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: 10680538
• 负责人: Jessica Renee Andrews-Hanna
• 金额: $ 84.02万
• 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 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680538
• 关键词: Acceleration; Adult; Age; Aging; Alzheimer disease detection; 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; Autobiography; Biological Assay; Biological Markers; Biology of Aging; Brain; Cause of Death; Cellular Phone; Characteristics; Classification; Clinical; Clinical Pathology; Clinical Trials; Cognition; Cognitive; Collaborations; Data; Dementia; Developing Countries; 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; Life; Longevity; Measures; Memory; Methods; Mind; National Institute on Aging; Neurocognitive; Neuropsychological Tests; Online Systems; Outcome; Patients; Phase; Phosphorylation; 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; 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; laboratory experiment; 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; 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）病理的早期阶段通常被描述为“临床沉默”，但先前的工作