馬麗娜 李 耘 王潔妤

(首都醫(yī)科大學(xué)宣武醫(yī)院綜合科，北京 100053)

輕度認(rèn)知功能障礙與抑郁的流行病學(xué)研究進(jìn)展

馬麗娜 李 耘 王潔妤

(首都醫(yī)科大學(xué)宣武醫(yī)院綜合科，北京 100053)

輕度認(rèn)知功能障礙；抑郁

抑郁是輕度認(rèn)知功能障礙(MCI)發(fā)展為阿爾茨海默病(AD)的重要危險因素〔1〕，MCI和抑郁是老年人常見的疾病，這兩者之間的關(guān)系復(fù)雜，本文對MCI與抑郁的流行病學(xué)進(jìn)行綜述。

1 MCI的定義

MCI 是介于正常認(rèn)知功能和臨床可能的AD之間的狀態(tài)〔2,3〕。MCI臨床表現(xiàn)為記憶力、語言功能，注意力、執(zhí)行功能、視空間結(jié)構(gòu)功能或計算力的減退，記憶力減退是最主要、最常見的臨床表現(xiàn)，以近期記憶力減退明顯。MCI診斷標(biāo)準(zhǔn)多采用Petersen〔4〕診斷標(biāo)準(zhǔn)：①存在由患者自己、家屬或知情人提供的記憶主訴；②記憶測驗成績低于年齡和文化程度匹配的正常對照1.5s；③總體認(rèn)知分級量表輕度異常，即總體衰退量表(GDS)2～3級或臨床癡呆評定量表(CDR) 0.5分；④一般認(rèn)知功能正常；⑤日常生活能力保持正常；⑥癡呆或任何可以導(dǎo)致腦功能紊亂的軀體和精神疾患除外。

2 MCI與抑郁的流行病學(xué)情況

2.1 MCI的發(fā)生率 由于MCI不同的診斷標(biāo)準(zhǔn)，不同研究中對人群中MCI的發(fā)生率存在很大差異，波動于0.5%～42%〔5〕。例如，在墨西哥人群中MCI發(fā)生率約為 6.45%,其中單區(qū)域遺忘型MCI(a-MCI-s)2.41%,多區(qū)域遺忘型MCI(a-MCI-md)2.56%,單區(qū)域非遺忘型MCI(na-MCI-s)1.18%，多區(qū)域非遺忘型MCI(na-MCI-md)0.30%,女性MCI發(fā)生率較男性高，分別為63.7%和36.3%〔6〕。在意大利人群中MCI發(fā)生率為6.0%,aMCI和naMCI單區(qū)域的發(fā)生率分別占4.3%和13.5%，aMCI和naMCI多區(qū)域的發(fā)生率分別占2.0%和4.5%〔7〕。在西班牙65歲以上的人群中認(rèn)知障礙的發(fā)生率為19%，其中非癡呆性認(rèn)知功能損害(CIND)發(fā)生率為14.7%，癡呆發(fā)生率為4.3%,調(diào)整了性別和年齡之后認(rèn)知障礙發(fā)生率為14.9%〔8〕。在瑞士,將近一半的50歲以上的就診人群中發(fā)生認(rèn)知障礙，占46.20%〔9〕。以上數(shù)據(jù)表明，認(rèn)知功能障礙的發(fā)生率較高，而認(rèn)知功能障礙的早期發(fā)現(xiàn)對于及時干預(yù)和評估措施的制定至關(guān)重要。

2.2 MCI患者中抑郁的發(fā)生率 目前諸多研究顯示抑郁癥狀與MCI相關(guān)。研究發(fā)現(xiàn)憤怒-抑郁被認(rèn)為是MCI 的重要的危險因子(OR=3.47,95%CI:1.61～7.51),考慮可能因為抑郁在MCI的病因?qū)W中發(fā)揮著重要作用〔6～8〕。但在MCI患者中抑郁癥狀的發(fā)生率的研究相對較少。一項研究發(fā)現(xiàn)在CIND患者中神經(jīng)心理學(xué)癥狀的發(fā)生率如下：抑郁16.9%,易怒9.8%,夜間行為7.6%,冷漠6.9%,憤怒5.4%〔10〕。

