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

根据国家老龄研究所的使命，拟议的研究试图使用多种方法 改善阿尔茨海默病(AD)相关认知异常的早期检测和缓解的方法 AD研究中现有的地理、社会经济和健康相关障碍，使这些标记物 广泛使用。我们项目的核心是我们团队的两款移动智能手机应用程序，我们将使用它们来 纵向追踪日常生活中的自传式思想。延续我们以前在这方面的工作，我们的 拟议的研究将a)考察现实世界中认知正常的年轻人的自传性思维， 中老年人会因AD的一个关键遗传风险因素的存在而发生变化，即 载脂蛋白E e4等位基因(APOE4，b)揭示了老年人这种改变的神经基础 以及认知和神经变化之间的关系，c)揭示了 测量老年人的自传性思维，以了解一系列纵向健康结果 阿尔茨海默病的临床前进展，以及d)揭示了与正常的“低-低”相关的神经认知特征。 风险“老化。格里利博士和安德鲁斯-汉纳博士组成了一个研究团队，他们的专长是 认知的自然主义评估，自传式思维，静息状态功能连通性，健康和 病理性老化和大数据集的纵向分析。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，利用实验室内、家庭和在线评估方法 将评估阿尔茨海默病风险和衰老与基因分型的1225人的自传性思想的关系 认知正常的成年人，其中一部分完成额外的实验室实验测试、神经成像和 纵向随访。在目标1中，我们将测试自传性思维在现实世界中评估的假设 根据APOE4的测量，环境对认知正常人群中AD风险的增加特别敏感 而默认网络静息状态功能连通性的改变调节了这些AD风险- 认知关系。《目标2》测试了这样一种假设，即衡量真实世界自传性思维的标准是 比基于实验室的未来神经测试(即，默认网络休眠状态功能连通性)更好的预测器， 认知、情感(即抑郁症状)和功能变化(即工具和社会功能) 建议临床前AD加速。目标3揭示了自传式思维的变化及其 从正常(即，低AD风险)老化中出现的潜在神经结构。这个项目既意义重大 和创新；据我们所知，它将是第一个使用智能手机跟踪自传想法的公司 识别AD风险的方法，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 准确的认知估计，并利用认知操作，负担AD的主要大脑路径。 最终，我们的移动工具可能会导致可访问的认知测试，以增加AD的风险，也许是关键 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都有广泛的影响。

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.