Phase IIB Plasticity-based Adaptive Cognitive Remediation for Alzheimers Disease

项目摘要摘要 当前项目的主要目标是：1)评估PACR-AD认知功能的长期疗效 训练(PACR-CT)在最初的10周训练结束5年后测量，2)以确定 初次训练结束5年后进行10周助推器训练的效果，以及3)重新设计 PACR-CT的最佳培训计划，以维持和潜在地进一步发展计划交付的好处。 我们将在5年后检查延长的PACR-CT疗效与主动对照(休闲游戏)的效果 通过比较1)认知和功能表现，2)结构(白质完整性和大脑)进行训练 体积)和脑功能改变(rsfMRI和TASK-fMRI)以及3)用血液评估神经退行性变- 基于生物标志物(ptau-181)预测AD风险。接下来，我们将检查常规助推器的功效(前与后 强化后培训)，以及通过比较变化来比较初始培训和强化培训之间的相互作用 不同组间的得分。最后，我们将使用最佳助推器训练间隔来修改PACR-CT时间表 根据从目标1测量的自然认知减退率和绩效计算 从AIM开始的10周助推器训练的改进2.PACR-CT长期效果的评估 助推器效应将被用来获得FDA对该计划的批准，并将其商业化 循证预防装置提示与年龄相关的认知能力下降。这个项目应该会导致 开发一种新的、强大的工具来提供有效的辅助治疗，从而产生更大的 阿尔茨海默病前期人群对认知损害的复原力明显更大。

Project Summary Abstract The primary objectives of the current project are 1) to evaluate the longer-term efficacy of PACR-AD cognitive training (PACR-CT) measured 5 years after the completion of initial 10 weeks of training, 2) to determine the efficacy of the 10 weeks of booster training after 5 years from the initial training completion, and 3) to redesign the PACR-CT for optimal training schedule to sustain and potentially further-grow program-delivered benefits. We will examine prolonged PACR-CT efficacy compared to Active Control (Casual Games) at 5 years after training by comparing 1) cognitive and functional performance, 2) structural (white matter integrity and brain volume) and functional brain changes (rsfMRI and task-fMRI) and 3) neurodegeneration assessed with blood- based biomarkers (pTau-181) predictive of AD risk. Next, we will examine the general booster efficacy (pre- vs. post-booster training), and the interaction between initial training and booster training by comparing the change scores between groups. Finally, we will modify PACR-CT schedule with the optimal booster training interval calculated based on the rate of natural cognitive decline measured from Aim 1 and the performance improvement from the 10 weeks of booster training from Aim 2. Evaluation of the longer-term effect PACR-CT and the booster effect will be used to obtain FDA clearance for the program and commercialize it as the evidence-based prevention device indicated for age-related cognitive decline. This project should result in the development of a new, and powerful tool to provide effective adjunctive therapy that results in far greater resilience against cognitive impairment in a substantially greater pre-AD population.