Preclinical markers of Alzheimer's disease using psycholinguistic semantic measures

使用心理语言语义测量的阿尔茨海默病临床前标记

• 批准号: 10617408
• 负责人: Jet M.J. Vonk
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617408
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Amyloid; Amyloid beta-Protein; Animals; Area Under Curve; Biological Markers; Black race; Canis familiaris; Caregivers; Categories; Clinical; Clinical Research; Cognitive; Data; Dementia; Demographic Factors; Diagnosis; Early Diagnosis; Education; Elderly; Epidemiology; Episodic memory; Equation; Ethnic Origin; Ethnic group; Foundations; Frequencies; Gender; Genes; Goals; Hippocampus (Brain); Hispanic; Iguanas; Impairment; Individual; Inherited; Intervention; Intervention Trial; Investigation; Knowledge; Language; Length; Light; Linear Models; Linguistics; Longitudinal cohort; Magnetic Resonance Imaging; Maps; Measures; Medial; Memory impairment; Modeling; Names; Neuropsychology; Outcome; Parietal; Participant; Patients; Performance; Persons; Phase; Population; Positron-Emission Tomography; Predictive Value; Problem Solving; Process; Psycholinguistics; Race; Research; Semantic memory; Semantics; Sensitivity and Specificity; Specificity; Statistical Data Interpretation; Symptoms; Testing; Thinness; Time; Training; Translating; Universities; Variant; Walking; Work; age effect; apolipoprotein E-4; base; clinical diagnosis; clinical predictors; cognitive testing; cohort; cost; demographics; diagnostic accuracy; early detection biomarkers; experience; gender difference; imaging biomarker; lexical; mutation carrier; neuroimaging marker; neuropathology; non-demented; normal aging; novel; pre-clinical; prognostic model; programs; semantic processing; sex; tool; trait

PROJECT ABSTRACT The clinical diagnosis of Alzheimer's disease (AD) is based on the core criterion of memory impairment, but biomarker-detectable pathophysiological changes start decades before clinical symptoms. This preclinical phase, in which someone has the neuropathology of AD but does not yet show clinical symptoms, is crucial for potential intervention and timely diagnosis for patient and caregiver. The preclinical phase is currently only detectable with expensive or invasive biomarkers. Because current cognitive measures are not sensitive to the preclinical phase of AD and have low specificity and large variation with regard to individuals' educational and cultural exposure, there is a critical need to develop sensitive, low-cost, and high-access cognitive markers for early detection in diverse older adults. The primary goal of this project is to investigate if novel psycholinguistic metrics of existing cognitive test data can accurately identify people in the earliest stages of AD. The semantic fluency task—naming as many animals in one minute—tests semantic memory, one of the first cognitive domains to become impaired in AD. Traditionally, semantic fluency is scored by the total number of items. However, there is a wealth of information at the item-level of this task, because words are organized in a semantic network that becomes vulnerable during AD, specifically for words that are poorly connected and not often used. These traits of words in the semantic network can be captured with novel psycholinguistic metrics, such as lexical frequency, e.g., `dog' is a high-frequent word in our language, as opposed to `iguana.' Nine novel item-level psycholinguistic metrics of semantic fluency have been selected to: investigate how AD imaging biomarkers in nondemented adults relate to psycholinguistic measures (Aim 1, K99); estimate the temporality of semantic impairment across the AD continuum (Aim 2, R00); and determine the sensitivity and specificity of psycholinguistic measures to predict progression to clinical AD (Aim 3, R00). Since the relationship of demographics to psycholinguistic metrics is not well understood, this project strives to deconstruct cultural and demographic effects on these metrics in order to maximize their potential utility in early diagnosis among diverse older adults. The project will employ advanced statistical analyses to investigate data from three large longitudinal cohorts with diverse participants and semantic fluency data in English, Spanish, and Dutch. This K99/R00 proposal lays the foundation for an independent research program focused on semantic processing in normal aging and across the AD continuum. The proposed project will provide the applicant with 1) new training in computational semantics and structural equation modeling, 2) experience with imaging biomarker data, and 3) a strong foundation in cultural neuropsychology. These experiences will supplement the applicant's strong background in Neurolinguistics and Epidemiology. The results of the proposed research have the potential to translate into a clinical tool that we can use across educationally, linguistically, and culturally diverse individuals to refine who to select for intervention trials.

项目摘要 阿尔茨海默氏病（AD）的临床诊断是基于记忆障碍的核心标准，但 生物标志物可检测的病理生理变化在临床症状之前数十年开始。这个临床前 阶段，其中某人具有AD的神经病理学但尚未显示临床符号，至关重要 潜在的干预和患者和护理人员的及时诊断。临床前阶段目前仅 可检测到昂贵或侵入性的生物标志物。因为当前的认知措施对 广告的临床前阶段，关于个人的教育和 文化曝光，至关重要的是，要为 潜水员老年人的早期发现。该项目的主要目标是调查新颖的心理语言 现有认知测试数据的指标可以准确地识别AD的最早阶段的人。语义 流利的任务 - 一分钟内的动物命名为多数动物 - 检验语义记忆，这是第一个认知领域之一 在广告中受到损害。传统上，语义流利性是由项目总数评分的。但是，那里 在此任务的项目级别上是大量信息，因为单词是在语义网络中组织的 在AD期间变得脆弱，特别是连接且不经常使用的单词。这些特征 语义网络中的单词可以用新颖的心理语言指标（例如词汇频率）来捕获 例如，“狗”在我们的语言中是一个高频的单词，而不是“鬣蜥”。九种新颖的项目级心理语言学 已经选择了语义流利度的指标来：研究AD成像生物标志物的非态度如何 成人与心理语言措施有关（AIM 1，K99）；估计语义障碍的暂时性 广告连续体（AIM 2，R00）；并确定心理语言测量的敏感性和特异性 预测临床AD的发展（AIM 3，R00）。由于人口统计学与心理语言的关系 指标尚不清楚，该项目致力于解构对这些的文化和人口影响 指标是为了最大程度地提高潜水员老年人早期诊断的潜在效用。该项目将 员工进行了高级统计分析，以调查来自潜水员的三个大型纵向人群的数据 参与者和语义流利数据，英语，西班牙语和荷兰语。这个K99/R00提案奠定了 独立研究计划的基础，侧重于正常衰老和跨越的语义处理 广告继续。拟议的项目将为申请人提供1）计算的新培训 语义和结构方程建模，2）成像生物标志物数据的经验； 3）强大 文化神经心理学的基础。这些经验将补充申请人的强大背景 神经语言学和流行病学。拟议研究的结果有可能转化为 我们可以在教育，语言和文化上多样化的个人中使用的临床工具来完善谁 选择干预试验。