The Analysis of Gene Variants Related to POCD in Elderly Patients

Study Overview
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Brief Summary
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The pathophysiology of postoperative cognitive dysfunction (POCD) following surgery may be related to Alzheimer's disease. Different studies show that; low levels of glial cell line-derived growth factor are found in both POCD and Alzheimer, and brain cholinergic markers like Choline acetyl transferase activity, High affinity choline uptake activity, and Acetil Choline (Ach) activity are decreased in Alzheimer disease.We know cholinergic inputs in the basal forebrain have a critical role in many other functions including memory, attention, arousal and sensory processing. Cholinergic neuron located basal section of forebrain degenerate extensively in Alzheimer disease which shares similarities with postoperative delirium and POCD. Ach binds to two well-known receptors in brain that are Nicotinic receptors which implicate several important functions such as memory, learning, arousal and reward and Muscarinic receptors which are widely distributed in forebrain and play an important role of development delirium and POCD. Dysfunction of cholinergic system may be one key aspect of postoperative DELIRIUM, POCD and ALZHEIMER disease. In this investigation; we would like to evaluate the relationship between genes encoding inflammation-related mediators detected in postoperative cognitive dysfunction and gene variants in Alzheimer's disease in a larger panel for elder patients undergoing major urologic surgery. Therefore our study will focus on demographic information of the patients (age, gender, comorbidity), neurocognitive tests (1 week before the surgery, postoperative 1st week and postoperative 3rd month), intraoperative data (mean arterial pressure, heart rate, need for inotrope, duration of mechanical ventilation, need for transfusion), and biochemical tests (Preoperative and postoperative blood samples for each patient) which are APOE, phosphatidylinositol-binding clathrin assembly protein, CR1 - complement receptor 1, ATP-binding cassette transporter, IL6, TREM.

Official Title
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The Analysis of Gene Variants Related to POCD in Elderly Patients: a Prospective, Observational Study

Conditions
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Cognitive Dysfunction

Intervention / Treatment
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* Procedure: Urologic Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over age of 60 years Patients scheduled for major urologic surgery Exclusion Criteria: Failure of the patient or the person with legal authority to make a decision about him/her. Patients with severe hearing-vision problems before surgery. Patients with severe neurological-psychiatric disorders before surgery. Patients who cannot find a common language. Emergency surgeries

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Major Urologic Surgery Group<br>Elder patients who undergo major urologic surgery will be investigated for the change in genomic protein that are related to cognition. These proteins are APOE, phosphatidyl-inositol-binding clathrin assembly protein, CR1 (complement receptor 1) , ATP-binding cassette transporter, IL6, Triggering receptor expressed on myeloid cells2 (TREM2) | Procedure: Urologic Surgery<br>* Patients undergoing major urologic surgery will be examined with blood samples that will be taken preoperatively and postoperatively. Accordingly several gene variants and proteins will be examined for patients with or without postoperative cognitive dysfunction. These proteins consist of APOE, phosphatidyl-inositol-binding clathrin assembly protein, CR1 - complement receptor 1 , ATP-binding cassette transporter, IL6, Triggering receptor expressed on myeloid cells2 (TREM2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Interleukin-6 levels in elder atients undergoing major urologic surgery | Major urologic surgery patients will be evaluated for their different genomic protein levels that are possibly related to cognitive disorders. These proteins consist of APOE, phosphatidylinositol-binding clathrin assembly protein, CR1 (complement receptor 1) , ATP-binding cassette transporter, Interleukin- 6, Triggering receptor expressed on myeloid cells2 (TREM2). Accordingly two blood samples will be gathered from each patient in the preoperative and postoperative period. | From preoperative 1 hour to postoperative 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Addenbrooke cognitive examinations change (Preoperative to postoperative) | Addenbrooke test will be applied the day before the surgery (T1) and 7 days after the surgery (T2). 0 reflecting the worst and 100 reflecting the best values, 1 standart deviation worsening between the tests will be accepted as Postoperative Cognitive Dysfunction (POCD). Patients with POCD will be accepted as Group POCD (+), without POCD will be accepted as Group POCD (-) | Up to Postoperative 7 days. | 
| Addenbrooke cognitive examinations change for the chronic period | Third Addenbrooke test will be applied on the postoperative third month (T3). Difference between T3 and T2 will be recorded | Up to postoperative three months | 
| The difference in IL-6 between the groups | Postoperative IL-6 level difference in Group POCD (+) versus Group POCD (-). | Up to postoperative 1 hour | 
| DNA sequence analysis of APOE gene | DNA sequence analysis of APOE in whole patient group. | Up to postoperative 1 hour | 
| DNA sequence analaysis of phospatydil-inositol binding clathrin gene | DNA sequence analaysis of phospatydil-inositol binding clathrin gene in whole patient group | Up to postoperative 1 hour | 
| DNA sequence analysis of complement receptor 1 protein gene | DNA sequence analaysis of complement receptor 1 protein gene in whole patient group | Up to postoperative 1 hour | 
| DNA sequence analysis of Triggering receptor expressed on myeloid cells2 (TREM2) | DNA sequence analysis of Triggering receptor expressed on myeloid cells2 (TREM2) in whole patient group | Up to postoperative 1 hour | 
| DNA sequence analysis of ATP-binding cassette transporter gene | DNA sequence analysis of ATP-binding cassette transporter gene in whole patient group | Up to postoperative 1 hour |