轻度脑白质病变工作记忆损伤的神经机制研究

White matter lesions (WMLs) are frequently seen in older people. In addition to normal aging, WMLs are also associated with stroke and dementia. WMLs can predict the risk of dementia, stroke and even death. WMLs may also predict the eventual conversion to mild cognitive impairment and Alzheimer’s disease (AD). The underlying neural mechanism of how WMLs affect the cognition is still controversial. One possible reason is, most existing studies of WMLs have focused on severe WMLs, but mild WMLs, which are clinically and fundamentally significant, have been largely neglected. There are a lot of confounding factors in severe WMLs, like stroke, AD and vascular dementia (VaD). One can hardly clarify the effects are from these diseases or WMLs itself. In this longitudinal study, we combined serial neuropsychological tests with multimodal Magnetic Resonance Imaging (MRI) to investigate the structural and functional change of working memory network in mild WMLs and the dynamic effect on working memory, taking advantages of its “pure” feature. This research has very important theoretical value to the future research on prevention and treatment of WMLs, as well as the related neurodegenerative diseases. The investigator of this study has research experience on cognitive neuroscience, brain imaging, and neurodegenerative diseases, and has 6 SCI research papers published as the first author, which will ensure the accomplishment of the current research.

老年人中常见的脑白质病变（WMLs）与年龄密切相关，会增加痴呆、中风及死亡的风险，也与阿尔茨海默病（AD）、轻度认知障碍（MCI）的转化有关。关于WMLs影响认知能力的神经机制充满了争议，其中一个主要的原因就是过去的研究几乎都集中在中重度WMLs患者中，混杂了中风、AD、血管性痴呆等其它复杂的疾病因素，也长期忽视了轻度WMLs的影响。本项目拟从轻度脑白质病变这个“单纯”的疾病模型入手，将神经心理学测验与多模态磁共振技术相结合，采用纵向追踪的实验设计，考察脑白质病变对工作记忆网络在结构与功能水平的改变,以及对工作记忆持续下降的动态影响。该项目的完成将有助于揭示WMLs的致病机制，对未来防治WMLs进展以及与之相关的神经退行性疾病都具有非常重要的理论价值和临床意义。申请人以第一作者身份发表SCI论文6篇，具有相关研究基础，能保证本项目顺利完成。

脑白质病变(white matter lesions, WMLs)与中风、阿尔茨海默病(Alzheimer’s Disease，AD)、血管性痴呆(Vascular Dementia, VaD)等密切相关，越来越被认识到是参与痴呆病因的主要血管性因素。AD发病率逐年增加，且隐匿起病持续进行性发展。研究发现WMLs可以预测痴呆的发病率，以及正常人向轻度认知障碍(mild cognitive impairment，MCI)、MCI向痴呆的转换。然而目前WMLs与工作记忆等认知能力之间的关系以及引发认知障碍的神经机制还不明确。本项目以老年人为研究对象，目标在于考察脑白质病变对工作记忆网络及工作记忆下降的影响，以及WMLs在结构与功能水平的改变，同时结合机器学习等方法建立认知功能预测模型。. 本项目在前期研究工作基础上建立了WMLs认知功能、多模态神经影像数据库，并在该数据库基础上对WMLs与工作记忆等认知功能的关系进行深入研究。项目团队评估了轻度WMLs对包括工作记忆在内的多项认知能力的影响，揭示了轻度WMLs患者工作记忆脑网络功能活动水平改变模式。项目团队还探索了不同认知障碍等级的WMLs灰质体积及静息态神经自发活动的改变模式，以及大脑功能及结构改变与工作记忆等认知功能损伤之间的联系，挖掘损伤的特征模式，有助于为将来AD的早期辅助诊断及认知功能的预测提供重要依据。此外，还分别基于临床数据与公开数据库数据开展了对WMLs认知障碍类型及程度的分类识别与预测研究，建立了WMLs认知障碍识别与预测模型。. 该项目的完成有助于揭示WMLs认知损伤的神经机制，可为临床辅助诊断提供有效的参考依据，对未来防治WMLs进展以及与之相关的神经退行性疾病都具有非常重要的理论价值和临床意义。