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.

项目总结/摘要 阿尔茨海默病（AD）生物标志物（包括淀粉样蛋白）的成像和基于液体的测定方法不断取得进展， tau蛋白和神经变性，证实AD过程在认知功能临床损害之前开始几十年 功能认知的微妙变化也可能在痴呆症临床诊断前几年共同发生 由于AD。目前迫切需要开发敏感的措施，微妙的认知能力下降相关的 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。的 拟议的调查是高度创新的，旨在利用现有的数据，从三个纵向队列 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，和 BIOCARD-使用一个经典的和广泛使用的认知测量：故事回忆任务。我们开发了一种新的 评分系统，我们假设目标语义和联想记忆过程：措施，捕捉 词汇类别和序列位置。我们的初步数据表明，专有名称回忆和序列位置 故事回忆的得分与正电子发射断层扫描的β-淀粉样蛋白状态显著相关 (PET)而传统的总分与淀粉样蛋白状态无关。在这个提议中，我们的中心假设 对来自几个纵向队列的现有故事回忆数据的项目级分析将产生一个或多个新的 与基础临床前AD病理学唯一相关的认知测量。具体目标 目的1：使用多个队列研究的数据，a）复制词汇水平和序列水平的初步研究结果， 来自延迟的故事回忆的位置标记与淀粉样蛋白阳性的风险增加相关，并且B）延长 分析以研究这些变量是否与PET tau、CSF Aβ和tau或MRI相关 神经变性的测量。目的2：比较测量的同时和预测有效性，以确定 新的测量是否与生物标志物、认知能力下降或进展更密切相关， 临床损伤水平比传统的总分测量。目标3：提高词汇水平和序列 位置分析与计算语言学分析的数字记录的语音从故事回忆，以确定 语义内容、言语流畅性、错误监控和序列位置回忆是否解释了 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 导致从一个经典的，常用的测试，发挥了核心的新的结果措施的发展， 在疾病检测中的作用。我们期望我们的高级语言和基于过程的度量将 在认知衰退的临床前阶段对AD生物标志物敏感。通过利用现有资源， 队列，我们可以在不增加参与者负担的情况下验证我们的研究结果，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患者记忆和交流障碍的潜在机制。