Association between visit-to-visit variability of HbA1c and cognitive decline: a pooled analysis of two prospective population-based cohorts

The aim of this study was to investigate the association between visit-to-visit variability in HbA1c and cognitive function decline in the elderly population. We performed a pooled analysis of two prospective population-based cohorts (the Health Retirement Study [HRS] and the English Longitudinal Study of Ageing [ELSA]). Cognitive function, including memory and executive function, were assessed at baseline and every 2 years, while HbA1c levels were assessed at baseline and every 4 years. Visit-to-visit variability (VVV) in HbA1c was calculated using the CV, SD and variation independent of the mean (VIM) during the follow-up period. Linear mixed models were used to evaluate the association between HbA1c variability and cognitive function decline with adjustment for demographics, mean HbA1c, education, smoking, alcohol consumption, BMI, baseline hypertension, baseline diabetes status and HDL-cholesterol. The study enrolled 6237 participants (58.23% women, mean age 63.38 ± 8.62 years) with at least three measurements of HbA1c. The median follow-up duration was 10.56 ± 1.86 years. In the overall sample, compared with the lowest quartile of HbA1c variability, participants in the highest quartile of HbA1c variability had a significantly worse memory decline rate (−0.094 SD/year, 95% CI −0.185, −0.003) and executive function decline rate (−0.083 SD/year, 95% CI −0.125, −0.041), irrespective of mean HbA1c values over time. Among individuals without diabetes, each 1-SD increment in HbA1c CV was associated with a significantly higher rate of memory z score decline (−0.029, 95% CI −0.052, −0.005) and executive function z score decline (−0.049, 95% CI −0.079, −0.018) in the fully adjusted model. We observed a significant association between long-term HbA1c variability and cognitive decline among the non-diabetic population in this study. The effect of maintaining steady glucose control on the rate of cognitive decline merits further investigation.