| BackgroundWith the rapid increase in life expectancy in the population,Dementia is becoming one of the important healthy problems.Mild cognitive impairment(MCI)refers to the transition clinical state between normal aging and dementia or Alzheimer?disease (AD) in which individuals experience memory loss or other cognitive deficit to a greater extent than one would expect for age,yet they do not meet currently accepted criteria for dementia.It?s valuable to study the cognitive characterization and natural history of MCI for the early detection and prevention of dementia.Objects1.To determine the prevalence and distribution of MCI in the aged population and analyze socio-demographic factors.2..To understand the influencing factor and the difference in the outcome of the conversion to cognitive decline among the MCI subjects with different socio-demographic and personality characteristics,disease history,and hereditary feature.3.To study independent role,united role of amyloid precursor protein blood fat apolipoprotein e during the period of conversion to cognitive decline among the MCI subjects and the relationship between them.4. To find out the characteristic of MCI during the earlier period of dementia and manifestation of memory decline associated with the conversion to dementia.5.To provide sensitive,Specific,cheap and pragmatic detection means and index for assessment of the conversion to dementia. Subjects and methodsThe initial phase 1 assessment took place in May 2007.A cross-sectional study was conducted among the community-dwelling elders aged over 65. A total of 6192 subjects (91.06% of the eligible subjects) participated in the baseline survey (2007.4-2007.6). According to the Petersen's diagnostic standard on mild cognitive impairment(MCI), 600 subjects with MCI were screened from the baseline population.all of which were treated as the cohort population. The follow-up interviews were performed at the following 2 years during phase 2 after the baseline assessment. Follow-up visits occurred annually, with the last examination occurring in November 2008.1.Baseline assessmentBy cluster random sampling,6192 aged people over 65 were ultimately involved. This survey composed of face-to-face interviews and self-administered questionnaires including questions on socio-demographic features, subjective ratings of memory and physical and emotional health and medical conditions such as medical history, current medication, and a subjective assessment of memory disturbances or depression. The scale such as MMSE,GDS and ADL have been performed to measure cognitive function.Information about the subjects was evaluated by a panel of neurologists, neuropsychologists, a geriatrician, and clinical nurses. Of all the 6192 community-dwelling participants aged 65 and older who underwent psychometric testing,, 600 subjects met our criteria for MCI.2.Case-control studyA n:m matched case-control study was conducted to analyze influencing factors of mild cognitive impairment among the elderly community-based population. Four hundred and twenty-three cases together with nine hundred and twenty-five controls were interviewed with a uniformed questionnaire .cases were matched with controls by age decade,education group(i.e.,less than 10 years of education or greater than or equal 10 years of education),and gender in a n:m ratio.All the subjects can accomplish psychological tests independently with adequate cognition and memory. Cox regression model of survival analysis was selected to deal with non-geometric proportional matched data which is difficult to analyze by Logistic regression model.the influencing factors analyzed included socio-demographic,life style disease history,personality characteristics,physiological functions,biochemical index in the serum and hereditary feature.3.Nested case-control study600 subjects with MCI were screened from the baseline population.all of which were treated as the cohort population.In each follow-up,cognitive decline was defined as at least a 1 SD drop in IQ Compared with the baseline survey. Subjects who conform to the cretia above can be included in cognitive decline group,while subjects who were normally cognitive can be included in stable group Each case was matched with one control by age decade,education group(i.e.,less than 10 years of education or greater than or equal 10 years of education),and gender.Exclusion criteria for controls were the same as those for cases. Of all these