A new five-year, $3.2 million R01 grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), will fund the first systematic investigation of how mild cognitive impairment (MCI) affects pain processing, postsurgical pain and opioid use across the perioperative period.

The prospective clinical study is led by Miklos D. Kertai, MD, PhD, Professor of Cardiothoracic Anesthesiology, and Stephen Bruehl, PhD, Professor of Anesthesiology.

More than 50 million major surgical procedures are performed each year in the United States, over half in older adults. At least 11% of older surgical patients — roughly 3 million people annually — have MCI, a condition linked to progression to Alzheimer’s disease (AD).

“Prior work by our group and others has shown that Alzheimer’s disease is associated with altered pain responsiveness and possible differences in opioid analgesic use,” Bruehl said. “But whether MCI is associated with similar alterations, and how that affects postoperative pain and opioid use, has never been tested.”

The study will compare 120 cognitively intact, older adults with120 adults with MCI who are undergoing major surgery, looking for differences in preoperative objective pain responsiveness and clinical pain; pain trajectory over six months of postoperative follow-up; and postoperative outpatient opioid use.

Objective pain responsiveness will be measured with quantitative sensory testing, and the team will also examine natural pain-inhibitory systems (indexed by heart rate variability).

The investigators will further explore whether two AD-risk biomarkers — APOE4 carrier status and the plasma Aβ42/40 ratio — influence MCI-related pain differences.

Kertai and Bruehl will lead a multidisciplinary team including orthopedic surgeon J. Ryan Martin, MD, spine surgeon Byron Stephens, MD, MSCI, neuropsychologist James Jackson, PsyD, biostatistician Matthew Shotwell, PhD, all from Vanderbilt Health, and Ronald Cowan, MD, PhD, Chair of Psychiatry at the University of Tennessee Health Sciences Center.

“This project will provide the high-quality data needed to characterize the impact of MCI on postsurgical pain experience and patterns of opioid use,” Kertai said. “That knowledge can then be used to optimize perioperative pain care for at-risk older adults with mild cognitive impairment.”

The research is supported by grant R01AG098934 from the National Institute on Aging of the National Institutes of Health.