U-shaped relationship between hemoglobin glycation index and cognitive outcome in older population in China: A population-based prospective study

BackgroundThe hemoglobin glycation index (HGI) effectively captures individual variations in glycation, its association with cognitive impairment remains unclear.ObjectiveThe purpose of this study was to investigate the relationship between HGI and cognitive impairment risk in the Chinese population.MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015 were analyzed. Cognitive function was assessed using the American Health and Retirement Study's methodology, which included episodic memory and mental status. Multivariate Cox proportional hazards models and restricted cubic splines were used to examine the link between HGI and the likelihood of cognitive impairment, specific cognitive domains included. Moreover, the potential inflection points were investigated using saturation threshold effect analysis, with bootstrap resampling applied for internal validation.ResultsA U-shaped relationship was observed between HGI and the risk of cognitive impairment, as demonstrated by the restricted cubic spline analysis (p for non-linearity <0.001). The primary analysis identified an inflection point at approximately 0.085. Internal validation via bootstrapping yielded a 95% empirical confidence interval of 0.013 to 0.255 for this point. Conversely, HGI levels above 0.085 resulted in a 70.6% increase in the hazard ratio of cognitive impairment (all p < 0.05).ConclusionsIn the Chinese population, our results point to a U-shaped association between HGI and the risk of cognitive impairment, suggesting that both very low and very high HGI levels raise the risk of cognitive impairment, especially execution and memory.