Apolipoprotein E and neurocognitive outcome from coronary artery surgery

Abstract

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 deposition 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 neurological deficit are risk factors for a decline in cognition 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. The incidence of palpable aortic atheroma (χ 2 =0.536, p=0.464) and preoperative (χ 2 =0.124, p=0.724) and postoperative (χ 2 =2.44, p=0.118) neurological deficits were not significantly affected by the APOE e4 allele.We tested the hypothesis that people with one or more APOE e4 alleles would have a worse cognitive outcome after CABG surgery. Thus, using analysis of covariance, follow up cognitive score was the outcome variable, preoperative cognitive score was controlled by entering it as a covariate, and APOE e4 status was a between ...

Apolipoprotein E Gene Variability and Cognitive Functions at Age 79: A Follow-Up of the Scottish Mental Survey of 1932.

“…One possible reason is because there are substantial aging effects on the cognitive domain of memory that are not shared with the effect of age on general cognition (Salthouse & Ferrer-Caja, 2003). However, in addition to memory, APOE status might influence verbal reasoning , verbal fluency (Robson et al, 2002), and visual attention (Greenwood, Sunderland, Friz, & Parasuraman, 2000).…”

“…Possession of the 4 allele of the APOE gene is associated with earlier death and increased risk of cardiovascular disease, stroke, and Alzheimer's dementia (Farrer et al, 1997;Smith, 2002). The APOE gene is associated with mild cognitive impairment (DeCarli et al, 2001) and perhaps with cognitive decline after head injury (Samatovicz, 2000), cardiac bypass surgery (Robson et al, 2002), and diabetes (Ferguson et al, 2003).…”

Mechanisms of Cerebral Injury from Cardiac Surgery

“…48 Data are inconsistent regarding the role of the apolipoprotein ε4 genotype in perioperative cerebral injury. 2,4,43,87,91,94 Other investigators have examined for a relationship between polymorphisms of genes involved in pathways regulating coagulation, cell adhesion, and inflammation with perioperative cerebral injury. Grocott et al 39 found that the combination of 2 minor alleles of C-reactive protein (CRP; 3′UTR 1846C/T) and interleukin-6 (IL-6; -174G/C) were significantly associated with stroke after cardiac surgery (odds ratio, 3.3; 95% CI, 1.4 to 8.1; P=0.0023).…”

Disfunção cognitiva após cirurgia cardíaca

“…The association between these SNPs and cognitive impairment was tested six months after surgery by multiple logistic regression adjusted by age, education, basal cognitive level and populational structure. A significant Steed et al [15] Robson et al [16] Askar et al [17] Lelis et al [13] Tagarakis et al [12] Arrowsmith et al [61] Roach et al [59] Mitchell et al [62] Wang et al [60] relationship was obtained among carriers of lower alleles of CRP and a reduction of risk for CD (Odds Ratio = 0.37; 95%CI: 0.16 -0.78; p-value = 0.013). In carriers of these lower alleles, the pre-operative levels of CRP were lower, ratifying biological support for the observed allelic association.…”

“…and postoperative (temperature) [1]. Additionally, some researchers have reported a genetic influence on the surgical outcome, in particular related to the presence of the apolipoprotein E å4 allele [12][13][14][15][16][17].…”