subjects,114 cognitive decline individuals and 114 cognitive stable individuals were selected to participate in the experiment reported here. they formed the final samles of the present study.Analysis are based on two groups.Cox regression model of survival analysis was applied to analyze influencing factors with SPSS 13.0 Software 4.Cohort study600 subjects with MCI were screened from the baseline population.All of which were treated as the cohort population. we employed the Chinese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to assess general intellectual ability and used the IQ value to assess cognitive variation among cohort population.The conversion rates to cognitive decline of MCI and cognitive normal subjects are calculated respectively. Cox regression model was performed to analyze prediction value of socio-demographic and personality characteristics,disease history,and hereditary feature on whether can be converted into cognitive decline or not.5.Experimental examinationBlood samples were drawn in the morning after overnight fasting, amyloid precursor protein,blood fat,apolipoprotein E were measured . We employed the Chinese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to assess general intellectual ability and 16PF to determine personality.6.Statistical AnalysisDatabase was constructed by EpiDate3.0 software,All the data information were input for two times. Statistical Analysis were performed by SPSS13.0 software..Results were analyzed in two ways:First, we examined the distribution of continuous and categorical variables using t-test andχ2-test.Second,we used logistic regression in univariate and multivariate modeling to estimate the association between influencing factors and cognitive decline as measured by domain-specific cognitive tests,adjust for possible confounding variables ,Cox regression model of survival analysis was selected to deal with non-geometric proportional matched data which is difficult to analyze by Logistic regression model.According to the follow-up information,incidence density of cognitive decline in both MCI group and normal cognitive group were calculated by person-years approach. RR ,together with 95%CI of the conversion to the outcome of cognitive decline in MCI group were compared with that in the normal cognitive group.Log-rank test was performed to make comparison with the different level in follow-up subjects? each index. All tests were two-sided and our level of significance wasα= 0.05.Cox Regression was adopted if the influencing factor was treated as uncontrollable variable,while Cox w/Time-Dep Cov was adopted if the influencing factor was treated as controllable variable.Results1.Baseline assessmentResults showed that an overall prevalence of MCI was 9.70% (95% CI: 9.62% to 9.77%).Univariate analyses showed that the prevalence of MCI were significantly different among different groups assigned according to age, gender, education level ,monthly household income and marital status( p < 0.01) ,but not among different occupation groups(P > 0.05). Considering the effect of the interactions between age and gender,educational level and occupation on multiple logistic regression,Significant predictor variables were as follows:age, gender, marital status, educational level and occupation( p < 0.01).However,OR of MCI between groups with different monthly household income was similar( P > 0.05).2.Case-control studyFour hundred and twenty-three cases together with nine hundred and twenty-five controls were interviewed with a uniformed questionnaire. By univariate and multivariate cox regression analysis, OR and 95%CI of these risk factors were physical labour(OR: 1.396 ,95%CI: 1.092-1.785);smoking(OR:1.551,95%CI:1.021-2.359);higher level of blood glucose(OR:1.354,95%CI:1.102-1.664);HDL in the serum(OR:1.543,95%CI:1.232-1.932);LDL in the serum(OR:1.299,95%CI:1.060-1.592);lower level of estrogen in the serum(OR:1.263 ,95%CI:1.031-1.547);hypertension(OR:1.967,95%CI:1.438-2.689);diabete(OR:1.381,95%CI:1.139-1.675);depressive disorder(OR:1.406,95%CI:1.110-1.780);cerebral thrombosis(OR:1.593,95%CI:1.307-1.943);higher SBP(OR:1.331,95%CI:1.129-1.569);ApoEε4 carrier(OR:1.462,95%CI:1.140-1.873). OR and 95%CI of protection factors were reading newspaper frequently:(OR:0.610,95%CI:0.503-0.740);doing household duties frequently(OR:0.804,95%CI:0.665-0.973);frequent social activities(OR:0.617,95%CI:0.502-0.757);reemployment after retirement(OR:0.759,95%CI: 0.636-0.906);acumen