主观认知下降社区筛查工具的应用现状

2017-01-17郝立晓贾建国

中国全科医学 2017年19期

郝立晓，韩璎，贾建国

·中国全科医疗/社区卫生服务工作研究·

主观认知下降社区筛查工具的应用现状

郝立晓1，2，韩璎2,3，4，5，6*，贾建国2*

阿尔茨海默病(AD)作为一种慢性神经退行性疾病，严重影响着人类健康，鉴于该病无有效治愈手段，预后差，实现“三早”尤为重要。主观认知下降(SCD)作为AD最早期阶段引起国内外学者的重视，但是目前国际上对于该阶段社区筛查工具的选择意见不一。本文对SCD社区筛查工具的应用情况进行总结归纳，以利于一个广泛有效的社区筛查工具的建立。

阿尔茨海默病；主观认知下降；社区；筛查工具

郝立晓，韩璎，贾建国.主观认知下降社区筛查工具的应用现状[J].中国全科医学，2017，20(19)：2324-2328.[www.chinagp.net]

HAO L X,HAN Y,JIA J G.Application status of screening tools for subjective cognitive decline in community[J].Chinese General Practice，2017，20(19)：2324-2328.

随着人口老龄化的出现，一些慢性病严重影响着人类健康，阿尔茨海默病(Alzheimer′s disease,AD)作为老年痴呆的主要类型，严重影响着人类健康。但是鉴于该病无法治愈，早期发现、诊断并及时干预尤显重要。主观认知下降(subjective cognitive decline,SCD)作为AD的临床前阶段，于2014年由JESSEN等[1]提出，SCD标化前后国内外学者对其进行了大量研究，包括流行病学[2-4]、基因〔载脂蛋白Eε4(APOEε4)〕[5-6]、生物标志物(tau蛋白、Aβ沉积)[7]、影像学[8-9]等方面，但是众多研究结论并不完全一致。综述文献，发现除纳入人群、样本量等不同外，研究选用筛查工具亦不一致。本文通过对目前SCD社区筛查工具的应用现状进行综述，为其筛查工具的标化提供帮助。

1 SCD定义及观念性的诊断框架

轻度认知障碍前阶段(pre-mild cognitive impairment,pre-MCI)作为AD早期阶段很久以前就引起国内外的重视并对其进行了大量研究，但是由于缺乏统一标准，研究结果差异很大，研究结论并不统一，经过多年努力，主观认知下降工作组(Subjective Cognitive Decline -Initiative，SCD-I)于2014年统一了这一术语，并制定了其观念性框架，他们认为SCD是患者的一种主观感受，患者自身感觉认知水平较前下降，但是客观检查没有达到轻度认知障碍(MCI)或痴呆的诊断标准，且这种认知下降是持续的，与急性事件无关，并非焦虑抑郁，或其他神经、精神系统疾病、代谢性疾病、中毒、药物滥用、感染以及系统性疾病等导致。同时提出AD临床前期SCD一般是指伴有主观记忆主诉(subjective memory complaint，SMC)，但是客观神经心理量表测试均在参考范围，起病时间不超过5年，起病年龄≥60岁，总是担心认知下降，感觉认知比同年龄组表现差，记忆减退需经知情者证实，APOEε4基因型阳性，以及并存脑组织Aβ沉积和脑脊液Aβ下降、T-tau和P-tau升高等证据[1]。

2 SCD认知筛查工具应用情况

2.1 整体认知功能简易智能精神状态量表(Mini-mental State Examination，MMSE)和蒙特利尔认知评估量表(Montreal Cognitive Assessment，MOCA)作为整体认知功能的筛查工具，得到了国际上的认可。在SCD筛查除外客观认知损伤的研究中，MMSE及其修改版(Modified Mini-mental State Examination，3MS)应用最广[4，10-20]，MOCA只被部分研究选用[19- 20]。研究表明，MOCA主要用于筛查MMSE评分在参考范围但是有轻度认知功能损害的老年人[21]，对MCI和痴呆均具有较高灵敏度[22-24]。在探测多域MCI患者中，MMSE和MOCA均具有较好的辨别效力[25]，但在SCD筛查中，部分研究未选用MOCA[2,4,10-13,16,26-27]，同时选用了两种整体认知功能筛查工具的为部分亚洲研究[17,19-20]。

