广东社区老年人尿液中多种金属混合暴露与轻度认知障碍的关联性

Association between urinary metal mixtures and mild cognitive impairment among elderly residents in Guangdong compounds

  • 摘要:
    背景 环境金属暴露与老年人轻度认知障碍(MCI)的发生与发展密切相关。有效识别有害金属暴露,评估其交互效应,具有重要的公共卫生学意义。
    目的 探讨社区老年人尿液单一金属和金属混合物暴露与MCI的关系。
    方法 本研究纳入中山市某区391名60岁以上社区居住老年人,采用电感耦合等离子体质谱法检测其尿中铁(Fe)、铜(Cu)、硒(Se)、砷(As)、镉(Cd)、锰(Mn)、铬(Cr)、镍(Ni)、钒(V)、钴(Co)、锑(Sb)、铊(Tl)、锌(Zn)、钙(Ca)、镁(Mg)15种金属或类金属的浓度,使用中文版《简易精神状态检查(MMSE)》量表评估老年人的认知功能。采用logistic回归探讨单一金属浓度与MCI的关系,使用LASSO回归和多金属logistic回归模型筛选出与MCI关联最强的重点金属离子,采用贝叶斯核机回归(BKMR)分析重点金属离子混合物与MCI之间的关系和金属间的交互作用。年龄、性别、文化程度、职业和身体质量指数作为协变量进行调整。
    结果 本研究调查的391名老年人中,78人(19.94%)被诊断为MCI(MCI组),另313人为对照组。MCI组尿液中Se、Cd、Mn、As水平高于对照组(P均<0.05)。单一金属模型显示,校正协变量后,以各金属浓度的第一四分位数(Q1)组为参照:Se的Q4组老年人患MCI的OR(95%CI)为2.190(1.017~4.716);Cd的Q3组的OR(95%CI)为2.345(1.041~5.283),Q4组为2.371(1.043~5.393);Mn的Q2组的OR(95%CI)为2.355(1.038~5.344);As的Q3组的OR(95%CI)为3.377(1.442~7.908),Q4组为2.886(1.227~6.788);Sb的Q2组的OR(95%CI)为2.779(1.234~6.257)。经自然对数转换后尿金属离子浓度作为连续变量纳入单一金属模型,发现Cd浓度与MCI呈正相关(OR=1.377;95%CI:1.008~1.882;P=0.044)。Cd、Se、Mg、Ca、Mn、As、Cr、Co、Tl、Sb由LASSO回归筛选后纳入多金属模型分析。多金属模型中,与Q1组相比:Co的Q2组老年人患MCI的OR(95%CI)为0.395(0.164~0.953),Q3组为0.390(0.167~0.911);Mn的Q2组老年人患MCI的OR(95%CI)为2.636(1.053~6.596);Sb的Q2组的OR(95%CI)为2.640(1.047~6.658)。作为连续变量的结果显示:Mg(OR=0.472;95%CI:0.248~0.899;P=0.022)、Co(OR=0.857;95%CI:0.737~0.996;P=0.044)浓度与老年人患MCI的风险呈负相关。BKMR混合物分析提示:Mg、Co与MCI的负相关存在协同效应,Mn、Sb与MCI的正相关存在协同效应,Mg与Co可减弱Mn、Sb与MCI的正相关效应,Mn可降低Mg、Co的负相关效应。
    结论 尿中Se、Cd、As、Mn、Sb水平升高可能增加老年人患MCI的风险,而Mg与Co水平升高却可减少患病风险。Mn、Sb、Mg、Co之间存在潜在的协同或拮抗作用,对老年人认知功能的影响不容忽视。

     

    Abstract:
    Background Environmental metal exposure is closely associated with the onset and progression of mild cognitive impairment (MCI) in the elderly. Effectively identifying hazardous metal exposure and assessing their interaction effects have significant public health implications.
    Objective To explore the relationship between urinary single metal and metal mixture exposure and MCI in elderly compound residents.
    Methods This study included 391 elderly individuals aged 60 and above from residential compounds in Zhongshan City, Guangdong Province. Concentrations of iron (Fe), copper (Cu), selenium (Se), arsenic (As), cadmium (Cd), manganese (Mn), chromium (Cr), nickel (Ni), vanadium (V), cobalt (Co), antimony (Sb), thallium (Tl), zinc (Zn), calcium (Ca), and magnesium (Mg) in urine were measured using inductively coupled plasma mass spectrometry. Cognitive function in the elderly was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Logistic regression was used to explore the relationship between single metal exposure level and MCI. LASSO regression and multi-metal logistic regression models were used to identify key metal ions associated with MCI. Bayesian kernel machine regression (BKMR) was employed to analyze the relationship between key metal ion mixtures and MCI, as well as the interactions between metals. Age, gender, education level, occupation, and body mass index were adjusted as covariates.
    Results A total of 78 among the 391 elderly individuals surveyed (19.94%) were diagnosed with MCI (MCI group), and the other 313 individuals were controls. The levels of Se, Cd, Mn, and As in the urine of the MCI group were significantly higher than those in the control group (P < 0.05). In the single-metal model, after adjusting for covariates and using the first quartile (Q1) of each metal concentration as the reference, the OR for MCI in the elderly in the Q4 group of Se was 2.190 (95%CI: 1.017, 4.716); for Cd, the OR was 2.345 (95%CI: 1.041, 5.283) in the Q3 group and 2.371 (95%CI: 1.043, 5.393) in the Q4 group; for Mn, the OR was 2.355 (95%CI: 1.038, 5.344) in the Q2 group; for As, the OR was 3.377 (95%CI: 1.442, 7.908) in the Q3 group and 2.886 (95%CI: 1.227, 6.788) in the Q4 group; for Sb, the OR was 2.779 (95%CI: 1.234, 6.257) in the Q2 group. When urinary metal concentrations were ln-transformed and included as continuous variables in the single-metal model, Cd concentration was positively correlated with MCI (OR=1.377; 95%CI: 1.008, 1.882; P=0.044). Cd, Se, Mg, Ca, Mn, As, Cr, Co, Tl, and Sb were selected by the LASSO regression model and included in the multi-metal model. In the multi-metal model, compared with Q1, the OR for MCI in the elderly was 0.395 (95%CI: 0.164, 0.953) in the Q2 group of Co and 0.390(95%CI: 0.167, 0.911) in the Q3 group of Co; for Mn, the OR in the Q2 group was 2.636 (95%CI: 1.053, 6.596); for Sb, the OR in the Q2 group was 2.640 (95%CI: 1.047, 6.658). As continuous variables, Mg (OR=0.472; 95%CI: 0.248, 0.899; P=0.022) and Co (OR=0.857; 95%CI: 0.737, 0.996; P=0.044) concentrations were negatively correlated with MCI. The BKMR mixture analysis suggested that Mg and Co exhibited a synergistic negative correlation with MCI, while Mn and Sb exhibited a synergistic positive correlation with MCI. Mg and Co attenuated the positive correlation of Mn and Sb with MCI, whereas Mn weakened the protective effects of Mg and Co.
    Conclusion Elevated levels of Se, Cd, As, Mn, and Sb in urine may increase the risk of MCI in the elderly, while Mg and Co have protective effects. Potential synergistic or antagonistic interactions may be found among Mn, Sb, Mg, and Co, which should not be overlooked in terms of their impact on the cognitive function of the elderly.

     

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