Biomarkers Associated With Postoperative Cognitive Dysfunction

NCT05464355 | Active Not Recruiting

• 3 other identifiers: PID16101302168Protocol version 13/06/2022
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Loss of cognitive function after major surgery is a significant risk in older people. It can occur acutely in the days after surgery as delirium or in months to years later as a persistent reduction in brain function termed neurocognitive decline. Together these conditions are called post operative cognitive dysfunction (POCD). They can be acutely distressing for patients and are associated with other problems after surgery. The causes of post operative cognitive dysfunction are poorly understood. Studies have been limited by a lack of biomarkers to predict which patients are at high risk of developing POCD. Research suggests silent strokes occurring during surgery and different sensitivities to anaesthetic medicines are associated with POCD. The project consists of a feasibility study to investigate markers that might predict people over 65 years old getting POCD. The first biomarker is a non-invasive monitor of anaesthetics effects on brain function called electroencephalography (EEG): The investigators will identify which EEG patterns predict delirium within five days surgery. The second set of biomarkers are two blood tests of proteins that increase after strokes: these are neurofilament light chains and tau proteins. The investigators will establish if these can be used to predict having POCD up to one year after surgery and long term cognitive impairment up to 5 years after surgery.

Conditions

Delirium; Postoperative Cognitive Dysfunction; Cognitive Decline; Cognitive Impairment

Keywords

Electroencephalography; Delirium; Neurofilament light chain; Tau protein

Outcome Measures

Primary Outcomes (1)

• Feasibility to conduct the study

  The total number of participants who are successfully recruited, receive the study procedures and complete both 90 day and 1 year follow up after surgery.

  1 year after surgery

Secondary Outcomes (5)

• Postoperative delirium incidence and severity

  Up to 5 days after surgery

• Days alive and at home up to 90 days after surgery

  90 days after surgery

• Change in neurofilament light chains and tau proteins levels pre- to post operatively

  Up to 2 days after surgery

• Postoperative neurocognitive dysfunction and severity

  Up to 1 year after surgery

• Long term cognitive impairment

  Up to 5 years after surgery

Study Arms (1)

Biomarker monitoring

Procedure: Intraoperative electroencephalography recording; Procedure: Neurofilament light chain measurement; Procedure: Tau protein measurement

Interventions

Intraoperative electroencephalography recording PROCEDURE

Intraoperative electroencephalography measurements, a non-invasive routine monitoring device used during anaesthesia to measure the brain's electrical activity

Also known as: EEG recording

Biomarker monitoring

Neurofilament light chain measurement PROCEDURE

Measurement of the level of neurofilament light chain in a blood sample

Also known as: NfL

Biomarker monitoring

Tau protein measurement PROCEDURE

Measurement of the level of tau protein in a blood sample

Biomarker monitoring

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults over 65 years of age having major elective surgery under general anaesthesia

You may qualify if:

• Greater than or equal to 65 years of age
• Having elective non-cardiac surgery under general anaesthesia
• Anticipated to have at least 48 hours of inpatient admission
• Able \& willing to give informed consent

You may not qualify if:

• Unable to participate in neurocognitive assessments
• Presence of delirium prior to surgery
• Contraindication to use of EEG electrodes (e.g. known allergy to a component of the electrodes)
• Known history of severe traumatic brain injury
• Learning disability specifically with a known structural brain lesion
• Known history of dementia
• Participants undergoing operations on the carotid artery

Sponsors & Collaborators

• University of Oxford: lead
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (1)

Royal Berkshire NHS Foundation Trust

Reading, Berkshire, RG1 5AN, United Kingdom

Location

Biospecimen

Retention: NONE RETAINED

Blood tests will be disposed of after analysis according to standard laboratory operating procedures

MeSH Terms

Conditions

Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction; Charcot-Marie-Tooth disease, Type 1F; Frontotemporal Dementia

Interventions

tau Proteins

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Postoperative Complications; Pathologic Processes; Cognition Disorders; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Microtubule-Associated Proteins; Microtubule Proteins; Cytoskeletal Proteins; Proteins; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins

Study Officials

• Martyn Ezra

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 19, 2022
• Study Start: January 5, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2030
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

GB (1)