Diversity: Preclinical markers of Alzheimer's disease using psycholinguistic semantic measures

多样性：使用心理语言语义测量的阿尔茨海默病临床前标志物

• 批准号: 10818171
• 负责人: Jet M.J. Vonk
• 金额: $ 8.81万
• 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/10818171
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Amyloid; 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; Episodic memory; Equation; Ethnic Origin; Foundations; Frequencies; Gender; Genes; Genetic; Goals; Hispanic; Iguanas; Impairment; Individual; Inherited; Intervention; Intervention Trial; Investigation; Knowledge; Language; Length; Linear Models; Linguistics; Longitudinal cohort; Magnetic Resonance Imaging; Maps; Measures; Memory Loss; Memory impairment; Modeling; Names; Neuropsychology; Outcome; Participant; Patients; Performance; Persons; Phase; Population; Positron-Emission Tomography; Predictive Value; Process; Psycholinguistics; Race; Research; Risk Factors; Semantic memory; Semantics; Sensitivity and Specificity; Specificity; Statistical Data Interpretation; Symptoms; Testing; Thinness; Time; Translating; Universities; Variant; Walking; Work; age effect; apolipoprotein E-4; autosome; brain volume; clinical diagnosis; clinical predictors; cognitive testing; cohort; cost; demographics; diagnostic accuracy; early detection biomarkers; gender difference; high risk population; imaging biomarker; lexical; mutation carrier; neuroimaging marker; neuropathology; normal aging; novel; pre-clinical; prognostic model; programs; semantic processing; sex; sociodemographics; 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.’ The K99 phase of this study showed that novel psycholinguistic item-level metrics related to memory decline over time over and above other traditional neuropsychological scores, related to brain volume over and above established genetic, subjective, and cognitive risk factors, and related to more cortical thinning across eights years in high-risk individuals without a dementia diagnosis. In the R00 phase, psycholinguistic metrics will be used to estimate the temporality of semantic impairment across the AD continuum (Aim 1) and determine the sensitivity and specificity of psycholinguistic measures to predict progression to clinical AD (Aim 2). 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. For the R00 aims, the project will employ advanced statistical analyses to investigate data from two large longitudinal cohorts with participants from a range of socio-demographic backgrounds and semantic fluency data in English and Spanish. The R00 proposal lays the foundation for an independent research program focused on semantic processing in normal aging and across the AD continuum. 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”是我们语言的高频，而不是“鬣蜥”。这项研究的K99阶段表明 那种新颖的心理语言项目级指标与记忆随着时间的推移随着时间的推移而下降而不是其他 传统的神经心理学评分，与大脑的体积相关，超过既不超过遗传，主观， 和认知危险因素，并且与没有的高风险个体的八年中的皮质稀疏有关 痴呆诊断。在R00阶段，心理语言指标将用于估计 跨广告连续体的语义障碍（AIM 1），并确定的灵敏度和特异性 心理语言措施预测临床AD的发展（AIM 2）。由于人口统计关系 对于心理语言指标尚不清楚，该项目致力于解构文化和人口统计 对这些指标的影响，以最大程度地提高潜水员老年人早期诊断的潜在效用。 对于R00的目标，该项目将采用高级统计分析来调查来自两个大型的数据 与来自一系列社会人口统计学背景和语义流利数据的参与者的纵向人群 用英语和西班牙语。 R00提案奠定了针对的独立研究计划的基础 正常衰老和AD连续性的语义处理。拟议研究的结果已有 转化为我们可以在教育，语言和文化上使用的临床工具的潜力 潜水员的个人来完善谁选择干预试验。

项目成果

Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia.

• DOI: 10.1080/23279095.2022.2060748
• 发表时间: 2024-07
• 期刊: Applied neuropsychology. Adult

Bear in mind: the role of personal background in semantic animal fluency - The SMART-MR study.

• DOI: 10.3389/fpsyg.2023.1227053
• 发表时间: 2023
• 期刊: FRONTIERS IN PSYCHOLOGY
• 影响因子: 3.8
• 作者: Smit, Annelot P;Beran, Magdalena;Twait, Emma L;Geerlings, Mirjam I;Vonk, Jet M J
• 通讯作者: Vonk, Jet M J