JNNP:肌萎缩侧索硬化症认知损害的危险因素:系统回顾和荟萃分析

2021-03-09 MedSci原创 MedSci原创

肌萎缩侧索硬化是一种致命的神经退行性疾病,主要影响上下运动神经元。ALS与额颞叶痴呆(FTD)在病理生物学和临床表现上存在重复。目前,已有证据表明,将ALS视为一种谱系障碍是合适的,它涉及核心运动神经

肌萎缩侧索硬化是一种致命的神经退行性疾病,主要影响上下运动神经元。ALS与额颞叶痴呆(FTD)在病理生物学和临床表现上存在重复。目前,已有证据表明,将ALS视为一种谱系障碍是合适的,它涉及核心运动神经元变性以外的认知功能障碍。约有30%-50%的ALS患者出现不同程度的认知障碍,约有5%-15%的ALS患者符合ALS-FTD的诊断标准。ALS患者的认知障碍特征存在显著的异质性,突出了四个特定的认知领域:运动功能,语言、记忆和社会认知根据修订后的ALS额颞谱系障碍诊断标准。多领域认知缺陷对预后、生活质量和对症治疗的依从性、以及家庭照顾者负担有深刻的负面影响。在不同程度的在认知障碍方面,ALS患者存在FTD与最短的生存时间和3.7-4.1倍的死亡风险相关。此外,运动性认知障碍(ECI)和其他各种认知障碍与较差的预后独立相关。因此,ALS患者认知功能障碍的早期发现和及时处理非常重要。
 
 
一些人口统计学、临床和遗传特征已被确定为ALS认知损害的预测因子。年龄、性别、文化程度、发病部位、病情严重程度、临床表型、C9orf72基因突变、神经退行性疾病家族史、呼吸功能、抑郁、日间嗜睡的关系。发病部位和性别对ALS认知的影响仍有待阐明。一些研究表明,延髓发作的患者比肢体发作的患者更易发生认知障碍,但其他研究发现延髓发作或肢体发作的ALS患者的认知功能没有差异。迄今为止,尚未对ALS患者认知损害的危险因素进行全面的meta分析。本文进行了系统的回顾和荟萃分析,以澄清和量化各种因素对ALS认知损害的影响。
 
 
据系统回顾和荟萃分析(2009)指南的首选报告项目和流行病学观察研究(MOOSE)声明的荟萃分析对MOOSE清单进行搜索。搜索了PubMed和EMBASE数据库中的研究报告ALS患者认知损害的预测因素。未应用任何语言或发布类型限制。使用以下关键词:“肌萎缩侧索硬化症”或“ALS”或“运动神经元疾病”或“MND”或“Gehrig*”和“认知能力”或“痴呆症”或“执行功能”或“语言”或“记忆”或“注意力”或“社会认知”或“视觉空间”或“心理测试”或“迷你型”“精神状态检查”或“蒙特利尔认知评估”或“正面评估组合”或“Stroop测试”。还手动搜索相关评论和包含所需数据的文章的参考文献列表,以确定遗漏的参考文献。最终搜索于2020年6月30日进行。符合meta分析条件的研究符合预先确定的标准:(1)病例对照或纵向研究,探讨至少一个与ALS认知损害相关的危险因素;(2)ALS患者被分为认知完整组和认知损害组;(3) 明确了ALS的诊断标准和认知障碍或痴呆的定义;(4)报告相对危险度(RR)和等效值,或根据原始数据计算。
Figure 1
 
