Behavioral an(j Neural Markers of Attentional Control: Antecedents for AD

越来越多的证据表明，注意力控制系统的崩溃以及随之而来的反应时(RT)变异性的增加可能反映了阿尔茨海默病(AD)的前驱阶段。最近的证据表明，对注意系统施加高负荷的任务在以下方面特别有用：(A)作为行为标记物区分健康衰老和早期DAT；(B)预测一组健康的中老年人的后期转化；以及(C)显示健康对照组个体与其他生物标记物的关系。这项拟议的研究将继续纵向跟踪成年儿童样本，他们具有患症状性AD的良好特征，以解决以下问题：首先，我们将检查一组以注意力选择、执行控制和注意力控制对记忆表现的贡献为目标的认知任务，并将这些测量与其他项目和核心的累积生物标记物(例如，PIB、CSF测量、AP0E4状态、结构和静息状态fMRI测量)联系起来。其次，我们将利用前高斯分析和扩散模型来探索RT分布性能的微妙特征，以检查不同的参数在多大程度上是患AD的风险的有用前兆标志。第三，我们将使用持续注意反应任务(SART)和简单的重复手指敲击任务作为行为标记物，来衡量任务对无关想法(即走神)的瞬间波动。第四，我们将在Stroop和Ending后续记忆范式中测量与任务相关的神经反应(通过fMRI)，以确定注意和/或默认模式神经网络是否在认知表现中断之前就开始受损，并将这些结果与其他项目中开发的生物标记物联系起来，特别是项目4中的休息状态fcMRI研究。第五，我们将检查人格特征与注意控制机制相关的程度，并调节大脑-行为关系。在成人儿童研究队列的限制性纵向研究中，这些目标、项目和核心的融合提供了一个独特的机会，可以发展对与AD相关的最早生物行为变化的多方面性质的理解。

There is accumulating evidence of a breakdown in attentional control systems and consequent increases in reaction time (RT) variability that may reflect a prodromal stage of Alzheimer's disease (AD). Recent evidence indicates that tasks which place a high load on attentional systems are particularly useful in (a) serving as a behavioral marker in discriminating healthy aging from early stage DAT, (b) predicting later conversion in a group of healthy middle-aged/older adults, and (c) showing relationships with other biomarkers in healthy control individuals. The proposed research will continue to longitudinally follow the adult child sample, who have well-characterized risk for developing symptomatic AD, to address the following issues: First, we will examine a set of cognitive tasks that target attentional selection, executive control, and attentional control contributions to memory performance and relate these measures to the accumulating biomarkers from the other projects and cores (e.g., PIB, CSF measures, AP0E4 status, structural and resting state fMRI measures). Second, we will explore subtle characteristics of RT distributional performance utilizing ex-Gaussian analyses and the diffusion model to examine the extent to which distinct parameters are useful prodromal markers for risk for developing AD. Third, we will use both a Sustained Attention to Respond task (SART) and a simple repetitive finger tapping task as behavioral markers for momentary fluctuations in task disengagement to irrelevant thoughts (i.e., mind wandering). Fourth, we will measure the task related neural response (via fMRI) in both a Stroop and Encoding Subsequent Memory paradigm to determine if attentional and/or default mode neural networks begin to be compromised before there is disruption in cognitive performance and relate these results to the biomarkers developing in the other projects, especially the resting state fcMRI studies in Project 4. Fifth, we will examine the extent to which personality characteristics are related to the attentional control mechanisms, and modulate the brain-behavior relationships. The convergence across these aims, projects, and cores in the confining longitudinal study of the Adult Children Study cohort affords a unique opportunity to develop an understanding of the multi-faceted nature of the earliest bio-behavioral changes associated with AD.