APOE-epsilon4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy.
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.


CONCLUSIONS
The APOE-epsilon4 allele is a robust independent predictor of neurocognitive decline 1 month following CEA.
Heyer
E J
EJ
Department of Neurological Surgery, Columbia University, New York, NY 10032, USA.
Wilson
D A
DA
Sahlein
D H
DH
Mocco
J
J
Williams
S C
SC
Sciacca
R
R
Rampersad
A
A
Komotar
R J
RJ
Zurica
J
J
Benvenisty
A
A
Quest
D O
DO
Todd
G
G
Solomon
R A
RA
Connolly
E S
ES
D000368:Aged; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D015984:Causality; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D048909:Diabetes Complications / Q000503:physiopathology; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009765:Obesity / Q000150:complications; D011237:Predictive Value of Tests; D011446:Prospective Studies
D053327:Apolipoprotein E4; D001057:Apolipoproteins E