Real-world and Innovative Multimodal Prediction and Prevention of Postoperative Mortality and Multi-morbidity

PROJECT SUMMARY Of the >50 million Americans who undergo surgery annually, ~40% are >65 years of age. Age — one of the strongest predictors of high risk for surgical complications — is associated with frailty, postoperative delirium, cognitive dysfunction, Alzheimer's disease (AD), AD related dementia (ADRD) and accelerated age-related cognitive decline (ARCD). These elderly surgical patients frequently present with multiple chronic conditions including cardiac and vascular disease, hypertension, and cognitive disorders, contributing to increased risk for poor perioperative outcomes. Thirty (30)-day postoperative mortality is the third leading cause of mortality in the U.S. Postoperative major adverse cardiac and cerebrovascular events (MACCE) occur in up to 15% of patients. Delirium and POCD are the most common perioperative complications in patients over 65 years (~30%), and early evidence suggest that delirium and POCD, which are preventable with specific interventions, may contribute to development or progression of AD/ADRD/ARCD. As severity of POD is associated with the greatest rate of cognitive decline, efforts to prevent POD and POCD may offer protection against long-term cognitive decline, AD and ADRD. Reducing unacceptably high postoperative mortality, costly and debilitating postoperative multiple morbidity including postoperative delirium, cognitive decline and MACCE in the vulnerable elderly surgical population is a critical unmet public health need. It is essential to develop an effective evidence-based approach to providing value-based perioperative care in the high-risk surgical patients. Currently, there is a lack of highly reliable, widely applicable, preoperative risk prediction tools for proactive identification of high-risk patients and lack of evidence-based personalized perioperative interventions with demonstrated efficacy on immediate and long-term postoperative cognitive and physical outcomes. Effective, standardized, and broad scalable implementation of value-based programs for high-risk patients requires automated and accurate risk models that can provide timely information prior to elective surgery, to allow for pre- intra- and post-operative interventions to be successful. The goal of this R01 is to combine robust, effective, and scalable preoperative and intraoperative risk-prediction tools for reliable stratification of high-risk patients, and enable proactive multimodal preoperative prehabilitation, and perioperative physical/behavioral/cognitive interventions to reduce postoperative delirium, cognitive decline, depression, MACCE, accelerated dementia and mortality. Proposed large rigorous perioperative longitudinal intervention trials will provide robust, prospective, and longitudinal evidence to support scalable and validated approaches for proactive risk mitigation with preoperative prehabilitation as well as proactive multimodal pre- and intraoperative interventions to significantly reduce postoperative delirium, cognitive decline, depression, MACCE, accelerated dementia and mortality in millions of vulnerable elderly Americans each year.