| Objective:1.To quantitatively examine and evaluate the correlation between peripheral blood inflammatory factors and mild cognitive impairment(MCI),and provide clues for further searching for early markers of Alzheimer's disease(AD).2.To investigate the association of Dementia with Alzheimer Type(DAT)and Mild Cognitive Impairment(MCI)with inflammatory factors in subjects'peripheral blood,andexamine the sensitivity and specificity of inflammatory markers in the diagnosis of MCI and DAT dementia,provide an important basis for early screening of the disease.Methods:1.The databases such as Pubmed,Ovid,Web of science,Cochrane library,China Knowledge Network(CNKI),China Biomedical Literature Database(CBM),VIP(WIP)and Wanfang(WanFang)were retrieved by using computer.The search time window was 1990-2017.In a case-control study involving peripheral blood inflammatory factors in MCI patients,two investigators independently extracted data according to inclusion and exclusion criteria and used the Newcastle-Ottawa Scale(NOS)to evaluate the quality of the included literature.The data was heterogeneity tested and meta-analysis using Review Manager 5.3 software.The chi-square test was used to analyze the heterogeneity of the data(test level is?=0.1),and the I~2statistics were used to determine size of the heterogeneity and identify inter-study variability and selection effect models.After selecting the effect model,perform a statistical test and plot the forest map.Meta-regression analysis of the data was performed using CMA 3.0software,and the influencing factors of heterogeneity between studies were explored.Subgroup analysis was performed using Review Manager 5.3 software.2.After detailed medical history collection,clinical physical examination,simple mental state examination(MMSE)and related laboratory examinations,the subjects were screened strictly according to the inclusion and exclusion criteria.A total of 98 subjects with DAT,102 subjects with MCI,and 101 subjects with normal cognitive function were selected and their fasting venous blood was drawn.The plasma concentrations of inflammatory factors such as IL-1?,IL-3,IL-8,IL-10,TNF-?,CRP,MCP-1,ICAM-1,VCAM-1 and RANTES were measured by Luminex.Relevant statistical analysis was performed using SPSS 16.0 software.The correlation between inflammatory factor levels and MMSE scores was analyzed by rank correlation.ROC analysis and discriminant analysis were used to test the sensitivity and specificity of inflammatory markers in the diagnosis of MCI and DAT dementia.Results:1.The levels of CRP,TNF-?,IL-1?,IL-6,MCP-1 and M-CSF and other9 kinds of inflammatory factors in 33 studies were included in the analysis.A total of 8742 subjects were enrolled,including 2398 patients and 6344 controls.T here was significant heterogeneity between the studies(?~2=21.33-470.59,I~2=91%-98%,P<0.05).The Meta-analysis showed that the levels of CRP[SMD=0.87,95%CI(0.48,1.26),P<0.0001],TNF-?[SMD=1.16,95%CI(0.32,2.00),P=0.007],IL-1?[SMD=0.96,95%CI(0.17,1.76),P=0.02],IL-6[SMD=1.07,95%CI(0.53,1.61),P<0.0001],IL-8[SM D=1.65,95%CI(0.36,2.93),P=0.01]in peripheral blood of patients with MCI were significantly higher than normal control group;however,there were no significant differences in IL-10,IL-12,MCP-1 and M-CSF levels between the two groups.Meta-regression analysis showed that the region was an important factor affecting CRP heterogeneity(?=-1.218,SE=0.4575,Z=-2.660,P=0.008),and the publicatio n year was an important factor affecting IL-6 heterogeneity(?=1.341,SE=0.553,Z=2.420,P=0.008).There was no statistical difference in the results of the Meta-regression analysis of TNF-?.2.Clinical studies showed that the concentrations of inflammatory factors such as IL-1?,IL-3,IL-10,ICAM-1,VCAM-1 and RANT ES were statistically significant among the three groups(P=0.000).The plasma le vels of IL-1?,IL-3,IL-10,RANTES,ICAM-1 and VCAM-1(5.90(0.50,22.18)pg/ml?0.20(0.10,0.40)pg/ml?1.10(0.50,3.10)pg/ml?137.21(109.31,159.67)pg/ml?909.15(748.12,1081.18)pg/ml?27.32(13.14,46.27)pg/ml)in DAT subjects were higher th an those in MCI group(0.40(0.00,4.80)pg/ml?0.10(0.10,0.20)pg/ml?0.70(0.30,1.40)pg/ml?109.30(88.49,137.96)ng/ml?701.05(564.52,870.61)ng/ml?12.72(5.26,24.09)n g/ml)and control group(2.00(0.10,13.10)pg/ml?0.10(0.10,0.20)pg/ml?0.60(0.20,1.45)pg/ml?87.06(68.23,125.82)ng/ml?602.42(382.25,789.80)ng/ml)?11.53(5.47,20.15)ng/ml)(P<0.05).The concentration of IL-1?(0.40(0.00,4.80)pg/ml)in the MCI gr oup was lower than that in the control group(2.00(0.10,13.10)pg/ml),and the lev el of ICAM-1(109.30(88.49,137.96)ng/ml)was higher than that in the control gro up(87.06(68.23,125.82)ng/ml),and the differences were statistically significant(P<0.05).There were no significant differences in the concentrations of inflammatory factors such as IL-8,TNF-?,CRP and MCP-1(P>0.05).Pearson correlation anal ysis showed that the MMSE score of DAT patients was negatively correlated wit h plasma IL-1?(r=-0.150,P=0.039),IL-3(r=-0.175,P=0.016),IL-10(r=-0.174,P=0.017),ICAM-1(r=-0.336,P=0.000),VCAM-1(r=-0.407,P=0.000)and RANTES(r=-0.422,P=0.000)levels.ROC analysis and discriminant analysis showed that IL-1?,ICA M-1,VCAM-1 and RANTES had moderate sensitivity or specificity in MCI or AD screening,and the correct classification rates were 59.1%-62.1%and 67.8%-70.4%,respectively.ICAM-1 combined with the MMSE scorecan improve the cla ssification accuracy rate,which is 83.3%and 91.0%,respectively.Conclusions:1.The levels of CRP,TNF-?,IL-1?,IL-6 and IL-8 were differentially expressed in peripheral blood of patients with MCI,which suggesting that these inflammatory factors may be involved in the development and progression of AD.2.The levels of IL-1?,IL-3,IL-10,ICAM-1,VCAM-1 and RANTES are differentially expressed in peripheral blood of patients with DAT and MCI,and those inflammation factors are associated with the extent of cognitive impairment.The detection of inflammatory markers such as IL-1?,ICAM-1,VCAM-1 and RANTEScan combined with the assessment of cognitive function,which will has certain clinical value in early screening of AD. |
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