吸烟与阿尔茨海默病发病风险关联性--病例对照研究和横断面研究数据的系统分析

Correlation between smoking and incidence of Alzheimer's disease——a systematic analysis of case-control studies and prevalence studies

目的系统分析基于横断面研究和病例对照研究不同设计的吸烟与阿尔茨海默病(AD)发病风险的关联性和设计方法评价。方法使用Cochrane Library和Medline检索英文文献和使用中国生物医学文献检索系统(CBMDISC)检索中文文献,收集符合NINCDS-ADRDA诊断标准病例,挑选符合入选标准的病例对照研究和横断面研究进行meta分析。结果共入选25个个体研究(2个配对设计,21个平行组设计,2个横断面研究),其中5个病例研究仅报道了未调整OR值,16个研究同时报道了未调整OR值和调整OR值。25个研究的固定效应模型合并效应值为0.877(95%CI:0.794,0.969),去除未调整OR值的研究,20个研究(2个配对设计+16个平行组设计+2个横断面研究)固定效应模型的调整OR值的合并效应值为0.886(95%CI:0.798,0.985);去除2个横断面研究后,18个病例对照研究固定效应模型调整OR值合并效应值估计为0.910(95%CI:0.816,1.016),无统计学意义;2个横断面研究固定效应模型调整OR值合并效应值估计为0.641(95%CI:0.436,0.941),有统计学意义。16个平行组设计和2个配对设计病例对照研究固定效应模型调整OR值合并效应值估计分别为0.911(95%CI:0.814,1.019)和0.896(95%CI:0.547,1.466)。16个研究的未调整OR值和调整OR值双变量分析固定效应模型合并效应值分别为0.739(95%CI:0.584,0.934)和0.911(95%CI:0.814.1.019),二者之间的差异有统计学意义。meta回归尚未显示平行组病例对照研究、配对病例对照研究和横断面研究设计之间合并效应值差异有统计学意义。Begg漏斗图和Egger检验表明病例对照研究设计中不存在发表偏性。结论无论是配对还是平行组设计病例对照研究,皆未表明吸烟是AD发病的影响因素;未调整的OR值和横断面研究设计降低了吸烟与AD之间关联性的效应值,但是皆不能作为因果关系的证据。

Objective To systematically analyze the correlation between smoking and Alzheimer＇s disease （AD） based on different study designs of case-control study and prevalence study and evaluate the design methods. Methods English literature was retrieved from Cochrane Library and Medline and Chinese literature was retrieved from CBMDISC. Cases that met the NINCDS-ADRDA diagnose criteria were collected. Case control study, prevalence study, and meta-analysis were conducted. Results A total of 25 individual studies were selected, including 2 matched case-control studies, 21 parallel case-control studies, and 2 cross-sectional studies. Among all studies, 5 case-control studies only reported crude odds ratios, 16 case-control studies reported crude and adjusted odds ratios, and 25 studies yielded a pooled odds ratio of 0. 877 （95% CI： O. 794, 0. 969）. Aftereliminating studies with crude odds ratios, 20 studies, which included 2 matched case-control studies, 16 parallel case control studies, and 2 cross-sectional studies, still yielded a pooled odds ratio of 0. 886 （950/o CI： O. 798, 0. 985）. After eliminating 2 cross-sectional studies, 18 case-control studies yielded a pooled odds ratio of 0. 910 （95o/0 CI： O. 816, 1. 016） and was not statistically significant, while 2 cross-sectional studies yielded a pooled odds ratio of 0. 641 （950/0 CI： O. 436, 0. 941）, which was statistically significant. Sixteen parallel case-control studies and 2 matched case-control studies yielded a pooled odds ratio of 0. 911 （95o/0 CI： O. 814, 1. 019） and 0. 896 （950/0 CI： O. 547, 1. 466）, respectively. Sixteen case-control studies yielded a pooled odds ratio of 0. 739 （95%. 0.584, 0.934） for crude odds ratio and 0.911 （950/0 C[： 0.814, 1.019） for adjusted odds ratio, respectively, and the difference was statistically significant. A meta regression showed that the differences of pooled odds ratio of parallel case-control studies, matched case-control studies, and prevalence design studies were statistically significant. Begg＇s funnel plot and Egger＇s test showed that there was no evidence of publication bias. Conclusion Matched case-control studies and parallel case-control studies show that smoking is not an influencing factor of the incidence of AD. Crude odds ratio and cross-sectional study design decrease the odds ratio of correlation between smoking and AD, but can not be regarded as an evidence of causal relationship.