【作者】 张耀东；

【导师】 徐勇；

【作者基本信息】 苏州大学 ， 流行病与卫生统计学， 2011， 博士

【摘要】 研究背景：随着世界人口老龄化发展,老年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(Mild cognitive impairment, MCI)是介于正常老化和老年痴呆之间的过渡阶段,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、探求MCI的危险因素及其综合干预办法对于实现痴呆的早期防治和临床前预警有重要价值。研究目的：1、了解苏州市市城区60岁以上老年人轻度认知障碍的现患率及人群分布特征；建立蒙特利尔量表苏州地区常模,为不同地区、不同人口特征老年人认知水平比较研究提供参照依据；探讨反应时(reaction time, RT)、运动时(movement time,MT)检测对MCI患者的判定价值。2、通过文献的Meta分析和流行病学的病例对照研究,探讨老年MCI的危险因素。3、探讨综合干预方法对老年轻度认知障碍患者的认知功能改善的效果,为进一步开展社区老年轻度认知障碍早期干预,提供科学依据。研究对象与研究方法1、现况调查采用整群抽样调查方法,抽取苏州市7个社区,共计5388名老年人,对其进行入户调查,调查内容包括体格检查、实验室检查和问卷调查。2、常模研究依据现况调查资料,分别建立蒙特利尔量表(Montreal Cognitive Assessment, MoCA)总体常模、性别常模、年龄常模和学历常模。3、应用受试者工作特性曲线(receiver operator characteristic curve, ROC)对691例MCI患者和健康对照的MT、RT检测结果进行分析评价。4、Meta分析收集1980年1月至2010年11月国内外公开发表的关于MCI发病危险因素的病例对照研究,并用RevMan5.0软件对这些文献进行综合定量,采用卡方值和P值分析各研究结果间的统计学异质性。5、病例对照研究病例和对照采用1：1等比匹配方法进行选取,按照既定标准入选MCI患者691人,对照与病例同性别、同文化程度、年龄±2岁。对数据进行Logistic回归分析,分析一般情况、生活方式、疾病史、家族疾病史等因素对MCI发生的影响。6、干预研究将130例轻度认知障碍患者随机分为干预组和对照组。干预组采用集体授课、技能训练(包括记忆力训练、注意力训练、执行能力训练、语言能力训练、图形识别能力训练、计算训练)和运动锻炼的干预方式。在基线、3个月以及6个月这三个时间点上,使用蒙特利尔量表评定两组患者的认知功能的变化情况。研究结果1、现况研究本研究结果表明,苏州市60岁以上居民MCI患病率为12.8%,男性患病率低于女性(χ2=15.414,P=0.000),MCI患病率随着年龄的增加而增加,差异有统计学意义,MCI患病率随着文化程度、月收入的提高而降低,差异有统计学意义。2、常模研究关于性别常模,男性和女性在抽象、语言、命名、视觉网与执行功能以及总分上有显著差异(P<0.05),男性得分显著高于女性。关于年龄常模,不同年龄段老人在蒙特利尔量表各维度及总分上有显著差异,整体表现为60～69年龄段>70-79年龄段>80～年龄段,60～69年龄段最优,显著高于70～79年龄段和80～年龄段,70-79年龄段也显著高于80～年龄段。关于文化程度常模,不同学历老年人在蒙特利尔量表各维度及总分上有显著差异。随着学历的提高,整体的蒙特利尔量表得分和量表所有因子都出现了升高的趋势。3、反应时、运动时与老年MCI的关系及ROC曲线评价MT与RT检测指标在两组资料间比较均有统计学意义(P<0.05),MT的敏感度、特异度和准确率分别为73.1、78.0和75.57,RT的敏感度、特异度和准确率别为80.7、67.2和73.93,MT与RT联合检测的的敏感度、特异度和准确率别为分别为84.92、68.20和76.56。MT、RT对MCI的判断临界点分别为4.25秒,4.35秒。4、Meta分析纳入本次Meta分析的文献共有23篇,MCI发生的危险因素合并相对危险度(OR)值及95%可信区间(95%CI)分别为：高血压,1.57(1.03-2.39)；糖尿病,1.77(1.32-2.36)；心脏病,1.42(1.08-1.87)；ApoEε4等位基因,5.86(3.05-11.25)；ApoEε4/ε4基因型,8.17(2.64-25.28)；ApoEε4/ε3基因型,4.99(3.00-8.29);MCI发生的相关因素合并均差(WMD)值及95%可信区间(95%CI)分别为：LDL,0.36(0.02-0.69)：TC,0.54(0.16-0.91)。5、病例对照研究最终入选病例691人,对照691人。通过单因素和多因素logistic回归分析,得出MCI发生危险因素,OR值及95%CI,分别是：体力劳动,4.020(1.873-8.624)；独居,1.886(1.063-3.346)；高血压,1.533(1.038-2.262)；糖尿病,2.346(1.256-4.384)；与子女关系淡漠,1.721(1.061-2.790)；抑郁症,1.193(1.108-1.690)；高血糖,2.246(1.036-4.853),高总胆固醇水平,2.132(1.435-3.742),高甘油三酯水平,1.51(1.312-1.932)；高低密度脂蛋白水平,1.331(1.137-1.621)。MCI发生的保护因素：较高月收入,0.752(0.578-0.956)；坚持体育锻炼,0.855(0.739-0.989)。6、干预研究采取记忆力训练、注意力训练、执行能力训练、语言能力训练、图形识别能力训练、计算训练和运动锻炼等综合干预方法,在干预6个月后,干预组与对照组在命名,语言表达、注意力、记忆力、定向力上都存在着显著差异。干预组在干预3个月和基线比较以及干预6个月与干预3个月比较,蒙特利尔量表得分均有所提高,差别有统计学意义P<0.05,对照组在基线和3个月比较以及3个月与6个月比较,蒙特利尔量表得分均有所减少,差别有统计学意义P<0.05。结论1、现状调查显示：苏州社区60岁以上老年人群存在较高MCI患病率,MCI患病率随着年龄的增加而增加,随着文化程度、月收入的提高而降低。2、老年人蒙特利尔量表测试得分存在显著的性别、年龄和学历差异。据此建立了总体常模、性别常模、年龄常模和学历常模,这些常模可以作为进一步研究的参考。3、反应时与运动时与老年MCI有关,在MCI的判定效果上,反应时与运动时检测有利于老年MCI的早期判定,且反应时与运动时联合检测优于反应时、运动时的单项检测。4、Meta分析显示：高血压、糖尿病、心脏病、ApoEε4等位基因、ApoEε4/ε4基因型、ApoEε4/ε3基因型、高低密度脂蛋白水平、高总胆固醇水平是MCI发生危险因素。5、病例对照研究显示：体力劳动、独居、高血压、糖尿病、与子女关系淡漠、抑郁、高血糖、高总胆固醇水平、高甘油三酯水平和高低密度脂蛋白水平是老年MCI发生的危险因素,较高月收入、坚持体育锻炼是MCI发生的保护因素。6、记忆力训练、注意力训练、执行能力训练、语言能力训练、图形识别能力训练、计算训练和运动锻炼等综合干预办法,有益于改善老年人的认知状况。更多还原

