说汉语中国老人的遗忘型轻度认知功能障碍和阿尔茨海默病的弥散张量成像和神经语言学研究

发布时间：2018-08-01 13:20

【摘要】：第一部分阿尔茨海默病和遗忘型轻度认知功能障碍患者的弥散张量成像研究背景：随着磁共振新技术的不断进步,大脑白质(White Matter, WM)微结构的改变可以通过弥散张量成像的方法被探测。阿尔茨海默病(Alzheimer Disease, AD)的WM改变的规律还远未被阐明。研究的目的是为了了解在AD的疾病发展过程中,脑WM微结构在病程的不同阶段是如何改变的；脑WM微结构的改变和神经心理学量表各分值的关系；探测出在疾病早期就发生变化的WM区域,并讨论能反映WM变化的敏感参数。对以上问题的讨论和阐述,是为了能帮助临床医师发现找到诊断早期AD的敏感指标。从而能更早期地发现临床早期,甚至是临床前期的患者,进行早期药物干预,并帮助患者尽可能长地保留住认知功能,延缓疾病的进展,从而降低总体疾病负担。方法：研究对象共分为3组,AD组,遗忘型轻度认知功能障碍(amnestic Mild Cognitive Impairment, a-MCI)组和正常对照(Normal Control, NC)组。入组的被试均为小学以上文化程度,病前有汉语读写能力的成人。对这3组被试的进行磁共振弥散张量成像研究,和神经心理学检查。磁共振方面：利用1.5T的磁共振对3组被试大脑的各个兴趣区进行扫描,主要包括尾状核、壳核、额顶枕颞的WM、丘脑和扣带回的脑组织的各向异性值(fractional anisotropy, FA)平均表观弥散系数(mean apparent diffusion coefficient, ADC)进行评价;神经心理学方面是用简明心理状况量表(Mini-mental sate Exam, MMSE),临床痴呆量表(Clinical Dementia scale, CDR)和Alzheimer病评定量表(Alzheimer disease Assessment Scale, ADAS)进行评定。患者均来自于神经内科记忆障碍门诊,正常被试来自神经科招募的健康被试。共有47名患者符合入组标准：共有17名符合美国国立神经病和交流障碍与卒中以及Alzheimer病和相关疾病委员会(the National insititute of Neurological and Communicative disease and stroke and the Alzheimer's Disease and Related Disorders Association, NINCDS-ADRDA)有关AD的诊断标准中很可能AD,14名被试符合Peterson有关轻度认知功能障碍的诊断标准,其临床记忆分值低于同年龄同性别同教育程度对照组临床记忆量表1.5标准差,社会和日常生活能力未受损,纳入标准使用CDR,对得分为0.5分者,纳入MCI组。16名被试纳入NC组,NC组没有认知损害的症状和主诉,神经心理学量表正常范围,半年内头颅磁共振或CT检查未见明显异常。结果： 1.MCI组和AD组的ADAS分值与NC组相比,MCI组在词语回忆、命名、和词语再认的分值更高,而认知总分和ADAS总分更高,差异具有统计学意义。与NC组相比,AD组在ADAS测验中除了精神病表现分测验值无差异以外,所有分测验值都更高；与MCI组相比,AD组MMSE总分更低,ADAS量表中除了命名、意向性练习、口语能力、找词困难、口语理解能力、精神病表现得分和心境因子分无显著性差异以外MMSE总分、单词回忆、命令、结构性练习、定向力、单词辨认、回忆测验指令注意力因子分、记忆力总分、语言因子分、实践能力因子、激越因子、非认知总分、认知总分和ADAS总分均较MCI组升高,并有统计学意义。 2.MCI组和AD组的FA值与NC组相比,AD组在双侧额叶白质呈现更低的FA值,与MCI组比较,AD组在所有ROI的FA值2组无统计学差异。NC组和MCI组相比在各ROI的FA值无显著性差异。NC组和AD组相比在除了额叶白质以外的各个兴趣区的FA值均未显示出差异。 3.MCI组和AD组的ADC值与NC组相比,AD组在双侧额叶和前后扣带回的ADC值更高,有显著性差异。与MCI组相比,AD组在右前扣带回和左后扣带回纤维的ADC值更高。NC组和MCI组相比,在包括前后扣带回、胼胝体(corpus callosum,CC)部位和其他ROI均未显示出差异。 4ADAS的因子分和FA值之间相关性分析结果显示记忆力因子分与双侧尾状核,额叶,左枕叶,左顶叶,胼胝体压部,左颞叶,右前扣带回部位的FA值显著相关,实践因子分与尾状核,枕叶,左顶叶,胼胝体压部,右前扣带回显著相关,实践能力因子分与右侧尾状核，左枕叶，，左顶叶,左前扣带回显著相关,心境与左侧尾状核,额叶显著相关,激越与尾状核,右枕叶,右前扣带回显著相关,精神病因子分与左后扣带回显著相关。 5ADAS的因子分和FA值之间相关性分析各因子分与各ROI的ADC值的相关分析得出以下结果,记忆力总分与双侧尾状核,右额叶,胼胝体膝部,左枕叶,左顶叶,颞叶,前扣带回显著相关；语言因子分与双侧尾状核,额叶,胼胝体膝部,右枕叶,颞叶,右丘脑,前扣带回显著相关,实践能力总分与尾状核,额叶,胼胝体膝部,左顶叶,颞叶,左前扣带回显著相关；心境因子分与各个ROI的ADC值无显著相关；激越因子分与双侧尾状核,额叶,胼胝体膝部,左枕叶,右丘脑,颞叶,右前扣带回显著相关。精神病因子分与额叶,右丘脑显著相关。结论：结果显示DTI可以探测AD和MCI患者脑WM微结构的改变。