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

项目摘要/摘要 阿尔茨海默病(AD)生物标记物的成像和基于液体的分析不断进步，包括淀粉样蛋白， Tau和神经退行性变，证实AD过程早于临床认知障碍几十年就开始了 功能。认知的细微变化也可能在临床诊断痴呆症的前几年同时发生。 由于AD的原因。迫切需要开发与以下方面相关的微妙认知下降的灵敏测量方法 AD生物标志物，特别是在临床试验中用于监测对早期干预治疗的反应。这个 拟议的调查具有很高的创新性，旨在利用来自三个纵向队列的现有数据 研究-威斯康星州阿尔茨海默氏症预防登记处，威斯康星州阿尔茨海默病研究中心，以及 Biocard-使用一种经典且广泛使用的认知测量方法：故事回忆任务。我们写了一本小说 我们假设针对语义和联想记忆过程的评分系统：捕获 词汇类别和系列位置。我们的初步数据显示，正确的名字回忆和连续的位置 故事回忆的分数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 对几个纵向队列中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 与潜在的临床前阿尔茨海默病病理独特相关的认知测量。具体目标 Aim1：使用来自多个队列研究的数据来a)复制词汇水平和序列水平的初步发现 延迟回忆故事的位置标记与淀粉样阳性和b)延长的风险增加相关 研究这些变量是否与PET tau、脑脊液Aβ和tau或磁共振相关的分析 神经退行性变测量。目标2：比较措施的同时有效性和预测性有效性，以确定 无论新的测量与生物标记物、认知能力下降或进展到 临床损害程度高于传统总分测量。目标3：提高词汇水平和系列性 用计算语言分析对来自故事回忆的数字记录的语音进行位置分析以确定 语义内容、语音流畅性、错误监控和连续位置回忆是否能解释 淀粉样蛋白和/或tau病理水平。影响：拟议的项目利用现有数据，预计将 导致从一个经典的、常用的测试中开发出新的结果衡量标准，该测试在 在疾病检测中的作用。我们预计，我们更高级别的语言和基于流程的措施将是 认知功能减退的临床前阶段对AD生物标志物的敏感性。通过利用来自不同部门的现有资源 队列，我们可以在不增加参与者负担的情况下验证我们的发现，并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 临床前阿尔茨海默病患者记忆和沟通障碍的潜在机制。

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.