Contributions of Alzheimer's Pathology and Cerebrovascular Factors to Cognitive Aging

阿尔茨海默病病理学和脑血管因素对认知衰老的影响

• 批准号: 9448188
• 负责人: BRIAN Timothy GOLD
• 金额: $ 48.8万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9448188
• 关键词: Affect; Aging; Alzheimer' s Disease; Amyloid beta-Protein; Biological Markers; Blood Vessels; Brain; Brain region; Brain scan; Cerebrospinal Fluid; Clinical; Cognition; Cognitive; Cognitive aging; Development; Diffusion Magnetic Resonance Imaging; Elderly; Event; Financial compensation; Functional Magnetic Resonance Imaging; Goals; Health; Hippocampus (Brain); Image; Impaired cognition; Individual; Intercept; Intervention; Life Style; Linear Regressions; Link; Magnetic Resonance Imaging; Maintenance; Measures; Memory Loss; Modeling; Neurocognitive; Neuropsychological Tests; Outcome Study; Participant; Pathologic; Pathology; Pathway interactions; Pattern; Performance; Plasticizers; Regression Analysis; Running; Short-Term Memory; Structure; System; Testing; Time; Visit; White Matter Hyperintensity; aging brain; base; behavior measurement; brain health; cerebral atrophy; cerebrovascular; clinical development; cognitive function; cognitive performance; cognitive reserve; executive function; frontal lobe; gray matter; hippocampal atrophy; indexing; lifestyle factors; neuroimaging; neuromechanism; prevent; rate of change; resilience; response; tau Proteins; tau-1; white matter

Alzheimer's disease is associated with the accumulation of pathological markers [amyloid-beta (Aβ) and tau], brain atrophy and a progressive loss of memory functions. However, a significant proportion of individuals with AD pathology do not develop cognitive impairment, indicating contributions of other factors to clinical AD. Increasing evidence suggests that factors strongly linked with brain aging, such as cerebrovascular alterations and declines in executive function, contribute to clinical AD. This link is not straightforward though as the effects of AD pathology and vascular alterations can be moderated by cognitive reserve and brain resilience. Our recent results suggest that levels of Aβ and tau in cerebrospinal fluid (CSF) and cerebrovascular declines associated with white matter hyperintensities (WMHs) are differentially related to patterns of executive function in cognitively normal older adults. In addition, our results suggest that some of the patterns appear modifiable based on positive lifestyle variables. This proposal seeks to define the interplay between AD pathology, cerebrovascular-related alterations and cognitive reserve that distinguish normal brain aging from AD-like cognitive declines. We propose to study of 120 cognitively normal older adults using measures of CSF Aβ, p-tau and t- tau, neuroimaging measures including event-related fMRI, multiple structural imaging measures. Structural neuroimaging measures will include volumetric measures, FLAIR imaging for quantification of WMH volumes and diffusion tensor imaging for quantification of regionally distributed white matter abnormalities. A subset of participants will complete the same CSF and imaging measures approximately 3 years later. We aim to (1) dissociate effects of AD pathology and brain aging on functional compensation (2) identify the separate and synergistic effects of AD pathology and cerebrovascular markers on cognitive declines over time and (3) identify reserve factors that moderate relationships between vascular and AD pathology markers on cognition. We will test hypotheses that AD pathology and cerebrovascular factors synergistically interact to predict AD-like cognitive declines. We will also test the hypothesis that reserve factors will offset the effects of some of these pathological and vascular changes on cognitive functions, via mechanisms of brain maintenance or plastic functional brain reorganization of large-scale brain functional networks in some older adults.

阿尔茨海默病与病理标志物[淀粉样蛋白-β]的积累有关 (Aβ) 和 tau]，脑萎缩和记忆功能逐渐丧失。然而，一个重要的 患有 AD 病理学的个体中，有一部分人没有出现认知障碍，这表明 其他因素对临床 AD 的贡献。越来越多的证据表明，因素强烈 与大脑衰老有关，例如脑血管改变和执行功能下降， 为临床AD做出贡献。但这种联系并不简单，因为 AD 病理学的影响 认知储备和大脑恢复能力可以调节血管变化。我们最近的 结果表明，脑脊液 (CSF) 和脑血管中的 Aβ 和 tau 水平 与白质高信号 (WMH) 相关的下降与 认知正常老年人的执行功能模式。此外，我们的结果表明 一些模式似乎可以根据积极的生活方式变量进行修改。这个提议 旨在定义 AD 病理学、脑血管相关改变和 认知储备可以区分正常的大脑衰老和类似 AD 的认知衰退。我们 提议使用 CSF Aβ、p-tau 和 t- 测量值对 120 名认知正常的老年人进行研究 tau、神经影像学测量，包括事件相关的功能磁共振成像、多重结构成像测量。 结构神经影像测量将包括体积测量、FLAIR 成像 WMH 体积的量化和扩散张量成像的区域量化 分布性白质异常。一部分参与者将完成相同的 CSF 和 大约3年后进行成像测量。我们的目标是 (1) 分离 AD 病理学的影响 和大脑衰老对功能补偿的影响 (2) 确定以下因素的单独和协同作用 随着时间的推移，AD 病理学和脑血管标志物会导致认知能力下降，并且 (3) 确定 调节血管和 AD 病理标志物之间关系的储备因子 认识。我们将检验 AD 病理学和脑血管因素协同作用的假设 相互作用来预测类似 AD 的认知能力下降。我们还将检验保留的假设 因素将抵消其中一些病理和血管变化对认知的影响 功能，通过大脑维护机制或可塑性功能性大脑重组 一些老年人的大规模大脑功能网络。