olfaction(OR:0.900,95%CI:0.845-0.958); extroversion character(OR:0.829,95%CI:0.699-0.984); decisive character(OR: 0.811,95%CI:0.662-0.993).3.Nested case-control studyUnivariate and multivariate cox regression analysis revealed that risk factors were physical labour(OR: 1.949,95%CI:1.041-3.637),smoking(OR: 2.062,95%CI:1.029-4.445),to stay alone(OR: 2.254,95%CI:1.029-4.937),higher level of blood glucose(OR:3.584 ,95%CI:1.891-6.791),cholesterol in the serum(OR:2.204,95%CI:1.137-4.275),lower level of estrogen in the serum(OR:1.946,95%CI:1.087-3.411),hypertension(OR:3.951,95%CI:1.822-4.637),diabete(OR:3.016,95%CI:1.886-4.157),hyperlipemia(OR:4.061,95%C:1.724-9.568),cerebral thrombosis(OR:2.347,95%CI:1.329-4.533),cerebral hemorrhage(OR:2.668,95%CI:1.579-4.802),higher SBP (OR:2.208,95%CI:1.343-3.629),ApoEε4 carrier(OR:2.717,95%CI:1.084-6.743),ApoEε4 carrier* cholesterol in the serum(OR:1.626,95%CI:1.011-2.618); Protection factors were reading newspaper(OR:0.203,95%CI:0.112-0.411) and doing household duties frequently(OR: 0.249,95%CI:0.135-0.528),extroversion character(OR:0.544,95%CI: 0.327-0.938).4.Cohort studyAccording to changes and trends of cognitive function, 112 pairs of cognitive decline subjects and stable subjects were identified,both of which were matched on sex, age and educational level in a 1:1 ratio.Incidence density of cognitive decline subjects is 14.70%(14.52%,15.29%),while that of stable subjects is 3.75%(3.56%,3.67%).By Log-rank test ,there is significant difference in Survival curve on the outcome of cognitive decline between cognitive decline group and stable group(χ2=11.643,P < 0.01).Among 600 follow-up subjects ,557 were ultimately included into study,For two-year follow-up, incidence density is 15.31%(13.99%,16.87%),By univariate and multivariate cox regression analysis, RR and 95%CI of these risk factors were age(RR:1.957;95%CI:1.916-1.999),sex(RR:2.713;95%CI:1.616-4.554),educational level(RR:0.662;95%CI:0.500-0.877),diabete(RR:2.890;95%CI:1.635-5.107),cerebral thrombosis(RR:1.898;95%CI:1.157-3.114),ApoEε4(RR:1.876;95%CI:1.139-3.090),introversion character(RR:1.876;95%CI:1.139-3.090),anxious characte(RR:2.515;95%CI:1.342-4.711),higher level of blood glucose(RR:1.3236;95%CI:1.193-1.470),higher level of cholesterol in the serum(RR:2.390;95%CI:1.288-4.436)。Conclusion1.This study confirms the high prevalence of MCI among the elderly community-based population aged above 65 in China, similar to previous epidemiological studies in other countries,2.MCI has been proved to be a step for the transition between normal aging and cognitive decline. The conversion rate of cognitive decline in MCI group is much higher than that in stable group,risk of the conversion to cognitive decline for MCI is much higher than that for normal control.3.Cross-sectional study shows that nearly all socio-demographic characteristics are associated with MCI. Age and sex can interact with each other, positive interaction existed between Age variable and sex variable in MCI,The putative risk factors identified merit further study4.Retrospective study shows that the major measures to prevent MCI are to go in for mental labour,healthy life style and decrease the risk to develop hypertension,diabete,depressive disorder,cerebrovascular disease. Olfactory hypoesthesia,cowardice and introvert character,ApoEε4 carrier can be treated as early indication to signify MCI.the interaction between ApoEε4 and LDL can be found.5.Perspective study shows that the risk factors of influencing conversion included socio-demographic (age,sex,educational level),personality characteristics(introversion character,anxious character),disease history(diabete,cerebral thrombosis),and hereditary feature(ApoEε4)higher level of cholesterol in the serum and higher level of blood glucose. The major measures to prevent cognitive impairment among aged population with MCI are to go in for mental labour,healthy life style and decrease the risk to develop hypertension,hyperlipemia,diabete,cerebrovascular disease. introvert character,ApoEε4 carrier can be treated as early indication to signify cognitive impairment among subjects with MCI. 6. By comparison of influencing factors between the onset of MCI and the conversion of cognitive decline,higher concordance has been found.Which indicated that early intervention on the community-based elderly population with MCI may play an important role on cognitive decline even dementia.
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