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）病理学的最早阶段通常被描述为“临床沉默”，但先前的工作 提出了早期AD与自传体思想的可检测改变相关的可能性-一类 包括记忆，计划和其他与我们个人生活有关的心理模拟。这里 我们介绍了两个多模式研究，调查早期AD神经病理学的认知标志物是否可以 通过部署智能手机应用程序（应用程序）来跟踪日常生活中的自传体思想。 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， a）检查真实世界自传体思想对AD血浆和脑生物标志物的敏感性， 临床正常的老年人，B）揭示了测量自传体的预测和可扩展的潜力， 老年人对许多纵向AD生物标志物和相关健康结果的想法，以及c） 神经认知自传体思维特征，可能区分正常与异常 认知和大脑老化。Grilli博士和Andrews-Hanna博士组成了一个研究小组， 在智能手机为基础的认知评估，自传体思维，功能磁 共振成像、健康和病理老化以及大型数据集的纵向分析。利用我们 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，利用在实验室，在家里， 和在线评估方法，将评估AD生物标志物和衰老与 1，225+成人的自传体思想，其中一个子集完成了额外的实验室实验认知 测试、神经成像、血浆生物标志物测定和纵向随访。在目标1中，我们将检验假设 在临床上正常的老年人中，智能手机对自传体思想的测量是敏感的， 血浆AD生物标志物和默认网络中的静息状态功能连接， 早期AD目的2测试这些智能手机测量预测未来血浆生物标志物的假设 在入组时临床正常的老年人中积累，以及未来的静息状态 默认网络的功能连接，以及日常心理社会/工具下降。Aim 3部署了一个 我们的智能手机应用程序的一个大型远程，临床正常，和基因型队列，提供了一个机会， 评估年龄和AD遗传风险对自传体思想的影响， 前所未有的规模。在这些目标中，我们还研究了智能手机如何衡量自传体 想法与实验室认知测试相比，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， 这个项目将是第一个使用智能手机来跟踪自传体思想的项目， 相关的AD生物标志物，尽管理论原则和证据表明，这样做可以利用主要 AD的脑通路最终，我们的移动的工具可能会导致更容易获得早期AD的认知测试， 包括淀粉样蛋白和tau蛋白的初始阶段，对全世界的科学家，临床医生和患者产生广泛影响。

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.