设计了一个标准化的提取表来记录每项研究的以下数据:第一作者的姓名、发表年份、国家、样本量、患者平均年龄、性别(男性患者的百分比)、ALS伴认知功能障碍和ALS-FTD患者的病例数、认知领域、就业的神经心理学组合和认知障碍的定义。两位研究者(TY和YH)独立选择了这些研究,并提取和交叉核对了数据。在研究中未报告OR、RR或等效值时,筛选原始数据以计算OR。主要结果是通过可能的危险因素评估ALS患者的整体认知损害。次要转归是可能的危险因素对ALS-FTD和ALS-ECI的影响。异质性采用I2统计进行评估。I2<25%被认为是同质性;25%≤I2<50%被认为是低异质性;50%≤I2<75%被认为是中度异质性,I2>75%被认为是实质异质性。如果研究有中度或实质异质性,使用随机效应模型进行荟萃分析;采用Begg检验和Egger检验检测对称性。对潜在因素(N≥3)进行敏感性分析,每次排除一项研究,以评估结果的稳定性并解释异质性的可能来源。所有分析均采用Stata V.14.1(StataCorp)进行。
Figure 2
 
在20501份记录中,有27篇符合条件的文章报道了6799个人。确定了9个预测因子:C9orf72(OR 3.62,95%CI 1.76~7.45)、发音障碍(OR 2.25,95%CI 1.20~4.22)、ALS家族史(OR 1.76,95%CI 1.18~2.61)、主要上运动神经元(PUMN)表型(OR 1.73,95%CI 1.09~2.73)和延髓发病(OR 1.54,95%可信区间(1.28~1.87)增加ALS患者认知功能障碍的危险因素。ALS功能评定量表修订分数、性别、年龄或教育程度与ALS患者认知功能障碍无显著相关。此外,C9orf72(OR=5.94)和延髓发作(OR=2.08)是ALS额颞部痴呆的强预测因子。女性比男性更易发生执行认知障(OR=1.82)。
 
有C9orf72重复扩张、构音障碍、ALS家族史、PUMN表型和延髓起病的患者有ALS认知功能障碍的高风险。这些联系可能有助于理解ALS的异质性。
 
 
 

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    2021-05-26 venlin
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href='/topic/show?id=e02ee6901a2' target=_blank style='color:#2F92EE;'>#系统回顾#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76901, encryptionId=e02ee6901a2, topicName=系统回顾)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=27e316318097, createdName=ms5822920152752585, createdTime=Thu Mar 11 13:34:58 CST 2021, time=2021-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=947121, encodeId=f8d294e12171, content=受益匪浅,厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb635444536, createdName=ms7000001469493960, createdTime=Wed Mar 10 14:49:39 CST 2021, time=2021-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=947080, encodeId=cd5694e08011, 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  4. [GetPortalCommentsPageByObjectIdResponse(id=1983163, encodeId=28d31983163f4, content=<a href='/topic/show?id=a7a7e359478' target=_blank style='color:#2F92EE;'>#硬化症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73594, encryptionId=a7a7e359478, topicName=硬化症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a691420, createdName=30397604, createdTime=Thu Dec 16 02:34:58 CST 2021, time=2021-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1681411, encodeId=f82a168141156, content=<a href='/topic/show?id=366b8e2299e' target=_blank style='color:#2F92EE;'>#荟萃#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=87229, encryptionId=366b8e2299e, topicName=荟萃)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c12d27855367, 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href='/topic/show?id=e02ee6901a2' target=_blank style='color:#2F92EE;'>#系统回顾#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76901, encryptionId=e02ee6901a2, topicName=系统回顾)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=27e316318097, createdName=ms5822920152752585, createdTime=Thu Mar 11 13:34:58 CST 2021, time=2021-03-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=947121, encodeId=f8d294e12171, content=受益匪浅,厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb635444536, createdName=ms7000001469493960, createdTime=Wed Mar 10 14:49:39 CST 2021, time=2021-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=947080, encodeId=cd5694e08011, content=肌萎缩的meta, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Wed Mar 10 13:03:54 CST 2021, time=2021-03-10, status=1, ipAttribution=)]
    2022-02-14 chendoc252
  5. 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content=肌萎缩的meta, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Wed Mar 10 13:03:54 CST 2021, time=2021-03-10, status=1, ipAttribution=)]
    2021-04-10 minzhusu

    0

  6. 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  7. 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    2021-03-10 ms7000001469493960

    受益匪浅,厉害

    0

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    2021-03-10 科研科研科研

    肌萎缩的meta

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