Each day in the United States, over 100,000 patients receive general anesthesia, with about 40% being aged 60 and above. The current practice of general anesthesia is prone to over-sedating patients, either due to the lack of brain monitoring or using brain monitors with inaccurate indices. Over-sedation (at 28% incidence) contributes to Post-Operative Delirium (POD) in elderly population (≥65yrs). Notably, 11% of these elderly patients suffer from Alzheimer’s Disease and Related Dementias, placing them at an even higher risk of POD. PASCALL was founded to introduce a novel neuroscience-based EEG-guided personalized anesthetic management. In our sister grant, AG066325, we proposed and achieved a) (AG066325 Aim 1,2) the design, development, and FDA 510(k) pre-market clearance of a wireless anesthetic brain monitor, designated as M0 and b) (AG066325 Aim 3) the development of personalized algorithms to monitor anesthetic brain state in aging, dementia, and Alzheimer’s disease patients. In this grant, we aim to fully address the problem by utilizing two recently developed, highly interpretable brain state markers, the Alpha Modulation Index (AMI) and Slow Frequency Modulation Index (SMI), along with a patient-specific instantaneous responsiveness algorithm (PSIRA). PSIRA can inform the anesthesia care giver about the dosing required to maintain a target level of unconsciousness, based on AMI and SMI indices. In this grant, we focus only on patients receiving propofol, the most widely used intravenous anesthetic agent. The primary innovations of this project are 1) the highly interpretable brain state markers and 2) the PSIRA algorithm for unconsciousness management to provide anesthetic dosage recommendation to minimize POD. We realize this innovation through 4 specific aims. Aim 1: Demonstrate the technical feasibility of the unconsciousness management system for intraoperative anesthesia based on AMI/SMI and PSIRA. Aim 2: develop an elderly patient-specific age- normalized AMI and SMI brain state markers. Aim 3: Fully implement the unconsciousness management system for general anesthesia with dosage guidance for intravenous propofol on the PASCALL FDA- cleared M0 monitor. Aim 4: Develop commercialization roadmap for the PSIRA system. If successful, this effort will bring neuroscience-based precision anesthesia care to millions of older patients, saving Medicare ~$44,000 per patient per year and eliminating needless suffering including long-term functional and cognitive disability.