Postsurgical Pain and Opioid Use in Older Adults: Effects of Mild Cognitive Impairment

NCT07885085 | Not Yet Recruiting DMC

• 2 other identifiers: 261018R01AG098934
• Study Type: observational
• Target: 552
• Locations: 1 country
• Sites: 1

Brief Summary

Mild cognitive impairment (MCI) affects a substantial proportion of older adults undergoing major surgery and may alter pain processing, pain experience, and opioid use after surgery. This prospective observational cohort study will compare older adults with MCI and cognitively intact older adults undergoing major orthopedic and complex spine procedures. Participants will undergo preoperative assessment of cognitive function, quantitative sensory testing, heart rate variability, clinical pain, and biomarkers associated with Alzheimer's disease risk. Postoperative pain trajectories, opioid use, pain responsiveness, and cognitive outcomes will be evaluated for six months following surgery. The study aims to determine whether MCI is associated with differences in postoperative pain and opioid use outcomes and whether APOE4 status and plasma amyloid beta 42/40 ratio contribute to observed differences.

Conditions

Mild Cognitive Impairment (MCI); Opioid Use; Postoperative Pain; Cognitive Dysfunction

Keywords

Mild Cognitive Impairment; MCI; Postoperative pain; Opioid Analgesics; Quantitative Sensory testing; Heart Rate Variability; APOE4; Amyloid Beta; Older Adults; Total Knee Arthroplasty; Total Hip Arthoplasty; Spine Fusion

Outcome Measures

Primary Outcomes (4)

• Past 24-Hour Average Pain Intensity

  Average postoperative pain intensity will be measured using an 11-point Numeric Rating Scale (NRS) ranging from 0 (No Pain) to 10 (Worst Possible Pain). Participants will rate their average pain during the previous 24 hours at each assessment. Results will be reported as the mean NRS score and standard deviation for each study group at each time point, as well as the mean change from baseline. Between-group differences in pain trajectories across the postoperative period will be assessed.

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

• Cumulative Postoperative Opioid Use

  Postoperative opioid use will be quantified through pill counts and electronic health record review. All opioid medications consumed will be converted to morphine milligram equivalents (MME). Results will be reported as the cumulative MME consumed during each follow-up interval and cumulatively through 6 months after surgery. Mean MME, standard deviation, median, and range will be reported for each study group.

  Postoperative Discharge through 6 months after surgery.

• Heat Pain Threshold Temperature

  Heat pain threshold will be assessed using the Medoc TSA2 Air quantitative sensory testing system. The outcome measure is the average temperature in degrees Celsius at which thermal stimulation is first perceived as painful across four testing trials. Results will be reported as mean threshold temperature (°C), standard deviation, and mean change from baseline. Lower temperatures indicate increased pain sensitivity.

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

• High-Frequency Heart Rate Variability (HF-HRV)

  Cardiac vagal regulation will be assessed from a 5-minute resting electrocardiographic recording. The primary outcome will be high-frequency heart rate variability derived using Kubios HRV software according to established HRV analysis methods. Results will be reported as mean HF-HRV values and mean change from baseline for each study group. Higher values indicate greater vagal inhibitory control.

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

Secondary Outcomes (14)

• Temporal Summation of Pain

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

• Suprathreshold Heat Pain Intensity Rating

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

• Suprathreshold Heat Pain Unpleasantness Rating

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

• Past 24-Hour Pain Unpleasantness

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

• Past 24-Hour Worst Pain Intensity

  Baseline, 2 weeks, 1 month, 3 months, and 6 months after surgery.

Other Outcomes (3)

• Difference in Pain Outcomes by APOE4 Carrier Status

  Baseline through 6 months after surgery.

• Difference in Pain Outcomes by Plasma Amyloid Beta 42/40 Ratio

  Baseline through 6 months after surgery.

• Change in Hopkins Verbal Learning Test-Revised Total Recall Score

  Baseline and 6 months after surgery

Study Arms (3)

Older Adults with Mild Cognitive Impairment

Older adults aged 65 years or older undergoing elective major orthopedic or complex spine surgery who meet protocol-defined psychometric criteria for mild cognitive impairment. Follow-up includes cognitive, pain, quantitative sensory testing, heart rate variability, biomarker, and opioid use assessments.

