阿尔茨海默病患病率的Meta分析

张宏博 徐 勇 陈 彬 钱登娟 杭 蕾

(苏州大学公共卫生学院，江苏 苏州 215123)

阿尔茨海默病(AD)是老年痴呆的主要亚型，占全部痴呆类型的60%～80%〔1〕。有研究显示，在高龄老人中，女性老年痴呆患病率高于男性，而在其亚型AD中，这种性别差异更加明显〔2～12〕。在研究对象为≥60岁老年人的研究中，一些研究显示女性老年痴呆患病率与男性并没有差异，其亚型血管性痴呆(VD)男性的发病风险高于女性〔13～30〕,而女性AD患病率仍高于男性〔6,8～10,18,26,27,29,31～44〕。目前全世界关于AD患病率的调查已有较多报道，然而由于受样本量、研究设计方案、调查对象年龄、调查区域等多方面的影响，AD患病率结果不一。因此，本研究采用 Meta 分析方法综合1990年以来已经发表的有关老年人群AD患病率结果，并主要针对性别差异进行亚组分析，以期了解现阶段老年人群AD的患病率。

1 资料与方法

1.1资料检索 通过计算机检索电子数据库，以“Alzheimer′ s disease OR AD”、“prevalence” 为检索词，检索 PubMed外文数据库中有关老年人群AD的文献，检索时间为1990年1月至2016年1月，并手工检索初步筛选文献的参考文献。

1.2纳入标准 ①以一般人群为基础并且样本量大于200的横断面调查；②研究为概率抽样；③有标准的疾病诊断方法；④语种限于英文。

1.3排除标准 ①特殊样本，不能代表一般人群，如以女性为研究对象、以医院患者为研究对象;②研究设计方案不明确;③文献中的原始数据无法进行提取或者无法转化的;④重复发表、重复收录或资料雷同的研究。

1.4文献摘录 用Microsoft excel 2010建立信息摘录数据库，从文献中摘录以下内容：作者、 发表时间、研究起止时间(或研究开始时间)、研究地区、设计类型、样本量、应答率、筛检试验、诊断试验、AD粗患病率(调整患病率)。

1.5文献质量评价 由2009年世界阿尔茨海默病报告(WAR)〔45〕建议的文献质量评分来评价文献质量：①样本量<500，0.5分；500～1 499，1分；1 500～2 999，1.5分；≥3 000，2分。②两阶段的设计方法如果没有筛检阴性者，0分；两阶段的设计方法有筛检阴性者但是没有权重，1分；有合适的抽样方法和权重的一阶段或2阶段设计方法。③应答率<60%，1分；60%～79%，2分；≥80%，3分。④诊断标准涉及成套多功能认知测试、常规残疾评估、信息采访、临床采访。

1.6统计学方法 使用Stata/SE12.0软件进行Meta分析。先进行异质性检验，当I2>50%时，认为存在异质性。存在异质性时选择随机效应模型的计算方法，否则选择固定效应模型。效应量采用单样本率及其95%CI得到合并的AD患病率、不同年龄段AD及不同性别AD患病率。

2 结 果

2.1纳入文献研究基本情况 根据上述检索方式，总共检索到963篇有关AD患病率的文献，根据纳入和排除标准最终纳入分析的有44篇〔46～89〕，涉及亚洲、欧洲、非洲和美洲，合计样本量为172 444例，其中AD患者6 093例。在所纳入的文献中，其中有18篇来自亚洲，3篇来自非洲，16篇来自欧洲，6篇来自美洲，1 篇涉及美洲和非洲;13篇调查人群为农村居民，6篇为城市居民，11篇农村和城市居民均有，14篇未提及；研究对象为60岁以上老年人的文献为36篇，AD患病率为1.1%～20.5%，研究对象为70岁以上老年人文献为6篇，AD患病率为3.0%～11.0%，研究对象为85岁以上老年人的文献为2篇，患病率分别为16.0%与21.5%。纳入文献的一般情况见表1。

表1 纳入文献的基本情况

续表1 纳入文献的基本情况

2.2异质性检验及总体患病率分析 异质性检验结果显示各研究间存在异质性(I2=98.6%，P<0.001),故采用随机效应模型进行Meta分析，纳入的44篇文献的合并效应量结果显示,AD患病率为4.9%(95%CI：4.3%～5.5%)。

2.3不同亚组AD患病率 对年龄、性别等不同特征进行亚组分析，结果显示，男性和女性AD患病率分别为3.0%(95%CI:2.5%～3.4%)和6.1%(95%CI:5.3%～6.9%)；各年龄亚组患病率见表2，各年龄亚组男性和女性AD患病率见表3。

2.4发表偏移评估 漏斗图(图1)结果显示研究可能不存在发表偏倚，Begg秩相关显示Z=2.80,P=0.005，见图2，Egger回归分析显示t=1.78,P=0.082，见图3。

表3 不同年龄亚组AD患病情况

表2 不同年龄性别亚组AD患病情况

图1 纳入文献漏斗图

图2 Begg秩相关

图3 Egger回归分析

3 讨 论

本研究得出老年人群AD患病率为4.9%(95%CI:4.3%～5.5%)，高于Suh等〔89〕通过综述得到的全世界患病率(4.3%)及Ferri等〔90〕对全世界AD患病率进行综述分析得到的患病率(3.9%)。AD是老年痴呆的主要亚型，但是其患病情况和老年痴呆及VD相比有差异，尤其在患病情况的性别差异方面。国内外较多研究显示，男女老年痴呆患病率并没有差异，而AD女性患病率总是高于男性，在较低年龄人群中男性AD患病率高于女性〔2～6,8～12,18,26,27,29,31～44〕。本研究亚组分析结果显示，总体女性AD患病率高于男性，并且在每个年龄亚组中，女性患病率仍高于男性。本研究年龄亚组分析结果显示，AD患病率随着年龄的升高而明显升高，并且在极高龄年龄组中(90～95岁)患病率仍呈现升高的趋势，但是由于极高龄人群数据资料有限，AD在极高年龄人群患病率是否仍然持续升高还有待更多研究加以证实。

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