通过ADC值探测扣带回和额叶WM微结构的变化,可能对诊断MCI和AD有帮助,随着病情的进展,受累的WM区域可以不局限在扣带回,可以累及其他脑叶的WM。本研究发现,在探测MCI和AD的WM演变过程中,ADC值有可能比FA值更敏感地反映病情的进程,与疾病的严重程度相关。在神经心理学研究中发现ADAS和MMSE均能反映病情的严重程度,但ADAS所探查的高级皮层功能更广泛,更能反映患者病情的变化,研究提示心境和精神病表现是比较后期出现的症状,在MCI和AD的早期和中期往往不受累。本研究通过因子分和弥散张量成像参数的相关性分析推测,探测双侧尾状核,额叶,左枕叶,左顶叶,胼胝体压部,左颞叶,右前扣带回部位的FA值和双侧尾状核,右额叶,胼胝体膝部,左枕叶,左顶叶,颞叶,前扣带回的ADC值对反映对反映患者认知功能神经心理学评定结果相关,说明在AD和MCI患者中这些部位WM微结构的改变与认知能力的改变有有密切的关系。这些WM在普通磁共振影像中时正常的,所以通过弥散张量成像能更敏感地探测WM微结构的改变,上述WM脑区的弥散张量的改变可能从某种程度上反映了被试认知功能的水平。弥散张量成像是一项客观检查,尤其适用于无法配合做神经心理学检查的患者,来帮助诊断a-MCI和AD。第二部分AD和遗忘型轻度认知功能障碍患者的汉语书写研究目的：研究说汉语的AD患者和轻度认知功能障碍患者的书写功能的变化,以及书写能力与认知的其他领域的相互关系以及变化的趋势。利用临床神经心理学方法对AD的汉语失语症进行研究,探索其与英语失语症的异同。方法：对47名被试,其中正常组16例,MCI组14例,以及AD组17例,对这些被试分别进行了MMSE, Alzheimer病评估量表(ADAS)和北大医院汉语失语检查。将书写的各因子分ADAS量表的各项分值进行比较。并对AD组患者的书写检查进行分析,讨论其不同于西语失语症的特点。结果：书写的各因子分与被试的年龄、性别、文化程度及是否患有糖尿病、高血压之间均无显著相关性。书写的各因子分与MMSE总分以及ADAS的各个认知因子分之间呈现极显著相关,但与非认知的因子分“心境”和“精神病表现”之间无显著相关。AD组书写各项分值与正常组和MCI组相比均存在显著性差异,MCI组和正常组相比,无显著性差异。AD的书写障碍出现了多种语言现象。结论：说汉语的AD和MCI患者的书写能力和ADAS的认知分值显著相关,提示书写能力受损与认知功能的减退的关系密切。说汉语的中国AD患者中构字障碍出现在疾病的不同时期,是最常见的书写障碍,而说英语患者的书写障碍早期表现为不规则词的拼写错误。而汉语没有不规则词的运用,呈现出汉语所特有的语言特征。这是写汉字和写英语的AD患者在失语症状学方面的区别。
[Abstract]:Part one diffusion tensor imaging study of Alzheimer's disease and amnestic mild cognitive impairment
Background:
With the development of new magnetic resonance technology, the changes in White Matter (WM) microstructures can be detected by diffusion tensor imaging. The regularity of WM changes in Alzheimer Disease (AD) is far from clarified. The purpose of this study is to understand the WM microstructure in the brain in the development of AD disease. The changes in the different stages of the process; the relationship between the changes in the WM microstructures of the brain and the scores of the neuropsychological scales; the detection of the WM region that changed in the early stage of the disease and the discussion of the sensitive parameters that can reflect the changes in the WM. The discussion and exposition of the above problems are designed to help clinicians find the sensitivity to the early diagnosis of the early diagnosis of AD. Indicators. Early detection of early clinical and even preclinical patients can be used to intervene early and help patients retain their cognitive functions as long as possible and delay the progression of the disease, thereby reducing the overall burden of disease.
