Abstract With the aging of the population, the risk for age-related conditions such as Alzheimer’s disease(AD) and its common precursor, MCI, is increasing. However, studies targeting prevention of MCI and AD have commonly failed and part of the reason may be failures in selection of a population that is still at risk and has not yet developed fully syndromal MCI. This project leverages our experience with novel semantic interference paradigms and proposes to develop a widely accessible version of the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L). As noted in the body of the application, the LASSI-L has shown significant promise for the early detection of pre-MCI, in both national and international studies including identification of individuals with evidence of amyloid deposition in the absence of detectable cognitive impairments with standard neuropsychological measures. A computerized version of the LASSI, the LASSI- Brief Computerized (LASSI-BC) version has been developed and validated on a preliminary basis in our NIH funded studies but requires significant refinement to make it applicable for commercial use. The goal of this phase II SBIR is to develop the next generation of semantic interference measures (LASSI-D), by making it feasible to remotely deliver and score, for both large-scale clinical trials screening and clinical use. Given the millions of individuals in the US and the rest of the world who are at risk for development of dementia, early intervention is critical and the availability of such as assessment strategy would broadly increase access to early screening and detection. The proposed Phase II SBIR is responsive to PAS-19-316, SBIR Phase II. In specific, this application is directly focused on development of: “Sensitive, specific, and standardized tests for diagnostic screening of mild cognitive impairment (MCI) and dementia, including the development of new, cost- effective, minimally-invasive biomarkers that could be used for screening in the general population and in community settings”. In this study we will evaluate whether the LASSI-D is also sensitive to the earliest phase of MCI as well as being related to blood-based amyloid and tau biomarkers. This system will be designed to be self- administered and hence to be widely useful for large- scale clinical trial screening in the general population and clinical use in community settings.Our company is conducting a phase II SBIR focused on a self-administered system for the treatment of functional deficits in MCI and the cloud-based platform for delivery ofthe functional skills assessment and training program (FUNSAT) will be used for the development of the LASSI-D. Our long-term goal is to develop a commercially successful suite of products that can help identify risk for, prevent, and treat cognitive and functional declines and maintain the cognitive health and functional independence of older adults. Commercialization efforts have begun f...