Exploring Cognitive Aging Using Reference Ability Neural Networks

项目总结： 本研究的重点是认知老化的最佳功能和结构成像特征。 临床前阿尔茨海默病(AD)。多年来的表现已被反复证明 不同认知测试的大电池的跨度可以用一组四个参考来简略地表示 能力：情景记忆、感知速度、流畅能力和词汇量。相比之下，神经成像 研究人员通常评估神经激活的年龄差异与单个 可能完全代表这些参考能力的特定任务，也可能不完全代表。成功识别 这些“参考能力神经网络”可能会导致年龄神经基础研究的范式转变。 通过关注几项任务共同的广泛和可复制的方面，而不是 个别任务可能具有的特殊特征。我们已经确定了潜在的大脑网络 成年期的四种参考能力中的每一种。在进行功能成像的同时，我们测试了大型 一组年龄在20岁到80岁之间的健康成年人，他们有一系列的12项认知任务，代表着四个参考 异能(每个构造物3个)。在空间协方差和其他fMRI成像分析方面使用独特的专业知识 数据，我们已经得到了4个与潜在认知相关的潜在空间、全脑fMRI网络 成年期参考能力的结构。我们目前正在对该小组进行5年的跟踪调查，并 开始描述这些网络的表达如何随着年龄的增长和轻度疾病的发病而变化 认知障碍和阿尔茨海默病。我们使用多模式成像来评估潜在的年龄和 与痴呆症相关的网络利用差异。这些变化包括大脑体积、皮质 厚度、白质高强度负荷；白质束完整性；静息脑血流量；静息大胆 网络。重要的是，我们使用正电子发射计算机断层扫描来评估淀粉样蛋白和tau负荷。我们现在建议延长后续行动 将这一重要群体的年龄延长到10年。这项拟议的研究开发了一种全新的成像方法来研究 认知老化和临床前阿尔茨海默病的研究，在年龄跨度上也是独一无二的。它有可能提供关键的 对认知老化背后的神经变化的本质和原因的洞察，更准确地 描述AD的临床前阶段。

PROJECT SUMMARY: This study focus on the optimal functional and structural imaging characterization of the cognitive aging and preclinical Alzheimer's disease (AD). It has been repeatedly demonstrated that performance across the age span on large batteries of diverse cognitive tests can be parsimoniously represented by a set of four reference abilities: episodic memory, perceptual speed, fluid ability, and vocabulary. In contrast, neuroimaging researchers typically evaluate age differences in neural activation associated with the performance of a single specific task that may or may not be fully representative of these reference abilities. Successful identification of these "reference ability neural networks" may lead to a paradigm shift in research on the neural bases of age differences in cognition by focusing on the broad and replicable aspects common to several tasks rather than the possibly idiosyncratic features of individual tasks. We have identified the latent brain networks associated with each of the four reference abilities across adulthood. While undergoing functional imaging, we tested large group of healthy adults aged 20 to 80 with a series of 12 cognitive tasks that represent the four reference abilities (3 per construct). Using unique expertise in spatial covariance and other analyses of the fMRI imaging data, we have derived 4 latent spatial, brain-wide fMRI networks that are associated with the latent cognitive structure of the reference abilities across adulthood. We are presently following up this group at 5 years and beginning to delineate how expression of these networks changes with aging and with the onset of mild cognitive impairment and AD. We use multimodal imaging to evaluate potential mediators of age and dementia-related differences in the utilization of the networks. These include change in brain volume, cortical thickness, white matter hyperintensity burden; integrity of white matter tracts; resting CBF; and resting BOLD networks. Importantly, we use PET to assess amyloid and tau burden. We now propose to extend the follow up of this important cohort to 10 years. The proposed study develops a completely new imaging approach to the study of cognitive aging and preclinical AD and is also unique in its age span. It has the potential to provide key insights into the nature and causes of the neural changes that underlie cognitive aging and to more accurately describe the preclinical phase of AD.