脑脊液生物标志物与^(11)C-PIB PET/CT显像对阿尔茨海默病的诊断准确率及相关性研究

Diagnostic accuracy and correlation between cerebrospinal fluid biomarkers and ^(11)C-PIB PET/CT imaging in Alzheimer disease

目的探讨脑脊液生物标志物与^(11)C-匹兹堡化合物B(PIB)PET/CT显像在阿尔茨海默病(AD)中的诊断准确率及相关性,确定脑脊液生物标志物诊断AD的最佳临界值。方法回顾性分析2011年1月至2020年3月在北部战区总医院行^(11)C-PIB PET/CT显像和腰椎穿刺的66名受试者的临床资料,其中男性32名、女性34名,年龄61~82(71.0±3.4)岁。根据诊断标准分为AD患者组(50例)和健康对照组(16名)。采用酶联免疫吸附测定法检测脑脊液生物标志物α突触核蛋白(α-syn)、β淀粉样蛋白(Aβ)40、Aβ42、t-tau、p-tau水平,并计算t-tau/Aβ42水平的比值(t-tau/Aβ42)、Aβ42/Aβ40水平的比值(Aβ42/Aβ40)。采用受试者工作特征(ROC)曲线分析脑脊液生物标志物诊断AD的最佳临界值、灵敏度和特异度。分析^(11)C-PIB PET/CT图像,计算平均Aβ沉积标准化摄取值比(SUVR),分析2组受试者脑脊液生物标志物与^(11)C-PIB PET/CT显像诊断AD的准确率及相关性。2组间脑脊液生物标志物水平的比较采用独立样本t检验,计数资料的比较采用χ^(2)检验,相关性采用Pearson相关性分析,一致性分析采用Kappa检验。结果AD患者组脑脊液生物标志物α-syn、t-tau、p-tau水平及t-tau/Aβ42均高于健康对照组(t=2.315、4.001、2.336、3.291,均P<0.01),而Aβ42水平和Aβ42/Aβ40均低于健康对照组(t=−5.443、−3.487,均P<0.05)。t-tau/Aβ42诊断AD的准确率最高(AUC=0.892,P<0.001),其次为Aβ42/Aβ40和α-syn(AUC=0.865、0.795,均P<0.01)。t-tau/Aβ42和Aβ42/Aβ40诊断AD的最佳临界值分别为0.509和0.072,α-syn诊断AD的最佳临界值为465 pg/mL。t-tau/Aβ42、Aβ42/Aβ40、α-syn和^(11)C-PIB PET/CT显像诊断的灵敏度分别为80.0%(40/50)、76.0%(38/50)、74.0%(37/50)和78.0%(39/50),前三者分别与后者联合诊断AD的灵敏度为96.0%(48/50)、94.0%(47/50)和94.0%(47/50),均高于其单独诊断(χ^(2)=5.316~7.440,均P<0.05);t-tau/Aβ42与^(11)C-PIB PET/CT显像联合诊断的准确率均高于其单独诊断(93.9%对80.3%,93.9%对77.2%),且差异有统计学意义(χ^(2)=5.469、7.439,均P<0.05)。t-tau/Aβ42、Aβ42/Aβ40和α-syn与^(11)C-PIB PET/CT显像的SUVR有显著相关性(r=0.555、−0.451、0.445,均P<0.01);t-tau/Aβ42、Aβ42/Aβ40和α-syn与^(11)C-PIB PET/CT显像诊断一致性的Kappa值分别为0.769、0.623、0.587,均P<0.001,其中t-tau/Aβ42与^(11)C-PIB PET/CT显像诊断的一致性较好。结论t-tau/Aβ42、Aβ42/Aβ40和α-syn均为理想的AD诊断标准,结合^(11)C-PIB PET/CT显像可提高对AD诊断的准确率。