【Abstract】 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 is valuable to study epidemiological characteristics, risk factors and early intervention of mild cognitive.Objects1. To determine the prevalence and distribution of MCI in the aged population.2. Develop the norm of Montreal Cognitive Assessment Scale in Suzhou to provide reference for the research on eldly people’s cognitive level in different areas or with different characteristics.3. To find out risk factors of MCI.4. To study the diagnostic value of RT, MT and the combined detection of MCI.5. To evaluate the effectiveness of comprehensive intervention for people with MCI.Subjects and methodsA total of 5388 subjects participated in the baseline survey. According to the Petersen’s diagnostic standard on MCI,691 subjects with MCI were screened from the baseline population. 1. Cross-sectional surveyBy cluster random sampling,5388 aged people over 60 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. MoCA was performed to measure cognitive function. Of all the 5388 community- dwelling participants aged 60 and older who underwent psychometric testing,691 subjects met our criteria for MCI.2. Norm of MoCABased on baseline survey data, this study founded 4 norms:the whole norm, the gender norm, the education norm and the ages norm3. Meta analysisThe results of case-control studies on risk factors of MCI in China published domestically and abroad from January 1980 to November 2010 were analyzed by meta-analysis method. Odds ratios and 95% confidence intervals (CIs) were then calculated and pooled using RevMan5.0 Software. Statistical heterogeneity was evaluated through the use ofχ2 and I2.4. Case-control studyA 1:1 matched case-control study was conducted to analyze influencing factors of mild cognitive impairment among the elderly community-based population. Six hundred and ninety-one cases together with six hundred and ninety-one controls were interviewed with a uniformed questionnaire, cases were matched with controls by age decade, education level and gender in a 1:1 ratio. All the subjects can accomplish psychological tests independently with adequate cognition and memory. Logistic regression model was selected to deal with data, the influencing factors analyzed included socio-demographic, life style disease history, personality characteristics, physiological functions and biochemical index in the serum.5. Application of ROCTo analyze the detection results of RT, MT, RT and MT from 691 MCI patients and 691 healthy controls by ROC curve.6. Comprehensive interventionThe samples were composed of 130 patients with mild cognitive impairment. They were divided into 2 group:the control group (n=65) received no special intervention, while the comprehensive interventions group (n=65) received both cognitive intervention and physical activity intervention. Cognitive level of the patients was assessed at baseline, the end of 3rd and 6th month.7. Statistical AnalysisDatabase was constructed by EpiDate3.0 software, All the data information were input for two times. Statistical Analysis was performed by SPSS 17.0 software.Results1. Cross-sectional surveyThe total prevalence of MCI among all elderly people aged 60 years and over was 12.8%. Prevalence in female was higher than in male (χ2=15.414, P=0.000).MCI prevalence increased with age, there was statistically significant difference.MCI prevalence decreased with education level, monthly income, there was statistically