Tooth Loss-associated Mechanisms that Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Changes
Tooth Loss-associated Mechanisms that Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Changes
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对认知功能产生负面影响的牙齿缺失相关机制：基于咬合支持缺失和认知变化的动物实验的系统回顾
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影响因子：
4.3
通讯作者：
Qingsong Jiang
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作者：
Xiaoyu Wang;Jiangqi Hu;Qingsong Jiang
背景：牙齿脱落与认知功能障碍之间存在剂量-反应关系，而牙齿脱落可能是阿尔茨海默病（AD）和血管性痴呆（VAD）的独立危险因素。牙齿脱落也会加速神经损伤和神经退化。目的：系统回顾近10年来关于丧失咬合支持导致认知能力下降的动物实验，总结可能的机制。方法：以“Tooth loss”、“Edentulous”、“拔牙与记忆丧失”、“cognitive Impairment”和“Dementia”为关键词，检索PubMed、Embase、SCI、Science Direct和Open Grey。2010 - 2021年共检索相关文献1317篇，其中26篇按照预定的纳入和排除标准筛选纳入本综述。使用ARRIVE指南评估全面性，使用SYCLE的偏倚风险评估工具评估偏倚风险。结果：咬合支持缺失导致认知功能障碍的可能机制如下：1)机械途径，即牙齿缺失导致咀嚼运动系统功能障碍。咀嚼器官活动和脑血流量减少。随着外周受体（如牙周膜）传入刺激的减少，神经通路之间的连接强度降低，相应的大脑区域退化；2)加重途径，即牙齿脱落加重已有的神经退行性改变。牙齿脱落可通过细胞凋亡和线粒体自噬加速神经损伤，增加脑内淀粉样蛋白沉积；3)长期炎症应激通路，包括代谢紊乱、微生物-肠-脑轴、小胶质细胞和星形胶质细胞的激活以及中枢神经系统的炎症级联效应。结论：咬合支持缺失可能通过咀嚼相关刺激减少、神经损伤加重和长期炎症应激导致认知功能障碍。
Background: There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and vascular dementia (VAD) . Tooth loss can also accelerate nerve damage and neurodegeneration. However, the associated mechanisms remain poorly understood..Objective: To conduct a systematic review of animal experiments on cognitive decline caused by the loss of occlusal support performed over the past 10 years and summarize the possible underlying mechanisms..Methods: “Tooth Loss”, “Edentulous”, “Tooth Extraction and Memory Loss”, “Cognition Impairment“, and “Dementia” were used as keywords to search PubMed, Embase, SCI, Science Direct, and Open Grey. A total of 1,317 related articles from 2010 to 2021 were retrieved, 26 of which were included in the review after screening according to predetermined inclusion and exclusion criteria. Comprehensiveness was evaluated using ARRIVE guidelines and the risk of bias was assessed using SYCLE’S risk of bias tool..Results: The putative mechanisms underlying the cognitive impairment resulting from the loss of occlusal support are as follows: 1) The mechanical pathway, whereby tooth loss leads to masticatory motor system functional disorders. Masticatory organ activity and cerebral blood flow decrease. With reduced afferent stimulation of peripheral receptors (such as in the periodontal membrane) the strength of the connections between neural pathways is decreased, and the corresponding brain regions degenerate; 2) the aggravation pathway, in which tooth loss aggravates existing neurodegenerative changes. Tooth loss can accelerates nerve damage through apoptosis and mitochondrial autophagy, increases amyloid deposition in the brain; and 3) the long-term inflammatory stress pathway, which involves metabolic disorders, microbial-gut-brain axis, the activation of microglia and astrocytes, and inflammatory cascade effect in central nervous system. .Conclusion: The loss of occlusal support may lead to cognitive dysfunction through the reduction of chewing-related stimuli, aggravation of nerve damage, and long-term inflammatory stress.