Association Between Advanced Glycosylation End Products In Plasma And Cognitive Performance Among Middle-Aged And Older Adults

Objective:The purpose of this study was to explore the relationship between AGEs and the risk of MCI,as well as the relationship between AGEs and total cognitive tests scores and cognitive domains.Methods:Sociodemographic information,living habits,and morbidity were obtained through face-to-face interviews.AGEs in plasma were measured by UPLC-MS/MS.Multivariate Logistic regression was used to analyze the relationship between AGEs（including Carboxymethyl lysine,CML、Carboxyethyl lysine,CEL、Methyl imidazolidone,MG-H1、Pyrraline,Pyr）in plasma with the MCI.Multiple linear regression was used to analyze the AGEs and total cognitive tests scores and cognitive domains,as well as the relationship between AGEs score with total cognitive tests scores and cognitive domains.Results:（1）A total of 425 subjects with a mean age of（61.23±7.2）were included in the study.There were 56 patients with mild recognition disorder,the average age was 66.07±6.17,accounting for 13.18%.In patients with mild cognitive impairment and cognitively normal population.CML was 65.82（51.15-102.38）nmol/L and53.63（36.57-73.14）nmol/L CEL were 79.23（63.38-110.92）nmol/L and 37.92（25.86-73.14）nmol/L.MG-H1 were 331.73（218.25-539.07）nmol/L and 296.81（218.25-411.39）nmol/L.Pyr were 13.72（5.54-19.60）nmol/L and 11.76（5.54-17.64）nmol/L.There were significant differences in plasma free CML and CEL in mild cognitive impairment and normal cognitive groups.There were no significant differences in MG-H1 and Pyr in the two groups.（2）Multivariate Logistic regression was used to analyze the relationship between four AGEs substances（CML,CEL,MG-H1,Pyr）in plasma and the risk of mild cognitive impairment.The OR（95%）of mild cognitive impairment was 1.02（1.01,1.04）for each standard deviation SD adjusted for CML.。（3）Multiple linear regression was used to analyze the correlation between AGEs and the total scores of cognitive function.Compared with the group with the lowest CML levels,higher CML had lower total scores of cognitive function（Q3:β=-0.28,95%CI:-0.46,-0.11;Q4:β=-0.38,95%CI:-0.58,-0.18）.Furthermore,for each log-adjusted standard deviation increase in CML,the beta value of total scores of cognitive function was-0.21(P _trend<0.001).After adjusting for confounding factors,subjects with high or higher CEL levels had lower overall cognitive scores than those in the group with the lowest CEL level（Q3:β=-0.18,95%CI:-0.34,-0.03;Q4:β=-0.22,95%CI:-0.40,-0.05）.In addition,the beta value of the total cognitive level score was-0.25(P_trend=0.002)for each log-adjusted standard deviation increase in CEL.No significant correlation was found between MG-H1 and Pyr.（4）CML and CEL were further analyzed.Plasma free CML and scores in various cognitive domains（AVLT,VFT,DSST,TMT-B）were analyzed by generalized linear model.After adjusting for confounding factors,groups with high or high levels of CML performed worse on the AVLT,DSST,and TMT-B tests than groups with the lowest levels of CML.The results of linear trend test showed that AVLT decreased by 2.2 points for each log-adjusted standard deviation increase of CML(P_trend=0.002).VFT decreased by 0.89 words(P _trend=0.003);DSST decreased by 2.51 points(P _trend<0.001);TMT-B extended 6.15 s(P _trend<0.001).The generalized linear model was used to analyze the plasma free CEL and scores in various cognitive domains（AVLT,VFT,DSST,TMT-B）.Compared with the group with the lowest CEL level,the group with higher CEL level had worse performance in the AVLT and VFT tests.Compared with the group with the lowest CEL level,the group with high CEL level had worse performance in the DSST test.The results of the linear trend test showed that the VFT decreased by 1.77 words for each logarithmic standard deviation adjusted by CML(P _trend=0.003);TMT-B extension of 6.30 seconds(P _trend=0.041).（5）In addition,we analyzed the association between total plasma AGEs and cognitive function.The total AGEs ranged from-2.38 to 2.56,and the higher the score,the greater AGEs.Compared with the group with the lowest total AGEs load,the group with the highest AGEs had worse performance on both the total cognitive test score and the AVLT.The results of linear trend test showed that the total score of cognitive level test decreased by 0.07 points for each unit increase in the total load of AGEs(P _trend=0.001),AVLT decreased by 1.06 points(P _trend=0.018).Conclusion:This study showed that people with higher levels of plasma AGEs were more likely to develop mild cognitive impairment.CML was a risk factor for mild cognitive impairment,and was negatively correlated with cognitive function,memory ability,executive ability,attention,and verbal fluency.CEL is negatively correlated with cognitive function,verbal fluency and executive ability.Those with higher total AGEs had worse performance on both total cognitive test score and AVLT.In conclusion,plasma free AGEs have potential reletionship to cognitive function,and the underlying mechanism still needs to be confirmed in future studies.