Tracking autobiographical thoughts: a smartphone-based approach to identifying cognitive correlates of Alzheimer's disease biomarkers and risk factors in clinically normal older adults

虽然阿尔茨海默病(AD)病理的最早阶段通常被描述为“临床沉默”，但以前的工作 增加了早期AD与可检测到的自传性思维变化相关的可能性--A类 认知包括记忆、计划和其他与我们的个人生活相关的心理模拟。这里 我们介绍了两项多模式研究，调查早期AD神经病理的认知标记物是否可以 通过部署智能手机应用程序(App)来跟踪日常生活中的自传式想法，从而被检测到。 使用我们团队开发的两个智能手机应用程序来自然地评估认知，拟议的研究 将a)检验真实世界的自传性思维对AD血浆和脑生物标记物的敏感性 临床正常的老年人，b)揭示了测量自传体的预测性和可伸缩性 老年人对一系列纵向AD生物标志物和相关健康结果的想法，以及c)脱落 可区分正常与异常的神经认知自传性思维特征 认知和大脑老化。MPIs格里利博士和安德鲁斯-汉纳博士组成了一个研究小组， 在基于智能手机的认知评估、自传式思维、功能磁性方面的专业知识 磁共振成像，健康和病理性老化，以及大数据集的纵向分析。利用我们的 团队的跨学科专业知识，我们将执行一个创新的双管齐下的项目，利用实验室内，在家里， 以及在线评估方法，将评估AD生物标记物和衰老与 1225多名成年人的自传性思维，其中一部分完成了额外的实验室实验认知 测试、神经成像、血浆生物标记物分析和纵向随访。在目标1中，我们将检验假设 在临床正常的老年人中，智能手机对自传性思维的测量对 血浆AD生物标志物，与静息状态下的默认网络功能连接，脑部网络靶向 到了公元早期。Aim 2测试了这样一种假设，即这些智能手机测量结果可以预测未来的血浆生物标记物 登记时临床正常的老年人的蓄积情况以及未来的休息状态 默认网络的功能连通性，以及日常心理社会/工具性下降。AIM 3部署了一台 我们的智能手机应用程序向大量远程、临床正常和基因分型的队列提供了一个机会 评估有关年龄和阿尔茨海默病遗传风险对自传性思维影响的问题 规模史无前例。纵观AIMS，我们还考察了智能手机如何衡量自传性 思维与实验室中的认知测试相比，以及它们是否提高了对衰老和AD风险的敏感性。据我们所知， 该项目将是第一个使用智能手机跟踪自传性想法以识别认知能力的项目 AD生物标记物的相关性，尽管理论原理和证据表明这样做可以利用主要的 阿尔茨海默病的脑通路。最终，我们的移动工具可能会导致对早期AD的更容易获得的认知测试， 包括淀粉样蛋白和tau蛋白的初始阶段，对世界各地的科学家、临床医生和患者具有广泛的影响。

While the earliest phase of Alzheimer’s disease (AD) pathology is often described as “clinically silent”, prior work raises the possibility that early AD is associated with detectable alterations in autobiographical thought – a class of cognition encompassing memories, plans, and other mental simulations related to our personal lives. Here we introduce two multi-modal studies that investigate whether cognitive markers of early AD neuropathology can be detected by deploying smartphone applications (apps) to track autobiographical thoughts in everyday life. Using two smartphone apps developed by our team to naturalistically assess cognition, the proposed studies will a) examine the sensitivity of real-world autobiographical thoughts to AD plasma and brain biomarkers in clinically normal older adults, b) reveal the predictive and scalable potential of measuring autobiographical thoughts in older adults for a host of longitudinal AD biomarker and associated health outcomes, and c) shed light on neurocognitive autobiographical thought characteristics that may separate normal from abnormal cognitive and brain aging. MPIs Dr. Grilli and Dr. Andrews-Hanna have formed a team of researchers with expertise in smartphone-based assessment of cognition, autobiographical thought, functional magnetic resonance imaging, healthy and pathological aging, and longitudinal analysis of large datasets. Leveraging our team’s interdisciplinary expertise, we will execute an innovative two-pronged project harnessing in-lab, at-home, and online assessment methods that will evaluate the relationships of AD biomarkers and aging to the autobiographical thoughts of 1,225+ adults, with a subset completing additional in-lab experimental cognitive tests, neuroimaging, plasma biomarker assays, and longitudinal follow-up. In Aim 1, we will test the hypothesis that among clinically normal older adults, smartphone measures of autobiographical thoughts are sensitive to plasma AD biomarkers, and resting state functional connectivity in the default network, a brain network targeted by early AD. Aim 2 tests the hypothesis that these smartphone measures predict future plasma biomarker accumulation among older adults who were clinically normal at enrollment, as well as future resting state functional connectivity of the default network, and daily psychosocial / instrumental decline. Aim 3 deploys one of our smartphone apps to a large remote, clinically normal, and genotyped cohort, providing an opportunity to evaluate questions about effects of age and genetic risk for AD on autobiographical thoughts at an unprecedented scale. Across the aims, we also examine how smartphone measures of autobiographical thoughts compare to in-lab cognitive tests, and if they improve sensitivity to aging and AD risk. To our knowledge, this project will be the first to use smartphones to track autobiographical thoughts as a means to identify cognitive correlates of AD biomarkers, despite theoretical tenets and evidence that doing so could tap into the primary brain pathway of AD. Ultimately, our mobile tools may lead to more accessible cognitive tests of early AD, including initial stages of amyloid and tau, with broad impact for scientists, clinicians and patients worldwide.