有研究發(fā)現(xiàn)MCI患者較正常認(rèn)知功能的患者更容易發(fā)展為抑郁，抑郁癥狀的發(fā)生率分別為26.3%和18.0%〔11〕。另外有研究發(fā)現(xiàn)在MCI人群中，抑郁癥狀、冷漠和重要抑郁癥狀的發(fā)生率分別高達(dá)20%、15%和16%〔2,12〕。與認(rèn)知功能正常的人群比較，MCI患者，尤其是aMCI患者，更容易發(fā)生抑郁癥狀〔13〕。MCI 合并抑郁情緒的患者出現(xiàn)更加嚴(yán)重的行為癥狀和語言激惹行為。MCI合并重要抑郁癥狀的患者較未合并抑郁癥狀的患者相比，其額葉和行為癥狀更為普遍和嚴(yán)重〔2〕。因此，評估和處理MCI患者中的抑郁癥狀非常重要。

3 MCI與抑郁的關(guān)系

3.2 抑郁與MCI轉(zhuǎn)化為AD有關(guān) MCI患者進(jìn)展為更嚴(yán)重認(rèn)知障礙的危險性增加〔20〕,在日常功能方面有輕微損害〔21〕,并且可同時發(fā)生抑郁癥狀〔22〕。神經(jīng)心理學(xué)癥狀包括抑郁和冷漠可能為AD臨床前期的最早期癥狀〔23〕,它們是AD癥狀學(xué)早期表現(xiàn)，并且可能是MCI進(jìn)展為癡呆的預(yù)測因子〔24～27〕。

抑郁是癡呆發(fā)生的主要危險因素，抑郁患者較正常人AD(RR:1.66,95%CI:1.29～2.14),血管性癡呆(VD)(RR:1.89,95%CI:1.19-3.01),癡呆(RR:1.55,95%CI:1.31～2.83)和MCI(RR:1.97,95%CI:1.53～2.54) 的發(fā)生率均較高〔28〕。抑郁癥狀與更嚴(yán)重的腦萎縮、增加的認(rèn)知下降、升高的AD轉(zhuǎn)化率有關(guān)。MCI個體的抑郁可能與潛在的包括前驅(qū)期AD的神經(jīng)病理學(xué)改變有關(guān)，并且可能是區(qū)別易進(jìn)展為AD的MCI患者的一個有用的臨床標(biāo)志物〔29〕。

3.3 抑郁與MCI無明顯相關(guān) 盡管大多數(shù)研究顯示抑郁與MCI的發(fā)生發(fā)展、MCI進(jìn)展為AD密切相關(guān)，但仍有其他研究持不同意見。Mackin等〔30〕發(fā)現(xiàn)轉(zhuǎn)化為癡呆的一個最重要的預(yù)測因子是記憶問題的持續(xù)增加，提示MCI患者中認(rèn)知問題較抑郁癥狀更為重要。另一項關(guān)于MCI患者的3年隨訪的前瞻性研究發(fā)現(xiàn)，冷漠得分高的患者進(jìn)展為AD的危險性較對照組高達(dá)7倍，而抑郁得分高的患者進(jìn)展為AD的危險性較對照組無明顯變化〔26〕。

4 MCI和抑郁相關(guān)性可能的機制

目前多數(shù)研究均顯示抑郁癥狀加速了MCI向臨床AD的進(jìn)展，但可能機制仍不明確〔31〕。Verdelho等〔32〕發(fā)現(xiàn)抑郁癥狀與認(rèn)知下降危險的增加相關(guān)，獨立于腦白質(zhì)變性(WMC)，可能由于一個增加的或協(xié)同的影響，因此,抑郁癥狀可能是代表一個細(xì)微的進(jìn)展的器官障礙。Hermida等〔33〕則提出了炎癥可能介導(dǎo)抑郁、MCI和癡呆之間的關(guān)聯(lián)。

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〔2015-12-25修回〕

(編輯 苑云杰/杜 娟)

教育部人文社科規(guī)劃基金(No.16YJAZH034)；北京市醫(yī)管局青苗人才計劃(QML20160804)；北京市優(yōu)秀人才 資助項目(No.20140000204400001)；首都醫(yī)科大學(xué)宣武醫(yī)院院級課題

馬麗娜(1983-)，女，醫(yī)學(xué)博士，副主任醫(yī)師，主要從事老年醫(yī)學(xué)臨床研究。

R749.1

A

1005-9202(2017)05-1285-03；

10.3969/j.issn.1005-9202.2017.05.113