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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Cognitive Dysfunction
• Intervention / Treatment: Genetic: Whole genome small nucleotide polymorphism genotyping

• Study Type: Observational
• Enrollment (Actual): 63

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients aged ≥65 years undergoing major noncardiac surgery under general anesthesia

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Nicolai Goettel, MD, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2007
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 8, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): April 25, 2018
• Last Update Submitted That Met QC Criteria: April 24, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Genetics; Postoperative cognitive dysfunction; Neuropsychology; Postoperative delirium; Cognitive outcome; Postoperative cognitive decline
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Postoperative Complications; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Postoperative Cognitive Complications
• Other Study ID Numbers: GenPOCD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO