# Cognitive and Physical Exercise to Improve Outcomes after Surgery in the Elderly

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $831,725

## Abstract

Project Summary
Cognitive decline with aging, including Alzheimer's Disease and Related Dementias (ADRD), is a public health
imperative that impacts quality of life and disability. Survivors of acute surgical or medical illness contribute
greatly to the crisis of cognitive decline. Hospitalization confers a 1.5-2-fold increase in the odds of new onset
dementia. Furthermore, over a third of critically ill patients have new ADRD by 1 year. Major risk factors for
ADRD after acute illness include pre-illness frailty and cognitive deficits and delirium in the hospital. Endothelial
and blood brain barrier (BBB) dysfunction, cerebral atrophy, and white matter connectivity changes have all
been linked to delirium and ADRD. Surgery is common in older adults but it (and its resulting hospitalization) is
associated with significant cognitive decline. Individual interventions to reduce this decline have exhibited
limited success. Prehabilitation is the process of enhancing capacity and reserve before an acute stressor to
improve tolerance of the upcoming insult. Older major surgical patients provide an ideal population for
prehabilitation. These patients have lead time prior to surgery, are frequently frail, have prolonged post-surgery
ICU and hospital courses, and are at high risk for new ADRD. Prehabilitation studies to date have primarily
focused on physical training to improve physical outcomes. Combined physical and computer-based cognitive
training programs have been associated with significant improvements in global cognitive function, and
computerized brain training exercises have demonstrated enhancement in memory, processing speed, and
multitasking. This training, however, has not been examined in surgical or hospitalized patients. We have
demonstrated that cognitive training and physical exercises are feasible prior to major surgery and in the
hospital, that a combined cognitive and physical rehabilitation program after discharge can reduce ADRD, and
that a computerized cognitive rehabilitation program can improve multiple cognitive domains in ICU survivors.
Further, exercise enhances endothelial and BBB function, reduces cerebral atrophy, and increases functional
connectivity, providing potential mechanistic basis for these improvements. Thus, a comprehensive mind and
body training program prior to (prehabilitation), during, and after (rehabilitation) hospitalization may be most
effective in reducing ADRD and disability after major surgery but has yet to be evaluated. The main
hypothesis of the COgnitive and Physical Exercise to improve Outcomes after Surgery (COPE-iOS)
study is that a program of cognitive and physical training throughout the perioperative period will
improve long-term cognitive and disability outcomes in older surgical patients at high risk for decline.
We will randomize 250 patients ≥60 years old undergoing elective major non-cardiac surgery with expected
hospitalization >3 days to a comprehensive training program or to active ...

## Key facts

- **NIH application ID:** 10355502
- **Project number:** 5R01AG061161-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Christopher Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $831,725
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355502

## Citation

> US National Institutes of Health, RePORTER application 10355502, Cognitive and Physical Exercise to Improve Outcomes after Surgery in the Elderly (5R01AG061161-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10355502. Licensed CC0.

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