and cognitive function tests [A] Displays the fit plot for regression of Mini-mental state examination (MMSE) and Hemoglobin A1c (HbA1c). There is no association between HbA1c and Mini-Mental State Examination score (P=0.07). [B] Displays the fit plot regression for Digit Symbol Substitution Test (DSST) and HbA1c. The average DSST score of a patient changes by β̂ =−7.79 units for each unit change in HbA1c (r=−0.27, P<0.0001), [C] Displays the fit plot for regression of Rey Auditory Verbal Learning Test (RAVLT) and HbA1c. The average RAVLT score of a patient changes by β̂= −3.44 units for each unit change in HbA1c (r=−0.27, P <0.0001). [D] Displays the fit plot for regression of Trail Making B and HbA1c, The average Trail Making B score of a patient changes by β̂=20.6 units for each unit change in HbA1c (r=0.27, P<0.0001) and [E] Displays the fit plot for regression of Categorical Verbal Fluency (CVF) and HbA1c. The average CVF score of a patient changes by β̂= −3.82 units for each unit change in HbA1c (r=−0.19, P=0.0042). To convert HbA1c: HbA1c(%) = [0.09148 * HbA1c (mmol/mol)] + 2.152.