| We conducted a large-sampled cross-sectional study in a community population. We obtained the epidemiological characteristics of cognitive impairment among elderly, including prevalences of dementia and MCI and their subtypes, characteristics of prevalence among difference sub-groups, as well as risk factors. We compared the differences between the polimorphisim distribution of CLU CRU PICALM SNPs among AD cases and aMCI cases through a case-control study design. The associations between polimorphisim of CLU CR1、 PICALM SNPs and AD or aMCI were also analyzed.Part1Population-based prevalence survey of cognitive impairment among elderlyObjective:To investigate the prevalence of dementia and mild cognitive impairment (MCI) among elderly in an urban community.Materials and Methods:This is a cross-sectional study. Three thousands and thirty-one residents with60years old and over were interviewed with neurological examination, neuropsychological tests, and risk factor questionnaires. Diagnosis of cognitive impairment was also made based on the international standard diagnosis criteria (DSM-IVfor dementia, NINCDS-ADRDA and NINDS-AIREN for AD and VaD, Petersen criteria for MCI) We calculated prevalences of dementia and MCI, percentages and prevalences of subtypes of dementia and MCI, and analyzed the characteristics of prevalence among difference sub-groups.Results:We diagnosed156cases of dementia and601cases of MCI. The prevalences of dementia and MCI were5.0%(95%CI:4.2-5.8%) and19.1%(95%CI:17.7-20.5%). The dementia prevalence of female (5.8%)was significantly higher than that of male (4.0%, p=0.012). Prevalences of dementia and MCI significantly increased by the enhanced age, and decreased by the enhanced education year(p<0.001). Cases with AD, vascular dementia (VaD), other types of dementia and unknown type occupied71.5%^15.8%、5.7%and7.0%respectively among dementia cases. The AD prevalence of female (4.7%) was significantly higher than that of male (2.3%, p<0.001). Prevalenced of AD and VaD significantly increased by enhanced age (p<0.001). Cases with MCI-SD, aMCI-MD, naMCI-SD and naMCI-MD occupied38.9%,26.5%,25.0%, and9.7%respectively among MCI cases. The aMCI-SD prevalence of male (10.0%) was the highest among4MCI subtypes. The aMCI-MD prevalence of female (6.3%) was the highest among4MCI subtypes. Prevalences of aMCI-SD among different age-groups were in a range of6.3%-9.8%, whereas prevalences of other3MCI subtypes showed the significantly increasing trend by the enhanced age (p<0.001).Conclusions:Instead of the traditional2-phase study, the current study firstly used1-phase method to conduct an epidemiological survey of cognitive impairment in a community population. Our study not only updated the epidemiological data of dementia, but also firstly obtained the prevalences of MCI and its subtypes, therefore demonstrated the epidemiological characteristics of cognitive impairment among elderly in China.Part2Risk factors of cognitive impairment among elderlyObjective:To explore the risk factor and protective factor associated with AD and aMCI, based on the prevalence survey of cognitive impairment among elderly.Materials and Methods:To each study subject, we collected the demographic data, information of family, personal experience, and life style. We conducted a neurological examination and measured the hight, weight, head circumference, etc., and asked the medical history. DNA was extracted from the blood and ApoE genotypes were examed. Distribution differences of above-mentioned variables among people with dementia (156cases), MCI(601cases) and normal (2384cases) were analyzed. Multivariate Logistic regression model was used to explore the associated risk and protective factors with significance. OR(95%CI) was used to indicate the association strength. Results:Multivariate analysis found that, the risk of AD increased19%by the enhancement of one year old of age [OR=1.19(1.13-1.25)](p<0.001). Subjects who carry the ApoE ε4allele had an OR for AD of2.31(1.22-4.38)](p=0.001). The risk of AD decreased10%by the enhancement of one education year [OR=0.90(0.84-0.97)](p=0.006). The risk of AD decreased8%by the enhancement of1cm of sitting hight [OR=0.92(0.87-0.99)](p=0.016). Tea drinkers had an OR for AD of0.36(0.17-0.75)](p=0.007). The risk of aMCI increased6%by the enhancement of one year old of age [0R=1.06(1.03-1.08)](p<0.001). Smokers had83%of the risk of aMCI higher than that of non-smokers [OR=1.83(1.17-2.87)](p=0.008). The risk of AD decreased6%by the enhancement of one education year [OR=0.94(0.90-0.97)](p=0.001). Subjects who experienced negative life events had and OR for aMCI of0.54(0.37-0.80)](p=0.002)。 Subjects with hyperlipidemia had a26%less risk of aMCI than those without hyperlipidemia [0R=0.74(0.55-1.00)](p=0.049).Conclusions:Enhancement of age and ApoE ε4(+) were the independent risk factors of AD. Longer education year, higher sitting hight and drinking tea were the independent protective factors of AD. Enhancement of age and smoking were the risk factors of aMCI. Longer education year, negative life events, and hyperlipidimia were the independent protective factor of aMCI.Part3Association of CR1, CLU and PICALM with AD and aMCIObjective:To test for replication of the association between variants in the CLU, CR1, and PICALM genes with AD and aMCI.Materials and Methods:We used Taqman SNP genotyping assay to determine the distribution of genotype and allele of7SNPs of CR1, CLU, PICALM (CR1:rs6656401,rs3818361;CLU:rs2279590,rs9331888, rs1113600;PICALM:rs541458, rs3851179), among subjects from community (54AD cases,266aMCI cases, and320normal controls). The7SNPs were tested for genotypic and allelic association with AD and aMCI by the multivariate Logistic regression model. OR(95%CI) was used to indicate the association strength.Results:We did not found the significant genotypic and allelic association of7SNPs with AD. There was a significant genotypic difference of CR1rs6656401between the aMCI and control groups (p=0.008). The frequency of AG genotype was significantly lower in aMCI group (3.9%) than that in control group (8.0%). The frequency of GG genotype was significantly higher in aMCI group (96.1%) than that in control group (92.0%). The frequency of A allele was significantly lower in aMCI group (1.9%) than that in control group (4.0%); the frequency of G allele was significantly higher in aMCI group (98.1%) than that in control group (96.0%)(p=0.049). Multivariate Logistic regression model revealed that, subjects who carry the CR1rs6656401GG genotype had an OR for aMCI of2.77(1.21-6.33)](p=0.016), comparing to subjects who carry the AG genotype. Subjects who carry CR1rs6656401G allele had63%higher of aMCI risk than those who carry A allele [OR=1.63(1.09-2.45)](p=0.045)。Conclusions:The significant association of CR1rs6656401polimorphisim with aMCI wasfound in the current study. |
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