老年遗忘型轻度认知障碍执行功能的神经机制及数字干预

Neural mechanisms and digital promotion of executive function in older adults with amnestic mild cognitive impairment

阿尔茨海默病具有极高的发病率和致死率。遗忘型轻度认知障碍(Amnestic Mild Cognitive Impairment,aMCI)作为临床前驱期,探究其形成和发展机制有助于预防阿尔茨海默病的发生。现有研究显示,多个执行域缺陷与aMCI记忆衰退密切相关,但尚未回答何种执行域是关键致病因子、关键干预治疗靶标等科学问题。为突破以往研究将执行功能视作整体抑或割裂元素的局限性,本研究拟从执行功能结构全貌着眼,在提出aMCI执行功能与记忆损害关系假说的基础上,利用脑电技术系统考察aMCI抑制、刷新和转换三种执行功能子成分的时域、时频和动态脑网络特征;并结合三维卷积神经网络筛选、识别执行功能缺陷的特异性神经靶标,探索将抑制域相关神经标记物加入aMCI早期识别的可能性;最后,通过纵向因果设计分析不同靶向数字干预对aMCI患者的训练效果及神经基础,以揭示抑制域相关额顶控制网络在干预中的重要作用。本研究有望从计算认知神经视角阐明抑制是aMCI执行功能缺损和干预的认知新靶点,进而为aMCI早期识别和制定精准化诊疗方案提供循证依据。

Alzheimer's disease(AD)is very common and is associated with a high mortality rate.Therefore,exploring the mechanisms of the onset and development of amnestic mild cognitive impairment(aMCI),a clinical prodromal stage of AD,can help prevent the disease.Previous studies have suggested a close relationship between memory decline in aMCI and multiple executive domain defects;however,key scientific questions,such as which executive domain is the key pathogenic factor,remain unanswered,and key intervention targets remain unknown.To overcome the limitations of previous studies that considered executive function as a whole or fragmented element,this study will focus on the overall structure of executive function based on the hypothesis that executive function in aMCI is associated with memory impairment.This study will use electroencephalography(EEG)technology to investigate the time domain,time-frequency,and dynamic brain network characteristics of three sub-components of executive function(inhibition,updating,and switching)in patients with aMCI.Using a three-dimensional convolutional neural network,specific neural targets of executive function defects will be identified,and the possibility of adding neural markers related to the inhibition domain for early identification of aMCI will be explored.In addition,the effects of training and the neural basis of different targeted digital interventions in patients with aMCI will be analyzed using a longitudinal design,thus revealing the crucial role of the inhibition domain-related frontal-parietal control network in the interventions.This study aims to elucidate inhibition as a new cognitive target for aMCI executive function defects and explore interventions from the perspective of computational cognitive neurology.It also aims to provide evidence-based support for the early identification,precise diagnosis,and development of treatment plans for aMCI.