Cognitive and Brain Changes in Preclinical Alzheimer's Disease

描述（由申请人提供）： 该拟议项目使用多模态认知和神经影像学方法来检查临床前AD（pcAD;定义为具有指示AD的CSF病理学的认知正常老年人）中语义记忆的早期变化。该项目有三个主要目标：（1）测试pcAD中语义记忆的认知模型，（2）检查pcAD中语义记忆任务的脑功能反应，以及（3）揭示pcAD中的神经血管功能。为了实现这些目标，我们系统地测试了pcAD中的语义记忆，以确定个人识别知识的困难是否[例如，Famous Faces（FF）]是由与检索帐户一致的语言访问困难或与检索帐户一致的类别特定缺陷引起的。 AD的存储帐户。在这个过程中，我们调查的自传意义的影响和对比历史与远程与最近的FF知识检查的时间梯度，揭示的贡献情节与语义记忆中的个人识别知识的pcAD。我们使用创新的校准功能磁共振成像技术来检查组的差异，在神经相关的人识别与对象识别语义知识。由于校准的功能磁共振成像提供了一个衡量脑代谢率的耗氧量（CMRO 2），我们检查之间的关系，静息和功能CBF，BOLD反应，CMRO 2，和心血管疾病的风险pcAD，以确定是否CMRO 2，是脑血管病变的敏感性低于功能磁共振成像BOLD反应，一致的概念，CMRO 2是一个更好的指标的神经功能。 通过整合功能和灌注脑标记与认知性能，我们彻底测试模型的神经募集作为一种补偿机制pcAD。检查脑血管疾病风险的可能调节作用（例如，卒中风险、PP、WML负担）对认知和脑功能的影响，将使我们更接近pcAD的综合生物标志物模型，以提高对与初期认知下降相关的最早认知和脑变化的诊断敏锐性和预后敏感性。总的来说，该项目旨在确定认知 和AD神经病理学症状前成人认知下降的定量功能性神经血管脑生物标志物。

DESCRIPTION (provided by applicant): This proposed project uses a multimodal cognitive and neuroimaging approach to examine early changes in semantic memory in preclinical AD (pcAD; defined as cognitively normal older adults with CSF pathology indicative of AD). The project has three main goals: (1) to test cognitive models of semantic memory in pcAD, (2) to examine functional brain response to semantic memory tasks in pcAD, and (3) to reveal neurovascular function in pcAD. To achieve these goals, we systematically test semantic memory in pcAD to determine whether difficulty with person-identification knowledge [e.g., Famous Faces (FF)] results from linguistic access difficulty consistent with the Retrieval Account or a category-specific deficit consistent with the Storage Account of AD. In the process, we investigate the influence of autobiographical significance and contrast historical vs. remote vs. recent FF knowledge to examine for a temporal gradient to reveal the contribution of episodic vs. semantic memory in person-identification knowledge in pcAD. We use the innovative calibrated fMRI technique to examine for group differences in the neural correlates of person-identification vs. object-identification semantic knowledge. Since calibrated fMRI provides a measure of the cerebral metabolic rate of oxygen consumption (CMRO2), we examine the relationship between resting and functional CBF, BOLD response, CMRO2, and CVD risk in pcAD to determine whether CMRO2, is less susceptible to cerebrovascular alteration than the fMRI BOLD response, consistent with the notion that CMRO2 is a better indicator of neural function. By integrating functional and perfusion brain markers with cognitive performance we thoroughly test models of neural recruitment as a compensatory mechanism in pcAD. Examination of the possible modulating effects of cerebrovascular disease risk (e.g., stroke risk, PP, WML burden) on cognition and brain function will bring us closer to a comprehensive biomarker model of pcAD to improve diagnostic acumen and prognostic sensitivity to the earliest cognitive and brain changes associated with incipient cognitive decline. Taken together, the project aims to identify cognitive and quantitative functional neurovascular brain biomarkers of cognitive decline in presymptomatic adults with AD neuropathology.