汉语肌萎缩侧索硬化患者语言障碍的脑结构与功能网络研究

Amyotrophic lateral sclerosis is a progressive neuro-degenerative disorder with poor prognosis. Cognitive disorder associated with ALS has attracted more and more attention because it could accelerate disease progression and increase caregiver burden. Recent studies have revealed great heterogeneity in cognitive symptoms of ALS, and language impairment could be an important subtype of it. However, research methods and conclusions of foreign studies could not be applied to Chinese patients directly due to the differences of language system and culture background. And this has adversely affected clinical diagnosis, treatment and making caring strategy for Chinese patients. We have previously established a cognitive assessment system suitable for ALS patients with Mandarin. Based on this system, we have found a relatively high proportion of cognitive impairment in Chinese ALS patients, and part of them presented with prominent language impairment. We aimed to further explored its underlying mechanism through following approaches: 1. systematically describe characteristics of language impairment in ALS patients with Mandarin; 2. explain its neuropsychological mechanism by the method of correlation analysis between language evaluation and results from other cognitive domains; 3. identify the responsible brain area and associated brain network change of language impairment through multimodal magnetic resonance imaging, and make network map for Chinese patients. By these efforts, we hope to provide clues for future pathogenesis study and new therapy development.

肌萎缩侧索硬化（ALS）是进行性加重的神经系统变性病，预后较差，而ALS相关的认知障碍因可加速疾病进展、加重照料者负担而日益引起关注。近期研究表明，ALS相关的认知症状具有较大异质性，语言障碍是其重要的表现形式。然而，由于语言及文化背景的差异，国外的研究方法与结论并不适用于中国患者，这妨碍了国人患者的临床诊治及照料策略的制定。申请人前期已构建了适合汉语ALS患者的认知评价系统，并且发现中国患者合并认知障碍比例较高，部分患者语言功能损害突出。在此基础之上，我们拟进一步深入探索其机制：1.系统描述汉语ALS患者语言障碍特征；2.将语言功能评价结果与其他认知域测验进行相关性分析，详解其神经心理学机制；3.运用多模式磁共振技术，发现汉语ALS患者语言障碍的责任脑区及相关的脑功能网络改变，绘制适合国人的功能网络图谱。通过这些，我们旨在为ALS的发病机制研究以及新治疗靶点的开发提供线索。

肌萎缩侧索硬化（ALS）是进行性加重的神经系统变性病，预后较差，而ALS相关的认知障碍因可加速疾病进展、加重照料者负担而日益引起关注。近期研究表明，ALS相关的认知症状具有较大异质性，语言障碍是其重要的表现形式。然而，由于语言及文化背景的差异，国外的研究方法与结论并不适用于中国患者，这妨碍了国人患者的临床诊治及照料策略的制定。本研究拟系统描述汉语ALS患者语言障碍特征；将语言功能评价结果与其他认知域测验进行相关性分析，详解其神经心理学制；同时运用多模式磁共振技术，发现汉语ALS患者语言障碍的责任脑区及相关的脑功能网络改变。研究结果表明：中国散发型ALS 患者中，约有19.7%合并认知功能异常，其中执行功能障碍是主要类型。本研究同时构建了适合国人的ALS筛查体系，应用ALS版额叶行为量表（ALS-FBI）、额叶评估量表（FAB）及简易精神状态量表（MMSE）或蒙特利尔认知评估（MoCA）可有效筛查ALS相关的认知与行为障碍以及ALS伴额颞叶变性（ALS-FTLD）。敏感性可达90%以上，特异性波动与40%~50%左右。汉字的失语性失写是中国患者特征性的语言障碍模式。