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

Postoperative Cognitive Dysfunction Clinical Trial

— GenPOCD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02864173
• Other study ID #: GenPOCD
• Status: Completed
• First received: August 4, 2016
• Last updated: April 24, 2018
• Start date: August 2007
• Est. completion date: October 2011

Study information

• Verified date: April 2018
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Postoperative Cognitive Dysfunction

Intervention

Genetic:
• Whole genome small nucleotide polymorphism genotyping

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mini-Mental State Examination (MMSE)		Postoperative day 7
Secondary	Trail Making Test Part A		Postoperative day 7
Secondary	Trail Making Test Part B		Postoperative day 7
Secondary	Phonemic Fluency Test (S-words)		Postoperative day 7