太原市社区老年人轻度认知功能障碍现患及转归流行病学研究

发布时间：2018-04-24 11:03

本文选题：轻度认知功能障碍 + 认知减退　；参考：《山西医科大学》2009年博士论文

【摘要】： 研究背景: 随着世界人口老龄化发展,痴呆正在成为一个全球性公共卫生问题。轻度认知功能障碍(MCI)是介于正常老化和痴呆或阿尔兹海默病(AD)之间过渡阶段,处于此阶段个体存在超出其年龄范围的记忆或其它认知障碍,但仍能维持功能完好,且达不到痴呆的诊断标准。研究MCI的人群分布特征和转归影响因素对于实现痴呆的早期防治和临床前预警有重要价值。目的 1.了解太原市城区65岁以上老年人轻度认知障碍的现患率及人群分布特征。 2.探明不同人口学特征、疾病史、遗传特征人群(不同ApoEε4)及人格特征人群(依据16种基本人格与4个次元因素)MCI转归结果及影响因素的差异。 3.探明全血APP基因、血脂及ApoEε4在由MCI发展为痴呆中独立作用、相互关系和联合作用。 4.探明老年痴呆早期认知功能障碍的特点,在MCI阶段中哪些指标是老年痴呆的危险信号? 5.提出判定发展为老年性痴呆敏感、特异、廉价、实用的检测手段及指标。对象和方法本研究采用传统、规范流行病学设计方案,分为现况研究、病例对照研究、巢氏病例对照研究和队列研究四个部分。 1.研究对象在太原市范围内,采用整群随机抽样方法调查社区65岁以上老年人6192人,在基底人群中筛选600 MCI对象构成队列人群,按半年一次随访计划,完成三次随访。 2.研究方法 ①基线调查对符合纳入标准的6192名老年人进行集中和入户调查,MCI诊断标准参考DSM-IV“轻微神经认知障碍”,采用MMSE、GDS、ADL,对研究人群进行认知功能评定,可疑MCI及老年痴呆患者由神经科医师进一步做出诊断,排除特定原因引起的MCI,从中筛查MCI者600人。 ②病例对照研究病例和对照采用n:m不等比匹配方法进行选取,按照前述标准入选患MCI者423人。对照年龄与病例年龄在±2岁,性别相同,文化程度一致,无严重躯体疾病能完成神经心理测验,上述记忆、认知等检查均正常,最终入选995人。应用cox回归模型进行不等比匹配Logistic回归分析,分析社会人口学、生活方式、疾病史、人格特征、生理、血清生化及基因型别指标对MCI发生的影响作用。 ③巢氏病例对照研究由600名患轻度认知功能损害的社区老年居民组成随访队列,与基线调查相比,智商降低1个SD被认为认知减退,按年龄、性别、文化程度1:1匹配后形成认知减退组和对照组后进行影响因素分析。 ④队列研究筛选600 MCI对象构成队列人群,按半年一次随访预定计划,分别于2007年11月、2008年6月、2008年12月完成三次随访。中文版MMSE、GDS、ADL、WAIS-RC比较MCI和认知正常受试者转化为痴呆、AD或VD的年转化率。采用cox回归模型分析上述基线指标(一般人口学特征、疾病史、基因标记、人格特征、血清生化指标)对MCI者发生认知减退转化的预测价值。 ⑤实验室检查对全部MCI和老年痴呆患者抽取静脉血,检测血中ApoEε4、全血APP基因表达、血脂系列。所有指标均设正常对照进行群组比较研究。对所有MCI和老年痴呆患者采用16PF测定人格,同时采用韦氏成人智力量表(WAIS-RC)进行智商评估。 ⑥统计分析 EpiDate3.0软件建立数据库进行两次数据录入。采用SPSS13.0软件进行分析,首先进行单因素分析,在此基础上结合专业知识,用多因素分析方法对某些可能引起混杂作用变量进行调整。多因素分析采用1:1匹配Logistic回归模型及n:m不等比匹配Logistic回归模型分析。随访资料按照人年法计算发病密度及比较转化为认知减退RR和95 %CI ;采用Log-rank检验对每一指标不同水平随访对象认知减退转归比较。所有统计检验均为双侧检验。转归影响因素筛选若是不可控制变量采用Cox Regression过程,可控制变量采用Cox w/Time-Dep Cov过程完成。结果 1.现况研究MCI人群发生率9.70% (95% CI: 9.62%- 9.77%),单因素结果显示年龄、性别、文化程度、月经济收入和婚姻状况( p 0.01),但与职业无关( P 0.05)。多因素Logistic回归分析结果显示:年龄、性别、文化程度、婚姻状况和职业、年龄和性别交互作用具有显著统计学意义( p 0.05)。 2.病例对照研究最终入选病例423人,对照925人。通过单因素和多因素cox回归分析,得出MCI发生危险因素,其OR值及95%CI分别是:从事体力劳动:1.396(1.092-1.785);吸烟:1.551(1.021-2.359);血清中较高血糖浓度:1.354(1.102-1.664);较高高密度脂蛋白水平:1.543(1.232-1.932);较高低密度脂蛋白水平:1.299(1.060-1.592);低雌激素水平:1.263(1.031-1.547);高血压:1.967(1.438-2.689);糖尿病:1.381(1.139-1.675);抑郁症:1.406(1.110-1.780);脑血栓:1.593(1.307-1.943);较高收缩压:1.331(1.129-1.569);ApoEε4型等位基因:1.462(1.140-1.873);保护因素有:常读书看报:0.610(0.503-0.740);常参加公益活动:0.617(0.502-0.757);常做家务:0.804(0.665-0.973);退休后有第二职业:0.759(0.636-0.906);嗅觉敏锐:0.900(0.845-0.958);外向人格:0.829(0.699-0.984);果断人格:0.811(0.662-0.993)。 3.巢氏病例对照研究危险因素有从事体力劳动(OR:1.9,95%CI:1.0-3.6)、吸烟(OR:2.1,95%CI:1.0-4.4)、喜欢呆在家里(OR:2.3,95%CI:1.0-4.9)、血清中较高血糖(OR:3.6,95%CI:1.9-6.8)、胆固醇(OR:2.2,95%CI:1.1-4.3)、低雌激素水平(OR:1.9,95%CI:1.1-3.4),高血压(OR:4.0,95%CI:1.8-4.6),糖尿病(OR:3.0,95%CI:1.9-4.2),高血脂(OR:4.1,95%CI:1.7-9.6),脑血栓(OR:2.3,95%CI:1.3-4.5),脑出血(OR: 2.7,95%CI:1.6-4.8),较高收缩压(OR:2.2,95%CI:1.3-3.6),ApoEε4型等位基因(OR:2.7,95%CI:1.1-6.7)、ApoEε4型等位基因*胆固醇(OR:1.6,95%CI:1.0-2.6);保护因素有:常读书看报(OR:0.2,95%CI: 0.1-0.4)、常做家务(OR:0.2,95%CI:0.1-0.5)、外向人格(OR: 0.5,95%CI: 0.3-0.9)。 4.队列研究 112对认知减退和正常对照纳入研究,认知减退组人年发病密度14.70%(14.52%,15.29%)和正常对照组3.75%(3.56%,3.67%)两组随访对象转化为认知减退结局的生存曲线经Log-rank检验差异有统计学意义(χ2=11.643,P 0.01) ,600随访对象,最终557人纳入研究,三年随访后人年发病密度15.31%(13.99%,16.87%)。采用cox回归模型进行单因素及多因素分析结果显示:MCI发生认知减退转归结局因素如下:年龄(RR:1.957;95%CI:1.916-1.999)、女性(RR:2.713;95%CI:1.616-4.554)、高文化程度(RR:0.662;95%CI:0.500-0.877)、糖尿病(RR:2.890;95%CI:1.635-5.107)、脑血栓(RR:1.898;95%CI: 1.157-3.114)、ApoEε4携带者(RR:1.876;95%CI: 1.139-3.090)、内向人格(RR:1.876;95%CI:1.139-3.090)、焦虑人格(RR:2.515;95%CI:1.342-4.711)、高血糖(RR:1.3236;95%CI: 1.193-1.470)、高胆固醇(RR:2.390;95%CI:1.288-4.436)。结论 1.社区65岁以上老年人群存在较高MCI发生率,此部分人群作为老年痴呆的高危人群给予足够关注,加强防范。 2.MCI是介于认知正常和认知减退之间的一种过渡阶段的认知障碍,MCI转化为认知减退结局的危险性远远大于认知正常受试者。 3.横断面研究显示:人口学特征中高龄、老年女性、较低文化程度、体力劳动、独身是MCI发生的危险因素。年龄与性别存在明显交互作用,提示高龄女性是MCI发生的高危人群,应引起重视。 4.回顾性研究显示:体力劳动、不健康生活方式、罹患糖尿病、高血压、高血糖、高血脂、抑郁症、脑血管病变发生风险是老年人MCI发生的可疑危险因素,嗅觉减退、内向人格、携带ApoEε4型等位基因可作为预示MCI发生的早期指征,ApoEε4基因型和LDL存在交互作用。 5.前瞻性研究显示:人口学特征(高龄、女性、较低文化程度)、疾病史(罹患糖尿病和脑出血)、ApoEε4基因型携带者、血清较高血糖、胆固醇及低密度脂蛋白及内向、焦虑人格特征是影响转归危险因素,坚持脑力劳动、健康生活方式、降低糖尿病、高血压、高血糖、高血脂、脑血管病变发生风险是预防老年人认知减退主要手段,内向人格、携带ApoEε4型等位基因可作为预示认知减退的早期指征。 6.通过对社区老年人群轻度认知功能障碍发生的影响因素与认知减退转归的影响因素的对比,发现具有较高的一致性,提示对社区MCI人群早期干预可能对认知减退甚至老年痴呆预防起到重要作用。
[Abstract]:Research background:
With the aging of the world's population, dementia is becoming a global public health problem. Mild cognitive dysfunction (MCI) is a transitional stage between normal aging and dementia or Alzheimer's disease (AD). At this stage, the individual has memory or other cognitive impairments beyond its age, but it still maintains functional integrity, and The diagnostic criteria of dementia can not be reached. It is of great value to study the distribution characteristics and the influencing factors of MCI in the early prevention and pre-warning of dementia.
objective
1. to understand the prevalence rate and distribution characteristics of mild cognitive impairment among the elderly over 65 years old in Taiyuan city.
