Alternative Measures of Hyperglycemia and Risk of Alzheimer's Disease in the Community: The Hisayama Study

J Clin Endocrinol Metab. 2017 Aug 1;102(8):3002-3010. doi: 10.1210/jc.2017-00439.


Context and objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD).

Design and participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years.

Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status.

Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Deoxyglucose / metabolism*
  • Female
  • Follow-Up Studies
  • Glucose Intolerance / epidemiology*
  • Glucose Intolerance / metabolism
  • Glycated Hemoglobin / metabolism*
  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Humans
  • Hyperglycemia / epidemiology*
  • Hyperglycemia / metabolism
  • Incidence
  • Independent Living
  • Japan / epidemiology
  • Male
  • Multivariate Analysis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Serum Albumin / metabolism*


  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Serum Albumin
  • hemoglobin A1c protein, human
  • 1,5-anhydroglucitol
  • Deoxyglucose
  • Glycated Serum Albumin