Project Summary Abstract Sleep disturbances are a common facet of Alzheimer’s disease (AD) affecting 20-40% of patients in the mild to moderate stage of the illness. There is strong evidence that poor sleep accelerates the progress of AD through the failure to clear brian toxins during sleep. Research has shown that promoting healthy sleep, specifically slow wave sleep (SWS), reversed the accelerating impacts of disrupted sleep in AD patients and reduced their annual increases in AD biomarkers, reduced cognitive decline, stabilized depressive symptoms, and improved psychopathological behavior. There is increasing evidence that promoting sleep, specifically healthy sleep architecture, reduces the risk of poor sleep accelerating AD. However, there are currently no approved therapies that are specifically designed to promote sleep and healthy sleep architecture in AD patients and patients at high risk for AD. Thus, there is a significant unmet clinical need to develop a sleep promoting device that is well tolerated by pre-AD and early-stage AD patients. Our innovation is a device that promotes sleep onset, sleep duration, and the ideal sleep stage architecture including SWS, to prevent the disease accelerating impacts of disrupted sleep on AD patients. The goal of this Phase I project is to create a testable prototype that can sense sleep architecture and provide peripheral neuromodulation stimulation to individuals over the age of 65, a group with an elevated risk of AD. Successful completion of this Phase I effort will position us to demonstrate in clinical studies that our device improves SWS in early-stage AD patients and reduces AD biomarkers. Our final commercialized device will be a comfortable low-profile medical device that promotes healthy sleep in high-risk and early-stage AD patients and reverses the accelerating effects of disrupted sleep for millions of AD patients.