APOE-epsilon4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy

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.

Figure

Association of APOE-ε4, diabetes mellitus, and obesity with post-endarterectomy neurocognitive injury. (A) APOE-ε4 –positive patients experienced a 41.7% incidence of neurocognitive dysfunction compared to 4.8% among APOE-ε4 –negative patients (p = 0.002). (B) The rate of dysfunction was 26.3% among those with diabetes and 5.4% among those without diabetes (p = 0.02). (C) 33.3% of obese and 6.3% of nonobese patients experienced neurocognitive decline (p = 0.02).