The Study Of Epidemiology And Early Blood Biomarker On Alzheimer's Disease And Mild Cognitive Impairment

Objectives:1.To study the prevalence and distribution characteristics of Alzheimer's disease(AD) and Mild Cognitive Impairment(MCI)among above 60 years old elderly popula-tion in Hubei Provence.2.To investigate and analyze the risk factors between the AD and MCI.3.To explore the level of symbolic serum protein among the AD,MCI and NC,and further research on AD etiology and early diagnosis,and provid the theoretical basis and prevention strategies.Methods:1.From January 2015 to December 2017,a population-based cross-sectional survey with a multistage stratified cluster sampling design was performed.We randomly drew samples from 60 years old elderly population in Hubei Provence,and obtained the morbidity and demographic distribution of AD and MCI.2.According to the first part,we carried a case-control study for AD group and MCI group.We analysed the risk factors on AD and MCI by paired t/?~2-test,single and multiple-factor logistic regression model analysis,and calculated the OR and 95%CI.3.According to the second part,we recruited 26 Alzheimer's Disease(AD)cases,26MCI cases,with a 1:1 case-control study,and 5ml blood samples in the fasted state were collected.Serum SIRT1,A?1-42,P-tau,T-tau and IL-6 level were measured by ELISA.Then we analysed the association between the above serum levels and MMSE average score.Results:1.The epidemiological investigation of the prevalence and distribution of AD and MCI1.1 A epidemiological survey of 4314 elderly people over 60 was carried out,finally including 4010 patients,excluding 304 invalid questionnaire,and the response rate was92.95%.There were 58 AD(1.44%),and 404 MCI(10.04%),with an average age(74.07±7.77)and(70.44±7.02)years old,respectively.And the average score of MMSE were(10.24±0.59)and(21.53±0.22).The prevalence of MCI was 53.22%in urban areas and 46.78%in rural areas.For male,the prevalence of AD was 29.31%,and70.69%for femal.But the prevalence of MCI was 37.13%and 62.87%,separately.The prevalence of AD and MCI was statistically significant between age and gender(P<0.05).1.2 The results of single factor analysis on AD and MCI(1)Demographic factorsGender,age,marital status,education and so on had effects on the prevalence of AD and MCI(P<0.05),which living conditions and physical examination just had effects on the prevalence of AD,but neighbor interaction and social activity had effects on the prevalence of MCI(P<0.05).(2)Body diseaseIntervertebral disc herniation and prostate patients showed higher AD risk(P<0.05),but hypertension,coronary heart disease and other cardiovascular disease hinted that people had higher MCI risk(P<0.05).Among them,there was no significant difference in the incidence of diabetes and chronic nephropathy between AD and MCI(P>0.05).(3)Life behavior factorsReading and chess had effects on the prevalence of AD and MCI(P<0.05),thus other factors on the AD and MCI prevalence showed no significant statistical difference(P>0.05).But drinking tea had effects on the prevalence of AD;smoking,exercise and the Internet had effects on the prevalence of MCI(P<0.05).(4)Physical characteristicsThe prevalence of AD,who had high BMI,wide waist circumference,were lower(P<0.05),and both prevalence were lower(P<0.05),who had high diastolic blood pressure.But other factors had no significant difference for both(P>0.05).2.In a case-control study,the single factor analysis for AD showed that as follows:(1)the protective factors:For influence of demographic factors and social contact and life events,such as,happy marriage(OR=0.69,95%CI:0.36-1.35),often communication with children(OR=0.71,95%CI:0.45-1.12),etc.For influence of life behavior factors,physical characteristics and interests,such as,periodic physical examination(OR=0.51,95%CI:0.28-0.93),reading(OR=0.17,95%CI:0.03-1.03),etc.(2)the risk factors:For influence of social contact and life events,life behavior factors,seldom take part in social activities(OR=1.00,95%CI:0.60-1.66),smoking(OR=1.55,95%CI:1.04-2.32),hypertension(OR=1.06,95%CI:0.57-1.97),etc.The single factor analysis for MCI showed that as follows:(1)the protective factors:For demographic factors,social contact and life events,such as,higher education(OR=0.65,95%CI:0.55-0.78),and living with family(OR=0.85,95%CI:0.57-1.26),etc.For influence of life behavior factors,physical characteristics and interests,such as,moderate tensity exercise(OR=0.89,95%CI:0.74-1.08),playing chess and card(OR=0.73,95%CI:0.50-1.06),etc.(2)the risk factors:For the influence of social contact and life events,life behavior factors,and physical characteristics,such as,sleep disorders(OR=2.21,95%CI:1.64-2.97),coronary heart disease(OR=2.27,95%CI:1.43-3.60),etc.3.The serum SIRT1,IL-6,A?1-42,P-tau and T-tau level of AD,MCI and NC group and the correlation between the serum level and MMSE average score3.1 Compared with NC group,for AD cases,the serum SIRT1 and IL-6 levels showed significant difference(P=0.000),but the serum A?1-42,P-tau and T-tau levels had no statistically significant difference(P>0.05).3.2 Compared with NC group,for MCI cases,the serum SIRT1,IL-6 and A?1-42levels showed significant difference(P<0.05),but P-tau and T-tau levels had no statistically significant difference(P>0.05).3.3 Compared with MCI group,for AD cases,the serum IL-6 levels showed significant difference(P=0.000),the serum SIRT1,A?1-42,P-tau and T-tau levels had no statistically significant difference(P>0.05).3.4 Serum SIRT1 level was strong positively correlated with MMSE score(rs=0.47,P=0.000),but serum IL-6,A?1-42,P-tau and T-tau levels showed strong negatively correlated with MMSE score(r_I=-0.73;r_A=-0.34;r_P=-0.58;r_T=-0.27,P=0.015),which were statistically significant difference(P<0.05).3.5 The sensitivity,specificity and AUC of serum P-tau,SIRT1,A?1-42,T-tau and IL-6 were decrease in turn.But for AUC,IL-6>P-tau>SIRT1>A?1-42>T-tau;Moreover,the differences in SIRT1,IL-6,P-tau and MMSE were statistically significant difference(P<0.05),while A?1-42 and T-tau had no statistically significant difference(P>0.05).Conclusions:1.In Hubei province,the prevalence of AD was 1.44%,lower than the average level(3.06%)for the elderly above 60 years old,and femal significantly higher than male.The prevalence of MCI was 10.04%,among the national level(5.2%~23.4%),and the difference showed the same trend as AD.2.From the city,higher education,happy marriage,often communication with children,modrate drinking and so on,were the protective factors of AD.Lack of social activity,smoking,seldom exercise,hypertension,etc,were risk factors for AD.Higher education,living with family,reading and so on,were the protective factors of MCI.Seldom communication with children,stroke and so on,were risk factors for MCI.3.Among the three groups,serum A?1-42,P-tau and T-tau levels were unstable;but serum SIRT1 levels decrease in turn(NC>MCI>AD),IL-6 levels increase in turn(NC<MCI<AD).Serum SIRT1 level was strong positively correlated with MMSE score,but serum IL-6,A?1-42,P-tau and T-tau levels showed strong negatively correlated with MMSE score;while the sensitivity,specificity and AUC of serum SIRT1was higher than A?1-42 and T-tau.Our findings showed that serum SIRT1 level may be a potential biomarker in the early stage of AD,which is of great theoretical significance for early screening of AD.