2.2 单项认知域筛查工具应用情况

2.2.1 记忆测试记忆测试被较多研究选用，应用工具包括听觉词语学习测试(Auditory Verbal Learning Test，AVLT)、Rey-AVLT[19]以及Buschke选择性回忆测试、自由和指定的选择回忆测试(Free and Cued Selective Reminding test，FCSR)、Benton视觉记忆测试、福尔德实物记忆评估(Fuld Objective Memory Evaluation，FOME)、记忆间隔和追踪-巴德利双重任务、词语记忆测试(Consortium to Establish a Registry for Alzheimer′s Disease，CERAD)等[10,13,28-29]。在西方国家，逻辑记忆(Logic Memory，LM)和AVLT在辨别客观记忆损伤中最常用[30]。情景记忆缺陷的精确测试对于发现早期认知损伤起着非常重要的作用，AVLT中的延迟回忆被认为是早期AD的最灵敏测量[31]。在辨别MCI方面，AVLT较Rey-Osterrieth复杂图形记忆测试(Complex Figure Test，CFT)更优[32]。

2.2.2 其他认知域测试执行功能：连线试验A和B[19,29,33-34]；定向：10个条目的精神状态问卷(Mental Status Questionnaire，MSQ)[35]；注意力：倒数3个数、数字符号替换试验(Digit Symbol Substitution Test，DSST)、Stroop测试、每天注意力测试(Test of Everyday Attention，TEA)[29,33,35]；推理：成对词语找相似性、韦氏成人智力表相似性测试[29,35]；语言：分类词语流畅性(Category Verbal Fluency Test，CVFT)、字母流畅性任务、CERAD测试组语义词语流畅性任务[13,27,29,33]。视空间：画钟[33]；命名：Boston命名测试。另外，还有警觉性测试以及额叶功能评定量表(Frontal Assessment Battery，FAB)等。

很多研究将焦点放在了用不同评分系统的画钟测试(Clock-Drawing Test，CDT)筛查痴呆和MCI[36-38]；在我国，为缩小文化差异的影响，形状连线测试(Shape Trail Test，STT)和颜色连线测试(Color Trail Test，CTT)被较为广泛地应用[39]；各研究选用认知筛查工具种类不一、数目不一、版本不一，亟待标化。

2.3 日常功能及与血管源性SCD鉴别筛查工具部分研究还选用了日常生活量表(Activity Daily Living，ADL)[10,13,40]或器具性的日常生活量表(Instrumental Activity Daily Living)[40-41]、功能活动问卷(Functional Activities Questionnaire，FAQ)[34]、临床痴呆评定量表(Clinical Dementia Rating，CDR)[10,13,27]以及Hachinski缺血量表[13]。缺血量表被部分研究选用，AD及血管性痴呆的辨别在参考该量表的同时，更多需依据病史及头部影像学的检查。

2.4 除外焦虑抑郁精神疾病所致SCD筛查工具研究多选用的是汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)[10,28]、老年抑郁量表(Geriatric Depression Scale)[13,20,28,33]，流病研究中心抑郁量表(Center for Epidemiological Studies-depression Scale，CES-D)[15]等。精神疾病除外诊断中，量表的选用需根据调研目的、场地(社区、医院)、调研人群(受教育年限)等具体情况而定。同时，精神疾病需由心理科医生做出诊断。

AD临床前期SCD的诊断需除外AD及MCI[1]，目前没有一个MCI的筛查测试能像MMSE用做除外痴呆那样得到国际上的认可[42-43]。虽说MCI有可控性的定义，但是专门的客观认知损伤的证据，不同研究意见不一，客观认知评估工具的构建对于横断面及纵向研究结果至关重要，取决于纳入的客观认知损伤测试的数目和客观认知损伤的截点[43]。对于某一认知域，单个工具的选择可能优于多种工具的联合应用[32]。我国上海华山医院郭起浩教授团队自行研发的记忆力执行筛查量表(Memory Executive Screening，MES)[43]在辨别单域和多域遗忘型MCI(amnestic MCI，aMCI)方面，是一项简单有效、高灵敏度和特异度的筛查工具，已经得到国际上的认可。SCD客观认知功能评定工具的选择，在结合各国量表使用情况的同时，需参照AD神经影像倡议(Alzheimer′s Disease Neuroimaging Initiative，ADNI)标准。

