郝立曉，韓 瓔，賈建國

·中國全科醫(yī)療/社區(qū)衛(wèi)生服務(wù)工作研究·

主觀認(rèn)知下降社區(qū)篩查工具的應(yīng)用現(xiàn)狀

郝立曉1，2，韓 瓔2,3，4，5，6*，賈建國2*

阿爾茨海默病(AD)作為一種慢性神經(jīng)退行性疾病，嚴(yán)重影響著人類健康，鑒于該病無有效治愈手段，預(yù)后差，實(shí)現(xiàn)“三早”尤為重要。主觀認(rèn)知下降(SCD)作為AD最早期階段引起國內(nèi)外學(xué)者的重視，但是目前國際上對于該階段社區(qū)篩查工具的選擇意見不一。本文對SCD社區(qū)篩查工具的應(yīng)用情況進(jìn)行總結(jié)歸納，以利于一個(gè)廣泛有效的社區(qū)篩查工具的建立。

阿爾茨海默??；主觀認(rèn)知下降；社區(qū)；篩查工具

郝立曉，韓瓔，賈建國.主觀認(rèn)知下降社區(qū)篩查工具的應(yīng)用現(xiàn)狀[J].中國全科醫(yī)學(xué)，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.

隨著人口老齡化的出現(xiàn)，一些慢性病嚴(yán)重影響著人類健康，阿爾茨海默病(Alzheimer′s disease,AD)作為老年癡呆的主要類型，嚴(yán)重影響著人類健康。但是鑒于該病無法治愈，早期發(fā)現(xiàn)、診斷并及時(shí)干預(yù)尤顯重要。主觀認(rèn)知下降(subjective cognitive decline,SCD)作為AD的臨床前階段，于2014年由JESSEN等[1]提出，SCD標(biāo)化前后國內(nèi)外學(xué)者對其進(jìn)行了大量研究，包括流行病學(xué)[2-4]、基因〔載脂蛋白Eε4(APOEε4)〕[5-6]、生物標(biāo)志物(tau蛋白、Aβ沉積)[7]、影像學(xué)[8-9]等方面，但是眾多研究結(jié)論并不完全一致。綜述文獻(xiàn)，發(fā)現(xiàn)除納入人群、樣本量等不同外，研究選用篩查工具亦不一致。本文通過對目前SCD社區(qū)篩查工具的應(yīng)用現(xiàn)狀進(jìn)行綜述，為其篩查工具的標(biāo)化提供幫助。

1 SCD定義及觀念性的診斷框架

輕度認(rèn)知障礙前階段(pre-mild cognitive impairment,pre-MCI)作為AD早期階段很久以前就引起國內(nèi)外的重視并對其進(jìn)行了大量研究，但是由于缺乏統(tǒng)一標(biāo)準(zhǔn)，研究結(jié)果差異很大，研究結(jié)論并不統(tǒng)一，經(jīng)過多年努力，主觀認(rèn)知下降工作組(Subjective Cognitive Decline -Initiative，SCD-I)于2014年統(tǒng)一了這一術(shù)語，并制定了其觀念性框架，他們認(rèn)為SCD是患者的一種主觀感受，患者自身感覺認(rèn)知水平較前下降，但是客觀檢查沒有達(dá)到輕度認(rèn)知障礙(MCI)或癡呆的診斷標(biāo)準(zhǔn)，且這種認(rèn)知下降是持續(xù)的，與急性事件無關(guān)，并非焦慮抑郁，或其他神經(jīng)、精神系統(tǒng)疾病、代謝性疾病、中毒、藥物濫用、感染以及系統(tǒng)性疾病等導(dǎo)致。同時(shí)提出AD臨床前期SCD一般是指伴有主觀記憶主訴(subjective memory complaint，SMC)，但是客觀神經(jīng)心理量表測試均在參考范圍，起病時(shí)間不超過5年，起病年齡≥60歲，總是擔(dān)心認(rèn)知下降，感覺認(rèn)知比同年齡組表現(xiàn)差，記憶減退需經(jīng)知情者證實(shí)，APOEε4基因型陽性，以及并存腦組織Aβ沉積和腦脊液Aβ下降、T-tau和P-tau升高等證據(jù)[1]。