2. the results of different demographic characteristics, disease history, hereditary population (different ApoE E 4) and personality traits (according to 16 basic personality and 4 dimensional factors) and the difference of influencing factors were identified.
3. it is proved that the whole blood APP gene, blood lipid and ApoE E 4 play an independent role in the development of MCI from dementia to dementia.
4. to identify the characteristics of early cognitive impairment in Alzheimer's disease. What indicators are the risk signals for Alzheimer's disease in the MCI stage?
5., we propose to develop sensitive, specific, inexpensive and practical detection methods and indicators for Alzheimer's disease.
Objects and methods
This study used traditional and standardized epidemiological design programs, which were divided into four parts: current research, case-control study, nested case-control study and cohort study.
1. research objects
In the Taiyuan City, a cluster random sampling method was used to investigate 6192 elderly people over 65 years old in the community, and 600 MCI objects were selected from the base population to form a cohort, and three follow-up was completed according to a half year follow-up plan.
2. research methods
Baseline survey
A survey was conducted on 6192 elderly people conforming to the inclusion criteria. The MCI diagnostic criteria referred to DSM-IV "mild neurocognitive impairment", using MMSE, GDS, and ADL to assess the cognitive function of the study population. The suspected MCI and Alzheimer's patients were further diagnosed by neurologist, excluding specific causes of MCI, and screened M from them. The CI was 600.
A case-control study
The cases and the controls were selected by the n:m unequal matching method, and 423 people with MCI were selected according to the previous standard. The age and age of the cases were at the age of + 2. The sex was the same, the cultural degree was the same, no serious physical disease could complete the neuropsychological test. The above memory and cognition were all normal, and 995 people were finally selected. The Cox regression model was used. Logistic regression analysis was used to analyze the effects of social demography, lifestyle, disease history, personality, physiology, serum biochemical and genotypic indicators on the occurrence of MCI.
