血清碳酸酐酶Ⅲ作为新型生物学标志物在阿尔茨海默病临床诊断中的应用价值OACSTPCD
Application value of serum carbonic anhydraseⅢas a new biomarker in the clinical diagnosis of Alzheimer disease
目的 探讨血清碳酸酐酶Ⅲ(carbonic anhydraseⅢ,CAⅢ)在轻中度阿尔茨海默病(Alzheimer disease,AD)临床诊断中的应用价值及相关因素.方法 选择 2020 年 10 月至 2022 年 11 月复旦大学附属华山医院初诊为轻中度AD的 106 例老年患者作为AD组,同期 89 名健康老年人作为对照组.检测两组受试者的肝肾功能、血脂、血糖、叶酸和同型半胱氨酸等血清生化指标;采用简易精神状态检查量表(Mini-mental State Examination,MMSE)评估认知水平,患者健康调查问卷(Patient Health Questionnaire-9,PHQ-9)及广泛性焦虑障碍量表(Generalized Anxiety Disorder-7,GAD-7)评估心理状况,改良Barthel指数量表(Barthel Index,BI)评估日常生活活动(activities of daily living,ADL)能力;使用酶联免疫吸附试验(ELISA)测定血清CAⅢ水平.采用相关性分析和多元线性回归分析血清CAⅢ水平的相关因素,受试者工作特征(receiver operating characteristic,ROC)曲线评价血清CAⅢ水平对老年轻中度AD患者的诊断价值.结果 AD组MMSE评分显著低于对照组(P<0.001),PHQ-9、GAD-7 评分显著高于对照组(P<0.001).AD组血清CAⅢ水平显著低于对照组(P<0.0001).AD患者中,病程>3 年、伴有抑郁或焦虑、中度AD、血肌酐≤111 μmol/L的患者血清CAⅢ水平显著低于病程≤3 年、情绪正常、轻度AD、血肌酐>111 μmol/L的患者(P<0.05).相关性分析和多元线性回归分析结果显示,AD患者血清CAⅢ水平与病程、PHQ-9 评分、GAD-7 评分和疾病严重程度负相关,与血肌酐正相关(P<0.05).PHQ-9 评分、病情严重程度、血肌酐水平是老年轻中度AD患者血清CAⅢ水平的独立相关因素(P<0.05).ROC曲线结果显示,血清CAⅢ诊断老年轻中度AD的曲线下面积(area under the curve,AUC)为 0.946,灵敏度和特异度分别为 88.79%和 96.74%.结论 老年轻中度AD患者血清CAⅢ水平高于健康人群,轻度AD、不伴有抑郁情绪、血肌酐水平升高是老年AD患者血清CAⅢ水平升高的相关因素.血清CAⅢ可能成为老年轻中度AD患者诊断的新型生物学标志物.
Objective To explore the application value and related factors of serum carbonic anhydraseⅢ(CAⅢ)in the clinical diagnosis of mild to moderate Alzheimer disease(AD).Methods A total of 106 elderly patients initially diagnosed with mild to moderate AD at Huashan Hospital,Fudan University from October 2020 to November 2022 were enrolled as the AD group,and 89 healthy elderly people during the same period were enrolled as the control group.The serum biochemical indicators including liver and kidney function,blood lipids,blood glucose,folic acid and homocysteine were detected in both groups.Cognitive function was assessed by Mini-mental State Examination(MMSE).Patient Health Questionnaire-9(PHQ-9)and Generalized Anxiety Disorder-7(GAD-7)were used to assess psychological status.The activities of daily living(ADL)were assessed by modified Barthel Index(BI).Serum CAⅢlevels were measured by enzyme-linked immunosorbent assay(ELISA).Correlation analysis and multivariate linear regression analysis were used to identify factors influencing serum CAⅢlevels,and receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of serum CAⅢlevels in elderly patients with mild to moderate AD.Results The MMSE score of the AD group was significantly lower than that of the control group(P<0.001),and the PHQ-9 and GAD-7 scores were significantly higher than those of the control group(P<0.001).The serum CAⅢlevel in the AD group was significantly lower than that in the control group(P<0.000 1).In patients with AD,serum CAⅢlevels in patients with a disease course>3 years,accompanied by depression or anxiety,moderate AD,and serum creatinine≤111 μmol/L were significantly lower than those in patients with a disease course≤3 years,normal emotions,mild AD,and serum creatinine>111 μmol/L(P<0.05).Correlation analysis and multivariate linear regression analysis showed that serum CAⅢlevels were negatively correlated with disease duration,PHQ-9 score,GAD-7 scores and severity degree,positively correlated with serum creatinine level(P<0.05).The PHQ-9 score,severity degree,and serum creatinine level were independent related factors for serum CAⅢlevel in mild to moderate AD elderly patients(P<0.05).ROC curve result showed that the area under the curve(AUC)of serum CAⅢin diagnosing mild to moderate AD in elderly patients was 0.946,with sensitivity and specificity of 88.79% and 96.74%,respectively.Conclusions Serum CAⅢlevels in elderly patients with mild to moderate AD are higher than those in healthy individuals.Mild AD,without depressive mood,and elevated serum creatinine levels are related factors for elevated serum CAⅢlevels in elderly AD patients.Serum CAⅢmay serve as a novel biological marker for the diagnosis of mild to moderate AD in the elderly.
任姣錡;王锦秀;王剑涛;张颜莉;王雪纯;郭景春;周厚广
复旦大学附属华山医院老年医学科,国家老年疾病临床医学研究中心,上海 200040南京鼓楼医院全科医学科,南京 210008复旦大学医学神经生物学国家重点实验室,上海 200032
临床医学
阿尔茨海默病碳酸酐酶Ⅲ生物学标志物抑郁焦虑
Alzheimer diseasecarbonic anhydrase Ⅲbiomarkersdepressionanxiety
《中国临床医学》 2024 (005)
696-704 / 9
国家自然科学基金(81871098).Supported by National Natural Science Foundation of China(81871098).
评论