Imaging of Cognition, Learning and Memory in Aging

描述(申请人提供)：拟议的研究旨在更好地了解认知储备(CR)的神经基础。我们假设CR在与年龄或阿尔茨海默病(AD)相关的脑病理和该病理的临床影响之间起调节作用。我们的工作假设是，CR通过大脑中处理任务的方式的个体差异来运作，我们可以使用fMRI测量的任务相关激活来理解这些处理差异。在年轻人和老年人中，我们都发现了由任务表现引起的脑网络效率和容量的个体差异，并注意到这些个体差异通常与测量的认知无线电有关。我们还确定了老年人使用不同代偿神经模式的情况。我们现在建议评估这些可能的CR神经实现是如何在存在与年龄和AD相关的大脑变化和病理的可量化测量的情况下表达的。这些将包括对脑体积、皮质厚度、白质高信号、静息脑血流和默认网络完整性的MR测量，以及18F-AV-45PET的淀粉样蛋白负荷的量化。这些措施将适用于50名年轻的健康参与者和150名年长的健康参与者，他们在接受功能磁共振成像的同时还将执行两项任务。这将使我们能够探索CR的神经实现，并确定CR如何在大脑变化和病理存在的情况下保持性能。我们还建议随着时间的推移跟踪我们的老年参与者，以确定这些CR网络在健康老年人中的差异表达是否与降低重要临床结果的风险有关，包括认知能力下降和发展为轻度认知障碍(MCI)或AD。这项工作将有助于更好地理解衰老和AD病理如何影响调节认知功能的神经系统，以及区分成功和不成功衰老的神经机制。反过来，它可能为补救或预防与年龄相关的认知变化和延缓AD的发病提供线索。

DESCRIPTION (provided by applicant): The proposed research is aimed at better understanding the neural underpinnings of cognitive reserve (CR). We have postulated that CR mediates the relationship between age- or Alzheimer's disease (AD)-related brain pathology and the clinical impact of that pathology. Our working hypothesis has been that CR operates through individual differences in how tasks are processed in the brain and that we can use fMRI-measured task-related activation to understand these processing differences. In both young and old, we have indentified individual differences in the efficiency and capacity of brain networks elicited by task performance, and have noted that these individual differences are often related to measured CR. We have also identified situations where older adults use different compensatory neural patterns. We now propose to assess how these possible neural implementations of CR are expressed in the presence of quantifiable measures of age- and AD-related brain changes and pathology. These will include MR measures of brain volume, cortical thickness, white matter hyperintensities, resting cerebral blood flow and default network integrity, as well quantified amyloid burden from 18F-AV-45 PET. These measures will be obtained for 50 young and 150 older healthy participants who will also perform two tasks while being imaged with fMRI. This will allow us to explore the neural implementation of CR and determine how CR maintains performance in the presence of brain changes and pathology. We also propose to follow our elder participants over time to determine whether differential expression of these CR networks in healthy elders is associated with reduced risk of important clinical outcomes including cognitive decline and developing mild cognitive impairment (MCI) or AD. This work will lead to better understanding of how aging and AD pathology impacts on the neural systems that mediate cognitive function and the neural mechanisms that differentiate successful and unsuccessful aging. In turn, it may provide clues for remediating or preventing age-related cognitive changes and delaying the onset of AD.