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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $654,476

## Abstract

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.

## Key facts

- **NIH application ID:** 10694011
- **Project number:** 5R01AG079263-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elizabeth Louisa Whitlock
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $654,476
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10694011

## Citation

> US National Institutes of Health, RePORTER application 10694011, Predicting long-term cognitive outcomes and Alzheimer’s disease and related dementias after major noncardiac surgery for older adults (5R01AG079263-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10694011. Licensed CC0.

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