Imaging of Cognition, Learning and Memory in Aging

该研究旨在更好地理解认知储备（CR）的神经基础。 我们已经假设CR调节年龄或阿尔茨海默病（AD）相关的 大脑病理学和病理学的临床影响。我们的研究结果表明，CR通过 任务在大脑中如何处理的个体差异，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。我们也开始研究影响 大脑完整性或大脑储备（BR）。更好地理解CR和BR的承诺是，这些概念 随着时间的推移，对功能的保存有影响，因此储备的神经机制是 在纵向背景下进行最佳研究。我们建议在5年时开始纵向随访， 特征明确的，最初健康的年轻（n=50）和老年（N=150）成人组，以阐明 神经机制的基础CR，帮助维持BR和成功的认知表现，面对 与年龄相关的大脑变化和AD病理学。这些参与者已经在 两个fMRI任务的基线，以及年龄和AD相关大脑变化的量化指标， 病理学，包括脑体积、皮质厚度、白色高信号、静息 脑血流量和默认网络完整性，以及来自Florbetaben PET的定量淀粉样蛋白负荷。我们 已经确定了CR的候选神经机制。我们将确定是否有差异 健康老年人中这些CR网络的表达与重要临床疾病的风险降低相关 结果包括认知下降和发展轻度认知障碍MCI或AD。我们还将 探索测量的CR和CR网络如何维持BR以及它们如何调节观察到的大脑的影响 改变并推进AD病理学，以保护认知功能。

The proposed research is aimed at better understanding the neural underpinnings of cognitive reserve (CR). We have postulated that CR moderates the relationship between age- or Alzheimer’s disease (AD)-related brain pathology and the clinical impact of that pathology. Our findings suggest 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. We have also begun to look at the factors influencing brain integrity, or brain reserve (BR). The promise of better understanding CR and BR is that these concepts have implications for preservation of function over time, so the neural mechanisms underlying reserve are optimally studied in a longitudinal context. We propose to initiate longitudinal follow-up at 5 years of a large, well characterized, initially healthy group of young (n=50) and older (N=150) adults, in order to elucidate the neural mechanism underlying CR that help maintain BR and successful cognitive performance in the face of advancing age-related brain changes and AD pathology. These participants have already been studied at baseline with two fMRI tasks, as well as quantified measures of age- and AD-related brain changes and pathology, including MR measures of brain volume, cortical thickness, white matter hyperintensities, resting cerebral blood flow and default network integrity, as well quantified amyloid burden from Florbetaben PET. We have already identified candidate neural mechanisms for CR. We will 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. We will also explore how measured CR and CR networks maintain BR and how they moderate the effect of observed brain changes and advancing AD pathology in order to preserve cognitive functioning.