记忆门诊阿尔茨海默病患者死亡原因及风险因素:一项长期临床随访研究  

Survival analysis and causes of death among patients with Alzheimer′s disease in memory clinic:a long-term follow-up study

作　　者：吴婕 肖朕旭 马小茜 梁小妞 郑琍 丁玎 赵倩华 Wu Jie;Xiao Zhenxu;Ma Xiaoxi;Liang Xiaoniu;Zheng Li;Ding Ding;Zhao Qianhua(Department of Neurology,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Neurology,Huashan Hospital,Fudan University,Center for Neurological Disorders,Huashan Hospital,Fudan University,National Clinical Research Center for Aging and Medicine,Shanghai 200040,China;Department of Neurology,Huashan Hospital,Fudan University,Center for Neurological Disorders,Huashan Hospital,Fudan University,National Clinical Research Center for Aging and Medicine,Frontiers Center for Brain Science,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院神经内科,上海200040 [2]复旦大学附属华山医院神经内科、复旦大学附属华山医院神经病学研究所、国家老年疾病临床医学研究中心,上海200040 [3]复旦大学附属华山医院神经内科、复旦大学附属华山医院神经病学研究所、国家老年疾病临床医学研究中心、复旦大学脑科学前沿中心,上海200040

出　　处：《中华神经科杂志》2024年第7期755-762,共8页Chinese Journal of Neurology

基　　金：国家自然科学基金(82071200,82371429)。

摘　　要：目的探究记忆门诊确诊的阿尔茨海默病(AD)患者的生存时间,分析其死亡原因及影响因素。方法纳入2002年8月至2006年12月于复旦大学附属华山医院记忆门诊就诊并确诊为AD的患者,采集其基线资料,截至2022年11月共进行7轮电话随访,追踪其临床结局。对于死亡病例,记录其死亡时间及死因。根据性别、基线认知功能[简易精神状态检查量表(MMSE)评分]对患者进行分组,使用Kaplan-Meier法及Cox回归分析患者生存时间及风险因素。结果共纳入499例患者,其中男性199例,女性300例,随访时间5.5(3.4,7.4)年,最长随访时间19.3年。起病后中位生存时间为11.8年(95%CI 10.2~13.4年),其中女性为12.4年(95%CI 11.2~13.5年),显著长于男性[10.2年(95%CI 9.6~10.8年),logrank检验,P=0.010]。确诊后中位生存时间为8.3年(95%CI 7.3~9.4年),其中女性为8.8年(95%CI 6.9~10.6年),显著长于男性[6.8年(95%CI 5.7~7.9年),logrank检验,P=0.001]。基线认知功能较好(MMSE评分≥15分)者(265例)确诊后中位生存时间为11.4年(95%CI 9.5~13.2年),较认知功能较差(MMSE评分<15分)者[234例,7.4年(95%CI 6.4~8.4年)]显著延长(logrank检验,P<0.001)。多因素Cox回归结果提示增龄(HR=1.027,95%CI 1.002~1.052,P=0.034)、体重指数低(HR=1.081,95%CI 1.023~1.139,P=0.007)、基线MMSE得分低(HR=1.056,95%CI 1.026~1.086,P<0.001)、糖尿病(HR=1.716,95%CI 1.076~2.735,P=0.023)、既往跌倒(HR=1.536,95%CI 1.007~2.341,P=0.046)是AD患者死亡的独立风险因素。随访期间死亡224例,除外62例死因不明者后,前6位死因分别为肺部感染(39例,24.1%)、脑血管病(24例,14.8%)、循环系统疾病(21例,13.0%)、多器官衰竭(17例,10.5%)、肿瘤(13例,8.0%)、进食障碍及营养不良(13例,8.0%)。结论在本研究中,AD患者起病后中位生存时间为11.8年。增龄、低体重指数、低认知功能、共患病以及既往跌倒是AD患者死亡的独立风险因素;肺部感染是最主要死亡原因。Objective To investigate the cause of death,survival time,and risk factors in patients diagnosed with Alzheimer′s disease(AD)at memory clinic.Methods The patients with AD were enrolled from the memory clinic at Huashan Hospital,Fudan University between August 2002 and December 2006.Baseline data were collected and 7 rounds of telephone follow-up visits were conducted to track clinical outcomes.For death cases,the date and cause of death were recorded.Patients were divided into several subgroups based on gender and baseline cognition[Mini-Mental State Examination(MMSE)score].Kaplan-Meier analysis and Cox proportional hazards regression models were constructed to analyze the survival time of patients and identify the risk factors.Results A total of 499 patients were enrolled,including 199 males and 300 females.The follow-up time was 5.5(3.4,7.4)years,with longest follow-up time of 19.3 years.The median survival time after symptom onset was 11.8 years(95%CI 10.2-13.4 years),which was 12.4 years(95%CI 11.2-13.5 years)in females,significantly longer than that in males(10.2 years,95%CI 9.6-10.8 years,logrank test,P=0.010).The median survival time after diagnosis was 8.3 years(95%CI 7.3-9.4 years),which was 8.8 years(95%CI 6.9-10.6 years)for women,significantly longer than that for men(6.8 years,95%CI 5.7-7.9 years,logrank test,P=0.001).Patients with baseline MMSE scores≥15(n=265)had a median survial of 11.4 years(95%CI 9.5-13.2 years),significantly longer than those with poorer cognitive function(baseline MMSE scores<15;n=234,7.4 years,95%CI 6.4-8.4 years,logrank test,P<0.001).Multivariable Cox proportional hazards regression analysis showed that aging(HR=1.027,95%CI 1.002-1.052,P=0.034),lower body mass index(BMI;HR=1.081,95%CI 1.023-1.139,P=0.007),lower baseline MMSE score(HR=1.056,95%CI 1.026-1.086,P<0.001),diabetes(HR=1.716,95%CI 1.076-2.735,P=0.023),and history of falls(HR=1.536,95%CI 1.007-2.341,P=0.046)were independent risk factors for death(all P<0.05).During the follow-up,224 of the participants died.Except

关 键 词：阿尔茨海默病 死亡原因 生存分析 

分 类 号：R749.16[医药卫生—神经病学与精神病学]