Effects of Brain Beta-Amyloid on Postoperative Cognition

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Cognitive Dysfunction
• Intervention / Treatment: Other: no intervention; Drug: Florbetapir F 18 (18F-AV-45)

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marek Brzezinski, MD, PhD; Phone Number: 877-487-2838; Email: brzezinm@anesthesia.ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • Recruiting
      • San Francisco VA Medical Center
      • Principal Investigator: Marek Brzezinski, MD, PhD
      • Sub-Investigator: Kim Hubert, MD, PhD
      • Sub-Investigator: Carina Mari Aparici, MD
      • Sub-Investigator: Michael Weiner, MD
      • Sub-Investigator: John Kornak, PhD
      • Sub-Investigator: Joel H Kramer, PsyD
      • Sub-Investigator: Mervyn Maze, MB, ChB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 63 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Surgical Group; 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); Single IV bolus injection of 370 MBq (10mCi) florbetapir will be administered approximately 50 minutes prior to a 10 minute PET scan.; Other Names: Florbetapir; Amyvid 18F-AV-45
Other: Non-surgical group; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Avid Radiopharmaceuticals; Alzheimer's Drug Discovery Foundation
• Investigators: Principal Investigator: Marek Brzezinski, MD, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 25, 2012

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Postoperative Cognitive Dysfunction; POCD; Postoperative Cognitive Decline; Florbetapir F 18 (18F-AV-45)
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications
• Other Study ID Numbers: 20110506; 18F-AV-45-A14 (Avid Radiopharmaceuticals)

Drug and device information, study documents

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