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）临床试验测试干预措施的成功，研究人员必须建立适当的受试者招募并测量治疗的临床疗效。脑事件相关电位（ERP）是在受试者完成具有设计的感知/认知需求的任务时获得的，它提供了一种测量受AD影响的大脑活动的非侵入性方法，一旦开发出来，就可以在没有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ERPs已被证明可以检测AD并预测患有该疾病临床前形式的个体的AD进展。我们的目标是扩展ERP的研究，将其时间和空间特性纳入新颖和创新的复合措施中，以：1）定义和完善AD受试者人群，以提高临床试验中适当的受试者入组率，即使是在痴呆前期AD中，2）开发大脑活动的测量方法，可以检测受试者随时间的变化，以衡量AD治疗的效果。使用已知的认知范式，以引起ERP代表的记忆编码和检索，刺激预期，和执行功能，我们将收集ERP从AD患者的早期疾病的过程中，MCI患者（其中相当大的比例发展AD在几年内），和正常的老年人。然后，我们将应用新的多变量技术，包括两步时空主成分分析和平行因素分析，以定义和测量潜在的时空成分的ERP，为了联合收割机结合的时间波形的ERP和它们的空间分布成有用的复合措施。这些时空ERP措施将被线性组合成判别函数，可以用来使组分配与定量措施的信心，在每个主题的分配，通过后验概率的组成员。还将研究这种技术，通过纵向重新分析组位置来检测随时间的变化。如果成功的话，这些ERP措施和多变量方法将提供重要的工具，提高临床试验的有效性，同时解决困难的巴里的经验和定量相结合的空间和时间的ERP措施，用于评估AD的整个过程。

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.