Interventions for Postoperative Delirium: Biomarker-3

Study Overview
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Brief Summary
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The IPOD-B3 study aims to characterize the relationship between premorbid brain activity and postoperative delirium in patients undergoing major surgery. This is a expansion of the NeuroVISION Bolt-On study, NCT01980511.

Detailed Description
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9/8/21-- Deleted two Outcome Measures pending IRB approval. 11/5/21-- added outcome measures after IRB approval.

Official Title
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Interventions for Postoperative Delirium: Biomarker-3

Conditions
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Delirium

Intervention / Treatment
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* Procedure: High Density-Electroencephalogram
* Procedure: Magnetic Resonance Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥65 years Anticipated length of hospital stay of at least 2 days after surgery that occurs under general or neuraxial anesthesia Written Informed Consent for potential participation prior to surgery Exclusion Criteria: Contraindication to EEG Unable or unwilling to attend the follow-up appointments Documented history of dementia Deemed incapable of providing consent by surgical team Residing in a nursing home Undergoing intracranial surgery Unable to complete neurocognitive testing due to language, vision or hearing impairment Unable to communicate with the research staff due to language barriers For optional MRI portion of the study: Contraindication to MRI (e.g., implanted devices not safe for MRI studies, claustrophobia, unable to lie flat or still)

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: High Density-Electroencephalogram|EEG is a safe non-invasive technology without complications that may be used to help diagnose delirium|
|Procedure: Magnetic Resonance Imaging|MRI scan of brain|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Connectivity | Change from baseline functional connectivity at immediate postoperative period and association between delirium (CAM) and functional connectivity of the cingulate cortex | Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Post-Operative days 1-4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation | Assess the changes from preoperative to postoperative EEG associated with delirium and change in plasma/cerebrospinal fluid (CSF) IL-6 or other biomarkers (e.g. other cytokines or markers of neronal injury) | Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: POD1-4 | 
| Biomarkers | Identify biomarkers of delirium and neural damage through changes in circulating plasma proteins and molecules (through mass spectometry) | Post-operative day 1 through 4 | 
| Brain measurements | Assess the association between preoperative white matter connectivity (DTI) and cortical thickness (derived from MRI) and postoperative delirium | Preoperative MRI will occur up to 4-weeks prior to surgery. Delirium is followed postoperatively, days 1-4 | 
| Long term cognition | Examine the incidence of delirium with change in cognition from preoperatively to one-year postoperatively. | Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Long term post-operative cognition measured 1 year after surgery. | 
| Long term cognition | Assess the impact of delirium, preoperative and postoperative imaging biomarkers with a change in long term cognition | Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Up to two years after surgery | 
| Baseline cognition, specific and global. | Examine the association between preoperative cognition using a neuropsychological battery, and postoperative delirium incidence. | Cognition is assessed preoperatively. Participants are followed for delirium on postoperative days 1-4 | 
| Biomarkers and brain measurements | Assess the changes in cognition and biomarkers over one year with EEG changes. | Pre-op measures: up to 4 weeks prior to surgery. Post-op measures: one year, and two years, after surgery. | 
| Representativeness of surgical population | Identify whether patients who consent to the MRI are reflective of the surgical population. | Pre-op MRI: up to 4 weeks prior to surgery. | 
| Genetics and delirium | Identify genetic and epigenetic changes associated with delirium and its pathogenesis. | Pre-op blood collected up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Post-operative blood collected on postoperative days 1-4. Long term blood collected 90 days and 1 year after surgery. | 
| Postoperative amyloid beta deposition and delirium | Identify associations between delirium and amyloid beta deposition detected by Positron Emission Tomography at 90 days after surgery in sub-study IPOD-PET. | Post-operative delirium measured on postoperative days 1-4. PET imaging will occur 90 days after surgery. | 
| Long term changes in amyloid beta deposition and delirium | Identify associations between delirium and amyloid beta deposition detected by Positron Emission Tomography preoperatively and 1 year after surgery in sub-study IPOD-PET2. | Pre-operative PET imaging will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Post-operative PET imaging will occur 1 year after surgery. | 
| Long term cognition | Identify predictors of delirium severity and incidence, for change in cognition from preoperatively to two-years postoperatively. | Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Long term post-operative cognition measured 2 years after surgery. |