ApoE-ε4等位基因对遗忘型轻度认知障碍患者认知功能及静息态功能MRI影响的前瞻性队列研究  

The effects of ApoE epsilon4 alleles on cognitive function and resting-state functional MRI in patients with amnestic mild cognitive impairment:a prospective cohort study

作　　者：王晓妮[1] 孙宇[1] 陈观群 盛灿 李轩宇[1] 李瑜霞[1] 杜文莹 王小琪 夏明睿[2] 韩璎[3] Wang Xiaoni;Sun Yu;Chen Guanqun;Sheng Can;Li Xuanyu;Li Yuxia;Du Wenying;Wang Xiaoqi;Xia Mingrui;Han Ying(Department of Neurology,Xuanwu Hospital of Capital Medical University,Beijing 100053,China;State Key Laboratory of Cognitive Neuroscience and Learning&IDG/McGovern Institute for Brain Research,Normai University,Beijing 100875,China;Department of Neurology,Xuanwu Hospital of Capital Medical University,Center of Alzheimer Disease,Beijing Institute for Brain Disorders,National Clinical Research Center for Geriatric Disorders,National Clinical Research Center for Geriatric Disorders(Xuanwu Hospital)-Alliance for Preclinical Alzheimer Disease in China,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院神经内科,北京100053 [2]北京师范大学认知神经科学与学习国家重点实验室&IDG/麦戈文脑科学研究院,100875 [3]首都医科大学宣武医院神经内科北京脑重大疾病研究院阿尔茨海默病研究所国家老年疾病临床医学研究中心国家老年疾病临床医学研究中心(宣武医院)-中国AD临床前期联盟,100053

出　　处：《中华放射学杂志》2020年第1期10-16,共7页Chinese Journal of Radiology

基　　金：国家重点研发计划(2016YFC1306300);国家自然科学基金(61633018,81430037,81801052,31371007,30970823);中国博士后基金(2018M641414);北京市自然科学基金(7161009);老年重大疾病关键技术研究(PXM2019_026283_000002)。

摘　　要：目的采取前瞻性队列研究探讨ApoE-ε4等位基因对遗忘型轻度认知障碍(aMCI)患者认知功能和静息态功能MRI(rs-fMRI)的影响。方法2009年9月至2015年11月对16例携带ApoE-ε4基因的aMCI患者(aMCI-ε4组)和24例非携带ApoE-ε4基因的aMCI患者(aMCI-nonε4组)进行前瞻性研究。两组受试在基线期和随访期完成成套的神经心理测评和rs-fMRI影像数据采集。进一步对rs-fMRI数据采用基于种子点功能连接分析方法,以左侧内侧前额叶(mPFC)和后扣带回(PCC)为种子点,计算两组患者基线期和随访期种子点的全脑功能连接。对有差异的脑区进行两因素(随访时间和ApoE-ε4等位基因)重复测量方差分析。两组人群的痴呆转化率比较采用卡方检验,对功能连接和临床资料等计量资料进行正态分布分析,服从正态分布,采用双样本t检验,不服从正态分布,采用Mann-Whitney秩和检验。最后采用一般线性模型对有组间差异脑区的功能连接值变化与神经心理测评结果变化进行相关性分析,及与ApoE基因的交互效应。结果(1)基线期和随访期aMCI-ε4组记忆功能均显著低于aMCI-nonε4组,aMCI-ε4组随访期内转化率(14/16)高于aMCI-nonε4组(13/24,χ2=4.862,P=0.027);(2)两组人群基线期功能连接无显著差异,随访期aMCI-ε4组左侧后扣带回和左侧角回之间的功能连接(0.23±0.11)显著高于aMCI-nonε4组(-0.03±0.13,t=4.800,簇大小1944 mm3,P=0.004),左侧内侧前额叶和左侧角回之间的功能连接(0.33±0.21)显著高于aMCI-nonε4组(-0.08±0.18,t=5.040,簇大小1836 mm3,P=0.006);重复测量方差提示随访时间与ApoE-ε4等位基因的交互作用对左侧PCC(F=10.833,P=0.002)和左侧mPFC(F=7.280,P=0.010)与角回功能连接的影响有统计学意义;(3)aMCI-ε4组左侧内侧前额叶皮层与左侧角回间功能连接的变化与即刻回忆评分变化显著正相关(r=0.692,P=0.018),aMCI-nonε4组中未发现显著相关性(r=-0.198,P=0.417),交互效应显著(F=8Objective To explore the effects of ApoE epsilon4(ApoE-ε4)alleles on cognitive function and resting-state functional MRI(rs-fMRI)in patients with amnestic mild cognitive impairment(aMCI)based on a prospective cohort study.Methods An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI.Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up.All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI.Two core regions of the default mode network(DMN),the left posterior cingulate cortex(PCC)and the medial prefrontal cortex(mPFC),were selected as seeds to calculate the functional connectivity.Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers,nonε4-carriers),interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test.For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up,the normal distribution test was carried out first.If the normal distribution was fitted,the two-sample t test was used,otherwise,the Mann-Whitney rank sum test was used.Finally,the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect.Results (1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up.The ApoE-ε4-carriers(14/16)presented a higher conversation rate than non-carriers(13/24,χ2=4.862,P=0.027)at follow-up.(2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular(ApoE-ε4-carriers:0.23�

关 键 词：阿尔茨海默病 认知障碍 载脂蛋白E3 磁共振成像 神经网络(计算机) 

分 类 号：R749.1[医药卫生—神经病学与精神病学] R445.2[医药卫生—临床医学]