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MCI认知损伤的特征及其早期识别体系的探索
其他题名Exploring the Cognitive Impairment Features and the Early Detection System for MCI
喻婧
学位类型博士
导师李娟
2012-05
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
关键词轻度认知障碍 早期识别 蒙特利尔认知量表 内源性甲醛 Fmri
摘要在过去的十年里,关于认知障碍研究的核心发生了重大转移。从对痴呆的病理和生化机制的研究逐渐转向了对其前临床期——轻度认知障碍(Mild Cognitive Impairment, MCI)的识别及干预。老年认知功能障碍的发展是个长期的过程,可能在临床前数年或数十年即已开始。在疾病进展的后期,特别是发生痴呆后再开始治疗,虽仍可能延缓认知功能衰退的进程,但已有的损害不能再逆转。如果能在临床诊断之前尽早发现潜在患者,延缓其转化为痴呆的速度甚至维持其认知稳定将极大地提高患者的精神健康和生活质量,减少家庭和政府的开支。 从多维度研究识别轻度认知障碍患者以及对痴呆病程敏感的指标已经成为国际该领域的一大热点。现有的MCI和轻度痴呆的识别和诊断方法主要有临床问诊、神经心理学筛查、功能影像学分析、以及生化学标记四类方法。每种技术和方法在区分认知正常、轻度认知障碍和痴呆人群上都有各自的优势和劣势。现在还没有一种方法可以独立地作为整个病程的单一指标而存在。 本研究依托课题组与上海交通大学附属精神卫生中心联合主持的国家科技支撑计划项目——中国老年心理问题的评估、预警与干预示范研究,获得了一批基于社区老人大样本取样的数据(n=1056, 其中临床诊断为认知正常老人865人,MCI老人115人,痴呆21人,其他45人),包含神经心理学筛查、医师评定、血常规、尿检以及部分被试的影像学数据,这为我们研究识别MCI的指标体系提供了可能。本文通过三个研究分别探讨生化学标记(内源性甲醛)、简易认知筛查量表(蒙特利尔认知量表)以及功能影像学指标(延迟匹配任务)在识别轻度认知障碍中的作用。我们假设:在基于社区的大样本MCI筛查过程中,首先使用方便快捷的外周生化学标记进行初步筛查,再在检出的可疑人群中进行一对一的神经心理学细筛,最后对细筛检出的个体进行功能影像学确诊,这样的理想流程会极大提高MCI识别的效率和准确率。 研究一通过对大样本社区老人尿甲醛的定量分析,考察内源性甲醛与认知功能之间的关系。研究结果显示,人体内源性甲醛与综合认知能力负相关,且该相关受到个体受教育水平的调节。但由于内源性甲醛在人群中识别MCI的效度较低,且影响因素尚待考察,目前而言暂不适合推荐作为临床诊断MCI的生化学指标。研究二考察北京版蒙特利尔认知量表(Beijing Version of the Montreal Cognitive Assessment, MoCA-BJ)在城市和农村社区老年群体中识别MCI个体的敏感性和特异性,并对该量表进行项目分析、临界值界定、地区差异分析,以及与简易智能精神状态量表(MMSE)进行比较。结果表明在中国老年人样本中MoCA-BJ筛查MCI具有较高的敏感性,但特异性较低,可以推荐给临床医师在诊断中参考使用。MoCA-BJ中有的项目受教育影响较大或具有文化特异性,对这些项目进行符合中国老年人的本土化修订,预期会大幅提升其在中国MCI筛查中的准确性。研究三采用延迟匹配任务范式(Delayed-match-to sample task, DMST)考察MCI被试外显和内隐记忆的神经机制,计算任务下脑激活和行为成绩的相关,同时考察轻度认知障碍对脑区功能连接的影响。研究结果发现轻度认知障碍老人外显记忆受损,内隐记忆相对保留。以组间差异最大的,负责执行操作的尾状核和负责控制提取的左侧额下回的激活值作为中枢指标,区别MCI组个体和正常对照组个体的敏感性和特异性分别能达到90%和70%以上。 在本研究中,由于内源性甲醛作为识别MCI的外周生化学标记需要进一步考察验证,MoCA-BJ个别项目尚需修订,我们综合三个维度的指标并没有发现比单一指标更高的筛查敏感性和特异性。在今后的研究中,细化和控制内源性甲醛的影响因素或探索更为稳定的外周生化指标、修订蒙特利尔认知量表,辅以功能影像学中枢指标,预期能进一步提高中国老年人轻度认知障碍识别的准确率。同时研究对深入理解MCI的认知损伤机制亦有贡献:认知能力与个体内源性甲醛含量呈负相关;情节记忆是MCI最先发生变化且最为敏感的认知维度;MCI外显记忆受损,内隐记忆相对保留。
其他摘要In the past ten years, a major transition of the research interests in cognitive impairment field has taken place, from the investigation of the pathological and biochemical mechanisms to the detection and prevention of the mild cognitive impairment (MCI), the preclinical stages of dementia. The development of elderly cognitive impairment could be a long process, probably beginning years before the clinical symptoms. Most investigators believe that if we wait for functional impairment, and perhaps even mild cognitive symptoms, to emerge, it may be too late to treat the underlying disease process. Ideally, if we could detect and prevent or postpone the disease process by intervening early, we could largely improve the life quality of the patients and reduce the expenses for both government and family per se. Exploring the sensitive makers for MCI detection from multi-dimensional and levels has become the hot issues in worldwide. There are four dimensions to detect MCI and early dementia: clinical scales, neuropsychological tests, neuroimaging, and biomarkers. As such, certain markers may be differentially sensitive and informative at different stages in the underlying progression of the diseases. No single measures will be uniformly predictive throughout the entire disease process. The present research based on the National Key Technology R&D Program of China directed by both Shanghai Mental Health Center and our lab: Mental health evaluation, warning system and intervention project on Chinese older adults. This project is a population-based study, including