Tracking autobiographical thoughts: a smartphone-based approach to identifying cognitive correlates of Alzheimer's disease biomarkers and risk factors in clinically normal older adults

追踪自传体思想：一种基于智能手机的方法，用于识别临床正常老年人阿尔茨海默病生物标志物和危险因素的认知相关性

• 批准号: 10523836
• 负责人: Jessica Renee Andrews-Hanna
• 金额: $ 89.48万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10523836
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Amyloid; Amyloid beta-Protein; Apolipoprotein E; Biological Assay; Biological Markers; Biology of Aging; Brain; Cause of Death; Cellular Phone; Characteristics; Clinical; Clinical Pathology; Clinical Trials; Cognition; Cognitive; Collaborations; Data; Disease; Disease Progression; Early Diagnosis; Early treatment; Elderly; Enrollment; Evaluation; Frequencies; Functional Magnetic Resonance Imaging; Future; Genes; Genetic Risk; Genotype; Goals; Health; Home; Impaired cognition; Individual; Intervention; Lead; Life; Light; Longevity; Measures; Memory; Methods; Mind; National Institute on Aging; Neurocognitive; Neuropsychological Tests; Online Systems; Outcome; Patients; Phase; Plasma; Prevention; Process; Psyche structure; Public Health; Research; Research Personnel; Rest; Risk Factors; Scientist; Specificity; Testing; Thinking; Time; Underserved Population; United States; Work; age effect; aging brain; base; brain pathway; clinical care; cognitive change; cognitive testing; cohort; daily functioning; disability; disease prognosis; early detection biomarkers; effective therapy; follow-up; functional decline; genetic testing; healthy aging; improved; indexing; innovation; large datasets; longitudinal analysis; middle age; mild cognitive impairment; multimodality; neuroimaging; neuroimaging marker; neuropathology; normal aging; pathological aging; pre-clinical; psychosocial; recruit; simulation; smartphone Application; smartphone based assessment; sociodemographic group; tau Proteins; tau-1; tool; underserved community; young adult

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.

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”，但之前的工作 提出了早期 AD 与自传思想中可检测到的改变有关的可能性——一类 认知包括记忆、计划和其他与我们个人生活相关的心理模拟。这里 我们介绍了两项多模式研究，调查早期 AD 神经病理学的认知标记是否可以 通过部署智能手机应用程序（apps）来跟踪日常生活中的自传式想法来检测。 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能力，拟议的研究 a) 检查现实世界的自传体思想对 AD 血浆和大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潜力 老年人对一系列纵向 AD 生物标志物和相关健康结果的想法，以及 c) 摆脱 揭示可能区分正常与异常的神经认知自传式思维特征 认知和大脑老化。 MPI 格里利博士和安德鲁斯-汉纳博士组建了一个研究小组 基于智能手机的认知评估、自传思想、功能磁学方面的专业知识 共振成像、健康和病理衰老以及大型数据集的纵向分析。利用我们的 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、 以及在线评估方法，评估 AD 生物标志物和衰老与 超过 1,225 名成年人的自传式想法，其中一部分完成了额外的实验室认知实验 测试、神经影像学、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 在临床正常的老年人中，智能手机对自传体思想的测量对 血浆 AD 生物标志物，以及默认网络（目标大脑网络）中的静息态功能连接 到公元早期。目标 2 检验以下假设：这些智能手机测量结果可预测未来的血浆生物标志物 入组时临床正常的老年人中的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/工具的下降。目标 3 部署一个 我们的智能手机应用程序向大型远程、临床正常且基因分型的队列提供了机会 评估有关年龄和 AD 遗传风险对自传思想的影响的问题 规模空前。在这些目标中，我们还研究了智能手机如何衡量自传体 与实验室认知测试进行比较，以及它们是否可以提高对衰老和 AD 风险的敏感性。据我们所知， 该项目将是第一个使用智能手机来跟踪自传思想作为识别认知的手段的项目 AD 生物标志物的相关性，尽管理论原则和证据表明这样做可以利用主要的 AD 的脑通路。最终，我们的移动工具可能会导致早期 AD 认知测试变得更容易进行， 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。