Apolipoprotein E and neurocognitive outcome from coronary artery surgery.

The apolipoprotein E (apoE) gene (APOE) is polymorphic with three alleles, e2, e3, and e4, which give rise to three isoforms, E2, E3 and E4. Many reports have now described a strong association between the e4 allele and risk of developing late onset Alzheimer's disease as the result of the E4 isoform binding to β-amyloid protein and accelerating the depo-sition of amyloid, which is the main constituent of senile plaques. 1 The APOE e4 allele also appears to be associated with deposition of β-amyloid after traumatic brain injury, which is also accompanied by increased APOE expression in the central and peripheral nervous systems. Neurological and cognitive decrements are well documented complications of coronary artery bypass grafting (CABG) surgery. Given that APOE e4 is associated with deposition of β-amyloid after traumatic brain injury, and poor neurological outcome after subarachnoid haemorrhage and stroke, it may also adversely influence neurocognitive outcome after CABG surgery. In a preliminary report, Tardiff and colleagues 2 found that the APOE e4 allele was associated with greater risk of cognitive impairment, especially in those patients with lower educational levels. More recently, Steed and colleagues 3 were unable to replicate the findings in a larger study. However, both of these studies had low incidences of APOE e4 allele, and thus its role remains equivocal. Previously, we have reported that palpable aortic atheroma and a preoperative neurologi-cal deficit are risk factors for a decline in cog-nition after CABG surgery. 4 Here we report the effect of the APOE e4 allele in 86 patients who formed a subgroup in that study. The day before and three months after CABG surgery, a battery of cognitive tests and a structured neurological examination were completed. Factor analysis of the cognitive test battery found that 52% of the test score variance before surgery on these six tests was explained by one component, validating the use of a General Cognitive Factor. The cognitive tests' z scores were summed to obtain an overall General Cognitive Score, which was shown to have a very high correlation (r=0.998) with the General Cognitive Factor. Blood (2.7 ml) was collected into potassium/EDTA (1.2 mg/ml) at the three month follow up appointment, and DNA was extracted for APOE genotyping. Fifty two patients were APOE e4 negative and 34 were APOE e4 positive. The allele frequencies for APOE e2, APOE e3, and APOE e4 were 0.07 (12/172), 0.72 (123/172), and 0.21 (37/172) respectively. …