老年阿尔茨海默病患者血清NRG1、Klotho水平与脑电图参数、预后的相关性

The correlation between serum NRG1,Klotho levels with EEG parameters,prognosis in elderly Alzheimer's disease patients

目的研究老年阿尔茨海默病(AD)患者血清神经调节蛋白1(NRG1)、Klotho与脑电图参数、预后的相关性。方法选取2021年1月—2023年12月西安国际医学中心医院神经内八科诊治的老年AD患者192例为病例组,根据预后情况分为预后不良亚组87例和预后良好亚组105例。另外选取健康体检者82例为健康对照组。利用脑电图仪检测并计算(δ+θ)/(α+β);ELISA试剂盒检测血清NRG1、Klotho;简单精神状态检查表(MMSE)评价AD患者的认知功能并根据评分分为无症状亚组(47例)、轻度亚组(66例)、中度亚组(70例)、重度亚组(9例);采用Spearman分析各指标间的相关性;Logistic回归分析AD患者预后的影响因素;受试者工作特征(ROC)曲线分析血清NRG1、Klotho对AD患者的预后预测价值。结果病例组NRG1、Klotho水平低于健康对照组,(δ+θ)/(α+β)高于健康对照组(t/P=11.822/<0.001、18.466/<0.001、17.806/<0.001);NRG1、Klotho、MMSE水平趋势为无症状亚组>轻度亚组>中度亚组>重度亚组,(δ+θ)/(α+β)水平趋势为无症状亚组<轻度亚组<中度亚组<重度亚组(F/P=30.523/<0.001、58.508/<0.001、411.618/<0.001、69.750<0.001);NRG1、Klotho与MMSE呈正相关(r/P=0.422/<0.001、0.439/<0.001),MMSE与(δ+θ)/(α+β)呈负相关(r/P=-0.418/0.001);预后不良亚组高密度脂蛋白胆固醇(HDL-C)、NRG1、Klotho、MMSE以及日常锻炼所占比例低于预后良好亚组,同型半胱氨酸(Hcy)、(δ+θ)/(α+β)高于预后良好亚组(t/χ2/P=3.979/<0.001、7.052/<0.001、8.769/<0.001、4.016/<0.001、11.305/0.001、5.936/<0.001、9.237/<0.001);Hcy、(δ+θ)/(α+β)升高是AD患者不良预后的危险因素[OR(95%CI)=2.266(1.493~3.440)、1.692(1.134~2.524)],NRG1、Klotho、MMSE升高是AD患者不良预后的保护因素[OR(95%CI)=0.315(0.228~0.434)、0.384(0.285~0.518)、0.401(0.269~0.598)];血清NRG1、Klotho及二者联合预测AD患者预后的AUC分别为0.751、0.783、0.901,二者联合优于各自单独预测效能(Z=4.031、3.985,P均<0.001)。结论老年阿尔茨海默病患者血清NRG1、Klotho水平降低,且与脑电图参数和预后相关。

Objective To investigate the correlation between serum Neuregulin 1(NRG1),Klotho with electroencephalogram parameters and prognosis in elderly patients with Alzheimer's disease.Methods A total of 192 elderly Alzheimer's disease patients who treated in the Department of Neurology Xi'an International Medical Center Hospital from January 2021 to December 2023 were included as the disease group,and were separated into a poor prognosis subgroup(87 cases)and a good prognosis subgroup(105 cases)according to their prognosis.In addition,82 healthy examinees were included as the healthy control group.Electroencephalogram detection was carried out,and(δ+θ)/(α+β)value was calculated.ELISA kit was applied to detect serum NRG1 and Klotho.The Mini Mental State Examination(MMSE)was applied to evaluate the cognitive function of AD patients,and grouped into asymptomatic subgroup(47 cases),mild subgroup(66 cases),moderate subgroup(70 cases),and severe subgroup(9 cases)based on the scores.General clinical data of the disease group were collected.Spearman was applied to analyze the correlation between various indicators.Logistic regression was applied to analyze the factors influencing the prognosis of Alzheimer's disease patients.ROC was applied to analyze the prognostic value of serum NRG1 and Klotho in Alzheimer's disease patients.Results The levels of NRG1 and Klotho in the disease group were lower than those in the healthy control group,and the(δ+θ)/(α+β)value was higher than that in the healthy control group(t/P=11.822/<0.001,18.466/<0.001,17.806/<0.001).The trends of NRG1,Klotho,and MMSE levels showed asymptomatic subgroup>mild subgroup>moderate subgroup>severe subgroup,and the trend of(δ+θ)/(α+β)value showed asymptomatic subgroup<mild subgroup<moderate subgroup<severe subgroup(F/P=30.523/<0.001,58.508/<0.001,411.618/<0.001,69.750<0.001).NRG1 and Klotho are positively correlated with MMSE,while MMSE is negatively correlated with(δ+θ)/(α+β)(r/P=0.422/<0.001,0.439/<0.001,-0.418/<0.001).The high-density lipoprotein cholesterol(HDL-C),NRG1,Klotho,MMSE,and proportion of daily exercise in the poor prognosis subgroup were lower than those in the good prognosis subgroup,while homocysteine(Hcy)and(δ+θ)/(α+β)value were higher than those in the good prognosis subgroup(t/χ^(2)/P=3.979/<0.001,7.052/<0.001,8.769/<0.001,4.016/<0.001,11.305/0.001,5.936/<0.001,9.237/<0.001).High Hcy and(δ+θ)/(α+β)were risk factors for the prognosis of AD patients,,while high NRG1,Klotho,and MMSE were protective factors for the prognosis of AD patients[OR(95%CI)=2.266(1.493-3.440),1.692(1.134-2.524),0.315(0.228-0.434),0.384(0.285-0.518),0.401(0.269-0.598)].The AUC of serum NRG1,Klotho,and their combination in predicting the prognosis of AD patients were 0.751,0.783,and 0.901,respectively.The combination of the two was superior to their individual predictive efficacy(Z=4.031,3.985,P<0.001 for all).Conclusion The expression of serum NRG1 and Klotho is low in elderly Alzheimer's disease patients,and their expression levels are correlated with EEG parameters and prognosis.