Identification Of Inflammatory And Metabolic Markers Associated With Mild Cognitive Impairment

Objective: With the development of global aging,the incidence of dementia in both developing countries including China and developed countries in the world is increasing.Dementia seriously threatens human health and has brought huge burden to the society and family.Patients with mild cognitive impairment(MCI)are at high risk for progression to dementia,thus early diagnosis and interventions of MCI is of great importance.Highly specific,highly sensitive and low-cost biomarkers have been the focus of MCI and dementia research.Studies have proved a certain role of inflammatory and metabolic markers in the pathogenesis of MCI.This study was designed to compare the level of inflammatory and metabolic markers in the plasma of Asian MCI patients with that of cognitively healthy controls in Singapore,and to investigate whether these biomarkers are associated with cognitive impairment.Methods: After strict quality control screening,a total of 114 samples(57 MCI patients and 57 cognitively healthy controls)were included in the case-control study.We reviewed relevant literature,selected 21 inflammatory or metabolic markers and measured their plasma concentrations.After that,we used the SPSS software and the Graphpad software to analyze the data and plot results.For normally distributed data,we used the independent sample t test to compare the MCI group with the control group.For those non-normally distributed,we used the Wilcoxon signed rank test for comparison between groups.Then,we adopted correlation analysis and regression analysis to further explore the possible relationship between plasma biomarker level and cognition level.Finally,considering the small sample size of this study,we used the PASS15 software to calculate the test performance.Results: Compared with cognitively healthy controls,MCI patients were older(P < 0.001)and less educated(P = 0.004),with no differences on other aspects such as diabetes prevalence,smoking,drinking and marriage(P > 0.05).Comparisons between the two groups showed that plasma levels of tumor necrosis factor alpha(TNF-?)(P = 0.045)and C-peptide(P = 0.004)were higher in MCI patients than in the control group,whereas vascular endothelial growth factor A(VEGF-A)(P = 0.042)and plasminogen activation inhibitor 1(PAI-1)(P = 0.019)was lower than that of the control group.In both the total sample population and MCI patients,correlation analysis showed that plasma levels of soluble interleukin 2 receptor alpha(sIL-2R?)and soluble tumor necrosis factor receptor 1(sTNFR-1)were negatively correlated with the scores of Montreal Cognitive Assessment Scale(MoCA)(P < 0.05).Conclusion: Our study provided evidence that individuals with MCI differed from cognitively healthy controls in the plasma expression of at least four markers: TNF-?,VEGF-A,C-peptide and PAI-1.These findings further support a role of inflammation and metabolic changes in the pathogenesis of MCI.In addition,plasma sIL-2R? and sTNFR-1 as potential indicators for cognition evaluation have certain research value for the diagnosis and monitoring of early cognitive impairment.