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

Study Overview
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Brief Summary
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(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.

Detailed Description
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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.

Official Title
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Investigating NeuroinflammaTion UnderlyIng Postoperative Brain Connectivity Changes, POCD, Delirium in Older Adults

Conditions
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Delirium

Intervention / Treatment
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* Device: Millipore biomarker assay plate


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Surgical patients<br>Surgical patients will undergo CSF biomarker assays, cognitive testing and fMRI scans. | Device: Millipore biomarker assay plate<br>* Millipore biomarker assay plate CSF cytokine assays as well as CSF flow cytometry<br>|

What is the study measuring?
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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 |