Tracking autobiographical thoughts: a smartphone-based approach to the detection of cognitive and neural markers of Alzheimer's disease risk

根据国家老龄化研究所的使命，拟议的研究试图使用多种方法 一种改善阿尔茨海默病（AD）相关认知畸变的早期检测并减轻 现有的地理，社会经济和健康相关的障碍，在AD研究，使这些标志物更多 广泛使用。我们项目的核心是我们团队的两个移动的智能手机应用程序，我们将使用它们来 纵向追踪日常生活中的自传体思想。为了扩展我们以前在这方面的工作， 拟议的研究将a）检查认知未受损的年轻人在现实世界中的自传体思想， 中年和老年人由于AD的关键遗传风险因素的存在而改变，即 载脂蛋白E e4等位基因（APOE 4），B）揭示了老年人中这种改变的神经基础 以及随着时间的推移认知和神经变化之间的关系，c）揭示了 测量老年人的自传体思想，以获得一系列纵向健康结果， AD的临床前进展，和d）阐明与正常“低- 风险”老化。Grilli博士和Andrews-Hanna博士组成了一个研究团队， 认知的自然主义评估，自传体思维，静息状态功能连接，健康和 病理老化和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，利用实验室，家庭和在线评估方法， 将评估AD风险和衰老与> 1，225个基因分型的自传体思想的关系 认知未受损的成年人，其中一部分完成额外的实验室实验测试，神经成像， 纵向跟踪。在目标1中，我们将检验自传体思想在现实世界中被评估的假设 在认知功能未受损的人群中，环境对AD风险增加特别敏感，如APOE 4所测 成年人，默认网络的静息状态功能连接的改变介导了这些AD风险- 认知关系目的2检验假设，即现实世界的自传体思想的措施是 比基于实验室的未来神经测试更好的预测器（即，默认网络静止状态功能连通性）， 认知的，情感的（即，抑郁症状），和功能改变（即，工具和社会功能） 提示临床前AD加速。目的3揭示自传体思想的变化及其 从正常（即，低AD风险）老化。这个项目既有意义， 据我们所知，它将是第一个使用智能手机跟踪自传体思想的公司。 识别AD风险的手段，尽管有强有力的理论原则和初步证据表明，这样做可以改善 认知估计的精确性，并利用对AD的主要大脑通路征税的认知操作。 最终，我们的移动的工具可能会导致AD风险增加的认知测试， AD的临床前标志物（即，淀粉样蛋白和tau），对全世界的临床医生和患者具有广泛的影响。

In line with the mission of the National Institute on Aging, the proposed studies seek to use a mutli-method approach to improve early detection of Alzheimer’s disease (AD)-related cognitive aberrations, and to mitigate existing geographic, socioeconomic and health-related barriers in AD research by making these markers more widely accessible. Central to our project are two of our team’s mobile smartphone apps, which we will use to longitudinally track autobiographical thoughts in everyday life. Extending our previous work in this area, our proposed studies will a) examine how real-world autobiographical thoughts in cognitively unimpaired young, middle-aged, and older adults are altered by the presence of a key genetic risk factor for AD, namely the apolipoprotein E e4 allele (APOE4), b) uncover the neural underpinnings of such alterations among older adults and relationships between cognitive and neural changes over time, c) reveal the prognostic potential of measuring autobiographical thoughts in older adults for a host of longitudinal health outcomes suggestive of the preclinical progression of AD, and d) shed light on neurocognitive characteristics associated with normal “low- risk” aging. MPIs Dr. Grilli and Dr. Andrews-Hanna have formed a team of researchers with expertise in naturalistic assessment of cognition, autobiographical thought, resting state functional connectivity, healthy and pathological aging, and longitudinal analysis of large datasets. Utilizing 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 risk and aging to the autobiographical thoughts of >1,225 genotyped cognitively unimpaired adults, with a subset completing additional in-lab experimental tests, neuroimaging, and longitudinal follow-up. In Aim 1, we will test the hypothesis that autobiographical thoughts assessed in real-world settings are particularly sensitive to increased AD risk, as measured by APOE4, among cognitively unimpaired adults, and that alterations in resting state functional connectivity of the default network mediate these AD risk- cognitive relationships. Aim 2 tests the hypothesis that measures of real-world autobiographical thoughts are better predictors than lab-based tests of future neural (i.e., default network resting state functional connectivity), cognitive, affective (i.e., depressive symptoms), and functional changes (i.e., instrument and social functioning) suggested by preclinical AD acceleration. Aim 3 uncovers changes in autobiographical thoughts and their underlying neural architecture that emerge from normal (i.e., low AD-risk) aging. This project is both significant and innovative; to our knowledge, it will be the first to use smartphones to track autobiographical thoughts as a means to identify AD risk, despite strong theoretical tenets and preliminary evidence that doing so could improve precision of cognitive estimation and tap into cognitive operations that tax the primary brain pathway of AD. Ultimately, our mobile tools may lead to accessible cognitive tests of increased risk for AD and perhaps key preclinical markers of AD (i.e., amyloid and tau), with broad impact for clinicians and patients worldwide.