AD Pilot Clinical Trials: Spatiotemporal Brain ERP Measures

描述（由申请人提供）：为了促进阿尔茨海默病（AD）干预措施的临床试验的成功，研究人员必须建立适当的受试者招募和测量治疗的临床疗效。脑事件相关电位（ERPs）是在受试者完成设计的感知/认知需求任务时获得的，它提供了一种非侵入性的方法来测量受AD影响的大脑活动，一旦开发出来，就可以在不需要特殊设备或特殊专业知识的情况下用于临床和研究。与复杂的多变量分析技术相结合，时间erp已被证明可以检测阿尔茨海默病并预测阿尔茨海默病临床前形式的个体的进展。我们的目标是扩大erp的研究，将其时间和空间特性纳入新颖和创新的复合测量中，以：1)定义和完善阿尔茨海默病受试者群体，以改善临床试验中适当的受试者招募，甚至在痴呆前的阿尔茨海默病中，2)开发可以检测受试者随时间变化的大脑活动测量，以衡量阿尔茨海默病治疗的效果。使用已知的认知范式来引发代表记忆编码和检索，刺激预期和执行功能的erp，我们将收集AD患者在疾病过程早期，MCI患者（其中相当大比例的人在几年内发展为AD）和正常老年人的erp。然后，我们将应用新的多元技术，包括两步时空主成分分析和平行因子分析来定义和测量erp的潜在时空成分，以便将erp的时间波形及其空间分布结合起来，形成有用的复合测量。这些时空ERP测量将线性组合成判别函数，可用于通过群体成员的后验概率对每个受试者的分配进行定量度量。这项技术也将被研究，以检测变化随着时间的推移，通过重新分析组放置纵向。如果成功，这些ERP措施和多变量方法将为提高临床试验的有效性提供重要工具，同时解决了在整个过程中使用经验和定量结合时空ERP措施来评估AD的困难障碍。

DESCRIPTION (provided by applicant): To promote the success of clinical trials testing interventions for Alzheimer's disease (AD), it is imperative that researchers establish proper subject enrollment and measure the clinical efficacy of the treatment. Brain Event-Related Potentials (ERPs), which are obtained while subjects do tasks with designed perceptual/cognitive demands, offer a noninvasive method of measuring brain activity affected by AD that, once developed, can be implemented for clinical and research use without special equipment or special expertise. In conjunction with sophisticated multivariate analytic techniques, temporal ERPs have been shown to detect AD and predict AD progression in individuals with pre-clinical form of the disease. Our aim is to expand the study of ERPs to incorporate both their temporal and spatial properties in novel and innovative composite measures to: 1) define and refine the AD subject population to improve proper subject enrollment in clinical trials even in predementia AD, and 2) develop measures of brain activity that can detect change in subjects over time in order to gauge the effects of AD treatments. Using a cognitive paradigm known to elicit ERPs representative of memory encoding and retrieval, stimulus expectancy, and executive functioning, we will collect ERPs from AD patients early in the course of the disorder, MCI patients (a sizeable percentage of whom develop AD within a few years), and normal elderly. We will then apply new multivariate techniques, including Two-step Spatiotemporal Principal Components Analysis and Parallel Factors Analysis to define and measure the underlying spatiotemporal components of the ERPs, in order to combine both the temporal waveforms of the ERPs and their spatial distributions into useful composite measures. These spatiotemporal ERP measures will be linearly combined into discriminant functions that can be used to make group assignments with a quantitative measure of confidence in each subject's assignment through posterior probabilities of group membership. This technique will also be studied to detect change over time by reanalyzing group placements longitudinally. If successful, these ERP measures and multivariate methods will provide important tools for improving the validity of clinical trials while addressing the difficult barrie of empirically and quantitatively combining spatial and temporal ERP measures for use in evaluating AD across its course.