阿尔茨海默氏病与牙周炎——令人难以捉摸的联系

2015-01-20 sunshine 译 MedSci原创

摘要阿尔茨海默氏病是痴呆症最显著的原因和最常见的类型。该病的临床特征是认知功能的进行性退化,首先表现为记忆力减退。其确切的病因及病理生理机制尚未完全清楚。但是目前的推测是,神经炎症在阿尔茨海默氏病发病机制中起着至关重要的作用。阿尔茨海默氏病的特点是有明显的炎症特征,表现为受累的部位小胶质细胞的激活以及促炎症因子水平的升高。研究表明,系统性感染可能会使中枢神经系统处于炎症状态。牙周炎是常见的口腔感染

摘要


阿尔茨海默氏病是痴呆症最显著的原因和最常见的类型。该病的临床特征是认知功能的进行性退化,首先表现为记忆力减退。其确切的病因及病理生理机制尚未完全清楚。但是目前的推测是,神经炎症在阿尔茨海默氏病发病机制中起着至关重要的作用。

阿尔茨海默氏病的特点是有明显的炎症特征,表现为受累的部位小胶质细胞的激活以及促炎症因子水平的升高。

研究表明,系统性感染可能会使中枢神经系统处于炎症状态。

牙周炎是常见的口腔感染性疾病,致病菌为革兰阴性厌氧菌,这种菌能导致局部和全身的感染。众所周知,牙周炎可将促炎症因子释放到体循环中,这样炎症可长期存在,牙周炎呈缓慢进展。本文阐述了牙周炎在加重阿尔茨海默氏病中可能起到的作用。

牙周炎可能对阿尔茨海默氏病的发生发展具有潜在的影响。牙周炎与阿尔茨海默氏病有两个相同的重要特征,即氧化应激和炎症,这是阿尔茨海默氏病脑部的病理学表现。牙周炎是可以治疗的,因此,它是阿尔茨海默氏病的一种可更改的危险因素。

引言

阿尔茨海默氏病是老年人群痴呆最普遍的原因,也是全世界老年人健康的一个主要问题。其发病率随年龄而显著上升,80岁老年人群中发病率接近50%。阿尔茨海默氏病通常认为是遗传因素和环境因素相互作用造成的。它的特征是进行性的认知障碍以及判断和决策能力受损,接着是心理行为障碍和语言障碍。

牙周炎是困扰人们的最常见的口腔感染性疾病。它普遍存在于世界范围内,是造成成人失牙的首要原因。本文阐述了阿尔茨海默氏病与牙周炎之间令人难以捉摸的关系,展示出这种关系的病理生理学以及可能的影响。本文通过筛查PubMed数据库编写,使用关键字“阿尔茨海默氏病”、“牙周炎”、“细胞因子”、“全身炎症反应”、“牙周病原菌”。查阅了1994年到2012年所有关于这个主题的综述、meta分析以及原创文章。斟酌了所有已发表的关于此病在人和动物身上研究的文献。

讨论

像阿尔茨海默氏病这样的认知功能障碍的疾病其发病率在发达国家人群中急剧上升。在发展中国家这种上升趋势则达到了令人震惊的程度。

目前公认的阿尔茨海默氏病的发病机制是AβP的过度积累,包括在患者大脑受累区域异常磷酸化的tau蛋白的积累。脑内炎症是阿尔茨海默氏病发病机制的一个主要因素。全身炎症通过激活的小胶质细胞促进了神经退行性病变的恶化。

牙周炎是多种微生物感染性疾病,其特点是牙周袋内存在多种细菌、病毒。这些致病原以及它们的毒性产物都能通过血脑屏障进入大脑。这些致病原通过破坏血管的完整性对大脑产生直接或间接的影响。侵入大脑的螺旋体通过激活宿主的先天性免疫反应,包括各种信号通路,引发长期的慢性炎症反应,最终导致神经退行性病变。病毒,特别是HSV,可以经血液或神经纤维进入脑组织。氧化应激和炎症可能会激活潜伏的病毒。

众所周知,牙龈卟啉单胞菌能促使血小板发生凝集反应以及诱导动脉粥样硬化。这可能是动脉粥样硬化的发病机制,并导致认知障碍和阿尔茨海默氏病。最近的文献提到了基因多态性与牙周病进展之间的关系。牙周炎易感者是潜在的高炎症表型。在面对抗原刺激时,这些易感者表达出多种促炎介质。基因多态性参与了牙周炎症的发生,并可能在牙周炎与阿尔茨海默氏病之间有一定的联系。

文献中提出炎症可能在牙周炎以及阿尔茨海默氏病的发病机制之间存在某种复杂的联系。到目前为止,没有任何证据可以表明牙周炎与阿尔茨海默氏病之间存在因果关系。牙周炎会增加全身的微生物总量,并且能促进全身的慢性炎症反应。它可能是阿尔茨海默氏病中永久的神经退行性病变的危险因素之一。

结论

阿尔茨海默氏病涉及到一系列复杂的病理生理过程,其确切的致病机理尚未清楚。文章提出炎症可能在阿尔茨海默氏病致病机制中起到核心作用。牙周炎和阿尔茨海默氏病之间存在的相同的慢性炎症特征,这是二者的共性。

目前,研究尚未表明牙周炎在认知功能方面的作用。应进行系统性、多中心。大样本量的纵向研究,以查明阿尔茨海默氏病与牙周炎之间的关系。牙周炎可能会加重认知功能障碍,并与其有共同的危险因素。对伴有轻度认知障碍的牙周炎患者应进行介入研究以评价其潜在的益处。牙周基础治疗之后前炎性介质的水平下降,同时全身的炎症反应也减轻。

目前,可以说,牙周炎是阿尔茨海默氏病的一个潜在危险因素。但是文献中证据不足无法说明二者之间存在因果关系。易感的目标人群,特别是老年人患者,应当调动其参加牙周维护的积极性且应适当增加参加牙周维护的频率。牙科专业人员和神经学家需一贯统筹老年患者的有条不紊的管理。

原始出处:

Gurav AN1.Alzheimer's disease and periodontitis--an elusive link.Rev Assoc Med Bras. 2014 Mar-Apr;60(2):173-80.


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    0

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