significant difference.2. Norm of MoCAIn genders, Visuospatial/excutive, Naming, Language, Abstraction, total scores were different, significantly, Male>Female, (P<0.05). In age groups, Visuospatial/ excutive, Naming, Memory, Attention, Language, Abstraction, Orientation and total scores were different, significantly>60～69 year age group>70～79 year age group>80～year age group (P<0.05).In education levels, Visuospatial/excutive, Naming, Memory, Attention, Language, Abstraction, Orientation and total scores were different (P<0.05), and increased with level of education.3. Meta analysis23 epidemiological studies on risk factors of MCI were analyzed synthetically by Meta-analysis. The pooled odds ratio(OR)values and 95% CIs were as follows: hypertension,1.57(1.03-2.39); diabetes mellitus,1.77(1.32-2.36); heart disease, 1.42(1.08-1.87); ApoEε4carrier,5.86(3.05-11.25), ApoEε4/ε4,8.17(2.64-25.28), ApoE ε4/ε3,4.99(3.00-8.29); ApoEε3/ε2,3.28(1.17-9.18).the WMD values and 95% CIs were as follows:LDL,0.36 (0.02-0.69); TC,0.54(0.16-0.91)4. Case-control studySix hundred and ninety-one cases together with six hundred and ninety-one controls were interviewed with a uniformed questionnaire, regression analysis revealed that risk factors were:physical labour:4.020(1.873-8.624); living alone: 1.886(1.063-3.346); hypertension:1.533(1.038-2.262); diabetes mellitus:2.346 (1.256-4.384);depression:1.193(1.108.022-1.690);not being close with their children: 1.721(1.061-2.790); higher level of blood glucose 2.246(1.036-4.853); TC 2.132, (1.435-3.742); TG,1.51(1.312-1.932); LDL,1.331(1.137-1.621).Protection factors were higher monthly income 0.752 (0.578-0.956); doing physical exercise frequently, 0.855(0.739-0.989).5. Application of ROCRT and MT were significantly different between case group and control group (P<0.05).Sensitivity, Specificity and Accuracy rate were as follows:MT.73.1,78.0, 75.57; RT.80.7,67.2,73.93; RT combined with MT.84.92,68.20,76.56. The diagnostic critical point of RT and MT in MCI were 4.23s,4.35s, respectively.6.InterventionCompared with baseline, the comprehensive intervention group showed a significant increase in the scores of MoCA.Conclusion1. This study finds the high prevalence of MCI among the elderly community-based population aged above.60 in Suzhou. The prevalence of MCI increases with the rising of age, deceases with increasing of educational level and monthly income.2. Significant main effects of MoCA exist in different age groups, gender and education level. Accordingly, we founded 4 norms:the whole norm, the gender norm.age norm and education level norm, which can serve as a reference for further research.3. Meta-analysis shows that risk factors for MCI were hypertension, diabetes mellitus, heart disease, ApoEε4 carrier, ApoEε4/ε4, ApoEε4/ε3, LDL, TC.4. Case-control study shows that risk factors for MCI were physical labour, living alone, hypertension, diabetes mellitus, depression, not being close with their children, higher level of blood glucose, TC, TG, LDL. Protective factors for MCI were higher monthly income, doing physical exercise frequently.5. The combined detection of RT and MT is better than RT or MT individual detection.6. Comprehensive intervention can improve cognitive function in patients with MCI更多还原