主觀認知下降社區篩查工具的應用現狀

郝立曉，韓 瓔，賈建國

·中國全科醫療/社區衛生服務工作研究·

主觀認知下降社區篩查工具的應用現狀

郝立曉1，2，韓 瓔2,3，4，5，6*，賈建國2*

阿爾茨海默病(AD)作為一種慢性神經退行性疾病，嚴重影響著人類健康，鑒于該病無有效治愈手段，預后差，實現“三早”尤為重要。主觀認知下降(SCD)作為AD最早期階段引起國內外學者的重視，但是目前國際上對于該階段社區篩查工具的選擇意見不一。本文對SCD社區篩查工具的應用情況進行總結歸納，以利于一個廣泛有效的社區篩查工具的建立。

阿爾茨海默??；主觀認知下降；社區；篩查工具

郝立曉，韓瓔，賈建國.主觀認知下降社區篩查工具的應用現狀[J].中國全科醫學，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，一些慢性病嚴重影響著人類健康，阿爾茨海默病(Alzheimer′s disease,AD)作為老年癡呆的主要類型，嚴重影響著人類健康。但是鑒于該病無法治愈，早期發現、診斷并及時干預尤顯重要。主觀認知下降(subjective cognitive decline,SCD)作為AD的臨床前階段，于2014年由JESSEN等[1]提出，SCD標化前后國內外學者對其進行了大量研究，包括流行病學[2-4]、基因〔載脂蛋白Eε4(APOEε4)〕[5-6]、生物標志物(tau蛋白、Aβ沉積)[7]、影像學[8-9]等方面，但是眾多研究結論并不完全一致。綜述文獻，發現除納入人群、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社區篩查工具的應用現狀進行綜述，為其篩查工具的標化提供幫助。

1 SCD定義及觀念性的診斷框架

輕度認知障礙前階段(pre-mild cognitive impairment,pre-MCI)作為AD早期階段很久以前就引起國內外的重視并對其進行了大量研究，但是由于缺乏統一標準，研究結果差異很大，研究結論并不統一，經過多年努力，主觀認知下降工作組(Subjective Cognitive Decline -Initiative，SCD-I)于2014年統一了這一術語，并制定了其觀念性框架，他們認為SCD是患者的一種主觀感受，患者自身感覺認知水平較前下降，但是客觀檢查沒有達到輕度認知障礙(MCI)或癡呆的診斷標準，且這種認知下降是持續的，與急性事件無關，并非焦慮抑郁，或其他神經、精神系統疾病、代謝性疾病、中毒、藥物濫用、感染以及系統性疾病等導致。同時提出AD臨床前期SCD一般是指伴有主觀記憶主訴(subjective memory complaint，SMC)，但是客觀神經心理量表測試均在參考范圍，起病時間不超過5年，起病年齡≥60歲，總是擔心認知下降，感覺認知比同年齡組表現差，記憶減退需經知情者證實，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[1]。

2 SCD認知篩查工具應用情況

2.1 整體認知功能 簡易智能精神狀態量表(Mini-mental State Examination，MMSE)和蒙特利爾認知評估量表(Montreal Cognitive Assessment，MOCA)作為整體認知功能的篩查工具，得到了國際上的認可。在SCD篩查除外客觀認知損傷的研究中，MMSE及其修改版(Modified Mini-mental State Examination，3MS)應用最廣[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]，同時選用了兩種整體認知功能篩查工具的為部分亞洲研究[17,19-20]。

2.2 單項認知域篩查工具應用情況

2.2.1 記憶測試 記憶測試被較多研究選用，應用工具包括聽覺詞語學習測試(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，FCSR)、Benton視覺記憶測試、福爾德實物記憶評估(Fuld Objective Memory Evaluation，FOME)、記憶間隔和追蹤-巴德利雙重任務、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現早期認知損傷起著非常重要的作用，AVLT中的延遲回憶被認為是早期AD的最靈敏測量[31]。在辨別MCI方面，AVLT較Rey-Osterrieth復雜圖形記憶測試(Complex Figure Test，CFT)更優[32]。

