Biomarkers Associated With Postoperative Cognitive Dysfunction

Sponsor

University of Oxford (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05464355

Collaborator

Oxford University Hospitals NHS Trust (Other)

Enrollment

67.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Delirium Postoperative Cognitive Dysfunction Cognitive Decline Cognitive Impairment	Procedure: Intraoperative electroencephalography recording Procedure: Neurofilament light chain measurement Procedure: Tau protein measurement

Study Design

Study Type:

Observational

Anticipated Enrollment :

45 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Feasibility Study of the Use of Biomarkers to Detect Perioperative Brain Injury: the Association Between Serum Neurofilament Light Chains, Tau Proteins, Continuous Intra-operative Electroencephalography, and the Development of Post Operative Cognitive Dysfunction After Surgery

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Feb 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Biomarker monitoring	Procedure: Intraoperative electroencephalography recording Intraoperative electroencephalography measurements, a non-invasive routine monitoring device used during anaesthesia to measure the brain's electrical activity Other Names: EEG recording Procedure: Neurofilament light chain measurement Measurement of the level of neurofilament light chain in a blood sample Other Names: NfL Procedure: Tau protein measurement Measurement of the level of tau protein in a blood sample

Arm

Intervention/Treatment

Biomarker monitoring

Procedure: Intraoperative electroencephalography recording

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

Other Names:

EEG recording

Procedure: Neurofilament light chain measurement

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

Other Names:

NfL

Procedure: Tau protein measurement

Measurement of the level of tau protein in a blood sample

Outcome Measures

Primary Outcome Measures

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

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.
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
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
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.
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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