Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort

Arch Intern Med. 2004 Jun 28;164(12):1327-33. doi: 10.1001/archinte.164.12.1327.


Background: A few studies have examined change in cognitive performance by diabetes status with disparate results. We examined the 4-year change in cognitive performance among older adults according to glucose tolerance status.

Methods: Three cognitive tests (Mini-Mental State Examination, Verbal Fluency [VF] test, and Trail-Making Test B) were measured 4 years apart in 999 white men and women aged 42 to 89 years, who were enrolled in the Rancho Bernardo Study. Participants were classified with normal (NGT), impaired (IGT) or diabetic glucose tolerance. Sex-specific linear regression models adjusted for age, education, depression score, apolipoprotein E epsilon4 allele, and current estrogen use. We checked for mediation by further adjusting for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; blood pressure; glycohemoglobin level; and microalbuminuria, retinopathy, stroke, or coronary heart disease.

Results: At baseline, mean cognitive function scores did not differ between glucose tolerance groups. Women with diabetes mellitus had a 4-fold increased risk of a major cognitive decline on the VF test after 4 years compared with nondiabetic women. After multivariate adjustment, VF test scores at follow-up for women were 15.2 +/- 0.6 for those with diabetes, 16.7 +/- 0.4 for those with IGT, and 17.2 +/- 0.2 for those with NGT (P =.007). Glycohemoglobin attenuated this effect, but lipid levels, blood pressure, and microvascular or macrovascular disease did not. Performance on Mini-Mental State Examination and Trail-Making Test B did not differ by baseline glucose status.

Conclusions: Elderly white women with diabetes had a more rapid decline in performance on the VF test compared with women with IGT or NGT. Better glucose control might ameliorate this decline.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Blood Pressure / physiology
  • California / epidemiology
  • Cholesterol, HDL / blood
  • Cognition / physiology*
  • Cohort Studies
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / physiopathology
  • Female
  • Follow-Up Studies
  • Glucose Intolerance / blood
  • Glucose Intolerance / physiopathology*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Sex Factors
  • Statistics as Topic
  • Systole / physiology
  • Vascular Diseases / blood
  • Vascular Diseases / physiopathology


  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL