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.

符合美国国家衰老研究所的使命，拟议的研究试图使用mutli-hethod 改善对阿尔茨海默氏病（AD）相关的认知畸变的早期发现的方法，并减轻通过使这些标记更多的标记，现有的地理，社会经济和与健康相关的障碍广泛访问。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，我们将使用它纵向跟踪日常生活中的自传思想。扩展我们以前在这方面的工作，我们的拟议的研究将a）研究现实世界中的自传思想如何在认知单pirip的年轻人中如何中年和老年人因AD的关键遗传危险因素而改变，即载脂蛋白E E4等位基因（APOE4），b）发现老年人这种改变的神经基础随着时间的流逝，认知和神经变化之间的关系，c）揭示了预后的潜力测量老年人的自传思想，以表明许多纵向健康结果 AD的临床前进展，d）阐明了与正常“低 - ”相关的神经认知特征风险。自然主义评估认知，自传思想，静止状态功能连接，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两管齐的项目，利用LAB，在家和在线评估方法，将评估AD风险和衰老与> 1,225个基因分型的自传思想的关系认知单载成人，子集完成了其他实验性实验测试，神经影像学和纵向随访。在AIM 1中，我们将检验以下假设，即在现实世界中评估的自传思想通过APOE4衡量，在认知单上的设置特别敏感的AD风险尤其敏感成年人，以及默认网络的静止状态功能连通性的变化调解了这些AD风险 - 认知关系。 AIM 2检验了一个假设，即现实世界自传思想的度量是比未来神经元的基于实验室的测试更好的预测因子（即默认网络静止状态功能连接），认知，情感（即抑郁症状）和功能变化（即仪器和社会功能）通过临床前广告加速度建议。 AIM 3发现自传思想的变化及其从正常（即低广告风险）衰老出现的基本神经结构。这个项目都是重要的和创新；据我们所知，这将是第一个使用智能手机跟踪自传思想的人识别广告风险，渴望强大的理论宗旨和初步证据表明这样做可以改善的方法认知估计的精度，并利用对AD的主要大脑途径征税的认知操作。最终，我们的移动工具可能会导致可访问的AD风险增加的可访问认知测试以及可能的关键。 AD的临床前标记（即淀粉样蛋白和TAU），对全球临床医生和患者产生了广泛的影响。