Project Summary / Abstract: Behavioral Intervention Core The overall goal for this Roybal Center Behavioral Intervention Development (BID) Core is to leverage technology to facilitate memory and cognitive function so that cognitive decline may be prevented or delayed in older adults and particularly those at-risk of Alzheimer's disease and related dementias (AD/ADRD). The Roybal Center BID Core will conduct Stage 0 through V studies in accordance with the multidirectional, translational NIH Stage Model, to produce potent and implementable principle-driven behavioral interventions. At UCSF Neuroscape, we have recently demonstrated our unique ability to take an idea for a behavioral intervention based on our previous work that elucidated brain networks enabling higher cognitive functions and see it through all six NIH Stages for intervention development (including all three Clinical Trial Phases) en route to FDA approval. Indeed, the first video-game based intervention we created at Neuroscape has become the first FDA approved, prescribed video-game, which is now an important non-drug treatment option for children with ADHD. In this vein, the BID Core will operate to achieve three aims. Aim 1. Assessment of efficacy and effectiveness of behavioral interventions in a community setting. The proposed research will begin with two clinical trials, each assessing a different tablet-based behavioral intervention. The two interventions target different aspects of cognitive function that we have shown via Stage 0 research to be deficient in advanced age and substantially impaired by dementia. Specifically, one intervention (Coherence) is designed to challenge timing and short-term memory ability whereas the other intervention (Labyrinth) will improve high-fidelity capability in long-term memory (LTM). Importantly, we have already demonstrated initial efficacy and effectiveness through Stage I-IV research in healthy older adults (aged 60+ years). Here, we propose to continue Stage III and Stage IV testing of these interventions by expanding to an older adult population with mild cognitive impairment (MCI) and test the hypothesized mechanisms of action for these interventions. Aim 2. Refine interventions, assess feasibility and initial efficacy in a research setting. We have recently demonstrated virtual reality (VR) engages attention more deeply than tablet-based platforms. Therefore, this aim will develop and assess VR-based interventions as a step towards advancing next- generation behavioral interventions with higher efficacy. These studies constitute Stages IA (refinement), IB (feasibility) and II (initial efficacy) of the NIH Stage Model for intervention development. Aim 3. Maintain, expand and enhance Nexus: A modern behavioral intervention platform. We have recently created Nexus – a HIPPA compliant web-based platform that facilitates clinical trial research through remote screening, intervention randomization, participant tracking, and outcome assess...