3 SCD自我报告问卷的应用情况

SCD如何能早期识别诊断，其问题条目的设定至关重要。有研究显示，部分SCD随访结果之所以与认知下降无关，是因为其问题的设定不够灵敏，部分SCD人群未筛查出[44]。学者们对SCD自我报告问题的设定进行了相关探索。GIFFORD等[45]采用条目应答理论(Item Response Theory，IRT)和计算机采纳测试(Computerized Adaptive Test，CAT)模型证实了SCD筛查的9个可信条目。RABIN等[46]通过综述SCD倡议组纳入文章，建议SCD条目的设定应根据具体情况而定，最终RABIN团队给出了10个自我报告SCD频率最高的筛查条目。另外，为实现SCD的量化目的，RAMI等[47]通过对主观认知下降问卷(Subjective Cognitive Decline Questionnaire，SCD-Q)进行了效度的检查，结果发现SCD-Q对于自我感觉的认知下降是一项有用的筛查工具。同时，SCD-Q不仅可用于记忆诊所，基层医疗也适用。

自我报告筛查方式不同，主要体现在管理模式[48-50]、条目数量[33,34,51-53]及选择类型应答[53-54]、条目的内容及复杂性(单一记忆域[13,55]以及是否合并其他认知域条目[47,56]、认知域条目缺失[57-58]、条目是注重当前认知能力/认知损伤还是个体内的变化[58-60]、条目询问是围绕整体还是特殊认知域)。工具的应用或是运用了完整的已发表的问卷[53,60-61]，或是现存条目的组合[62-63]或是出于特殊目的开发新的条目[64-67]。

4 小结

既往研究因SCD定义未标化，筛查工具选择不同，得出研究结论不一致。自2014年SCD提出并标化后，为除外客观认知损伤，各个国家的学者分别就自身国度量表应用情况选择量表，主要体现在问题的基本属性、认知域的选择及条目的设定缺乏一致性[1,44]，故筛查出的SCD人群不完全具可比性，致使后续研究结论并不完全统一。较少有研究进行知情者的心理状态及认知评估[47]。基于全科医学开放及便于接触患者的特性，全科医生有辨别痴呆早期的潜力[18]，然而，一个有效的能够广泛接受的探测SCD的测试还未建立[68]。

目前，整体认知功能的筛查MMSE国际上较认可，SCD自我报告量表仍在不断探索完善中，特定认知域的筛查工具的设定需进一步标化。SCD筛查工具的制定需根据SCD标化后的定义及提出的诊断框架，进一步的确定仍需根据随访数据。

作者贡献：郝立晓进行文章的构思与设计、文献/资料收集与整理、撰写论文；韩璎、贾建国进行文章的可行性分析、论文的中英文修订，负责文章的质量控制及审校，对文章整体负责，监督管理。

本文无利益冲突。

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(本文编辑：崔沙沙)

Application Status of Screening Tools for Subjective Cognitive Decline in Community

HAOLi-xiao1，2,HANYing2,3，4，5，6*,JIAJian-guo2*

1.SchoolofGeneralPracticeandContinuingEducation,CapitalMedicalUniversity,Beijing100069，China2.XuanwuHospital,CapitalMedicalUniversity,Beijing100053，China3.CenterofAlzheimer′sDisease,BeijingInstituteforBrainDisorders,Beijing100069，China4.BeijingInstituteofGeriatrics,Beijing100730，China5.NationalClinicalResearchCenterforGeriatricDisorders,Beijing100730，China6.PKUCareRehabilitationHospital,Beijing102206，China*Correspondingauthor:HANYing,Chiefphysician,Professor,Doctoralsupervisor;E-mail:13621011941@163.comJIAJian-guo,Chiefphysician,Professor,Doctoralsupervisor;E-mail:jiajianguo_1@126.com

As a chronic neurodegenerative disease,Alzheimer′s disease(AD) seriously affects the health of human.Since there are no effective means of cure for AD whose prognosis is also poor，the early finding,early diagnosis and early treatment are utmost important.As the earliest stage of AD,subjective cognitive decline(SCD) has caused the attention of scholars all over the world.However,the choices of screening tools for AD are different among the international society.This paper summarizes the application status of screening tool for SCD in the community and tries to help the establishment of a broad and effective screening tool for community.

Alzheimer disease;Subjective cognitive decline;Communities;Screening tool

国家自然科学基金资助项目(61633018)——基于神经影像技术的认知功能预测及应用；北京市顺义区卫计委基金资助项目——北京市顺义区阿尔茨海默病临床前期主观认知下降患病率调查

R 592

10.3969/j.issn.1007-9572.2017.19.006

2017-03-12；

2017-05-24)

1.100069北京市，首都医科大学全科医学与继续教育学院

2.100053北京市，首都医科大学宣武医院

3.100069北京市，北京脑重大疾病研究院阿尔茨海默病研究所

4.100730北京市，北京老年病研究所

5.100730北京市，国家老年病临床研究中心

6.102206北京市，北大医疗康复医院