Biomarkers Associated With Postoperative Cognitive Dysfunction

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Delirium, Postoperative Cognitive Dysfunction, Cognitive Decline, Cognitive Impairment

Intervention / Treatment
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* Procedure: Intraoperative electroencephalography recording
* Procedure: Neurofilament light chain measurement
* Procedure: Tau protein measurement


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative delirium incidence and severity | 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. | Up to 5 days after surgery | 
| Days alive and at home up to 90 days after surgery | The number of days a participant is alive and how many are spent at home after surgery | 90 days after surgery | 
| Change in neurofilament light chains and tau proteins levels pre- to post operatively | Measurements of the level of the biomarkers neurofilament light chain and tau protein in plasma | Up to 2 days after surgery | 
| Postoperative neurocognitive dysfunction and severity | Cognitive impairment measured on Montreal Objective Cognitive Assessment administered by telephone. The scale is 0-22 with higher scores representing better outcome. | Up to 1 year after surgery | 
| Long term cognitive impairment | Incidence of new diagnosis in primary or secondary care of dementia or mild cognitive impairment | Up to 5 years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electroencephalography, Delirium, Neurofilament light chain, Tau protein