title: 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.
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Radhika
authors.initials: R
authors.lastname: Avadhani
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Kristen
authors.initials: K
authors.lastname: Fowler
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Corinne
authors.initials: C
authors.lastname: Barbato
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Sherine
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Winnie
authors.initials: W
authors.lastname: Wong
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Camille
authors.initials: C
authors.lastname: Paul
authors.affiliation: Joslin Diabetes Center, Boston, Mass.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Aksakal
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Harvard University, Boston, Mass.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hauser
authors.affiliation: Joslin Diabetes Center, Boston, Mass; Harvard Medical School, Harvard University, Boston, Mass.
authors.forename: Katie
authors.initials: K
authors.lastname: Weinger
authors.affiliation: Joslin Diabetes Center, Boston, Mass; Beth Israel Deaconess Medical Center, Boston, Mass; Harvard Medical School, Harvard University, Boston, Mass. Electronic address: allison.goldfine@joslin.harvard.edu.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
mesh_terms: D000368:Aged; D003071:Cognition; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000523:psychology*; D003920:Diabetes Mellitus / Q000097:blood / Q000523:psychology*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000523:psychology*; D008875:Middle Aged
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
keywords: Cardiovascular disease; Cognitive function; Glycemia; Hemoglobin A(1c)