Predicting long-term cognitive outcomes and Alzheimer’s disease and related dementias after major noncardiac surgery for older adults

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PROJECT SUMMARY / ABSTRACT Up to 10% of older adults experience durable postoperative cognitive decline at 1 year or beyond after major noncardiac surgery, which is associated with up to 50% increased risk for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD). However, most older adults will be cognitively unharmed by, and will enjoy longer life and/or improved function because of, surgery. Very little information about anticipated cognitive outcome is available to guide older adults considering elective surgery, because prior research has not incorporated longitudinal pre-surgical trajectories, focused on clinically relevant cognitive outcomes, or been designed to facilitate individualized predictions. Although it has been called “ethically imperative” that physicians discuss adverse postoperative cognitive outcomes as part of surgical informed consent, they lack accurate, individualized information to share with patients. In this study, we propose to use large, population- representative, longitudinal data sources to develop and validate clinical prediction models for long-term cognitive outcomes, including AD/ADRD, after elective major surgery in older adults. We will (AIM 1) use the Health and Retirement Study (HRS), linked to Medicare billing data, to develop clinical prediction models based on preoperatively-known factors to predict (a) memory, (b) risk of AD/ADRD, and (c) ability to independently manage one’s finances and medication, two cognitively-intensive instrumental activities of daily living (IADLs), at two years after surgery. Methodologically, we will balance model complexity with clinical practicality and use methods to account for selective survival. We will (AIM 2) augment the clinical prediction models with complications or adverse events that occur after surgery, e.g., delirium, hospital readmission, and new moderate-severe pain. Findings from this Aim will enhance understanding of “best case, worst case” cognitive outcomes (memory, AD/ADRD, and cognitive-functional) to include in preoperative cognitive risk discussion. These findings will also support future hypotheses about key mechanisms that lead to adverse outcomes, guiding priorities for post-surgical management to improve long-term cognitive outcomes. Finally, we will (AIM 3) externally validate the HRS models using the National Health and Aging Trends study, again linked to Medicare data, to assess generalizability of the models predicting memory, AD/ADRD, and IADL independence after surgery. After validation, these models can be used clinically to predict 2-year cognitive outcomes, including AD/ADRD risk, so that older adults have accurate, personalized information on the likely cognitive outcomes with or without surgery. This information will enable inclusion of long-term cognitive outcomes in surgical shared decision-making, a transformative advance for older surgical patients.