Method:
The subjects were divided into 3 groups, AD group, amnestic Mild Cognitive Impairment, a-MCI group and normal control group (Normal Control, NC). The subjects in the group were all the above primary school education, and the adults who had the ability to read and write Chinese before the disease. The 3 groups were studied by magnetic resonance diffusion tensor imaging and God. Psychologic examination. Magnetic resonance: 1.5T magnetic resonance (MRI) was used to scan various regions of interest of the 3 groups of subjects, including the caudate nucleus, the putamen, the WM of the frontal occipital temporal, the anisotropic values of the brain tissue of the thalamus and cingulate gyrus (fractional anisotropy, FA), the average apparent diffusion coefficient (mean apparent diffusion coefficient, ADC). The neuropsychological aspects were evaluated with the Mini-mental sate Exam (MMSE), the clinical dementia scale (Clinical Dementia scale, CDR) and the Alzheimer disease assessment scale (Alzheimer disease Assessment).
All the patients were from the neurology department of memory disorders, and normal subjects were recruited from the Department of Neurology. A total of 47 patients met the standard of entry. A total of 17 were in line with the national neuropathy and communication disorders and stroke, and the the National Insititute of Neurological and Communicative. Disease and stroke and the Alzheimer's Disease and Related Disorders Association, NINCDS-ADRDA) the diagnostic criteria of the 14 subjects were in accordance with the diagnostic criteria for mild cognitive impairment. The clinical memory score was lower than the same age homosexual and educational control group clinical memory scale 1.5. The standard deviation, the social and daily life ability was not damaged, included in the standard use of CDR, the score of 0.5 points, included in group MCI.16 subjects into the NC group, NC group no symptoms and complaints of cognitive impairment, the normal range of neuropsychological scale, half of the head magnetic resonance or CT examination no significant abnormalities in half a year.
Result:
ADAS score of 1.MCI group and AD group
Compared with the NC group, the score of the MCI group was higher in terms of word memory, naming and word recognition, while the total score of cognition and the total score of ADAS were higher, and the difference was statistically significant. Compared with the NC group, the AD group was higher in all the subtests in the ADAS test than in the psychosis performance test. Compared with the MCI group, the total MMSE score of the AD group was lower, ADAS. Besides naming, intentional exercise, oral ability, difficulty finding words, oral comprehension, psychosis scores and mood factors, there were no significant differences in MMSE total score, word recall, command, structural exercise, orientation, word recognition, memory test instruction attention factor, memory score, language factor, practical ability. The total score of cognition and total score of ADAS were higher than those of MCI group, and there was statistical significance.
The FA value of the 2.MCI group and the AD group
Compared with the NC group, the AD group showed a lower FA value in the bilateral frontal lobes. Compared with the MCI group, there was no statistical difference between the AD group and the AD group in the FA value of all ROI. There was no significant difference between the.NC group and the MCI group in the FA value of the ROI, compared with the MCI group.
The ADC value of the 3.MCI group and the AD group
Compared with the NC group, the ADC value of the AD group was higher in the bilateral frontal and posterior cingulate gyrus. Compared with the MCI group, the ADC value of the AD group in the right anterior cingulate gyrus and the posterior cingulate gyrus was higher in the.NC group than in the MCI group, and there was no difference between the anterior cingulate gyrus, the corpus callosum (corpus callosum, CC), and the other ROI.
Correlation analysis between the factor of 4ADAS and the value of FA
The results showed that the memory factor was significantly related to the FA value of the bilateral caudate nucleus, frontal lobe, left occipital lobe, left parietal lobe, corpus callosum pressure, left temporal lobe and right anterior cingulate gyrus. The practical factor was significantly related to caudate nucleus, occipital lobe, left parietal lobe, corpus callosum pressure, right anterior cingulate gyrus, left occipital lobe, left parietal lobe, left anterior lobe. The cingulate gyrus was significantly correlated with the left caudate nucleus and the frontal lobe, which was significantly related to the caudate nucleus, the right occipital lobe and the right anterior cingulate gyrus, and the psychosis factor was significantly related to the left posterior cingulate gyrus.
