Cognitive and Brain Changes in Preclinical Alzheimer's Disease

临床前阿尔茨海默病的认知和大脑变化

• 批准号: 8442137
• 负责人: CHRISTINA E WIERENGA
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8442137
• 关键词: Accounting; Adult; Age; Aging; Alzheimer' s Disease; American; Amyloid beta-Protein; Biological Markers; Blood Vessels; Brain; Categories; Cerebrospinal Fluid; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Characteristics; Clinical; Cognition; Cognitive; Data; Dementia; Diagnosis; Diagnostic; Disease; Early Intervention; Elderly; Episodic memory; Face; Functional Magnetic Resonance Imaging; Future; Goals; Health Care Costs; Impaired cognition; Incidence; Intervention; Knowledge; Life; Linguistics; Link; Measures; Medicare; Memory; Metabolic; Mission; Modeling; Nature; Neurophysiology - biologic function; Neuropsychological Tests; Outcome; Oxygen Consumption; Pathology; Patient Selection; Patients; Performance; Perfusion; Persons; Phase; Pre-Clinical Model; Predisposition; Procedures; Process; Rest; Retrieval; Risk; Risk Factors; Semantic memory; Semantics; Stroke; Syndrome; System; Techniques; Testing; Therapeutic Intervention; Time; blood oxygen level dependent; cerebrovascular; cognitive change; cost; disorder risk; improved; innovation; lexical retrieval; neural recruitment; neuroimaging; neuropathology; neuropsychological; pre-clinical; prognostic; public health relevance; relating to nervous system; response; tau Proteins

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.

描述（由申请人提供）： 该提出的项目采用多模式的认知和神经影像学方法来检查临床前AD中语义记忆的早期变化（PCAD；定义为具有AD的CSF病理学的认知正常老年人）。该项目具有三个主要目标：（1）测试PCAD中语义记忆的认知模型，（2）检查PCAD中对语义记忆任务的功能性脑反应，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，以确定语言访问难度与检索帐户一致的语言访问难度或与特定类别的赤字一致的语言访问难度的难度[例如，著名的面孔（FF）]是一致的。 广告的存储帐户。在此过程中，我们研究了自传意义和对比的历史与远程与最近的FF知识的影响，以检查时间梯度，以揭示PCAD中人为识别知识的情节性语义记忆和语义记忆的贡献。我们使用创新的FMRI技术来检查人识别与对象识别语义知识的神经相关性的群体差异。由于经过校准的fMRI提供了对氧气消耗的脑代谢率（CMRO2）的量度，因此我们检查了PCAD中静止和功能性CBF，BOLD响应，CMRO2和CVD风险之间的关系，以确定CMRO2的风险确定对脑臂的响应是否易于易于使用，而不是fmri Bold Neyion compro的cm cm cm cm cm compro的指标。 通过将功能性和灌注脑标记与认知性能相结合，我们将神经募集的模型彻底测试是PCAD中的补偿机制。检查脑血管疾病风险（例如中风风险，PP，WML负担）对认知和大脑功能的可能调节作用的检查将使我们更接近PCAD的全面生物标志物模型，以改善诊断敏锐度和预后敏感性，从而最早的认知和大脑变化与不知情的认知衰落相关。综上所述，该项目旨在识别认知 和AD神经病理学的症状性成年人认知下降的定量功能性神经血管生物标志物。