Project Summary Abstract The primary objective of the current project is to improve and evaluate the efficacy of on-line brain plasticity- based computerized assessment tool and training program for the prevention and delay of the onset of Alzheimer?s disease (AD). This novel therapeutic strategy is designed 1) to increase feed-forward power in brain systems in ways that are designed to reactivate them, and 2) to directly exercise highest-level neurological (DN) processes. We will rapidly develop an enhanced PACR-AD 2.0 program with older adult specific website wrapper, video instructions and motivation videos, which will facilitate greater program engagement and adherence. Next, we will launch a large sample, two-site, double-blind RCT of the program with older adults. This RCT will be powered for clinically significant efficacy outcomes; in it, PACR-AD 2.0 will be compared to an active control of computer games that are matched for the multiple factors of challenge, computer time and research staff interaction during the intervention period. For the intervention trial, we have partnered with University of Iowa and University of Texas at Dallas. These sites will comprehensively evaluate immediate as well as sustained outcomes of the PACR-AD 2.0 vs. control intervention in cognitive, functional and, neurological measures. Successful evaluation of PACR-AD 2.0 will be used to obtain FDA clearance for the program and commercialize it as the first evidence-based prevention device indicated for age-related cognitive decline. Given the ease of access of online-based assessment and training, this project should result in the development of a new, powerful tool to assess and prevent the risk of onset of AD, and to provide effective adjunctive therapy that results in far greater resilience against cognitive impairment in a substantially greater pre-AD population.