neuropsychological tests, clinical diagnosis, serial blood, urine samples and when applicable, neuroimaging examinations. This large database provides us the possibilities to investigate the different markers for Chinese MCI detection. In present study, we investigate the accuracy of biomarker (endogenous formaldehyde), brief neuropsychological test (Beijing version of Montreal cognitive assessment), and neuroimaging (delayed-match-to sample task, DMST) to screen the MCI in Chinese older adults. Our hypothesis is, if we use the convenient biomarkers from peripheral nervous system to do the initial screen, and use the neuropsychological test to do the individual screening for the potential subjects who was detected by the initial screening, and finally we use neuroimaging examination to diagnose every single patient. From these processes, the accuracy of the detection will be much more improved and more efficient. In studyⅠ, we analyzed formaldehyde level by high-performance liquid chromatography to investigate the correlation of endogenous formaldehyde in urine of older adults and their cognitive ability. The results showed the endogenous formaldehyde was negatively correlated with general cognitive ability, and this correlation was moderated by individual’s educational level. Because of the instability of human’s endogenous formaldehyde, this biomarker from peripheral nervous system was not suitable for using in the diagnosis of MCI at this point of time. In study Ⅱ, we examined the sensitivity and specificity of MoCA-BJ screening for MCI in a community-based population residing in both urban and rural areas of Beijing. Moreover, detailed analyses including item analysis, examination of the optimal cut-off scores, area analysis, and the comparison with the MMSE were performed. The MoCA-BJ, in general, is a relatively mediocre screening tool for detecting MCI and could be recommended to clinicians for reference. Specific items of MoCA-BJ limited by culture and education should be modified in the future to achieve more ideal detection performance of MCI. In study Ⅲ, we used functional MRI (fMRI) to examine the brain activations and brain functional connectivity in specific regions while the subjects are performing the DMST which included both explicit and implicit memory, and further to find out how the mild cognitive impairment affected in these activations and connectivity. The results showed the MCI group demonstrated impaired explicit memory, but relatively intact implicit memory (distractor repetition). Using the most impaired activation changes in caudate and left inferior frontal gyrus as the central nervous markers, the sensitivity and specificity for MCI detection can reach to 90% and 70%, respectively. In current studies, due to the instability of endogenous formaldehyde as the biomarker from peripheral nervous system, and the MoCA-BJ in which some items still need further modification, we didn’t find much better indexes for MCI screening accuracy when combined the three markers. In future research, we can investigate some other biomarkers with more stable and sensitive characteristics, combined with modified MoCA-BJ and suitable fMRI tasks. In this way, we could expect much more improvement in the accuracy of Chinese elderly MCI screening.
学科领域发展与教育心理学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/20441
专题认知与发展心理学研究室
作者单位中国科学院心理研究所
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喻婧. MCI认知损伤的特征及其早期识别体系的探索[D]. 北京. 中国科学院研究生院,2012.
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