Investigating NeuroinflammaTion UnderlyIng Postoperative Brain Connectivity Changes, POCD, Delirium in Older Adults (INTUIT)

(From NIH reporter) Each year >16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer's disease. Understanding the etiology of POCD will likely help promote strategies to treat and/or prevent it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. The preliminary data of this team strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, the investigators will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow the investigators to evaluate the role of specific neuro-inflammatory processes in POCD and its underlying brain connectivity changes.

Study Overview

• Status: Completed
• Conditions: Delirium
• Intervention / Treatment: Device: Millipore biomarker assay plate

Detailed Description

Each year >16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer's disease. Understanding the etiology of POCD will likely help promote strategies to treat and/or prevent it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. The preliminary data of this team strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, the investigators will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow the investigators to evaluate the role of specific neuro-inflammatory processes in POCD and its underlying brain connectivity changes.

• Study Type: Observational
• Enrollment (Actual): 201

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27712
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 130 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Surgical patients age 60 and above, as described above.

Description

Inclusion Criteria:

• Age 60 and above
• Having surgery scheduled to last > or = to 2 hours at Duke University Medical Center (ie Duke Hospital, Duke Medicine Pavilion, Duke Regional Hospital, Durham VA, Duke Raleigh Hospital)

Exclusion Criteria:

• Anticoagulants (per ASRA guidelines)
• Current use of chemotherapeutic agents with known cognitive effects.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Surgical patients; Surgical patients will undergo CSF biomarker assays, cognitive testing and fMRI scans.	Device: Millipore biomarker assay plate; Millipore biomarker assay plate CSF cytokine assays as well as CSF flow cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between Perioperative changes in CSF Monocytes and perioperative changes in cognition (continuous cognitive index change)	as above	from before to 6 weeks after anesthesia/surgery

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• Berger M, Murdoch DM, Staats JS, Chan C, Thomas JP, Garrigues GE, Browndyke JN, Cooter M, Quinones QJ, Mathew JP, Weinhold KJ; MADCO-PC Study Team. Flow Cytometry Characterization of Cerebrospinal Fluid Monocytes in Patients With Postoperative Cognitive Dysfunction: A Pilot Study. Anesth Analg. 2019 Nov;129(5):e150-e154. doi: 10.1213/ANE.0000000000004179.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 15, 2017
• Primary Completion (ACTUAL): November 11, 2021
• Study Completion (ACTUAL): October 21, 2022

Study Registration Dates

• First Submitted: September 3, 2017
• First Submitted That Met QC Criteria: September 3, 2017
• First Posted (ACTUAL): September 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium
• Other Study ID Numbers: Pro00083288; 1K76AG057022 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No