Biomarkers Associated With Postoperative Cognitive Dysfunction

Recruiting

• Conditions: Postoperative Cognitive Dysfunction; Cognitive Impairment; Cognitive Decline; Delirium
• Interventions: Procedure: Intraoperative electroencephalography recording; Procedure: Neurofilament light chain measurement; Procedure: Tau protein measurement

• Registration Number: NCT05464355
• Lead Sponsor: University of Oxford

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-11
• Study First Submitted QC: 2022-07-15
• Study First Posted: 2022-07-19
• Study Start: 2023-01-05
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-04
• Last Update Posted: 2023-12-05
• Primary Completion: 2024-11
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Biomarker monitoring	Tau protein measurement	-
Biomarker monitoring	Neurofilament light chain measurement	-
Biomarker monitoring	Intraoperative electroencephalography recording	-

Primary Outcome Measures

Name	Time	Method
Feasibility to conduct the study	1 year after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Postoperative delirium incidence and severity	Up to 5 days after surgery	Postoperative delirium identified as being present according to a positive result using 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and severity according to the absolute value on the 3D-CAM-Severity which is a scale converting the 3-Minute Diagnostic Interview for Confusion Assessment Method into a scale from 0-7. Higher scores are associated with worse outcome.
Long term cognitive impairment	Up to 5 years after surgery	Incidence of new diagnosis in primary or secondary care of dementia or mild cognitive impairment
Days alive and at home up to 90 days after surgery	90 days after surgery	The number of days a participant is alive and how many are spent at home after surgery
Postoperative neurocognitive dysfunction and severity	Up to 1 year after surgery	Cognitive impairment measured on Montreal Objective Cognitive Assessment administered by telephone. The scale is 0-22 with higher scores representing better outcome.
Change in neurofilament light chains and tau proteins levels pre- to post operatively	Up to 2 days after surgery	Measurements of the level of the biomarkers neurofilament light chain and tau protein in plasma

Trial Locations

Locations (1)

Royal Berkshire NHS Foundation Trust; 🇬🇧 Reading, Berkshire, United Kingdom