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: 10609442
• 负责人: Kimberly D Mueller
• 金额: $ 38.44万
• 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/10609442
• 关键词: Adult; Alzheimer disease detection; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; 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; Digital biomarker; Discourse analysis; Disease; Early Diagnosis; Early Intervention; Episodic memory; Event; Image; Impaired cognition; Impairment; Individual; Inherited; Investigation; Language; 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; Registries; Research; Research Priority; Resources; Retrieval; Risk; Role; Semantic memory; Semantics; Signal Transduction; Speech; Symptoms; System; Temporal Lobe; Testing; Wisconsin; 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.

项目概要/摘要 阿尔茨海默病 (AD) 生物标志物（包括淀粉样蛋白、 tau 蛋白和神经退行性变，证实 AD 过程早于临床认知障碍数十年就开始 认知功能的微妙变化也可能在痴呆症临床诊断前数年同时发生。 迫切需要开发与 AD 相关的微妙认知衰退的敏感措施。 AD 生物标志物，特别是用于监测临床试验中早期干预治疗的反应。 拟议的调查具有高度创新性，旨在利用三个纵向队列的现有数据 研究——威斯康星州阿尔茨海默病预防登记处、威斯康星州阿尔茨海默病研究中心，以及 BIOCARD——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项新颖的任务。 我们追求的评分系统针对语义和联想记忆过程：捕获的度量 我们的初步数据显示专有名称回忆和序列位置。 故事回忆得分与正电子发射断层扫描的β-淀粉样蛋白状态显着相关 （PET），而传统的总分与淀粉样蛋白状态无关。在该提案中，我们的中心假设是。 对来自多个纵向队列的现有故事回忆数据进行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测量。 目标 1：使用多个队列研究的数据 a) 复制词汇层面和序列层面的初步发现 延迟故事回忆的位置标记与淀粉样蛋白阳性风险增加相关，并且 b) 延长 分析以调查这些变量是否与 PET tau、CSF Aβ 和 tau 或 MRI 相关 目标 2：比较措施的并发有效性和预测有效性。 这些新措施是否与生物标志物、认知能力下降或进展密切相关 目标 3：增强词汇水平和系列性。 位置分析，通过对故事回忆中数字记录的语音进行计算语言分析来确定 语义内容、言语流畅性、错误监控和序列位置回忆是否可以解释 淀粉样蛋白和/或 tau 病理学水平 影响：拟议项目利用现有数据，预计将 导致从经典的、常用的测试中开发出新的结果测量，该测试发挥了核心作用 我们期望我们的更高级别的语言和基于过程的措施将是 通过利用不同的现有资源，在认知能力下降的临床前阶段对 AD 生物标志物敏感。 队列，我们​​可以在不增加参与者负担的情况下验证我们的发现，与其他队列分享这些方法 研究，进一步开发语音和认知的数字标记，并有助于更好地理解 临床前 AD 中记忆和沟通障碍的潜在机制。