2.2.2 其他認知域測試 執行功能：連線試驗A和B[19,29,33-34]；定向：10個條目的精神狀態問卷(Mental Status Questionnaire，MSQ)[35]；注意力：倒數3個數、數字符號替換試驗(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、CERAD測試組語義詞語流暢性任務[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，FAB)等。

很多研究將焦點放在了用不同評分系統的畫鐘測試(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)被較為廣泛地應用[39]；各研究選用認知篩查工具種類不一、數目不一、版本不一，亟待標化。

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]、功能活動問卷(Functional Activities Questionnaire，FAQ)[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，更多需依據病史及頭部影像學的檢查。

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，量表的選用需根據調研目的、場地(社區、醫院)、調研人群(受教育年限)等具體情況而定。同時，精神疾病需由心理科醫生做出診斷。

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

3 SCD自我報告問卷的應用情況

SCD如何能早期識別診斷，其問題條目的設定至關重要。有研究顯示，部分SCD隨訪結果之所以與認知下降無關，是因為其問題的設定不夠靈敏，部分SCD人群未篩查出[44]。學者們對SCD自我報告問題的設定進行了相關探索。GIFFORD等[45]采用條目應答理論(Item Response Theory，IRT)和計算機采納測試(Computerized Adaptive Test，CAT)模型證實了SCD篩查的9個可信條目。RABIN等[46]通過綜述SCD倡議組納入文章，建議SCD條目的設定應根據具體情況而定，最終RABIN團隊給出了10個自我報告SCD頻率最高的篩查條目。另外，為實現SCD的量化目的，RAMI等[47]通過對主觀認知下降問卷(Subjective Cognitive Decline Questionnaire，SCD-Q)進行了效度的檢查，結果發現SCD-Q對于自我感覺的認知下降是一項有用的篩查工具。同時，SCD-Q不僅可用于記憶診所，基層醫療也適用。

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

4 小結

既往研究因SCD定義未標化，篩查工具選擇不同，得出研究結論不一致。自2014年SCD提出并標化后，為除外客觀認知損傷，各個國家的學者分別就自身國度量表應用情況選擇量表，主要體現在問題的基本屬性、認知域的選擇及條目的設定缺乏一致性[1,44]，故篩查出的SCD人群不完全具可比性，致使后續研究結論并不完全統一。較少有研究進行知情者的心理狀態及認知評估[47]?；谌漆t學開放及便于接觸患者的特性，全科醫生有辨別癡呆早期的潛力[18]，然而，一個有效的能夠廣泛接受的探測SCD的測試還未建立[68]。

目前，整體認知功能的篩查MMSE國際上較認可，SCD自我報告量表仍在不斷探索完善中，特定認知域的篩查工具的設定需進一步標化。SCD篩查工具的制定需根據SCD標化后的定義及提出的診斷框架，進一步的確定仍需根據隨訪數據。

作者貢獻：郝立曉進行文章的構思與設計、文獻/資料收集與整理、撰寫論文；韓瓔、賈建國進行文章的可行性分析、論文的中英文修訂，負責文章的質量控制及審校，對文章整體負責，監督管理。

本文無利益沖突。

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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

國家自然科學基金資助項目(61633018)——基于神經影像技術的認知功能預測及應用；北京市順義區衛計委基金資助項目——北京市順義區阿爾茨海默病臨床前期主觀認知下降患病率調查

R 592

A

10.3969/j.issn.1007-9572.2017.19.006

2017-03-12；

2017-05-24)

1.100069北京市，首都醫科大學全科醫學與繼續教育學院

2.100053北京市，首都醫科大學宣武醫院

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，北大醫療康復醫院

*通信作者：韓瓔，主任醫師，教授，博士生導師；

E-mail:13621011941@163.com

賈建國，主任醫師，教授，博士生導師；

E-mail:jiajianguo_1@126.com