胆碱能神经通路在阿尔茨海默病痴呆前阶段及认知训练中的作用机制

阿尔茨海默病（AD）研究的焦点已从痴呆阶段转移到痴呆前阶段，计算机辅助的认知训练为AD痴呆前阶段患者提供了一种简便、无明显不良反应的早期干预方法，但其作用机制亟待明确。作为AD发病的关键机制之一，胆碱能神经通路在AD痴呆前阶段以及认知训练中的确切机制仍然不清，研究的瓶颈是缺乏有效的脑内检测手段。我们在前期工作中在国际上率先建立了精准的胆碱能神经通路活体脑内检测方法，基于家族性AD这一痴呆前阶段的理想研究人群，本项目将纳入90例家族性AD痴呆前阶段患者作为研究对象，设立对照，进行系统完整的神经心理学评价，联合胆碱能核团容积和通路弥散指数分析，明确胆碱能通路在AD痴呆前阶段的作用机制。随后受试者接受为期六个月的先进的认知训练，分别在干预结束时和一年后随访，再次完善神经心理学评价和胆碱能通路检测分析，最终明确胆碱能神经通路以及相关脑区/功能网络变化在认知训练中的作用机制，为AD早期干预服务。

The focus of research and intervention in Alzheimer’s disease (AD) has shifted from the dementia phase to the pre-dementia phase. As a promising early intervention for AD, the underlying mechanism of cognitive training is still an ongoing topic. Impairment of cholinergic system is a well-established fact in AD but there is controversy about its relevance at the early stages of the disease, especially its role in cognitive training. Familial AD gathers the core pathophysiological features of AD, and is an ideal study population for pre-dementia research. Based on our previously established methods for in vivo measurement of the nucleus basalis of Meynert (NbM) and the two major cholinergic pathways, and the familial AD patients cohort, the current study is to investigate the role of cholinergic pathway in the pathogenesis of pre-dementia phase of AD and cognitive training. In this project, 90 familial AD patients in pre-dementia phase and 90 healthy controls will be enrolled. All participants will undergo detailed neuropsychological evaluations, NbM measurement and cholinergic pathway diffusivity indices analysis to determine the role of cholinergic system in the pathogenesis of pre-dementia phase of AD. Subsequently all participants will be randomized to computerized cognitive training group and placebo training group and undertake intervention for six months. The participants will be followed up after six months of intervention and one year after the intervention. With the neuropsychological evaluations, NbM measurement and cholinergic pathway diffusivity indices analysis, the current study will illustrate the role of cholinergic pathway in the cognitive training in the pre-dementia phase of Alzheimer's disease.