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.

Project Narrative The goal of this project is to evaluate the long-term efficacy of a Plasticity-based Adaptive Cognitive Remediation program (PACR-CT v.2.0) for the prevention of Alzheimer’s disease (AD). This proposal aims to examine the longer-term benefits of a novel, neuroplasticity-based, computerized & web-deliverable training program suite five years from the initial 10 weeks of training and test the interactive effect of previous training and 10 weeks of booster training. These outcomes will provide deeper understanding of the neurobehavioral status of a study population 5-years after the initial 10 weeks of program completion and of the benefit of the booster training and its interaction with prior-training. Based on the results of our study, the optimal training schedule to sustain and potentially further-grow program-delivered benefits will be implemented.