轻度认知障碍和皮层下血管性认知障碍的共病机制探讨--基于遗传基础及神经影像环路机制的研究

Mild cognitive impairment (MCI) and subcortical vascular cognitive impairment (SVCI) are associated with the high risk of Alzheimer's disease (AD). These genes of lipid metabolism, vascular and inflammatory pathway may be involved in the clinical phenotype and the conversion of AD in MCI and SVCI. Therefore, it is urgent for the researchers to explore the association mechanism of genetic factors and cognitive dysfunction. Based on our previous findings of MCI and the combination of full-scale neuropsychological tests and multi-modality fMRI, this project will explore the characteristics of abnormal brain structural and functional networks which are associated with the effects of these pathway genes in MCI, SVCI and healthy control group of Chinese Han population. This is the first study to reveal the topologically convergent and divergent patterns of structural and functional networks between MCI and SVCI patients. Furthermore, we want to elucidate the genetic factors and their interactions in the neuropathological mechanism of cognitive dysfunctions, which could provide theoretical basis of comorbidity and characteristic endophenotype between MCI and SVCI and important biological indicators in the early diagnosis, prognosis and treatment of AD.

轻度认知障碍（MCI）和皮层下血管性认知障碍（SVCI）具有阿尔茨海默病（AD）转化的风险。脂质代谢通路、血管源性通路和免疫炎症通路相关易感基因可能与MCI和SVCI的临床表型有关，并与AD转化关系密切，明确遗传因素与认知功能障碍关联机制是本领域亟待解决的科学问题。本研究团队将基于在MCI 研究领域的前期积累，结合多维度认知神经心理评估和多模态功能磁共振成像（fMRI），在中国汉族人群中同期选择MCI 、SVCI及匹配的健康对照组重点探讨脂质代谢通路、血管源性通路和免疫炎症通路，从多基因水平揭示认知障碍患者脑功能和结构网络异常变化特征。在国际上首次探讨多基因集聚效应对MCI和SVCI神经环路内在关联及相互差异的影响模式，为阐明MCI和SVCI可能的“共病”机制及特征内表型提供理论依据，并为AD患者的早期诊断、转归及治疗等提供重要的生物学指标。

本项目基于通路水平的遗传影像学策略，以阿尔茨海默病（AD）风险人群为主要研究对象，结合多维度认知神经心理量表评估，从多基因水平上深入探讨AD风险人群神经环路的异同，揭示遗传因素的集聚效应与认知关键脑区和全脑神经网络的关系，为AD风险人群早期诊断、早期干预寻找科学依据和新的思路。本项目研究成果：①利用基于通路水平的遗传影像学策略探讨AD高危人群轻度认知障碍（MCI）的神经影像损害模式。②基于关键基因的遗传影像学策略在AD风险人群中的应用。③阐述认知障碍患者的神经网络完整性与血管危险因素负荷的关联性。④揭示认知障碍患者功能环路与结构环路的损害基础。根据本研究临床基础资料和数据，已正式发表或已接收第一作者及通讯作者SCI收录论文14篇。申请人在项目资助期间获得国家优秀青年基金、中国杰出青年神经内科医师、南京市第十批有突出贡献中青年专家、南京市中青年拔尖人才等人才称号。正是由于该项目较为突出的工作积累，申请人进一步申请并获得主持国家自然科学基金优青项目及面上项目。