载脂蛋白Eε4基因型对阿尔茨海默病患者脑血流的影响分析

Analysis of the effect of apolipoprotein Eε4 genotype on cerebral blood flow in patients with Alzheimer's disease

目的分析载脂蛋白E(APOE)ε4基因型对阿尔茨海默病(AD)患者脑血流的影响。方法选择2020年4月至2021年4月深圳市罗湖区人民医院收治的AD患者31例为观察组;另选择同期认知功能正常的老年健康者25名为对照组。所有患者采用简明精神状态量表(MMSE)评估认知功能。采用经颅多普勒超声(TCD)检测颅内动脉的平均血流速度(MFV)和搏动指数(PI)。采用实时荧光定量聚合酶链式反应(qRT-PCR)检测AD患者的APOE基因型,分析APOEε4基因型对AD患者脑血流的影响。结果观察组双侧大脑中动脉(MCA)、大脑前动脉(ACA)、大脑后动脉(PCA)、椎动脉(VA)以及基底动脉(BA)的MFV均低于对照组,PI高于对照组,差异有统计学意义(P<0.05)。Pearson相关性分析结果显示,AD患者的MMSE评分与颅内动脉的MFV呈正相关(P<0.05),与PI呈负相关(P<0.05)。ROC曲线分析结果显示,颅内动脉的MFV和PI均有诊断AD的应用价值(P<0.05),各指标的AUC>0.70。31例AD患者中有26例患者行APOE基因检测,11例(42.31%)为APOEε4型。APOEε4型组的MMSE评分较非APOEε4型组低,差异有统计学意义[(19.50±8.62)分vs(24.15±5.14)分;t=2.322,P=0.030]。APOEε4型组颅内动脉的MFV较非APOEε4型组低,PI较非APOEε4型组高,差异均有统计学意义(P<0.05)。结论AD患者存在以MFV降低、PI升高为特征的脑血流动力学改变,认知功能损害程度与脑血流动力学变化显著相关,且携带APOEε4基因型可引起更严重的认知功能损害和脑血流动力学改变。

Objective To analyze the effect of apolipoprotein E(APOE)ε4 genotype on cerebral blood flow in patients with Alzheimer's disease(AD).Methods Thirty-one AD patients admitted to Shenzhen Luohu District People's Hospital from April 2020 to April 2021 were selected as the observation group,and other 25 elderly individuals with normal cognitive function during the same period were selected as the control group.Cognitive function was assessed by the Mini-mental State Examination(MMSE)scale in all the patients.The mean blood flow velocity(MFV)and pulsatility index(PI)of intracranial arteries were detected by transcranial Doppler sonography(TCD).The APOE genotype of the AD patients was detected by quantitative real-time polymerase chain reaction(qRT-PCR),and the effect of APOEε4 genotype on cerebral blood flow in the AD patients was analyzed.Results The MFV values of the bilateral middle cerebral artery(MCA),anterior cerebral artery(ACA),posterior cerebral artery(PCA),vertebral artery(VA)and basilar artery(BA)in the observation group were lower than those in the control group,and the PI of the observation group was higher than that of the control group,and the differences were statistically significant(P<0.05).The results of Pearson correlation analysis showed that the MMSE score of the AD patients was positively correlated with MFV of intracranial arteries(P<0.05),and negatively correlated with PI(P<0.05).The results of receiver operator characteristic(ROC)curve analysis showed that both MFV and PI of intracranial arteris had application value in the diagnosis of AD(P<0.05),and the AUC of each index was more than 0.70.Among the 31 AD patients,26 cases underwent APOE gene detection,of whom 11 cases(42.31%)were APOEε4 genotype.The MMSE scores of the APOEε4 genotype group were lower than those of the non-APOEε4 genotype group,and the differences were statistically significant[(19.50±8.62)points vs(24.15±5.14)points;t=2.322,P=0.030].The MFV of the intracranial arteries in the APOEε4 genotype group was lower than that in the non-APOEε4 genotype group,and the PI in the APOEε4 genotype group was higher than that in the non-APOEε4 genotype group,and the differences were statistically significant(P<0.05).Conclusion AD patients have cerebral hemodynamic changes characterized by decreased MFV and increased PI.The degree of cognitive impairment is significantly correlated with cerebral hemodynamic changes,and the patients carrying the APOEε4 genotype have more severe cognitive impairment and cerebral hemodynamic changes.