Cognitively Intact Older Adults

Older adults aged 65 years or older undergoing elective major orthopedic or complex spine surgery who do not meet criteria for mild cognitive impairment. Participants undergo the same longitudinal assessments as the MCI cohort.

Caregiver Participants

Adult informal caregivers of enrolled patient participants. Caregivers may serve as spouses/partners, adult family members, or other unpaid caregivers. Caregiver participants complete questionnaires regarding observations of patient pain, recovery, medication management, and home opioid use during postoperative follow-up. Caregiver enrollment is voluntary and independent of patient enrollment except when a caregiver serves as a surrogate/LAR for consent purposes.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes two cohorts of surgical patients aged 65 years and older undergoing elective orthopedic or complex spine surgery and one cohort of adult informal caregivers aged 18 years and older associated with enrolled patients.

You may qualify if:

• PATIENT PARTICIPANTS:
• Aged 65 years or older
• Ability to provide informed consent
• English literacy sufficient to complete study measures
• No daily opioid use in the prior 3 months
• Residence within a 1-hour drive of Nashville
• Deemed healthy enough for quantitative sensory testing (QST) procedures by surgical Co-Investigators
• Undergoing elective surgical procedures including tier 2 or 3 procedures (e.g., posterior cervical fusion, thoracic/lumbar fusion \>= 3 levels)
• CAREGIVER PARTICIPANTS:
• Age \>= 18 years at the time of consent
• Identified as the patient's spouse/partner, adult family member, or other unpaid informal caregiver-and, for a patient scoring \<= 14.5 on the University of California San Diego Brief Assessment of Capacity to Consent (UBACC), the designated surrogate/legally authorized representative (LAR) under the applicable institutional and state hierarchy
• In regular contact with the patient (in person, by phone, or by video) across the 6-month follow-up period, sufficient to observe the patient's home opioid use
• Able to read and respond to study materials in English
• Able and willing to provide written consent-for their own participation and/or on the patient's behalf as surrogate/LAR
• Passes the pre-consent caregiver cognitive/capacity screen

You may not qualify if:

• PATIENT PARTICIPANTS:
• Emergency or urgent surgeries
• Reoperation after prior total hip, knee, or complex spine surgery
• Current or past dementia diagnosis
• History of cerebrovascular disease or stroke
• Diagnosis of postoperative or post-intensive care neurocognitive disorder within the 12 months
• CAREGIVER PARTICIPANTS:
• Unable or unwilling to provide written consent
• Evidence of impaired decisional capacity (e.g., known dementia, acute intoxication, or acute medical or psychiatric condition)-disqualifying particularly for a caregiver serving as surrogate/LAR
• Sensory, motor, cognitive, or language limitation precluding reliable self-completion of questionnaires
• Paid/professional caregiver serving in a formal capacity (e.g., hired aide or private-duty nurse), as the study targets informal caregiving
• Declines participation

Sponsors & Collaborators

• Miklos Kertai: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Vanderbilt Health

Nashville, Tennessee, 37212, United States

Location

Related Publications (3)

• Monroe TB, Gibson SJ, Bruehl SP, Gore JC, Dietrich MS, Newhouse P, Atalla S, Cowan RL. Contact heat sensitivity and reports of unpleasantness in communicative people with mild to moderate cognitive impairment in Alzheimer's disease: a cross-sectional study. BMC Med. 2016 May 10;14:74. doi: 10.1186/s12916-016-0619-1.

  PMID: 27164846 BACKGROUND

• Cowan RL, Beach PA, Atalla SW, Dietrich MS, Bruehl SP, Deng J, Wang J, Newhouse PA, Gore JC, Monroe TB. Sex Differences in the Psychophysical Response to Contact Heat in Moderate Cognitive Impairment Alzheimer's Disease: A Cross-Sectional Brief Report. J Alzheimers Dis. 2017;60(4):1633-1640. doi: 10.3233/JAD-170532.

  PMID: 28968238 BACKGROUND

• Kertai MD, Monroe TB, Cowan RL, Bruehl S. Mild cognitive impairment and postsurgical pain in older adults: A call for research. J Clin Anesth. 2025 Jan;100:111669. doi: 10.1016/j.jclinane.2024.111669. Epub 2024 Nov 1. No abstract available.

  PMID: 39488443 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Pain, Postoperative; Plaque, Amyloid

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Anatomical

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: October 13, 2026
• First Posted: October 21, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2032
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)