Phase IIB Plasticity-based Adaptive Cognitive Remediation for Alzheimers Disease

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.