权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The episodic autobiographical memory hypothesis of preclinical Alzheimer's disease: Developing a new approach for early cognitive detection and measurement of Alzheimer's disease

临床前阿尔茨海默病的情景自传体记忆假说：开发一种阿尔茨海默病早期认知检测和测量的新方法

基本信息

批准号：
9912065
负责人：
Matthew D Grilli
金额：
$ 7.68万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2022-03-31
项目状态：
已结题

项目摘要

Neuropsychological tests are central to the detection of Alzheimer’s disease (AD), but currently available tests are not sufficiently sensitive to AD neuropathology until the disease has progressed for years. We recently introduced and provided preliminary support for an episodic autobiographical memory (EAM) hypothesis of preclinical AD. This hypothesis states that because EAM places high demands on a neural network that is targeted by the initial stages of AD, EAM testing can improve “preclinical” (i.e., early) cognitive detection of AD. This R03 proposal builds on our novel hypothesis and seeks to advance the development of EAM tests for preclinical AD by filling two gaps in current knowledge. Specifically, our objectives for this proposal are to better understand (1) the cognitive sub- components of EAM that are sensitive to preclinical AD and (2) at what stage of preclinical AD (mild versus severe) EAM disruption is detectable. To achieve these objectives, we formed a team of researchers with expertise in the neuropsychology of autobiographical memory and aging (PI Grilli), the default mode network (DMN) and resting state functional connectivity (RSFC) (Co-I Andrews- Hanna), and the neuroimaging of cognitive aging (Co-I Ryan). Our approach is to study EAM and investigate the relation of EAM to DMN RSFC in cognitively normal older adults, half of whom are carriers of the apolipoprotein E ε4 allele, which increases risk for preclinical AD. We have two specific aims: (1) to reveal that core EAM sub-components are disrupted in cognitively normal older ε4 carriers and (2) to demonstrate that EAM disruption is associated with altered DMN RSFC. Under the first aim, we will investigate established and novel behavioral tasks, each emphasizing a different EAM cognitive sub-component that we hypothesize is compromised in preclinical AD. Under the second aim, we will investigate whether poorer performance on any of the EAM tasks studied under Aim 1 is associated with hyper- and/or hypo-RSFC in regions of the DMN that have been identified as particularly sensitive to preclinical AD. Our reasoning is that if cognitively normal ε4 carriers exhibit worse EAM performance on the behavioral tasks relative to non-carriers, we have gained insight into EAM cognitive sub- components that are vulnerable to preclinical AD. Also, by studying the relation of EAM to DMN RSFC, we can shed light on whether disrupted EAM is sensitive to mild or severe preclinical AD, and by extension, the sensitivity of EAM to two key AD processes. This research is significant because it ultimately could lead to the development of neuropsychological tests and cognitive outcome measures that can detect preclinical AD, which currently do not exist. This research is innovative because the EAM hypothesis is a novel idea for cognitive detection of preclinical AD, and this project will be the first to test whether EAM is related to RSFC signatures of mild or severe preclinical AD.

神经心理学测试是阿尔茨海默病（AD）检测的核心，但目前现有的测试对AD神经病理学不够敏感，直到疾病进展到年我们最近介绍并提供了初步的支持，临床前AD的记忆（EAM）假说。这个假设指出，由于EAM的地方高，对于AD初始阶段针对的神经网络的需求，EAM测试可以提高 “临床前”（即，AD的早期认知检测。R 03提案建立在我们的新假设之上并寻求通过填补目前的两个空白来推进临床前AD的EAM测试的发展，知识具体来说，我们的目标是更好地理解（1）认知子，对临床前AD敏感的EAM组分和（2）在临床前AD的哪个阶段（轻度相对于严重）EAM中断是可检测的。为了实现这些目标，我们成立了一个团队，自传体记忆和衰老的神经心理学专家（PI Grilli），默认模式网络（DMN）和静息状态功能连接（RSFC）（Co-I Andrews- 汉娜），和认知老化的神经成像（Co-I瑞安）。我们的方法是研究EAM，研究认知正常的老年人中EAM与DMN RSFC的关系，其中一半是载脂蛋白E ε4等位基因携带者，这增加了临床前AD的风险。我们有两个具体的目的：（1）揭示认知正常的老年ε4携带者的核心EAM亚组分被破坏（2）证明EAM破坏与DMN RSFC改变有关。在第一个目标下，我们将调查既定的和新的行为任务，每一个强调不同的EAM认知我们假设在临床前AD中受损的子组分。在第二个目标下，我们将调查在目标1下研究的任何EAM任务上的较差性能是否与在DMN区域中具有高和/或低RSFC，这些区域已被确定为特别敏感到临床前AD我们的推理是，如果认知正常的ε4携带者表现出更差的EAM性能，在相对于非运营商的行为任务上，我们已经深入了解了EAM认知子系统，易受临床前AD影响的成分。同时，通过研究EAM与DMN RSFC的关系，我们可以阐明破坏的EAM是否对轻度或重度临床前AD敏感，扩展，EAM对两个关键AD过程的敏感性。这项研究意义重大，因为它最终可能导致神经心理学测试和认知结果测量的发展可以检测临床前AD，目前还不存在。这项研究是创新的，因为 EAM假说是临床前AD认知检测的一个新想法，本项目将是首先测试EAM是否与轻度或重度临床前AD的RSFC特征相关。