Novel Story Recall Measures as Indicators of Cognitive Decline Associated with Alzheimer's Disease and Related Disorders Biomarkers: A Collaborative Study of Existing Data

小说故事回忆措施作为与阿尔茨海默病和相关疾病生物标志物相关的认知衰退指标：现有数据的合作研究

• 批准号: 10331821
• 负责人: Kimberly D Mueller
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10331821
• 关键词: Adult; Alzheimer disease detection; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Anterior; Area; Biological Assay; Biological Markers; Categories; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Communication; Computational Linguistics; Data; Data Set; Dementia; Detection; Development; Discourse analysis; Disease; Early Diagnosis; Early Intervention; Episodic memory; Event; Image; Impaired cognition; Impairment; Individual; Inherited; Investigation; Language; Lead; Learning; Left; Linguistics; Link; Liquid substance; Longitudinal cohort; Longitudinal cohort study; Magnetic Resonance Imaging; Measures; Memory; Methodology; Methods; Modeling; Monitor; Names; Nerve Degeneration; Outcome; Outcome Measure; Participant; Pathology; Performance; Persons; Phase; Play; Positioning Attribute; Positron-Emission Tomography; Process; Process Measure; Registries; Research; Research Priority; Resources; Retrieval; Risk; Role; Semantic memory; Semantics; Signal Transduction; Speech; Symptoms; System; Temporal Lobe; Testing; Wisconsin; base; clinical diagnosis; cognitive function; cohort; design; digital; improved; innovation; lexical; lexical retrieval; magnetic resonance imaging biomarker; memory process; mild cognitive impairment; novel; novel marker; pre-clinical; response; tau Proteins

PROJECT SUMMARY/ABSTRACT Growing advances in imaging and fluid-based assays of Alzheimer's disease (AD) biomarkers including amyloid, tau and neurodegeneration, confirm that AD processes begin decades before clinical impairment in cognitive function. Subtle changes to cognition are also likely to co-occur years before a clinical diagnosis of dementia due to AD. There is an urgent need to develop sensitive measures of subtle cognitive decline associated with AD biomarkers, particularly for monitoring response to early intervention treatments in clinical trials. The proposed investigation is highly innovative and designed to leverage existing data from three longitudinal cohort studies—Wisconsin Registry for Alzheimer's Prevention, Wisconsin Alzheimer's Disease Research Center, and BIOCARD–using a classic and widely used measure of cognition: the story recall task. We developed a novel scoring system that we hypothesize targets semantic and associative memory processes: measures that capture lexical categories and serial position. Our preliminary data shows that proper name recall and serial position scores from story recall are significantly associated with beta-amyloid status from positron emission tomography (PET), while the traditional total score was not related to amyloid status. In this proposal, our central hypothesis is that item-level analysis of existing story recall data from several longitudinal cohorts will yield one or more new measures of cognition that are uniquely associated with underlying preclinical AD pathology. The specific aims are: Aim1: Use data from multiple cohort studies to a) replicate preliminary findings that lexical-level and serial position markers from delayed story recall are associated with increased risk of amyloid positivity and b) extend analyses to investigate whether these variables are associated with PET tau, CSF Aβ and tau, or MRI neurodegeneration measures. Aim 2: Compare concurrent and predictive validity of measures to determine whether the novel measures are more strongly associated with biomarkers, cognitive decline, or progression to clinical levels of impairment than traditional total score measures. Aim 3: Enhance the lexical-level and serial position analysis with computational linguistic analysis of digitally recorded speech from story recall to determine whether semantic content, speech fluency, error-monitoring, and serial position recall explain unique variance in levels of amyloid and/or tau pathology. Impact: The proposed project leverages existing data and is expected to lead to the development of new outcome measures from a classic, commonly used test that has played a central role in detection of disease. We expect that our higher-level language and process-based measures will be sensitive to AD biomarkers in preclinical phases of cognitive decline. By utilizing existing resources from differing cohorts, we can validate our findings without adding participant burden, share these methods with other cohort studies, further develop a digital marker of speech and cognition, and contribute an improved understanding of the underlying mechanisms of memory and communication breakdowns in preclinical AD.

项目摘要/摘要 在成像和基于液体的阿尔茨海默氏病（AD）生物标志物（包括淀粉样蛋白， tau和神经变性，确认广告过程在认知临床障碍之前数十年开始 功能。认知的细微变化也可能在痴呆诊断之前几年同时出现 由于广告。迫切需要制定与 AD生物标志物，特别是用于监测临床试验中对早期干预治疗的反应。 拟议的调查具有很高的创新性，旨在利用三个纵向队列的现有数据 研究 - 威斯康星州的阿尔茨海默氏症预防注册中心，威斯康星州阿尔茨海默氏病研究中心和 生物卡 - 使用经典且广泛使用的认知测量：故事回忆任务。我们开发了一本小说 我们假设目标语义和关联记忆过程的评分系统：捕获的度量 词汇类别和串行位置。我们的初步数据表明，专有名称召回和串行位置 故事回忆的分数与beta淀粉样蛋白发射断层扫描显着相关 （PET），而传统的总分数与淀粉样蛋白状态无关。在此提案中，我们的中心假设 是从几个纵向人群中对现有故事回忆数据的项目级分析将产生一个或多个新的 与潜在的临床前AD病理学独特相关的认知度量。具体目标 是：AIM1：使用多个队列研究的数据到a）复制词汇水平和串行的初步发现 延迟故事回忆的位置标记与淀粉样蛋白阳性的风险增加有关，b）扩展 分析这些变量是否与PET TAU，CSFAβ和TAU或MRI有关 神经变性措施。目标2：比较措施的并发和预测有效性以确定 新颖的措施是否与生物标志物，认知能力下降或发展到 临床损害水平比传统的总得分度量。目标3：增强词汇水平和串行 位置分析，通过计算语言分析对故事回忆的数字记录的语音分析以确定 语义内容，语音流利性，错误监控和串行位置是否解释说明独特的差异 淀粉样蛋白和/或TAU病理的水平。影响：拟议的项目利用现有数据，预计将 通过经典的，常用的测试进行了新的结局措施制定新的结果措施 在疾病发现中的作用。我们希望我们的高级语言和基于过程的措施是 在认知下降的临床前阶段对AD生物标志物敏感。通过使用与区分的现有资源 队列，我们​​可以在不增加参与者的情况下验证我们的发现，与其他队列共享这些方法 研究，进一步发展语音和认知的数字标记，并有助于提高对 临床前广告中记忆和通信崩溃的基本机制。