脑微出血β淀粉样蛋白阳性患者载脂蛋白E基因型及认知特点

Characteristics of apolipoprotein E genotype and cognitive impairment in patients with cerebral microbleeds and positive β amyloid

目的通过[18F]-AV45正电子发射计算机断层显像(PET)观察β淀粉样蛋白(Aβ)阳性的颅内微出血(CMBs)患者的载脂蛋白E(ApoE)基因型及认知特点。方法回顾性研究,连续入选2015年9月至2018年5月在中日友好医院神经内科记忆障碍门诊就诊,有认知障碍主诉且简易智能状态检查量表(MMSE)≤26分,蒙特利尔认知评估量表(MoCA)≤25分,且头MRI的SWI序列上有CMBs的患者152例。通过制定排除标准,最终入组69例,年龄(68.8±9.3)岁。进行认知量表测定、ApoE基因筛查及[18F]-AV45 PET检查后,分为Aβ阳性组37例、Aβ阴性组32例,入选同期体检中心健康老年人21例为对照组。比较3组入选者认知量表和ApoE基因结果。结果90例入选者ApoEε4型基因的阳性率35.6%(32例),Aβ阳性、阴性和对照组ApoEε4型基因阳性率分别为56.8%(21例)、18.8%(6例)、23.9%(5例),3组比较差异有统计学意义(χ^2=12.467,P<0.01);进一步两两比较,Aβ阳性组和对照组、Aβ阳性和阴性组间差异亦有统计学意义(χ^2值分别为5.880、10.407,P<0.05、P<0.01)。Aβ阴性组较阳性组深部微出血患者多[56.3%(18例)比8.1%(3例),χ^2=18.784,P<0.01],脑叶微出血少[12.5%(4例)比45.9%(17例),χ^2=9.066,P<0.01],混合型微出血差异无统计学意义(χ^2=1.556,P<0.05)。Aβ阳性组与对照组比较,所有认知领域差异均有统计学意义(均P<0.05),与阴性组患者比较记忆力、执行、视空间、和语言功能差异有统计学意义(均P<0.05)。而Aβ阴性组与对照组执行功能、视空间及注意力比较,差异有统计学意义(均P<0.05)。结论有Aβ沉积的CMBs患者其认知障碍损伤更广泛、更严重,且与ApoEε4等位基因的阳性有关。

Objective To analyze the characteristics of the apolipoprotein E(Apo E)genotype and cognitive impairment in patients with cerebral microbleeds(CMBs)and positiveβ-amyloid(Aβ)by using[18F]-AV45 positron emission tomography(PET).Methods From September 2015 to May 2018,152 patients with cognitive impairment and CMBs on the susceptibility-weighted imaging(SWI)sequence of head MRI at the neurology department of our hospital,assessed by mini-mental status examination(MMSE)score≤26 and Montreal cognitive assessment(MoCA)≤25,were consecutively recruited in this retrospective study.After assessment with the inclusion and exclusion criteria,69 patients aged 68.8±9.3 years were considered eligible for further analysis.Patients were divided into the Aβ-positive group(Aβ+Group,n=37)and the Aβ-negative group(Aβ-Group,n=32)after cognitive assessment,ApoE genotyping and[18F]-AV45 PET examination.Twenty-one healthy elderly controls(HC Group)who took health examination during the same period were enrolled.The results of cognitive assessment and Apo E genotyping were compared between the three groups.Results The positive rate of the ApoEε4 allele was 35.6%(32/90),56.8%(21/37),18.8%(6/32),and 23.9%(5/21)in the Aβ+,Aβ-and HC groups,respectively,with statistical significant differences between the groups(χ^2=12.467,P<0.01).There were significant differences in the positive rate of the ApoEε4 allele between the Aβ+and HC groups and between the Aβ+and Aβ-groups(χ^2=5.880 and 10.407,P<0.05 and P<0.01).The percentage of patients with deep cerebral microbleeds was higher(56.3%or 18/32 vs.8.1%or 3/37,χ^2=18.784,P<0.01)and of patients with lobar hemorrhage was lower(12.5%or 4/32 vs.45.9%or 17/37,χ^2=9.066,P<0.01)in the Aβ-group than in the Aβ+group,while there was no significant difference in the percentage of patients with mixed cerebral microbleeds between the Aβ-and Aβ+groups(χ^2=1.556,P>0.05).There were significant differences in cognitive function between the Aβ+and HC groups,in memory,executive function,visuospatial ability and language between the Aβ+and Aβ-groups,and in executive function,visuospatial ability and attention between the Aβ-and HC groups.Conclusions Cognitive impairment is more extensive and severe in CMBs patients with Aβdeposition and is associated with positive ApoEε4.