2 SCD認(rèn)知篩查工具應(yīng)用情況

2.1 整體認(rèn)知功能 簡易智能精神狀態(tài)量表(Mini-mental State Examination，MMSE)和蒙特利爾認(rèn)知評估量表(Montreal Cognitive Assessment，MOCA)作為整體認(rèn)知功能的篩查工具，得到了國際上的認(rèn)可。在SCD篩查除外客觀認(rèn)知損傷的研究中，MMSE及其修改版(Modified Mini-mental State Examination，3MS)應(yīng)用最廣[4，10-20]，MOCA只被部分研究選用[19- 20]。研究表明，MOCA主要用于篩查MMSE評分在參考范圍但是有輕度認(rèn)知功能損害的老年人[21]，對MCI和癡呆均具有較高靈敏度[22-24]。在探測多域MCI患者中，MMSE和MOCA均具有較好的辨別效力[25]，但在SCD篩查中，部分研究未選用MOCA[2,4,10-13,16,26-27]，同時(shí)選用了兩種整體認(rèn)知功能篩查工具的為部分亞洲研究[17,19-20]。

2.2 單項(xiàng)認(rèn)知域篩查工具應(yīng)用情況

2.2.1 記憶測試 記憶測試被較多研究選用，應(yīng)用工具包括聽覺詞語學(xué)習(xí)測試(Auditory Verbal Learning Test，AVLT)、Rey-AVLT[19]以及Buschke選擇性回憶測試、自由和指定的選擇回憶測試(Free and Cued Selective Reminding test，F(xiàn)CSR)、Benton視覺記憶測試、福爾德實(shí)物記憶評估(Fuld Objective Memory Evaluation，F(xiàn)OME)、記憶間隔和追蹤-巴德利雙重任務(wù)、詞語記憶測試(Consortium to Establish a Registry for Alzheimer′s Disease，CERAD)等[10,13,28-29]。在西方國家，邏輯記憶(Logic Memory，LM)和AVLT在辨別客觀記憶損傷中最常用[30]。情景記憶缺陷的精確測試對于發(fā)現(xiàn)早期認(rèn)知損傷起著非常重要的作用，AVLT中的延遲回憶被認(rèn)為是早期AD的最靈敏測量[31]。在辨別MCI方面，AVLT較Rey-Osterrieth復(fù)雜圖形記憶測試(Complex Figure Test，CFT)更優(yōu)[32]。

2.2.2 其他認(rèn)知域測試 執(zhí)行功能：連線試驗(yàn)A和B[19,29,33-34]；定向：10個(gè)條目的精神狀態(tài)問卷(Mental Status Questionnaire，MSQ)[35]；注意力：倒數(shù)3個(gè)數(shù)、數(shù)字符號替換試驗(yàn)(Digit Symbol Substitution Test，DSST)、Stroop測試、每天注意力測試(Test of Everyday Attention，TEA)[29,33,35]；推理：成對詞語找相似性、韋氏成人智力表相似性測試[29,35]；語言：分類詞語流暢性(Category Verbal Fluency Test，CVFT)、字母流暢性任務(wù)、CERAD測試組語義詞語流暢性任務(wù)[13,27,29,33]。視空間：畫鐘[33]；命名：Boston命名測試。另外，還有警覺性測試以及額葉功能評定量表(Frontal Assessment Battery，F(xiàn)AB)等。

很多研究將焦點(diǎn)放在了用不同評分系統(tǒng)的畫鐘測試(Clock-Drawing Test，CDT)篩查癡呆和MCI[36-38]；在我國，為縮小文化差異的影響，形狀連線測試(Shape Trail Test，STT)和顏色連線測試(Color Trail Test，CTT)被較為廣泛地應(yīng)用[39]；各研究選用認(rèn)知篩查工具種類不一、數(shù)目不一、版本不一，亟待標(biāo)化。

