APOE-epsilon4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy

Neurology. 2005 Dec 13;65(11):1759-63. doi: 10.1212/01.wnl.0000184579.23624.6b. Epub 2005 Oct 5.

Abstract

Background: Between 9% and 23% of patients undergoing otherwise uncomplicated carotid endarterectomy (CEA) develop subtle cognitive decline 1 month postoperatively. The APOE-epsilon4 allele has been associated with worse outcome following stroke.

Objective: To investigate the ability of APOE-epsilon4 to predict post-CEA neurocognitive dysfunction.

Methods: Seventy-five patients with CEA undergoing elective CEA were prospectively recruited in this nested cohort study and demographic variables were recorded. Patients were evaluated before and 1 month after surgery with a standard battery of five neuropsychological tests. APOE genotyping was performed by restriction fragment length polymorphism analysis in all patients. Neuropsychological deficits were identified by comparing changes (before to 1 month post-operation) in individual performance on the test battery. Logistic regression was performed for APOE-epsilon4 and previously identified risk factors.

Results: Twelve of 75 (16%) CEA patients possessed the APOE-epsilon4 allele. Eight of 75 (11%) patients experienced neurocognitive dysfunction on postoperative day 30. One month post-CEA, APOE-epsilon4-positive patients were more likely to be cognitively injured (42%) than APOE-epsilon4-negative patients (5%) (p = 0.002). In multivariate analysis, the presence of the APOE-epsilon4 allele increased the risk of neurocognitive dysfunction at 1 month 62-fold (62.28, 3.15 to 1229, p = 0.007). Diabetes (51.42, 1.94 to 1363, p = 0.02), and obesity (24.43, 1.41 to 422.9, p = 0.03) also predisposed to injury.

Conclusion: The APOE-epsilon4 allele is a robust independent predictor of neurocognitive decline 1 month following CEA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Causality
  • Cognition Disorders / genetics*
  • Cognition Disorders / physiopathology
  • Cognition Disorders / psychology
  • Cohort Studies
  • DNA Mutational Analysis
  • Diabetes Complications / physiopathology
  • Endarterectomy, Carotid / adverse effects*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Ischemic Attack, Transient / genetics
  • Ischemic Attack, Transient / physiopathology
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Obesity / complications
  • Predictive Value of Tests
  • Prospective Studies

Substances

  • Apolipoprotein E4
  • Apolipoproteins E