Heyer EJ et al. (2005) APOE-ε4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy. Neurology [doi: 10.1212/01.wnl.0000184579.23624.6b]

Approximately 25% of patients undergoing carotid endarterectomy (CEA) experience anesthesia-unrelated cognitive dysfunction immediately afterwards; many show continued dysfunction a month later. The presence of the apolipoprotein E (APOE)-ε4 allele has been associated with worse outcome after traumatic and ischemic brain injuries. To determine whether this allele can be used to improve selection of patients for CEA, Heyer and colleagues studied the relationship between presence of the allele and development of neurocognitive impairment in 75 prospectively recruited patients undergoing CEA. Patients undergoing lumbar laminectomy (n = 46), matched for age and education, acted as the control group with regard to surgical anesthesia.

APOE genotype was determined using polymerase chain reaction amplification of restriction fragment length polymorphisms. Patients undertook five neuropsychological tests before and 1 month after surgery to produce a total deficit score.

Frequency of the APOE-ε4 allele was similar to that in the general population, with 12/75 CEA patients (16%) carrying it; 5 of these experienced cognitive deficit 30 days after surgery, compared with 3/63 without the allele (P = 0.002). Furthermore, carriers' deficits were greater than those of patients in whom the APOE-ε4 allele was absent (P = 0.02). Multivariate analysis showed that having the APOE-ε4 allele resulted in a greatly increased risk of neurocognitive dysfunction 1 month after CEA (odds ratio 62.28); obesity and diabetes mellitus were also independent predictors (odds ratios 24.43 and 51.42, respectively).

The allele's strong, independent association with cognitive impairment means that it could be used to help identify patients for whom risk of cognitive impairment outweighs the benefit of CEA.