Cognitive and Brain Changes in Preclinical Alzheimer's Disease

描述(由申请人提供)： 这项拟议的项目使用多模式认知和神经成像方法来检查临床前AD(PCAD；定义为认知正常的老年人，脑脊液病理表明AD)的早期语义记忆变化。该项目有三个主要目标：(1)测试PCAD的语义记忆认知模型，(2)检查PCAD对语义记忆任务的脑功能反应，(3)揭示PCAD的神经血管功能。为了实现这些目标，我们在PCAD中系统地测试了语义记忆，以确定在个人识别知识[例如，著名面孔(FF)]方面的困难是由于与检索账户一致的语言获取困难还是与检索账户一致的类别特定缺陷 AD的存储帐户。在这个过程中，我们考察了自传性意义的影响，并对比了历史与遥远与最近的FF知识，以检验时间梯度，以揭示情景记忆与语义记忆在个人识别知识中的贡献。我们使用创新的校准功能磁共振成像技术来检查个体识别与物体识别语义知识的神经关联的群体差异。由于校准的fMRI提供了大脑耗氧代谢率(CMRO2)的测量，我们研究了休息与PCAD的功能性CBF、BOLD反应、CMRO2和心血管风险之间的关系，以确定CMRO2是否比fMRI BOLD反应更不容易受到脑血管变化的影响，这与CMRO2是更好的神经功能指标的观点一致。通过将功能性和灌注性脑标志物与认知表现相结合，我们彻底测试了神经招募模型作为PCAD的一种补偿机制。研究脑血管疾病风险(如中风风险、PP、WML负担)对认知和脑功能的可能调节作用将使我们更接近PCAD的全面生物标记物模型，以提高诊断敏感度和对与早期认知功能下降相关的最早认知和大脑变化的预后敏感性。综上所述，该项目旨在识别认知 以及阿尔茨海默病症状前成年神经病理患者认知功能下降的定量功能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.