Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders (BBBSx)

August 10, 2023 updated by: Rajesh Kumar, PhD, University of California, Los Angeles

Blood Brain Barrier Dysfunction and Postoperative Neurocognitive Disorders in Older Adults

Postoperative neurocognitive disorders (PND), which include postoperative delirium and both acute and longlasting neurocognitive deficits, are a significant public health problem, leading to a cascade of deleterious complications. Older adults are particularly at-risk of developing PND both in the short and long term. Although age is consistently reported as an important risk factor, the exact pathophysiology of PND remains poorly understood, but may include postsurgery-compromised blood brain barrier (BBB) function. This project proposes that perioperative BBB dysfunction is associated with measurable brain morphologic findings in cognitive control areas that can be discovered with non-invasive magnetic resonance imaging (MRI). Patients scheduled for surgery with an age range of 65-75 years of age, will participate in brain diffusion-weighted pseudo-continuous arterial spin labeling (DW-pCASL) and diffusion tensor imaging (DTI), cognitive assessments, and evaluation of a BBB marker from blood (at baseline, at two weeks, and at six months after surgery).

All patients will have a brain scan (MRI) within before surgery and two weeks and six months after surgery. During this visit cognitive function will be assessed. Patients will also be asked to participate in a blood draw.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators will examine the potential mechanisms contributing to PND in an older surgical population. It is proposed that BBB will be altered contributing to brain tissue changes in cognitive control areas that can be examined with MD measures and blood biomarkers. Therefore, the specific aims are to:

AIM #1: Examine BBB function, using DW-pCASL procedures, and BBB marker (S100β levels), in older adult subjects between pre- ) and post-surgery

AIM #2: Assess brain tissue changes, using DTI-based MD measures, and cognition function, between pre- and post-surgery in older adult subjects.

AIM #3: Examine the relationships between BBB blood biomarker, BBB function index, and MD values from cognitive control areas (prefrontal cortex, caudate, and hippocampus) between pre- and post-surgery in an older surgical population.

A One-group comparative and longitudinal study design will be used in this proposal. A total of 34 older subjects scheduled for surgery will be recruited. Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic.

To assess cognitive function, the WRAML2 and MoCA tests will be performed within one week before surgery and at two weeks and six months after surgery. These tests have been used by our team in several conditions, and will be introduced just before MRI procedures. An average mean score of 100±15 on WRAML2 and a score ≥26 on MoCA will be considered normal.

Examination of BBB integrity from blood. To account for interindividual variation, baseline systemic biomarkers will be measured preoperatively (within one week before surgery). Postoperative samples will also be collected at two weeks and 6 months of surgery. Samples will be batch analyzed using Enzyme-linked immunosorbent assay (S100β) by the UCLA Department of Pathology & Laboratory Medicine.

Magnetic Resonance Imaging. All brain MRI studies will be performed on a 3.0-Tesla MRI scanner (Siemens, Magnetom, Prisma) at the Department of Radiology, UCLA. MRI studies will be performed within one week before surgery, and at two weeks and six months after surgery.

Study Type

Observational

Enrollment (Estimated)

34

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • Ronald Reagan UCLA Medical Center, Department of Anesthesiology & Perioperative Medicine
        • Principal Investigator:
          • Rajesh Kumar, PhD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

63 years to 73 years (Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients of either sex, in the age range 65-75 years scheduled for abdominal, gynecologic or urologic surgery.

Description

Inclusion Criteria:

  • 65-75 years old
  • Scheduled for abdominal, gynecologic or urological surgery

Exclusion Criteria:

  • Subjects undergoing surgery with a previous history of stroke, myocardial infarction, current pregnancy (if female), diagnosed neuropsychological and neuropsychiatric diseases, airway or chest deformities that would interfere with breathing, chronic obstructive pulmonary disease, cystic fibrosis, presence of space-occupying brain lesions, any history of drug abuse (e.g., cocaine or tobacco use), chronic kidney disease requiring dialysis.
  • Body weight >300 pounds (restrictions of MRI scanner table).
  • All subjects with any contraindication to the MRI procedures, such as metallic and electronic implants (phrenic or cardiac pacemakers), claustrophobia, metallic-based tattoos, will also be excluded. Non-english speaking patients will also be excluded as the cognitive tests have not been validated in other languages.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Study Group
Brain scans, cognitive tests, blood biomarkers
Diagnostic test: Brain Imaging
Magnetic Resonance Imaging (MRI) using diffusion weighted pseudo-continuous arterial spin labeling (DW-pCASL) .
Diagnostic test: Cognitive Testing
Wide Range Assessment of Memory and Learning (WRAML 2) and Montreal Cognitive Assessment (MoCA)
Diagnostic test: Blood Biomarkers
Inflammatory Markers

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preoperative cognitive function
Time Frame: pre-surgery (within five days before)
Montreal Cognitive Assessment (MoCA) test
pre-surgery (within five days before)
Postoperative cognitive dysfunction - delayed cognitive recovery
Time Frame: Post-surgery (within two weeks post surgery)
Montreal Cognitive Assessment (MoCA) test
Post-surgery (within two weeks post surgery)
Postoperative cognitive dysfunction - neurocognitive disorder
Time Frame: Post-surgery (6 months after surgery)
Montreal Cognitive Assessment (MoCA) test
Post-surgery (6 months after surgery)
Preoperative cognitive function II
Time Frame: Pre-surgery (within five days before surgery)
Wide Range Assessment of Memory and Learning (WRAML2)
Pre-surgery (within five days before surgery)
Postoperative cognitive dysfunction - delayed cognitive recovery II
Time Frame: Post-surgery (within two weeks post surgery)
Wide Range Assessment of Memory and Learning (WRAML2)
Post-surgery (within two weeks post surgery)
Postoperative cognitive dysfunction - neurocognitive disorder II
Time Frame: Post-surgery (6 months after surgery)
Assessment of Memory and Learning (WRAML2)
Post-surgery (6 months after surgery)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Serum anti-inflammatory Biomarkers
Time Frame: pre- (within five days before surgery)
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
Time Frame: post-surgery (within two weeks of surgery)
Assess blood inflammatory biomarkers (IL6, TNFa and IL1B) using enzyme-linked immunosorbent assay
post-surgery (within two weeks of surgery)
Brain changes
Time Frame: pre- surgery (within five days before)
Using non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)
pre- surgery (within five days before)
Brain changes II
Time Frame: Post-surgery (within two days post surgery)
non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)
Post-surgery (within two days post surgery)
Brain changes III
Time Frame: Post-surgery (within six months post surgery)
Using non-invasive magnetic resonance imaging diffusion weighted (DW) pseudo-continuous arterial spin labeling (pCASL)
Post-surgery (within six months post surgery)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Investigators

  • Principal Investigator: Rajesh Kumar, Ph.D, rkumar@mednet.ucla.edu
  • Principal Investigator: Susana Vacas, M.D., Ph.D., Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 3, 2020

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

July 31, 2024

Study Registration Dates

First Submitted

September 22, 2020

First Submitted That Met QC Criteria

September 22, 2020

First Posted (Actual)

September 28, 2020

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 10, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBBSx 20-001456

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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