Relationship Between Baseline Glycemic Control and Cognitive Function in Individuals With Type 2 Diabetes and Other Cardiovascular Risk Factors

The Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) trial

  1. Tali Cukierman-Yaffe, MD, MSC12,
  2. Hertzel C. Gerstein, MD, MSC2,
  3. Jeff D. Williamson, MD, MPH3,
  4. Ronald M. Lazar, PHD4,
  5. Laura Lovato, MS5,
  6. Michael E. Miller, PHD5,
  7. Laura H. Coker, PHD6,
  8. Anne Murray, MD7,
  9. Mark D. Sullivan, MD, PHD8,
  10. Santica M. Marcovina, PHD, SCD9,
  11. Lenore J. Launer, PHD10 and
  12. for the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Investigators*
  1. 1Gertner Institute for Epidemiology and Health Policy Research, Endocrinology Institute Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  2. 2Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
  3. 3Roena B. Kulynych Center for Memory, Cognition Research, Department of Internal Medicine, Wake Forest University, Winston-Salem, North Carolina
  4. 4Departments of Neurology and Neurological Surgery, Columbia University College of Physicians and Surgeons, New York, New York
  5. 5Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  6. 6Roena B. Kulynych Center for Memory, Cognition Research, Department of Social Sciences and Health Policy, Wake Forest University, Winston-Salem, North Carolina
  7. 7Hennepin County Medical Center and Chronic Disease Research Group, Minneapolis, Minnesota
  8. 8University of Washington, Seattle, Washington
  9. 9Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, Washington
  10. 10Intramural Research Programme, National Institute on Aging. National Institutes of Health, Bethesda, Maryland
  1. Corresponding author: Tali Cukierman-Yaffe, cukierm{at}


OBJECTIVE—Diabetes is associated with cognitive decline and dementia. However, the relationship between the degree of hyperglycemia and cognitive status remains unclear. This was explored using baseline cognitive measures collected in the ongoing Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

RESEARCH DESIGN AND METHODS—The relationship of A1C and fasting plasma glucose (FPG) levels to performance on four cognitive tests was assessed, adjusting for age and other determinants of cognitive status. The tests were the Digit Symbol Substitution Test (DSST), Mini Mental Status Examination (MMSE), Rey Auditory Verbal Learning Test, and Stroop Test.

RESULTS—A statistically significant age-adjusted association was observed between the A1C level and the score on all four cognitive tests. Specifically, a 1% higher A1C value was associated with a significant 1.75-point lower DSST score (95% CI −1.22 to −2.28; P < 0.0001), a 0.20-point lower MMSE score (−0.11 to −0.28; P < 0.0001), a 0.11-point lower memory score (−0.02 to −0.19, P = 0.0142), and a worse score (i.e., 0.75 s more) on the Stroop Test (1.31–0.19, P = 0.0094). The association between the DSST score and A1C persisted in all multiple linear regression models. FPG was not associated with test performance.

CONCLUSIONS—Higher A1C levels are associated with lower cognitive function in individuals with diabetes. The effect of glucose lowering on cognitive function will be determined by the ongoing ACCORD-MIND trial.


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    * A complete list of the Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Memory in Diabetes (MIND) investigators can be found in the appendix.

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    • Accepted October 16, 2008.
    • Received June 26, 2008.
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