2.3 日常功能及與血管源性SCD鑒別篩查工具 部分研究還選用了日常生活量表(Activity Daily Living，ADL)[10,13,40]或器具性的日常生活量表(Instrumental Activity Daily Living)[40-41]、功能活動(dòng)問卷(Functional Activities Questionnaire，F(xiàn)AQ)[34]、臨床癡呆評定量表(Clinical Dementia Rating，CDR)[10,13,27]以及Hachinski缺血量表[13]。缺血量表被部分研究選用，AD及血管性癡呆的辨別在參考該量表的同時(shí)，更多需依據(jù)病史及頭部影像學(xué)的檢查。

2.4 除外焦慮抑郁精神疾病所致SCD篩查工具 研究多選用的是漢密爾頓抑郁量表(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。精神疾病除外診斷中，量表的選用需根據(jù)調(diào)研目的、場地(社區(qū)、醫(yī)院)、調(diào)研人群(受教育年限)等具體情況而定。同時(shí)，精神疾病需由心理科醫(yī)生做出診斷。

AD臨床前期SCD的診斷需除外AD及MCI[1]，目前沒有一個(gè)MCI的篩查測試能像MMSE用做除外癡呆那樣得到國際上的認(rèn)可[42-43]。雖說MCI有可控性的定義，但是專門的客觀認(rèn)知損傷的證據(jù)，不同研究意見不一，客觀認(rèn)知評估工具的構(gòu)建對于橫斷面及縱向研究結(jié)果至關(guān)重要，取決于納入的客觀認(rèn)知損傷測試的數(shù)目和客觀認(rèn)知損傷的截點(diǎn)[43]。對于某一認(rèn)知域，單個(gè)工具的選擇可能優(yōu)于多種工具的聯(lián)合應(yīng)用[32]。我國上海華山醫(yī)院郭起浩教授團(tuán)隊(duì)自行研發(fā)的記憶力執(zhí)行篩查量表(Memory Executive Screening，MES)[43]在辨別單域和多域遺忘型MCI(amnestic MCI，aMCI)方面，是一項(xiàng)簡單有效、高靈敏度和特異度的篩查工具，已經(jīng)得到國際上的認(rèn)可。SCD客觀認(rèn)知功能評定工具的選擇，在結(jié)合各國量表使用情況的同時(shí)，需參照AD神經(jīng)影像倡議(Alzheimer′s Disease Neuroimaging Initiative，ADNI)標(biāo)準(zhǔn)。

3 SCD自我報(bào)告問卷的應(yīng)用情況

SCD如何能早期識別診斷，其問題條目的設(shè)定至關(guān)重要。有研究顯示，部分SCD隨訪結(jié)果之所以與認(rèn)知下降無關(guān)，是因?yàn)槠鋯栴}的設(shè)定不夠靈敏，部分SCD人群未篩查出[44]。學(xué)者們對SCD自我報(bào)告問題的設(shè)定進(jìn)行了相關(guān)探索。GIFFORD等[45]采用條目應(yīng)答理論(Item Response Theory，IRT)和計(jì)算機(jī)采納測試(Computerized Adaptive Test，CAT)模型證實(shí)了SCD篩查的9個(gè)可信條目。RABIN等[46]通過綜述SCD倡議組納入文章，建議SCD條目的設(shè)定應(yīng)根據(jù)具體情況而定，最終RABIN團(tuán)隊(duì)給出了10個(gè)自我報(bào)告SCD頻率最高的篩查條目。另外，為實(shí)現(xiàn)SCD的量化目的，RAMI等[47]通過對主觀認(rèn)知下降問卷(Subjective Cognitive Decline Questionnaire，SCD-Q)進(jìn)行了效度的檢查，結(jié)果發(fā)現(xiàn)SCD-Q對于自我感覺的認(rèn)知下降是一項(xiàng)有用的篩查工具。同時(shí)，SCD-Q不僅可用于記憶診所，基層醫(yī)療也適用。

