Effects of Brain Beta-Amyloid on Postoperative Cognition

Study Overview
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Brief Summary
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Postoperative cognitive decline (POCD) affects up to 50% of non-cardiac surgical patients greater than or equal to 65 years of age. This study will test the hypothesis that preoperative presence of brain beta-amyloid plaques in non-demented subjects increases postoperative cognitive decline (POCD) in elderly subjects scheduled for hip or knee replacement. The investigators hypothesize that preoperative beta-amyloid plaques will predict postoperative cognitive decline.

Official Title
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Effects of Brain Beta Amyloid on Postoperative Cognition and 18F-AV-45-A14: Clinical Evaluation of Florbetapir F 18 (18F-AV-45)

Conditions
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Postoperative Cognitive Dysfunction

Intervention / Treatment
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* Drug: Florbetapir F 18 (18F-AV-45)
* Other: no intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for total knee arthroplasty or total hip arthroplasty under general anesthesia (primary arthroplasties and revisions) English speaking Anticipated stay in the hospital Not anticipated to stay intubated postoperatively Patients who live with or have regular visits from an individual (study partner) willing to provide information about the patient's cognitive status Willing and able to undergo all testing procedures including neuroimaging and agree to longitudinal follow up Adequate visual and auditory acuity to allow neuropsychological testing Subjects with Clinical Dementia Rating Scale (CDR) of 0-0.5 Patients who are not demented Subjects sho signed an IRB approved informed consent prior to any study procedures Exclusion Criteria: Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances as indicated by history, which in the opinion of the investigator might pose a potential safety risk to the subject Current clinically significant cardiovascular disease. History of drug or alcohol abuse within the last year, or prior prolonged history of abuse Clinically significant infections disease, including Acquired Immune Deficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection or previous positive test for hepatitis History of relevant severe drug allergy or hypersensitivity Received an investigational medication under an FDA IND protocol within the last 30 days. Current clinically significant unstable medical comorbidities, as indicated by history or physical exam, that pose a potential safety risk to the subject Received a radiopharmaceutical for imaging or therapy within the past 24 hours prior to the imaging session for this study Severe psychiatric disorders including schizophrenia, bipolar disorders, and major depression as described in DSM-IV within the past year (medical record, GDS score, interview with the patient and study partner) Obvious causes for their cognitive impairment (e.g. onset coincides with recent head trauma or stroke) Dementia of any cause CDR score > 0.5 Expressed the preference to undergo the procedure under regional anesthesia in form of spinal or epidural anesthesia Patients who, in the opinion of the investigator, are otherwise unsuitable for a study of this type

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Surgical Group<br>Subjects scheduled to undergo total knee or total hip replacement at the SFVAMC. Subjects in this arm of the study will undergo the florbetapir PET scan once prior to their surgery. Subjects in this arm of the study will undergo serial neurocognitive assessment, heart rate variability measurement, and blood draws for genetic and inflammatory markers. | Drug: Florbetapir F 18 (18F-AV-45)<br>* Single IV bolus injection of 370 MBq (10mCi) florbetapir will be administered approximately 50 minutes prior to a 10 minute PET scan.<br>* Other names: Amyvid 18F-AV-45;|
| Other: Non-surgical group<br>Subjects being seen in at the SFVAMC orthopedic clinic for knee or hip pain but are not anticipating surgical intervention. Subjects in this arm will not undergo the florbetapir PET scan. Subjects in this arm of the study will undergo serial neurocognitive assessment, heart rate variability measurement, and blood draws for genetic and inflammatory markers. | Other: no intervention<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Decline | Measured using comprehensive neurocognitive test battery | At the time of discharge (or at the latest on the 7th postoperative day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic Polymorphisms | Measured by obtaining blood sample | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Vagus nerve tone assessment | Measured using Heart Rate Variability (HRV) | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Inflammatory Markers | Measured by obtaining blood samples | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Perioperative Complications | Measured using patient medical records | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Delirium | Measured using the Confusion Assessment Method rating scale (CAM) or the CAM-ICU if admitted to the intensive care unit | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Coma Assessment | Measured using the Richmond Agitation Sedation Scale (RASS) | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Hospital Length of Stay | Measured using patient medical records | Participants will be followed for the duration of hospital stay, an expected average of 1 week | 
| Postoperative Complications | Measured using patient medical records | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Change in Cognition | Measured using comprehensive neurocognitive test battery | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Quality of Life | Measured by assessing functional status using the Functional Activities Questionnaire and depression using the Geriatric Depression Scale | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Mortality | Measured using patient medical records | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Pain intensity | Measured using the Numerical Rating Scale | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Pain unpleasantness | Measured using the Numerical Rating Scale | Participants will be followed from preoperative baseline to 1 year postoperative | 
| Post-traumatic Stress Disorder symptomatology | Measured using the PTSD Checklist | Participants will be followed from preoperative baseline to 1 year postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative Cognitive Dysfunction, Postoperative Cognitive Decline, POCD, Alzheimer's disease, Florbetapir F 18 (18F-AV-45)