Neuroinflammation and Alzheimer's Pathology in POCD

NCT ID: NCT05378659

Last Updated: 2022-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

120 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-11-01

Study Completion Date

2022-09-30

Brief Summary

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The purpose of this project is to investigate the role of both neural inflammation and pre-existing neurodegenerative pathology in the risk and pathogenesis of post-operative cognitive dysfunction (POCD). To achieve this goal, the investigators will combine blood and cerebrospinal fluid (CSF) sampling, standardized cognitive tests, and dynamic neurophysiological markers of cortical network dysfunction in the form of event-related potentials (ERPs), to assess the link between neurodegeneration and neuroinflammation in the pathogenesis of POCD.

Detailed Description

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The purpose of this project is to investigate the role of both neural inflammation and pre-existing neurodegenerative pathology in the risk and pathogenesis of post-operative cognitive dysfunction (POCD) in 120 patients who will undergo a Total Knee Arthroscopy. The investigators will also explore neuropsychological, functional and biological measures as pre-operative risk indicators. To achieve this goal, the investigators will combine blood and cerebrospinal fluid (CSF) sampling, standardized cognitive tests, and dynamic neurophysiological markers of cortical network dysfunction in the form of event-related potentials (ERPs), to assess the link between neurodegeneration and neuroinflammation in the pathogenesis of POCD. To separate potential effects of general anesthesia from those of neuroinflammation, The investigators will recruit patients undergoing total knee replacement with the use of sedation and spinal anesthesia. To address the age risk factor, the investigators are targeting patients ages 60 and older. By using both validated and experimental biomarkers, this novel study design will isolate the effects of POCD due to systemic and neural inflammation and examine the links to pre-surgical cognitive impairment and underlying neurodegeneration as susceptibility factors.

Baseline (On the day of their final preoperative surgical visit prior to their TKA) the plan is to collect:

1. Cognitive assessments

a. Montreal Cognitive Assessment b. Stroop Test c. Symbol Digit Modalities Test d. Oral Trail Making Test
2. Collect two 4-ml blood samples for biomarker evaluation

Visit 2 Pre-op (day of scheduled TKA surgery) the plan is to collect:

1. Repeat cognitive testing

a. Montreal Cognitive Assessment b. Stroop Test c. Symbol Digit Modalities Test d. Oral Trail Making Test
2. Collect two 4-ml blood samples for biomarker evaluation
3. Collect 2cc of cerebral spinal fluid

Visit 2 Post-op:

1. 4 AT test for delirium
2. Collect two 4ml blood samples will be taken

Visit 3 (Forty-eight hours after discharge):

1\. brief cognitive testing via telephone or video conferencing.

1. Blind Montreal Cognitive Assessment
2. Oral Trail Making Test

Visit 4 (two weeks for their post-operative visit):

1\. Repeat cognitive testing

1\. Montreal Cognitive Assessment 2. Stroop Test 3. Symbol Digit Modalities Test 2. Oral Trail Making Test 3. Collect two 4ml blood samples for biomarker testing.

For patients who had pre-operative cognitive impairment, their participation in the study will end here

For 20 participants with no indication of pre-surgical cognitive impairment (10 with no post-operative impairment and 10 with presumed POCD)

Visit 5 (\~ 6 weeks post-op) the plan is to collect:
1. Complete initial neurophysiological recording of event-related potentials (ERPs). This ERP session is performed to establish baseline cortical network function. Neurophysiological studies will be conducted using a 128-electrode EEG system.
2. Collect two 4-ml blood samples

Visit 6 End of Study (At 6 months):
1. Collect a final assessment of cognition
2. ERP assessment

Conditions

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Post-Operative Confusion Neuroinflammatory Response Alzheimer Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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With Post-Operative Cognitive Dysfunction

Subjects determined to have post-operative cognitive dysfunction based on the results of:

1. 4AT Delirium Test
2. Scoring on :

1. Montreal Cognitive Assessment
2. Oral Trails Test
3. Stroop Test
4. Symbol Digit Modalities Test

All subjects will undergo:

1. Blood sample collection
2. Cerebral spinal fluid collection
3. ERP testing
4. NACC Cognitive Battery
5. Grooved Pegboard testing

Montreal Cognitive Assessment

Intervention Type BEHAVIORAL

Cognitive evaluation of short term memory, visuospatial abilities, executive functioning, attention, concentration, working memory, language, and orientation to time and place

Stroop Test

Intervention Type BEHAVIORAL

Evaluates Processing Speed and Executive Control

4AT Delirium

Intervention Type DIAGNOSTIC_TEST

Screening tool to test for delirium post surgery

Grooved Pegboard

Intervention Type BEHAVIORAL

Evaluation testing for dominant and non dominant sensory-motor speed

NACC Cognitive Battery

Intervention Type BEHAVIORAL

A series of tests that evaluate attention, concentration, immediate verbal memory, immediate visual memory, discrimination, processing/motor speed, and validity and effort.

ERP Testing

Intervention Type DIAGNOSTIC_TEST

An event-related potential ( ERP) is the measured brain response that is the direct result of a specific sensory, cognitive, or motor event. More formally, it is any stereotyped electrophysiological response to a stimulus. The study of the brain in this way provides a noninvasive means of evaluating brain functioning.

