Whole Genome Single Nucleotide Polymorphisms in Elderly Patients With Postoperative Cognitive Dysfunction

Study Overview
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Brief Summary
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Postoperative cognitive dysfunction (POCD) presents as a long-lasting decline in cognitive function following surgery. Recognized as an important neuropsychological complication of anesthesia and surgery, POCD occurs predominantly in elderly patients, and even after minor procedures. It affects 41% of patients over the age of 60 years one week after major noncardiac surgery, and persists until the third postoperative month in 13% of cases. POCD has an adverse impact on quality of life, may result in prolonged hospitalization and increased health care costs, and is associated with the risk of leaving the labor market prematurely and dependency on social transfer payments, as well as increased one-year mortality. Elderly patients are particularly at risk. Other risk factors include a pre-existing cognitive impairment, cerebral, cardiac or vascular disease, diabetes, alcohol consumption and a lower level of education. The occurrence of postoperative delirium seems to predispose patients to POCD. However, POCD itself is not associated with the development of dementia. The pathogenic mechanism leading to POCD remains unclear. Numerous etiologic pathways have been suggested: cerebral ischemia due to impaired intraoperative cerebral perfusion and/or oxygenation, systemic inflammation and the effect of proinflammatory cytokines on the brain, altered cholinergic neurotransmission, anesthetic neurotoxicity, hormonal changes induced by surgical stress, sleep or circadian disturbances, or genetic factors. Several studies have explored possible associations between a specific genotype and POCD; however, these were predominantly performed in patients undergoing cardiac surgery or carotid endarterectomy. Previous reports primarily focused on the analysis of the apolipoprotein E genotype as a predisposing factor for POCD. Results of some of these studies have been pooled in a recent meta-analysis. Other studies have investigated polymorphisms of the human circadian clock gene HPER3, complement, cytochrome P450, platelet glycoprotein IIIa, phosphodiesterase 4D, P-selectin, C-reactive protein, and the inducible nitric oxide synthase promoter. The primary aim of this retrospective study of available cohort data is to investigate a specific genotype and to identify single nucleotide polymorphisms (SNPs) which may predispose elderly patients undergoing major noncardiac surgery to POCD.

Official Title
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Whole Genome Single Nucleotide Polymorphisms in Elderly Patients With Postoperative Cognitive Dysfunction

Conditions
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Postoperative Cognitive Dysfunction

Intervention / Treatment
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* Genetic: Whole genome small nucleotide polymorphism genotyping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists (ASA) physical status I-IV Major noncardiac surgery under general anesthesia Native German or French speakers Exclusion Criteria: Cardiac surgery Neurosurgery Surgery within 12 months prior to inclusion History of intracranial or cerebrovascular pathology Preoperative Mini-Mental State Examination (MMSE) score <24 Psychiatric disease and long-term psychopharmacological treatment

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

| Intervention/Treatment |
| --- |
|Genetic: Whole genome small nucleotide polymorphism genotyping|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) scores at one week |  | Postoperative day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-Mental State Examination (MMSE) |  | Postoperative day 7 | 
| Trail Making Test Part A |  | Postoperative day 7 | 
| Trail Making Test Part B |  | Postoperative day 7 | 
| Phonemic Fluency Test (S-words) |  | Postoperative day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative cognitive dysfunction, Postoperative cognitive decline, Postoperative delirium, Cognitive outcome, Neuropsychology, Genetics