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: 10629395
• 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/10629395
• 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 Population; Foundations; Frequencies; Gender; Genes; Goals; Hippocampus; Hispanic; Iguanas; Impairment; Individual; Inherited; Intervention; Intervention Trial; Investigation; Knowledge; Language; Length; 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; 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; autosome; 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; racial population; 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 阿尔茨海默病（AD）的临床诊断是以记忆障碍为核心标准，但 生物标志物可检测的病理生理变化在临床症状出现前几十年就开始了。这个临床前 阶段，即某人患有 AD 神经病理学但尚未表现出临床症状的阶段，对于 为患者和护理人员提供潜在的干预和及时的诊断。目前仅处于临床前阶段 可使用昂贵或侵入性生物标志物进行检测。因为当前的认知测量对 AD 的临床前阶段，特异性较低，且个体教育程度和个体差异较大 文化接触，迫切需要开发敏感的、低成本的、高访问性的认知标记 不同老年人的早期发现。该项目的主要目标是调查新颖的心理语言学是否 现有认知测试数据的指标可以准确识别处于 AD 早期阶段的人。语义 流畅性任务——在一分钟内命名尽可能多的动物——测试语义记忆，这是最早的认知领域之一 AD 受损。传统上，语义流畅度是通过项目总数来评分的。然而，有 是该任务的项目级别的大量信息，因为单词是在语义网络中组织的 在 AD 期间变得容易受到攻击，特别是对于那些关联性较差且不经常使用的单词。这些特质 语义网络中的单词可以通过新颖的心理语言学指标来捕获，例如词汇频率， 例如，“狗”在我们的语言中是一个高频词，而不是“鬣蜥”。九本小说项目级心理语言学 选择语义流畅度的指标是为了： 研究 AD 成像生物标志物如何在非痴呆患者中进行成像 成人与心理语言学措施相关（目标 1，K99）；估计语义障碍的暂时性 AD 连续体（目标 2，R00）；并确定心理语言学措施的敏感性和特异性 预测临床 AD 的进展（目标 3，R00）。由于人口统计学与心理语言学的关系 指标尚未被充分理解，该项目致力于解构文化和人口对这些指标的影响 指标，以最大限度地发挥其在不同老年人早期诊断中的潜在效用。该项目将 采用先进的统计分析来调查来自三个具有不同特征的大型纵向队列的数据 英语、西班牙语和荷兰语的参与者和语义流畅度数据。该 K99/R00 提案奠定了 独立研究项目的基础，重点关注正常衰老和跨领域的语义处理 AD连续体。拟议项目将为申请人提供 1）新的计算培训 语义和结构方程建模，2) 成像生物标志物数据的经验，以及 3) 强大的 文化神经心理学基础。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、语言和文化上不同的个体中使用该临床工具来优化谁 选择干预试验。

项目成果

Cross-sectional associations of tau protein biomarkers with semantic and episodic memory in older adults without dementia: A systematic review and meta-analysis.

tau 蛋白生物标志物与无痴呆老年人语义和情景记忆的横断面关联：系统评价和荟萃分析。

• DOI: 10.1016/j.arr.2021.101449
• 发表时间: 2021
• 期刊: Ageing research reviews
• 影响因子: 13.1
• 作者: Pelgrim,TeuntjeAD;Beran,Magdalena;Twait,EmmaL;Geerlings,MirjamI;Vonk,JetMJ
• 通讯作者: Vonk,JetMJ

The role of cognitive and brain reserve in memory decline and atrophy rate in mid and late-life: The SMART-MR study.

认知和大脑储备在中晚年记忆衰退和萎缩率中的作用：SMART-MR 研究。

• DOI: 10.1016/j.cortex.2021.11.022
• 发表时间: 2022
• 期刊: Cortex; a journal devoted to the study of the nervous system and behavior
• 作者: Vonk,JetMJ;Ghaznawi,Rashid;Zwartbol,MaartenHT;Stern,Yaakov;Geerlings,MirjamI;UCC-SMART-StudyGroup
• 通讯作者: UCC-SMART-StudyGroup

The cross-sectional association between amyloid burden and white matter hyperintensities in older adults without cognitive impairment: A systematic review and meta-analysis.

无认知障碍老年人淀粉样蛋白负荷与白质高信号之间的横断面关联：系统评价和荟萃分析。

• DOI: 10.1016/j.arr.2023.101952
• 发表时间: 2023
• 期刊: Ageing research reviews
• 影响因子: 13.1
• 作者: Twait,EmmaL;Min,Britt;Beran,Magdalena;Vonk,JetMJ;Geerlings,MirjamI
• 通讯作者: Geerlings,MirjamI

Cross-sectional associations of amyloid burden with semantic cognition in older adults without dementia: A systematic review and meta-analysis.

• DOI: 10.1016/j.mad.2020.111386
• 发表时间: 2020-12
• 期刊: Mechanisms of ageing and development
• 影响因子: 5.3
• 作者: Vonk JMJ;Twait EL;Scholten RJPM;Geerlings MI
• 通讯作者: Geerlings MI