The Relationship Between Plasma DPP4 Activity To BDNF Ratio And Mild Cognitive Impairment In Elderly Population With Normal Glucose Tolerance

Objective: Mild cognitive impairment(MCI)is between normal cognitive function and Alzheimer disease(AD),in which patients have objective disturbances and cognitive complaints on cognitive examinations,but in which their ability to carry out daily life activities are not affected.Since decreased brain-derived neurotrophic factor(BDNF)and increased dipeptidyl peptidase-4(DPP4)activity have both been implicated in the pathogenesis of MCI in elderly population with normal glucose tolerance(NGT).Therefore,the aim of our study was to evaluate the association of MCI with plasma DPP4 activity to BDNF ratio(DBR)in elderly population with normal glucose tolerance,whether there is a negative correlation between DPP4 activity and BDNF content,and what factors mediate the correlation.Methods: A total of 1066 elderly people with normal glucose tolerance were enrolled in this study.Their educational background,smoking and drinking history,past history and other personal data were collected through questionnaires.We cross-sectionally measured C-reactive protein,interleukin-6,nitrotyrosine,8-iso-PGF2 a,DPP4 activity,BDNF and calculated DBR.MCI was determined by the Montreal Cognitive Assessment(MoCA)scale.,MCI was determined by MoCA and finally confirmed by neurologists.All data were analyzed by SPSS 16.0 software(SPPS,Chicago,IL),using covariance analysis,chi-square or T-test,partial correlation analysis,multiple logistic regression analysis,mediation analysis and other statistical methods.Results: MoCA score was negatively correlated with DBR(r=-0.254,P<0.001).DPP4 activity was negatively correlated with BDNF level(r=-0.456,P <0.001).The negative correlation may be mediated by nitrotyrosine and 8-iso-PGF2 a.In the quartiles of DBR,nitrotyrosine,8-iso-PGF2 a,CRP and IL-6 progressively increased,while MoCA score progressively decreased.Subjects in the lowest quartile of BDNF and highest quartiles of DBR and DPP4 activity had higher MCI risk compared with subjects in the highest quartile of BDNF and lowest quartiles of DBR and DPP4 activity,respectively(all P<0.05).The odds ratios for MCI became more pronounced with decreased BDNF and increased DPP4.Conclusions: In conclusion,a negative correlation was found between DPP4 activity and BDNF and this negative correlation was partly mediated by oxidative stress,not inflammation.DBR was positively associated with MCI and thus may be used as a novel risk biomarker for MCI in elderly population with normal glucose tolerance.