A case-control study of nests
600 elderly residents with mild cognitive impairment were followed up in a follow-up cohort. Compared with the baseline survey, the decrease of IQ of 1 SD was considered to be cognitive impairment, and the influence factors were analyzed after the age, gender, and educational level of 1:1 matched the cognitive impairment group and the control group.
Cohort study
A cohort of 600 MCI was selected to form a cohort and three follow-up visits were completed in November 2007, June 2008, and December 2008 respectively. The Chinese version of MMSE, GDS, ADL, WAIS-RC, MCI and cognitive normal subjects were transformed into dementia, AD or VD's annual conversion rate. The above baseline indicators were analyzed by the Cox regression model (general Demography). Characteristics, disease history, genetic markers, personality characteristics and serum biochemical markers were predictive values of cognitive decline in MCI patients.
Laboratory examination
The venous blood was extracted from all MCI and Alzheimer's patients. The blood ApoE E 4, the whole blood APP gene expression and the blood lipid series were measured. All the indexes were compared with the normal control group. All MCI and Alzheimer's patients were determined by 16PF, and the Wechsler Adult Intelligence Scale (WAIS-RC) was used to evaluate the IQ.
Statistical analysis
The EpiDate3.0 software establishes the database for two data entry. The SPSS13.0 software is used to analyze the data. First, the single factor analysis is carried out. On this basis, a combination of professional knowledge and multi factor analysis method is used to adjust some possible mixed variables. The multi factor analysis adopts the 1:1 matching Logistic regression model and the n:m unequal ratio matching L. Ogistic regression model analysis. The follow-up data were calculated according to the human year method and converted to cognitive impairment RR and 95%CI. Log-rank test was used to compare the cognitive impairment of the follow-up subjects at the different levels of each index. All the statistical tests were both bilateral tests. If the factors were not controlled by Cox Regres, the influence factors were selected. The sion process can be controlled by Cox w/Time-Dep Cov process.
Result
1. the prevalence of MCI was 9.70% (95% CI: 9.62%- 9.77%). Single factor results showed age, sex, education, monthly economic income and marital status (P 0.01), but not related to occupation (P 0.05). The results of multiple factor Logistic regression analysis showed age, sex, marital status and occupation, age and sex interaction. There was significant statistical significance (P 0.05).
2. case control study
423 people were selected and 925 people were selected as control. By single factor and multiple factor Cox regression analysis, the risk factors of MCI were found. The OR value and 95%CI were 1.396 (1.092-1.785); smoking: 1.551 (1.021-2.359); high blood glucose concentration in the serum, 1.354 (1.102-1.664); higher HDL level: 1.543 (1.232-1.932); compared with high density lipoprotein (1.232-1.932); High and low density lipoprotein levels: 1.299 (1.060-1.592); low estrogen level: 1.263 (1.031-1.547); hypertension: 1.967 (1.438-2.689); diabetes: 1.381 (1.139-1.675); depression: 1.406 (1.110-1.780); cerebral thrombosis: 1.593 (1.307-1.943); higher systolic pressure: 1.331 (1.129-1.569); ApoE E 4); 1.462 (1.140-1.873); protective factors: often Reading and reading newspapers: 0.610 (0.503-0.740); often participating in public welfare activities: 0.617 (0.502-0.757); often doing housework: 0.804 (0.665-0.973); after retirement there are second occupations: 0.759 (0.636-0.906); acute smell: 0.900 (0.845-0.958); extrovert personality 0.829 (0.699-0.984); decisive personality: 0.811 (0.662-0.993).
