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

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