血清Aβ1-42及P-tau-181与老年2型糖尿病轻度认知功能障碍的关系

Association of serum Aβ1-42,P-tau-181 and mild cognitive impairment in older adults with type 2 diabetes mellitus

目的探讨人血清β淀粉样蛋白1-42(Aβ1-42)、磷酸化tau-181(P-tau-181)蛋白与老年2型糖尿病(T2DM)患者合并轻度认知功能障碍(MCI)的相关性。方法选取2019年7月至2020年7月徐州医科大学附属医院内分泌科收治入院的60岁以上的T2DM患者共180例,根据简易蒙特利尔认知评估(MoCA)量表评价结果分为T2DM认知功能正常组(NCI组)83例和T2DM轻度认知功能障碍组(MCI组)97例,用酶联免疫吸附试验(ELISA)检测血清Aβ1-42及P-tau-181水平,用Spearman相关和偏相关分析血清Aβ1-42、P-tau-181与MoCA评分及各临床指标的相关性,用单因素logistic回归分析各临床指标与MCI的相关性,用多因素logistic回归分析Aβ1-42、P-tau-181的不同水平(按三等分位分组)与MCI的相关性及发生MCI的相对风险。结果MCI组患者血清Aβ1-42和P-tau-181水平均高于NCI组(P<0.05);且Spearman相关性分析结果显示Aβ1-42、P-tau-181水平均与MoCA得分呈显著负相关(r=-0.511,-0.484,均P<0.01);矫正了年龄和性别因素的偏相关分析结果显示,血清Aβ1-42、P-tau-181水平与MCI的负相关性较之前减弱(ρ=-0.504,-0.376,均P<0.01);单因素logistic回归分析结果显示,年龄、受教育程度、糖尿病病程、胆固醇、三酰甘油、低密度脂蛋白胆固醇、肌酐及血清Aβ1-42、P-tau-181均与MCI发生有关(均P<0.05);多因素logistic回归结果显示,校正了年龄、性别、糖尿病病程、受教育程度、吸烟史、卒中史、血压、BMI和生化指标变量后,血清Aβ1-42及P-tau-181的第二、三分位组与第一分位组相比均为MCI的危险因素,且Aβ1-42和P-tau-181水平每增加一个标准差,患者发生MCI的风险分别增加4.88和0.88倍。结论T2DM患者血清Aβ1-42和P-tau-181水平与MCI密切相关,检测Aβ1-42、P-tau-181水平可早期诊断及预防老年T2DM患者合并早期的认知功能损害。

Objective To analyze and investigate the correlation between human serumβ-amyloid 1-42(Aβ1-42)and phosphorylated tau-181(P-tau-181)proteins and combined mild cognitive impairment(MCI)in elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 180 T2DM patients aged 60 years or older admitted to the Department of Endocrinology of the Affiliated Hospital of Xuzhou Medical University from July 2019 to July 2020 were selected.According to the results of the Simple Montreal Cognitive Assessment(MoCA)scale,83 cases were divided into the group with normal cognitive function in T2DM(NCI group)and 97 cases in the group with mild cognitive impairment in T2DM(MCI group).The clinical data of the two groups were compared.Serum Aβ1-42 and P-tau-181 levels were measured by the enzyme-linked immuno-double antibody sandwich(ELISA),and the correlation between serum Aβ1-42 and P-tau-181 and MoCA score and each clinical index was analyzed by Spearman correlation and partial correlation,and the correlation between each clinical index and MCI was analyzed by one-way logistic regression.The correlation between different levels of Aβ1-42 and P-tau-181(grouped in three quartiles)and MCI and the relative risk of developing MCI were analysed by multi-factor logistic regression.Results Serum Aβ1-42 and P-tau-181 levels were both higher in the MCI group than in the NCI group(P<0.05).The results of Spearman′s correlation analysis showed a significant negative correlation with MoCA scores(r=-0.511,-0.484,both P<0.01).Skewed correlation analysis corrected for age and gender showed that serum Aβ1-42 and P-tau-181 levels were less negatively correlated with MCI than before(ρ=-0.504,-0.376,both P<0.01).The univariate logistic regression analysis showed that age,education,duration of diabetes,TG,TC,LDL-C,Cr,and serum Aβ1-42 and P-tau-181 were all associated with the development of MCI(all P<0.05).The multifactorial logistic regression results showed that after correcting for age,gender,duration of diabetes,education,smoking history,stroke history,blood pressure,BMI and biochemical index variables,serum Aβ1-42 and P-tau-181 were risk factors for cognitive impairment in the second and third quartiles compared to the first quartile.And each standard deviation increases in Aβ1-42 and P-tau-181 was associated with a 4.88 and 0.88-fold increase in the risk of MCI in patients,respectively.Conclusion Serum Aβ1-42 and P-tau-181 levels in T2DM patients are closely related to the development of MCI,and their detection can be used clinically for early diagnosis and prevention of cognitive impairment in the elderly patients of T2DM combined with early cognitive function.