Correlation analysis between the factor of 5ADAS and the value of FA
The correlation analysis between the factors and the ADC values of each ROI showed that the total memory score was significantly related to the bilateral caudate nucleus, the right frontal lobe, the genu of the corpus callosum, the left occipital lobe, the left parietal lobe, the temporal lobe, and the anterior cingulate gyrus; the language factor was significantly related to the bilateral caudate nucleus, the frontal lobe, the corpus callosum, the right occipital lobe, the temporal lobe, right thalamus, and the anterior cingulate gyrus. The total score is significantly related to the caudate nucleus, the frontal lobe, the genu of the corpus callosum, the left parietal lobe, the temporal lobe and the left anterior cingulate gyrus, and there is no significant correlation between the mood factor and the ADC value of each ROI; the score of the shock factor is significantly related to the bilateral caudate nucleus, the frontal lobe, the genu of the corpus callosum, the left occipital lobe, the right thalamus, the temporal lobe, and the right anterior cingulate gyrus. Relevant.
Conclusion:
The results show that DTI can detect changes in the WM microstructures in the brain of patients with AD and MCI. Detection of the changes in the cingulate gyrus and the WM microstructures of the frontal cortex by ADC may be helpful for the diagnosis of MCI and AD. As the condition progresses, the WM region involved is not limited to the cingulate gyrus, and the WM. of the other brain may be involved in the detection of MCI and AD. In the process, the ADC value may be more sensitive than FA to reflect the progression of the disease, which is related to the severity of the disease. In the neuropsychological study, both ADAS and MMSE are found to reflect the severity of the disease, but the advanced cortex function explored by ADAS is more extensive and more capable of reflecting the changes in the patient's condition. The study suggests that mood and mental symptoms are compared. Symptoms at later stages are often not involved in the early and middle stages of MCI and AD.
In this study, we speculated that the FA value of bilateral caudate nucleus, frontal, left occipital lobe, left parietal lobe, left parietal lobe, left parietal lobe, left temporal lobe, right anterior cingulate cortex, right frontal lobe, right frontal lobe, corpus callosum, left occipital lobe, left parietal lobe, left parietal lobe, left parietal lobe, temporal lobe and anterior cingulate gyrus were reflected to reflect the ADC value of the patients. The results of cognitive functional neuropsychological assessment are related, indicating that there is a close relationship between the changes of WM microstructures in these sites and changes in cognitive ability in AD and MCI patients. These WM are normal in common magnetic resonance imaging, so the change of the microstructures of WM can be detected more sensitively by diffusion tensor imaging, and the diffusion tensor of the above WM brain regions is more sensitive. The change may reflect the cognitive function of the subjects to some extent.
Diffusion tensor imaging (DTI) is an objective examination, especially suitable for patients who can not cooperate with neuropsychological examination to help diagnose a-MCI and AD.
The second part is the study of Chinese writing in AD and amnestic mild cognitive impairment patients.
Objective:
The study of the changes in writing function of Chinese AD patients and patients with mild cognitive impairment, as well as the relationship between writing ability and other areas of cognition, and the trend of change. The study of Chinese aphasia in AD by clinical neuropsychological methods was used to explore the similarities and differences between the Chinese aphasia and English aphasia.
Method:
In 47 subjects, 16 cases in normal group, 14 cases in group MCI, and 17 cases in group AD, the subjects were examined by MMSE, Alzheimer disease assessment scale (ADAS) and Chinese aphasia in Peking University Hospital. The scores of each factor ADAS scale were compared. The writing examination of the patients in the AD group was analyzed to discuss the difference from the western language loss. The characteristics of the language disorder.
Result:
There was no significant correlation between the factors of writing and the age, sex, educational level, diabetes and hypertension. There was a very significant correlation between the factors of writing and the total scores of MMSE and the cognitive factors of ADAS, but there was no significant difference between the "mood" and "psychosis" of non cognitive factors. There were significant differences in the scores between the.AD group and the normal group and the MCI group. Compared with the normal group, there was no significant difference between the MCI group and the normal group, and there was a variety of language phenomena in the writing barrier of.AD.
Conclusion:
The writing ability of Chinese AD and MCI patients is closely related to the cognitive score of ADAS, suggesting that the impairment of writing ability is closely related to the impairment of cognitive function. The spelling of words is wrong. But in Chinese, there is no use of the irregular words, which presents the characteristic of the Chinese language. This is the difference between the AD patients who write and write English in aphasia.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R749.16

【参考文献】