3. nests case control study
Risk factors include OR:1.9,95%CI:1.0-3.6, OR:2.1,95%CI:1.0-4.4, OR:2.3,95%CI:1.0-4.9, high blood sugar (OR:3.6,95%CI:1.9-6.8), cholesterol (OR:2.2,95%CI:1.1-4.3), low estrogen (OR:1.9,95%CI:1.1-3.4), OR:4.0,95%CI:1.8-4.6, and diabetes (OR:3.0,95%CI:1). .9-4.2), hyperlipidemia (OR:4.1,95%CI:1.7-9.6), cerebral thrombosis (OR:2.3,95%CI:1.3-4.5), cerebral hemorrhage (OR: 2.7,95%CI:1.6-4.8), higher systolic pressure (OR:2.2,95%CI:1.3-3.6), ApoE epsilon 4 allele (OR:2.7,95%CI:1.1-6.7) and ApoE - 4 allele * cholesterol (OR:1.6,95%CI:1.0-2.6); protective factors are: reading newspapers (OR:0.2,95%CI: 0.1-0.4), I often do housework (OR:0.2,95%CI:0.1-0.5) and OR: 0.5,95%CI: 0.3-0.9.
4. cohort study
112 of cognitive hypogonties and normal controls were included in the study. The annual density of the cognitive impairment group was 14.70% (14.52%, 15.29%) and 3.75% (3.56%, 3.67%) in the normal control group (3.56%, 3.67%). The survival curves converted to cognitive decline were statistically significant (x 2=11.643, P 0.01), 600 follow-up subjects, and 557 were finally included in the study. The annual incidence of the three year follow-up was 15.31% (13.99%, 16.87%). The results of single factor and multi factor analysis by Cox regression model showed that the factors of cognitive impairment outcome in MCI were as follows: age (RR:1.957; 95%CI:1.916-1.999), women (RR:2.713; 95%CI: 1.616-4.554), high education (RR:0.662; 95%CI:0.500-0.877), and diabetes mellitus (RR:2.8). 90; 95%CI:1.635-5.107), brain thrombus (RR:1.898; 95%CI: 1.157-3.114), ApoE epsilon 4 carrier (RR:1.876; 95%CI: 1.139-3.090), introverted personality (RR:1.876; 95%CI:1.139-3.090), anxiety personality (RR:2.515; 95%CI:1.342-4.711), hyperglycemia, high cholesterol (95%), high cholesterol.
conclusion
1. there is a high incidence of MCI in the community over 65 years old. This group of people as a high-risk group of Alzheimer's disease should pay enough attention to strengthen prevention.
2.MCI is a cognitive disorder in the transitional stage between cognitive normal and cognitive impairment, and the risk of transforming MCI into cognitive impairment is far greater than that of cognitive subjects.
3. the cross-sectional study shows that age and sex are the risk factors for MCI in the age of demographics, older women, lower cultural level, physical labor and single body. Age and sex have obvious interaction, suggesting that older women are high-risk groups of MCI and should be paid attention to.
4. retrospective studies have shown that physical labor, unhealthy lifestyle, diabetes, hypertension, hyperglycemia, hyperlipidemia, depression, and cerebrovascular disease risk are suspected risk factors for the occurrence of MCI in the elderly, olfactory hypothyroidism, introverted personality, and the ApoE epsilon type 4 allele can be used as an early indication for the occurrence of MCI, ApoE E 4 genotype and L DL has interaction.
5. prospective studies show: demographic characteristics (age, female, lower level of Education), history of disease (diabetes and cerebral hemorrhage), ApoE - E 4 genotype carriers, high blood sugar, cholesterol and LDL and introversion, anxiety personality characteristics are the risk factors affecting the outcome, insisting on mental labor, healthy lifestyle, and reducing diabetes, Hypertension, hyperglycemia, hyperlipidemia, and the risk of cerebrovascular disease are the main means to prevent cognitive impairment of the elderly. Introverted personality and carrying ApoE - epsilon 4 allele can be used as an early indication of cognitive impairment.
6. by comparing the influencing factors of the occurrence of mild cognitive impairment in the elderly population with the influence factors of cognitive impairment, it is found that there is a high consistency, suggesting that early intervention in the community MCI population may play an important role in the prevention of cognitive impairment and even the prevention of Alzheimer's disease.

【学位授予单位】：山西医科大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R749.1;R181.3

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