TWO PRECLINICAL LATENT SCORES TO PREDICT OCCURRENCE OF DAT

用于预测 DAT 发生的两个临床前潜在评分

• 批准号: 7986462
• 负责人: CHENGJIE XIONG
• 金额: $ 34.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7986462
• 关键词: Age; Aging; Alleles; Alzheimer' s Disease; Amyloid; Apolipoprotein E; Arts; Binding; Bioinformatics; Biological Markers; Brain; Caring; Cerebrospinal Fluid; Cognitive; Coupled; Data; Data Quality; Data Set; Dementia; Detection; Development; Diagnosis; Disease; Disease Progression; Early identification; Education; Educational Background; Elderly; Episodic memory; Future; Genotype; Growth; Hippocampus (Brain); Impaired cognition; Individual; Knowledge; Magnetic Resonance Imaging; Measures; Medicine; Methods; Molecular; Noise; Pattern; Pittsburgh Compound-B; Prevention; Preventive; Proxy; Psychometrics; Randomized Clinical Trials; Relative (related person); Reporting; Research; Research Personnel; Sample Size; Statistical Methods; Symptoms; Techniques; Testing; Therapeutic; Therapeutic Intervention; Therapy Clinical Trials; Time; Universities; Visuospatial; Washington; apolipoprotein E-4; brain volume; clinical Diagnosis; cognitive reserve; college; cooperative study; design; functional decline; functional disability; improved; innovation; mild neurocognitive impairment; neuroimaging; normal aging; novel; pre-clinical; public health relevance; response; tau Proteins; theories; tool; uptake

DESCRIPTION (provided by applicant): Two Preclinical Latent Scores to Predict Occurrence of DAT The cognitive decline associated with Alzheimer's disease (AD) occurs years prior to the clinical diagnosis. However, the emergence of the earliest cognitive and functional impairment and the precise duration of the preclinical progression remain poorly understood by clinicians. Better methods are therefore urgently needed to reliably detect the antecedent cognitive and functional changes before the onset of the dementia of Alzheimer type (DAT). Whereas the conventional scores of the standard cognitive and functional batteries are successful in discriminating fully expressed DAT from normal aging, their ability to track subtle preclinical disease progression is uncertain, although it is possible that many individual items from them may predict the symptomatic onset of AD. Using rich and high quality longitudinal data from Washington University (WU) Alzheimer's Disease Research Center (ADRC), Rush University (RU) Alzheimer's Disease Center (ADC), and the Einstein Aging Study (EAS) and the Bronx Aging Study (BAS) at Albert Einstein College of Medicine (AECOM), this project will first conduct longitudinal item analyses to determine whether and to what degree individual item scores from tests of the 4 cognitive and functional batteries are sensitive and informative to longitudinal preclinical changes and predictive to the development of DAT, and how these item changes are correlated with cognitive reserve proxies (e.g., education and cognitive activities), ApoE genotype, preclinical measures of biomarkers including cerebrospinal fluid (CSF) molecular biomarkers, MRI brain volumetric markers, amyloid neuroimaging with PIB, as well as neuropathological diagnoses. Second, informative items will be optimally integrated through Item Response Theory (IRT) to estimate the preclinical latent cognitive and functional constructs and assess the longitudinal growth pattern of these constructs as well as the precise duration of the preclinical AD. Third, we will compare the predictive power of DAT between the estimated preclinical latent cognitive and functional constructs and the conventional test scores. Finally, we will develop clinically useful score reports for the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) to summarize the optimally estimated preclinical latent cognitive and functional constructs for tracking the antecedent longitudinal changes of AD. We will also provide optimally estimated design parameters (e.g., sample sizes) for the Alzheimer's Disease Cooperative Study (ADCS) to conduct future preventive and therapeutic trials on Mild Cognitive Impairment (MCI) when the estimated preclinical latent cognitive and functional constructs are used as primary efficacy endpoints. Our interdisciplinary team of investigators at the WU ADRC, RU ADC, and AECOM will demonstrate the degree of improved detection of preclinical longitudinal cognitive and functional changes of AD using the state-of-the-art longitudinal statistical methods, modern psychometric theory (i.e., IRT), and cutting-edge bioinformatics techniques. PUBLIC HEALTH RELEVANCE: This project will focus on detecting the earliest possible signs of preclinical cognitive and functional changes of Alzheimer's disease. This project is significant because understanding very early cognitive and functional changes antecedent to the onset of DAT will allow therapeutic interventions to be administered well before dementia symptoms are fully developed and a clinical diagnosis is rendered. The knowledge obtained will greatly help develop early therapeutic treatments or preventions of the disease before it is too late.

描述(申请人提供)：预测DAT发生的两个临床前潜伏期评分阿尔茨海默病(AD)相关的认知能力下降发生在临床诊断前几年。然而，临床医生对最早的认知和功能损害的出现以及临床前进展的确切持续时间仍然知之甚少。因此，迫切需要更好的方法来可靠地检测阿尔茨海默型痴呆(DAT)发病前的认知和功能变化。虽然标准认知和功能电池的常规评分可以成功地区分完全表达的DAT和正常衰老，但它们跟踪细微的临床前疾病进展的能力尚不确定，尽管它们中的许多单独项目可能预测AD的症状性发作。使用来自华盛顿大学(Wu)阿尔茨海默病研究中心(ADRC)、拉什大学(RU)阿尔茨海默病中心(ADC)以及阿尔伯特·爱因斯坦医学院(AECOM)的爱因斯坦老龄化研究(EAS)和布朗克斯老龄化研究(BAS)的丰富和高质量的纵向数据，该项目将首先进行纵向项目分析，以确定从4个认知和功能电池测试的单个项目分数是否敏感和在多大程度上对纵向临床前变化和预测DAT的发展，以及这些项目变化如何与认知储备代理人(例如，教育和认知活动)，ApoE基因，临床前生物标记物的测量包括脑脊液(CSF)分子生物标记物、MRI脑体积标记物、PIB淀粉样神经成像以及神经病理诊断。第二，信息性项目将通过项目反应理论(IRT)进行最佳整合，以估计临床前潜在的认知和功能结构，并评估这些结构的纵向增长模式以及临床前AD的准确持续时间。第三，我们将比较DAT在估计的临床前潜在认知和功能结构与常规测试分数之间的预测能力。最后，我们将为国家阿尔茨海默病协调中心(NACC)统一数据集(UDS)开发临床有用的评分报告，以总结跟踪AD前期纵向变化的最佳估计的临床前潜在认知和功能结构。我们还将为阿尔茨海默病合作研究(ADCS)提供最佳估计的设计参数(例如，样本量)，以便在将估计的临床前潜在认知和功能结构用作主要疗效终点时，进行未来的轻度认知障碍(MCI)预防和治疗试验。我们在WU ADRC、RU ADC和AECOM的跨学科研究团队将使用最先进的纵向统计方法、现代心理测量学理论(即IRT)和尖端生物信息学技术，展示对AD临床前纵向认知和功能变化的改进检测程度。 公共卫生相关性：该项目将专注于检测阿尔茨海默病临床前认知和功能变化的可能早期迹象。这个项目意义重大，因为在DAT发作之前非常早期地了解认知和功能变化，将使治疗干预措施能够在痴呆症症状完全发展和临床诊断之前实施。所获得的知识将极大地帮助开发这种疾病的早期治疗方法或预防措施，以免为时已晚。