自我報(bào)告篩查方式不同，主要體現(xiàn)在管理模式[48-50]、條目數(shù)量[33,34,51-53]及選擇類型應(yīng)答[53-54]、條目的內(nèi)容及復(fù)雜性(單一記憶域[13,55]以及是否合并其他認(rèn)知域條目[47,56]、認(rèn)知域條目缺失[57-58]、條目是注重當(dāng)前認(rèn)知能力/認(rèn)知損傷還是個(gè)體內(nèi)的變化[58-60]、條目詢問是圍繞整體還是特殊認(rèn)知域)。工具的應(yīng)用或是運(yùn)用了完整的已發(fā)表的問卷[53,60-61]，或是現(xiàn)存條目的組合[62-63]或是出于特殊目的開發(fā)新的條目[64-67]。

4 小結(jié)

既往研究因SCD定義未標(biāo)化，篩查工具選擇不同，得出研究結(jié)論不一致。自2014年SCD提出并標(biāo)化后，為除外客觀認(rèn)知損傷，各個(gè)國家的學(xué)者分別就自身國度量表應(yīng)用情況選擇量表，主要體現(xiàn)在問題的基本屬性、認(rèn)知域的選擇及條目的設(shè)定缺乏一致性[1,44]，故篩查出的SCD人群不完全具可比性，致使后續(xù)研究結(jié)論并不完全統(tǒng)一。較少有研究進(jìn)行知情者的心理狀態(tài)及認(rèn)知評估[47]?；谌漆t(yī)學(xué)開放及便于接觸患者的特性，全科醫(yī)生有辨別癡呆早期的潛力[18]，然而，一個(gè)有效的能夠廣泛接受的探測SCD的測試還未建立[68]。

目前，整體認(rèn)知功能的篩查MMSE國際上較認(rèn)可，SCD自我報(bào)告量表仍在不斷探索完善中，特定認(rèn)知域的篩查工具的設(shè)定需進(jìn)一步標(biāo)化。SCD篩查工具的制定需根據(jù)SCD標(biāo)化后的定義及提出的診斷框架，進(jìn)一步的確定仍需根據(jù)隨訪數(shù)據(jù)。

作者貢獻(xiàn)：郝立曉進(jìn)行文章的構(gòu)思與設(shè)計(jì)、文獻(xiàn)/資料收集與整理、撰寫論文；韓瓔、賈建國進(jìn)行文章的可行性分析、論文的中英文修訂，負(fù)責(zé)文章的質(zhì)量控制及審校，對文章整體負(fù)責(zé)，監(jiān)督管理。

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(本文編輯：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

國家自然科學(xué)基金資助項(xiàng)目(61633018)——基于神經(jīng)影像技術(shù)的認(rèn)知功能預(yù)測及應(yīng)用；北京市順義區(qū)衛(wèi)計(jì)委基金資助項(xiàng)目——北京市順義區(qū)阿爾茨海默病臨床前期主觀認(rèn)知下降患病率調(diào)查

R 592

A

10.3969/j.issn.1007-9572.2017.19.006

2017-03-12；

2017-05-24)

1.100069北京市，首都醫(yī)科大學(xué)全科醫(yī)學(xué)與繼續(xù)教育學(xué)院

2.100053北京市，首都醫(yī)科大學(xué)宣武醫(yī)院

3.100069北京市，北京腦重大疾病研究院 阿爾茨海默病研究所

4.100730北京市，北京老年病研究所

5.100730北京市，國家老年病臨床研究中心

6.102206北京市，北大醫(yī)療康復(fù)醫(yī)院

*通信作者：韓瓔，主任醫(yī)師，教授，博士生導(dǎo)師；

E-mail:13621011941@163.com

賈建國，主任醫(yī)師，教授，博士生導(dǎo)師；

E-mail:jiajianguo_1@126.com