Postoperative Neurocognitive Disorders

Study Overview
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Brief Summary
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The purpose of this study is to examine the mechanisms of brain injury contributing to postoperative neurocognitive disorders (PNCD) in an at-risk population (obstructive sleep apnea (OSA)) undergoing surgery. The investigators will enroll 50 OSA patients scheduled for surgery. All patients will have a brain scan (fMRI) within five days before surgery and two days and six months after surgery. During this visit cognitive function will be assessed using the Wide Range Assessment of Memory and Learning (WRAML2) and Montreal Cognitive Assessment (MoCA) tests. Patients will also be asked to participate in a blood draw during the first 2 visits for fMRI (within five days of surgery and two days after surgery). The Confusion Assessment Method (CAM-S) test, will be used to examine postoperative delirium.

Detailed Description
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The investigators will examine the potential mechanisms of brain injury contributing to postoperative neurocognitive disorders (PNCD) in an at-risk population (obstructive sleep apnea (OSA)). This study proposes that neuro-inflammation is associated with measurable tissue changes that can be examined with MD measures and blood biomarkers. On the day of surgery, standard of care procedures will take place. Hemodynamic vitals will be continuously monitored. As per the latest guidelines and recommendations from the American Society of Anesthesiologists (ASA), mean arterial pressure (MAP) will be targeted to > 60 mmHg or within 20% of baseline values, and processed EEG-guided anesthesia will be monitored to maintain a patient state index between 20-50. Electronic medical records and intraoperative integrated physiologic waveform will be collected. In summary, the investigators will examine the potential mechanisms of brain injury contributing to postoperative delirium (POD) and acute and long-lasting neurocognitive deficits in an at-risk population (OSA).

Official Title
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Mechanisms Mediating Postoperative Neurocognitive Disorders

Conditions
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Obstructive Sleep Apnea, Neurocognitive Disorders

Intervention / Treatment
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* Diagnostic Test: Brain Imaging
* Diagnostic Test: Cognitive testing
* Diagnostic Test: Blood Biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of moderate-to-severe OSA (apnea hypopnea index [AHI]>15 events/hour confirmed by overnight polysomnography), scheduled for open or robotic surgery (abdominal, gynecologic, or urologic), and upper or lower extremity orthopedic procedures

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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 |
| --- | --- |
| Study Group<br>brain scans, cognitive tests, blood biomarkers | Diagnostic Test: Brain Imaging<br>* Magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI)-based mean diffusivity (MD) measures.<br>Diagnostic Test: Cognitive testing<br>* Wide Range Assessment of Memory and Learning (WRAML2), Montreal Cognitive Assessment (MoCA), and Confusion Assessment Method for the ICU -severity (CAM-ICU S) tests.<br>Diagnostic Test: Blood Biomarkers<br>* Inflammatory markers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preoperative cognitive function | Montreal Cognitive Assessment (MoCA) test | pre-surgery (within five days before) | 
| Postoperative cognitive dysfunction - delayed cognitive recovery | Montreal Cognitive Assessment (MoCA) test | Post-surgery (within two days post surgery). | 
| Postoperative cognitive dysfunction - neurocognitive disorder | Montreal Cognitive Assessment (MoCA) test | Post-surgery (6 months after surgery). | 
| Preoperative cognitive function II | Wide Range Assessment of Memory and Learning (WRAML2) | pre-surgery (within five days before surgery) | 
| Postoperative cognitive dysfunction - delayed cognitive recovery II | Wide Range Assessment of Memory and Learning (WRAML2) | Post-surgery (within two days post surgery). | 
| Postoperative cognitive dysfunction - neurocognitive disorder II | Wide Range Assessment of Memory and Learning (WRAML2) | Post-surgery (6 months after surgery). | 
| Postoperative Delirium | The Confusion Assessment Method (CAM-S) test | A two times per day for up to three days or discharge from the hospital. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Serum anti-inflammatory Biomarkers | Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay | pre- (within five days before surgery) | 
| Blood Serum anti-inflammatory Biomarkers II | Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay | post-surgery (within two days of surgery). | 
| Brain changes | Using non-invasive magnetic resonance imaging based diffusion tensor imaging | pre- (within five days before) and post-surgery (within two days and 6 months). | 
| Brain changes II | Using non-invasive magnetic resonance imaging based diffusion tensor imaging | Post-surgery (within two days post surgery). | 
| Brain changes III | Using non-invasive magnetic resonance imaging based diffusion tensor imaging | Post-surgery (within six months post surgery). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain imaging, neurocognitive testing