HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing

Diabetologia. 2018 Apr;61(4):839-848. doi: 10.1007/s00125-017-4541-7. Epub 2018 Jan 25.


Aims/hypothesis: The aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period.

Methods: Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations.

Results: The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes.

Conclusions/interpretation: Significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.

Keywords: Cognitive decline; Diabetes; HbA1c; Trajectory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Cognition
  • Cognitive Dysfunction / blood*
  • Cognitive Dysfunction / complications*
  • Cross-Sectional Studies
  • Diabetes Complications / blood
  • Diabetes Complications / complications
  • Diabetes Mellitus / blood*
  • England
  • Executive Function
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis*
  • Humans
  • Longitudinal Studies
  • Male
  • Memory
  • Middle Aged
  • Reproducibility of Results
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human