Blood Plasma and Serum sampling

Intervention Type DIAGNOSTIC_TEST

Up to six 4 ml samples of both serum and plasma will be obtained to assess for inflammatory markers.

Cerebral Spinal Fluid Sample

Intervention Type DIAGNOSTIC_TEST

At the time the spinal is placed for anesthetic purposes, 2ml of cerebral spinal fluid will be obtained to assess for inflammatory markers.

Without Post-Operative Cognitive Dysfunction

Subjects determined to not have post-operative cognitive dysfunction based on the results of:

1. 4AT Delirium Test
2. Scoring on :

1. Montreal Cognitive Assessment
2. Oral Trails Test
3. Stroop Test
4. Symbol Digit Modalities Test

All subjects will undergo:

1. Blood sample collection
2. Cerebral spinal fluid collection
3. ERP testing
4. NACC Cognitive Battery
5. Grooved Pegboard testing

Montreal Cognitive Assessment

Intervention Type BEHAVIORAL

Cognitive evaluation of short term memory, visuospatial abilities, executive functioning, attention, concentration, working memory, language, and orientation to time and place

Stroop Test

Intervention Type BEHAVIORAL

Evaluates Processing Speed and Executive Control

4AT Delirium

Intervention Type DIAGNOSTIC_TEST

Screening tool to test for delirium post surgery

Grooved Pegboard

Intervention Type BEHAVIORAL

Evaluation testing for dominant and non dominant sensory-motor speed

NACC Cognitive Battery

Intervention Type BEHAVIORAL

A series of tests that evaluate attention, concentration, immediate verbal memory, immediate visual memory, discrimination, processing/motor speed, and validity and effort.

ERP Testing

Intervention Type DIAGNOSTIC_TEST

An event-related potential ( ERP) is the measured brain response that is the direct result of a specific sensory, cognitive, or motor event. More formally, it is any stereotyped electrophysiological response to a stimulus. The study of the brain in this way provides a noninvasive means of evaluating brain functioning.

Blood Plasma and Serum sampling

Intervention Type DIAGNOSTIC_TEST

Up to six 4 ml samples of both serum and plasma will be obtained to assess for inflammatory markers.

Cerebral Spinal Fluid Sample

Intervention Type DIAGNOSTIC_TEST

At the time the spinal is placed for anesthetic purposes, 2ml of cerebral spinal fluid will be obtained to assess for inflammatory markers.

Interventions

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Montreal Cognitive Assessment

Cognitive evaluation of short term memory, visuospatial abilities, executive functioning, attention, concentration, working memory, language, and orientation to time and place

Intervention Type BEHAVIORAL

Stroop Test

Evaluates Processing Speed and Executive Control

Intervention Type BEHAVIORAL

4AT Delirium

Screening tool to test for delirium post surgery

Intervention Type DIAGNOSTIC_TEST

Grooved Pegboard

Evaluation testing for dominant and non dominant sensory-motor speed

Intervention Type BEHAVIORAL

NACC Cognitive Battery

A series of tests that evaluate attention, concentration, immediate verbal memory, immediate visual memory, discrimination, processing/motor speed, and validity and effort.

Intervention Type BEHAVIORAL

ERP Testing

An event-related potential ( ERP) is the measured brain response that is the direct result of a specific sensory, cognitive, or motor event. More formally, it is any stereotyped electrophysiological response to a stimulus. The study of the brain in this way provides a noninvasive means of evaluating brain functioning.

Intervention Type DIAGNOSTIC_TEST

Blood Plasma and Serum sampling

Up to six 4 ml samples of both serum and plasma will be obtained to assess for inflammatory markers.

Intervention Type DIAGNOSTIC_TEST

Cerebral Spinal Fluid Sample

At the time the spinal is placed for anesthetic purposes, 2ml of cerebral spinal fluid will be obtained to assess for inflammatory markers.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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MOCA

Eligibility Criteria

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Inclusion Criteria

* Males and females 60 years or older in age
* Subjects scheduled to undergo TKA
* Fluent and literate in English
* Able to give consent for themselves based upon the MacArthur Competence Assessment Tool for Clinical Research
* Able to have a subarachnoid block with only intravenous sedation

Exclusion Criteria

* Less than 60 years of age
* Cognitively impaired to the point where they are unable to give consent for themselves
* Blindness or partial blindness
* Pre-existing neurodegenerative conditions
* Contraindication for subarachnoid block and/or requiring general anesthesia
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Alzheimer's Association

OTHER

Sponsor Role collaborator

University of Tennessee Graduate School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert M Craft, MD

Role: PRINCIPAL_INVESTIGATOR

University of Tennessee Graduate School of Medicine

Locations

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Robert M Craft

Knoxville, Tennessee, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Department of Anesthesiology Chair

Role: CONTACT

8653059220

Aimee Pehrson, MPH

Role: CONTACT

8653055432

Facility Contacts

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Robert M Craft, MD

Role: primary

865-305-9220

Aimee Pehrson, MPH

Role: backup

8653055432

References

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Other Identifiers

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4790

Identifier Type: -

Identifier Source: org_study_id

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