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

追踪自传思想：一种基于智能手机的方法来检测阿尔茨海默病风险的认知和神经标记

基本信息

批准号：
10228998
负责人：
Jessica Renee Andrews-Hanna
金额：
$ 64.22万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2022-08-31
项目状态：
已结题

项目摘要

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.

根据国家老龄化研究所的使命，拟议的研究寻求使用多种方法改善阿尔茨海默氏病（AD）相关认知畸变的早期检测并减轻通过使这些标记更加突出，消除 AD 研究中现有的地理、社会经济和健康相关障碍我们项目的核心是我们团队的两个移动智能手机应用程序，我们将使用它们。纵向追踪日常生活中的自传式思想，扩展了我们之前在这一领域的工作。拟议的研究将a）研究认知未受损的年轻人在现实世界中的自传体思想如何， AD 的一个关键遗传风险因素（即载脂蛋白 E e4 等位基因 (APOE4)，b) 揭示了老年人中此类变化的神经基础以及认知和神经随时间变化之间的关系，c）揭示了预后的潜力测量老年人的自传体思想，以了解一系列纵向健康结果，表明 AD 的临床前进展，d) 揭示了与正常“低认知”相关的神经认知特征 MPI 的 Grilli 博士和 Andrews-Hanna 博士组建了一支具有专业知识的研究团队。认知的自然评估、自传思想、静息状态功能连接、健康和利用我们团队的跨学科专业知识，我们进行了病理老化和大型数据集的纵向分析。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 名基因型患者的自传思想之间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、神经影像学和在目标 1 中，我们将检验自传式思想在现实世界中进行评估的假设。根据 APOE4 的测量，在认知未受损的人群中，环境对 AD 风险增加特别敏感成年人，默认网络静息状态功能连接的改变介导了这些 AD 风险目标 2 检验了现实世界自传式思想的衡量标准这一假设。比基于实验室的未来神经测试更好的预测器（即默认网络静息状态功能连接），认知、情感（即抑郁症状）和功能变化（即工具和社会功能）临床前 AD 加速表明，目标 3 揭示了自传体思想及其变化。正常（即低 AD 风险）衰老过程中出现的潜在神经结构这个项目意义重大。据我们所知，它将是第一个使用智能手机来追踪自传思想的公司。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 AD 风险，但仍意味着识别 AD 风险认知估计的准确性，并利用对 AD 主要大脑通路造成负担的认知操作。最终，我们的移动工具可能会带来可访问的认知测试，以增加 AD 风险，也许是关键 AD 的临床前标志物（即淀粉样蛋白和 tau 蛋白），对全世界的殖民者和患者产生广泛影响。