轻度认知功能障碍与抑郁的流行病学研究进展

马丽娜 李 耘 王洁妤

(首都医科大学宣武医院综合科，北京 100053)

轻度认知功能障碍与抑郁的流行病学研究进展

马丽娜 李 耘 王洁妤

(首都医科大学宣武医院综合科，北京 100053)

轻度认知功能障碍；抑郁

抑郁是轻度认知功能障碍(MCI)发展为阿尔茨海默病(AD)的重要危险因素〔1〕，MCI和抑郁是老年人常见的疾病，这两者之间的关系复杂，本文对MCI与抑郁的流行病学进行综述。

1 MCI的定义

MCI 是介于正常认知功能和临床可能的AD之间的状态〔2,3〕。MCI临床表现为记忆力、语言功能，注意力、执行功能、视空间结构功能或计算力的减退，记忆力减退是最主要、最常见的临床表现，以近期记忆力减退明显。MCI诊断标准多采用Petersen〔4〕诊断标准：①存在由患者自己、家属或知情人提供的记忆主诉；②记忆测验成绩低于年龄和文化程度匹配的正常对照1.5s；③总体认知分级量表轻度异常，即总体衰退量表(GDS)2～3级或临床痴呆评定量表(CDR) 0.5分；④一般认知功能正常；⑤日常生活能力保持正常；⑥痴呆或任何可以导致脑功能紊乱的躯体和精神疾患除外。

2 MCI与抑郁的流行病学情况

2.1 MCI的发生率 由于MCI不同的诊断标准，不同研究中对人群中MCI的发生率存在很大差异，波动于0.5%～42%〔5〕。例如，在墨西哥人群中MCI发生率约为 6.45%,其中单区域遗忘型MCI(a-MCI-s)2.41%,多区域遗忘型MCI(a-MCI-md)2.56%,单区域非遗忘型MCI(na-MCI-s)1.18%，多区域非遗忘型MCI(na-MCI-md)0.30%,女性MCI发生率较男性高，分别为63.7%和36.3%〔6〕。在意大利人群中MCI发生率为6.0%,aMCI和naMCI单区域的发生率分别占4.3%和13.5%，aMCI和naMCI多区域的发生率分别占2.0%和4.5%〔7〕。在西班牙65岁以上的人群中认知障碍的发生率为19%，其中非痴呆性认知功能损害(CIND)发生率为14.7%，痴呆发生率为4.3%,调整了性别和年龄之后认知障碍发生率为14.9%〔8〕。在瑞士,将近一半的50岁以上的就诊人群中发生认知障碍，占46.20%〔9〕。以上数据表明，认知功能障碍的发生率较高，而认知功能障碍的早期发现对于及时干预和评估措施的制定至关重要。

2.2 MCI患者中抑郁的发生率 目前诸多研究显示抑郁症状与MCI相关。研究发现愤怒-抑郁被认为是MCI 的重要的危险因子(OR=3.47,95%CI:1.61～7.51),考虑可能因为抑郁在MCI的病因学中发挥着重要作用〔6～8〕。但在MCI患者中抑郁症状的发生率的研究相对较少。一项研究发现在CIND患者中神经心理学症状的发生率如下：抑郁16.9%,易怒9.8%,夜间行为7.6%,冷漠6.9%,愤怒5.4%〔10〕。

有研究发现MCI患者较正常认知功能的患者更容易发展为抑郁，抑郁症状的发生率分别为26.3%和18.0%〔11〕。另外有研究发现在MCI人群中，抑郁症状、冷漠和重要抑郁症状的发生率分别高达20%、15%和16%〔2,12〕。与认知功能正常的人群比较，MCI患者，尤其是aMCI患者，更容易发生抑郁症状〔13〕。MCI 合并抑郁情绪的患者出现更加严重的行为症状和语言激惹行为。MCI合并重要抑郁症状的患者较未合并抑郁症状的患者相比，其额叶和行为症状更为普遍和严重〔2〕。因此，评估和处理MCI患者中的抑郁症状非常重要。

3 MCI与抑郁的关系

3.2 抑郁与MCI转化为AD有关 MCI患者进展为更严重认知障碍的危险性增加〔20〕,在日常功能方面有轻微损害〔21〕,并且可同时发生抑郁症状〔22〕。神经心理学症状包括抑郁和冷漠可能为AD临床前期的最早期症状〔23〕,它们是AD症状学早期表现，并且可能是MCI进展为痴呆的预测因子〔24～27〕。

抑郁是痴呆发生的主要危险因素，抑郁患者较正常人AD(RR:1.66,95%CI:1.29～2.14),血管性痴呆(VD)(RR:1.89,95%CI:1.19-3.01),痴呆(RR:1.55,95%CI:1.31～2.83)和MCI(RR:1.97,95%CI:1.53～2.54) 的发生率均较高〔28〕。抑郁症状与更严重的脑萎缩、增加的认知下降、升高的AD转化率有关。MCI个体的抑郁可能与潜在的包括前驱期AD的神经病理学改变有关，并且可能是区别易进展为AD的MCI患者的一个有用的临床标志物〔29〕。

3.3 抑郁与MCI无明显相关 尽管大多数研究显示抑郁与MCI的发生发展、MCI进展为AD密切相关，但仍有其他研究持不同意见。Mackin等〔30〕发现转化为痴呆的一个最重要的预测因子是记忆问题的持续增加，提示MCI患者中认知问题较抑郁症状更为重要。另一项关于MCI患者的3年随访的前瞻性研究发现，冷漠得分高的患者进展为AD的危险性较对照组高达7倍，而抑郁得分高的患者进展为AD的危险性较对照组无明显变化〔26〕。

4 MCI和抑郁相关性可能的机制

目前多数研究均显示抑郁症状加速了MCI向临床AD的进展，但可能机制仍不明确〔31〕。Verdelho等〔32〕发现抑郁症状与认知下降危险的增加相关，独立于脑白质变性(WMC)，可能由于一个增加的或协同的影响，因此,抑郁症状可能是代表一个细微的进展的器官障碍。Hermida等〔33〕则提出了炎症可能介导抑郁、MCI和痴呆之间的关联。

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〔2015-12-25修回〕

(编辑 苑云杰/杜 娟)

教育部人文社科规划基金(No.16YJAZH034)；北京市医管局青苗人才计划(QML20160804)；北京市优秀人才 资助项目(No.20140000204400001)；首都医科大学宣武医院院级课题

马丽娜(1983-)，女，医学博士，副主任医师，主要从事老年医学临床研究。

R749.1

A

1005-9202(2017)05-1285-03；

10.3969/j.issn.1005-9202.2017.05.113