甲基丙二酸与认知之间的关联：一项系统综述与荟萃分析
Association Between Methylmalonic Acid and Cognition: A Systematic Review and Meta-Analysis.
作者信息
Wang Chao, Zhang Ying, Shu Jianbo, Gu Chunyu, Yu Yuping, Liu Wei
机构信息
Tianjin Pediatric Research Institute, Tianjin Children's Hospital, Children's Hospital of Tianjin University, Tianjin, China.
Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin, China.
出版信息
Front Pediatr. 2022 Jun 29;10:901956. doi: 10.3389/fped.2022.901956. eCollection 2022.
BACKGROUND
Methylmalonic acid (MMA) is an intermediate metabolite of human body. The content of MMA in the blood of healthy people is very low, and its concentration will increase in some diseases and elderly people. Recent studies have shown that MMA has a variety of biological functions. The correlation between MMA and cognition, one of the important functions of the nervous system, is still uncertain.
OBJECTIVE
Meta-analyses were performed to assess whether elevated MMA was associated with the risk of cognitive decline.
MATERIALS AND METHODS
Cross-sectional studies, randomized controlled studies, and case-control studies on the relationship between MMA and cognition were obtained by searching PubMed, Web of Science, EMBASE, ProQuest, WANFANG MED ONLINE, China National Knowledge Infrastructure (CNKI) and Chongqing VIP until May 2022. Two researchers independently selected studies according to inclusion and exclusion criteria, evaluated study quality and extracted data. Meta-analyses were performed using Review Manager 5.4 software. The sensitivity analysis of meta-analysis was performed by One by one exclusion method.
RESULTS
A total of 11 studies were included, including six cross-sectional studies, two randomized controlled studies, and three case-control studies, with a sample of 16,533 subjects. Meta-analysis showed that there was no significant difference in cognitive level between high-level MMA subjects and low-level MMA subjects in the general population [SMD = -2.19, 95% CI (-4.76 ∼ 0.38), = 1.67, = 0.09]. In the population supplemented with VitB12, the increase of MMA level caused by VitB12 supplementation was not related to the change of cognition [SMD = 0.32, 95% CI (-0.19 ∼ 0.84) = 1.22, = 0.22]. There was also no significant difference in MMA levels between patients with dementia and the control group [WMD = 20.89, 95% CI (-5.13 ∼ 46.92), = 1.57, = 0.12].
CONCLUSION
In the general population, whether VitB12 is supplemented or not, there is no correlation between the increase of MMA level and the decrease of cognitive level. In dementia diseases, the level of MMA did not change significantly. High levels of MMA may not be a risk factor for cognitive impairment. The exact relationship between MMA and cognition needs further research.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266310], identifier [CRD42021266310].
背景
甲基丙二酸（MMA）是人体的一种中间代谢产物。健康人血液中MMA的含量很低，在某些疾病患者及老年人中其浓度会升高。近期研究表明，MMA具有多种生物学功能。MMA与神经系统重要功能之一的认知之间的相关性仍不确定。
目的
进行荟萃分析以评估MMA升高是否与认知能力下降风险相关。
材料与方法
通过检索PubMed、Web of Science、EMBASE、ProQuest、万方医学网、中国知网和重庆维普，获取截至2022年5月关于MMA与认知关系的横断面研究、随机对照研究和病例对照研究。两名研究人员根据纳入和排除标准独立选择研究、评估研究质量并提取数据。使用Review Manager 5.4软件进行荟萃分析。采用逐一排除法进行荟萃分析的敏感性分析。
结果
共纳入11项研究，包括6项横断面研究、2项随机对照研究和3项病例对照研究，样本量为16533名受试者。荟萃分析表明，在一般人群中，MMA高水平组与低水平组的认知水平无显著差异[标准化均数差（SMD）=-2.19，95%可信区间（CI）（-4.76～0.38），I²=1.67，P=0.09]。在补充维生素B12的人群中，补充维生素B12导致的MMA水平升高与认知变化无关[SMD=0.32，95%CI（-0.19～0.84），I²=1.22，P=0.22]。痴呆患者与对照组之间的MMA水平也无显著差异[加权均数差（WMD）=20.89，95%CI（-5.13～46.92），I²=1.57，P=0.12]。
结论
在一般人群中，无论是否补充维生素B12，MMA水平升高与认知水平下降均无相关性。在痴呆疾病中，MMA水平无显著变化。MMA高水平可能不是认知障碍的危险因素。MMA与认知的确切关系有待进一步研究。
系统评价注册
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266310]，标识符[CRD42021266310]。
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