ApoE基因及脑结构改变对中枢神经系统脱髓鞘疾病认知障碍的作用机制探讨

发布时间：2019-06-29 19:29

【摘要】：多发性硬化(MS)和视神经脊髓炎(NMO)是两种较常见的中枢神经系统脱髓鞘疾病。除运动、感觉及视力障碍等异常表现外,半数患者存在认知障碍,其可能是多因素作用的结果。其中,载脂蛋白E(ApoE)ε4基因可能参与MS认知障碍的形成,而关于MS和NMO认知障碍是脑白质还是灰质病变引起尚有争议。本文采用基因检测联合多模态MRI技术的方法旨在进一步研究中枢神经系统脱髓鞘疾病认知障碍形成的相关机制以便采取针对性的干预措施。研究内容：研究一、评估MS患者认知功能、确定ApoE基因型并采用弥散张量成像联合体素形态学定量分析脑白质及灰质的改变,探讨基因对认知及脑内结构是否有影响,以及不同认知水平的患者脑内结构是否有差别。研究二、评估NMO患者认知功能并进行影像学检查,分析NMO患者认知功能的特点以及可能导致认知改变的脑内结构基础。结果：研究一、1)MS患者信息处理速度和工作记忆比对照组下降。学习年限、扩展残疾度(EDSS)、焦虑(HAMA)及抑郁(HAMD)评分与多项认知评分相关,年龄与语言流畅性相关,病程与语言记忆相关。患者脑白质的微结构存在广泛性破坏；左侧扣带回、右侧岛叶、额下回及额中回灰质密度减少。2)MS认知障碍(CI)组14例(35.9%),认知保留(CP)组25例。相比CP组,CI组的学习年限低,EDSS、HAMA及HAMD评分高,其语言流畅性、信息处理速度、视觉记忆及执行功能均较差。CI组患者存在广泛白质完整性破坏；其双侧尾状核、左侧岛叶及右侧颞极灰质密度减少。EDSS评分是MS认知障碍形成的危险因素。3)10例(25.64%)MS患者APOEε4基因阳性,余29例阴性,基因阳性组的情景记忆、信息处理速度及工作记忆较差。两组间脑白质弥散参数及灰质密度均无明显差别。研究二、1)NMO患者信息处理速度和工作记忆较对照组差。学习年限与所有认知评分相关,病程与情景记忆相关,HAMD评分与执行功能相关。2)NMO患者存在广泛的脑白质微观结构破坏,其脑灰质密度无明显变化。结论：①MS和NMO患者均可出现认知功能改变。MS患者的认知损害可能与白质髓鞘的脱失以及灰质密度的降低有关,而NMO的可能仅与白质脱髓鞘有关,未发现灰质密度变化。②MS患者无论ApoEε4基因阳性与否,其脑内白质及灰质病变程度相似,但基因阳性的认知损害更重,ApoEε4基因可能参与认知障碍的形成。
[Abstract]:Multiple sclerosis (MS) and optic neuromyelitis (NMO) are two common demyelination diseases of central nervous system. In addition to abnormal manifestations of motor, sensory and visual impairment, half of the patients had cognitive impairment, which may be the result of multiple factors. Among them, apolipoproteins E (ApoE) 蔚 4 gene may be involved in the formation of MS cognitive impairment, and it is controversial whether MS and NMO cognitive impairment is white matter or gray matter disease. In this paper, gene detection combined with multimodal MRI was used to further study the mechanism of cognitive impairment in central nervous system demyelination disease in order to take targeted intervention measures. Study 1. To evaluate the cognitive function of MS patients, to determine the ApoE genotype and to quantitatively analyze the changes of white matter and gray matter by diffusion tensor imaging combined with morphology. to explore whether genes have effects on cognition and brain structure, and whether there are differences in brain structure in patients with different cognitive levels. In the second study, the cognitive function of NMO patients was evaluated and the imaging examination was performed to analyze the characteristics of cognitive function of NMO patients and the structural basis of brain which may lead to cognitive changes. Results: 1. 1) the speed of information processing and working memory in patients with MS were lower than those in the control group. Learning years, extended disability (EDSS), anxiety (HAMA) and depression (HAMD) scores were correlated with multiple cognitive scores, age and language fluency, and the course of disease was related to language memory. The gray matter density of left cingulate gyrus, right insular lobe, inferior frontalis and middle frontal gyrus decreased. 2) there were 14 cases (35.9%) in MS cognitive impairment group and 25 cases in cognitive retention (CP) group. Compared with CP group, CI group had lower learning years, higher EDSS,HAMA and HAMD scores, poor language fluency, information processing speed, visual memory and executive function. The density of gray matter in bilateral caudate nucleus, left insular lobe and right temporal pole decreased. EDSs score was a risk factor for the formation of cognitive impairment in MS. 3) 10 cases (25.64%) of MS patients were APOE 蔚 4 gene positive, the remaining 29 cases were negative, the situational memory, information processing speed and working memory of gene positive group were poor. There was no significant difference in white matter diffusion parameters and gray matter density between the two groups. Study 2, 1) the information processing speed and working memory of NMO patients were worse than those of the control group. The length of study was correlated with all cognitive scores, the course of disease was correlated with situational memory, and the HAMD score was correlated with executive function. 2) there was extensive damage to the microstructure of white matter in patients with NMO, and there was no significant change in gray matter density. Conclusion: cognitive function changes can occur in both 1MS and NMO patients. The cognitive impairment of MS patients may be related to the loss of white matter myelin sheath and the decrease of gray matter density, while the NMO may only be related to white matter demyelination, and no change of gray matter density is found. 2When ApoE 蔚 4 gene is positive or not, the degree of white matter and gray matter lesions in the brain is similar, but the gene positive cognitive damage is more serious. ApoE 蔚 4 gene may be involved in the formation of cognitive impairment.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R744.5

【相似文献】