Objective To investigate the diagnostic accuracy and correlation between cerebrospinal fluid biomarkers and ^(11)C-Pittsburgh compound-B(PIB)PET/CT imaging in Alzheimer disease(AD).The optimal cut-off values of cerebrospinal fluid biomarkers are also determined.Methods The clinical data of 66 subjects who underwent ^(11)C-PIB PET/CT imaging and lumbar puncture at the General Hospital of Northern Theater Command from January 2011 to March 2020 were retrospectively analyzed.The participants included 32 males and 34 females aged 61–82(71.0±3.4)years and were divided into the AD patient group(n=50)and the healthy control group(n=16)according to established criteria.Enzyme-linked immunosorbent assay was used to detect levels of the cerebrospinal fluid biomarkersα-synuclein(α-syn),β-amyloid(Aβ)40,Aβ42,t-tau and p-tau.The level ratios of t-tau to Aβ42(t-tau/Aβ42)and Aβ42 to Aβ40(Aβ42/Aβ40)were calculated.The receiver operator characteristic(ROC)curve was used to analyze the diagnostic optimal cut-off value,sensitivity,and specificity of the cerebrospinal fluid biomarkers.^(11)C-PIB PET/CT images were analyzed.The average Aβdeposition standardized uptake value ratio(SUVR)was calculated,and the accuracy and correlation between the two groups of cerebrospinal fluid biomarkers and ^(11)C-PIB PET/CT imaging in the diagnosis of AD were analyzed.The levels of cerebrospinal fluid biomarkers between the two groups was compared by independent-sample t test,and the count data were compared byχ^(2) test.Pearson correlation coefficients were calculated for correlation analysis,and consistency was determined using the Kappa test.Results The levels of cerebrospinal fluid biomarkersα-syn,t-tau andp-tau as well as t-tau/Aβ42 in the AD patient group were higher than those in the healthy control group(t=2.315,4.001,2.336,3.291,all P<0.01),while the Aβ42 level and Aβ42/Aβ40 were lower than those in the healthy control group(t=−5.443,−3.487,both P<0.05).T-tau/Aβ42 revealed the highest diagnostic accuracy for AD(AUC=0.892,P<0.001),followed by Aβ42/Aβ40 andα-syn(AUC=0.865,0.795,both P<0.01).The optimal cut-off values of t-tau/Aβ42 and Aβ42/Aβ40 were 0.509 and 0.072,respectively,and the aptimal cut-off value ofα-syn was 465 pg/mL.The sensitivities of t-tau/Aβ42,Aβ42/Aβ40,α-syn and ^(11)C-PIB PET/CT imaging for predicting AD were 80.0%(40/50),76.0%(38/50),74.0%(37/50)and 78.0%(39/50),respectively.The sensitivities of the first three methods in combination with ^(11)C-PIB PET/CT imaging for predicting AD were 96.0%(48/50),94.0%(47/50)and 94.0%(47/50),respectively,which were all higher than a single method(χ^(2)=5.316–7.440,all P<0.05).The combined diagnostic accuracy of t-tau/Aβ42 and ^(11)C-PIB PET/CT imaging was greater than that of a single diagnostic method(93.9%vs.80.3%,93.9%vs.77.2%),and the difference noted was statistically significant(χ^(2)=5.469,7.439,both P<0.05).T-tau/Aβ42,Aβ42/Aβ40 andα-syn level were significantly correlated with ^(11)C-PIB PET/CT SUVR(r=0.555,−0.451,0.445,all P<0.01).The Kappa value of diagnostic consistencies of t-tau/Aβ42,Aβ42/Aβ40 andα-syn with ^(11)C-PIB PET/CT imaging were 0.769,0.623 and 0.587,respectively(all P<0.001).Among the criteria considered,t-tau/Aβ42 demonstrated great diagnostic consistency with ^(11)C-PIB PET/CT.Conclusions T-tau/Aβ42,Aβ42/Aβ40 andα-syn are ideal diagnostic criteria for AD.Combining these parameters with ^(11)C-PIB PET/CT imaging could improve the accuracy of AD diagnosis.