Meta-Analysis of APOE4 Allele and Outcome after Traumatic Brain Injury

Abstract

There is conflicting evidence regarding a possible association between the apolipoprotein E4 (APOE4) allele and the consequences of traumatic brain injury (TBI). Our aim was to carry out a meta-analysis of cohort studies of sufficient rigor to determine whether the presence of the APOE4 allele contributes to initial injury severity and/or poor outcome following TBI. MEDLINE, EMBase, CBMdisc, and CNKI databases were searched for literature published from January 1993 to October 2007. Of the 100 identified studies, 14 cohort studies were selected for analysis based on comprehensive quality assessment using a standardized scale. Data from the 14 eligible cohort studies included a total of 2527 participants, 736 with and 1791 without the APOE4 allele. The APOE4 allele was not associated with initial injury severity of TBI. The pooled RR were 1.11 (95% confidence interval [CI], 0.91 to 1.35) for severe injury, 1.06 (95% CI, 0.86-1.31) for moderate injury and 0.93 (95% CI, 0.81-1.06) for mild injury. However, the APOE4 allele was significantly associated with a poor outcome of TBI at 6 months after injury (RR = 1.36; 95% CI, 1.04-1.78). The association remained significant in sensitivity tests. This meta-analysis indicates that the presence of the APOE4 allele is not associated with the initial severity of brain injury following TBI but is associated with increased risk of poor long-term outcome at 6 months after injury.

Apolipoprotein E mimetic peptide, CN‐105, improves outcomes in ischemic stroke

“…ApoE exists in humans as three common isoforms, differing by single amino acid substitutions at residues 112 and 158 24. Isoform‐specific protective effects on endogenous neuroinflammatory responses have been observed in humans across different acute brain injuries25, 26 but not in cerebral ischemia 27, 28. Due to its large size, apoE does not cross the blood–brain barrier (BBB) and its therapeutic potential is limited.…”

Cognitive Function After Major Noncardiac Surgery, Apolipoprotein E4 Genotype, and Biomarkers of Brain Injury

“…30 The influence of genetics upon POCD, however, is not as clear, particularly in noncardiac surgical patients. Despite the robust connection between APOE4 genotype and outcome after a variety of brain injuries including traumatic brain injury, 7 aneurysmal subarachnoid hemorrhage, 8 and intracerebral hemorrhage, 15 a link to POCD has been elusive. Abildstrom et al studied the relationship between APOE4 and cognitive dysfunction after major noncardiac surgery in 972 patients from the International Study of Postoperative Cognitive Dysfunction 2 and found no difference in the incidence of POCD (10.3% vs. 9.9%) between patients with and without the APOE4 allele.…”

“…Potential etiologies include APOE specific effects on cerebral blood flow (CBF), 31,32 altered responses to neuronal injury, 7 cerebral metabolic decline, 33 and/or increased cerebral microemboli secondary to increased atheroma burden. 10 Furthermore, multiple lines of evidence support the involvement of APOE4 in the inflammatory response.…”

“…A dominant APOE4 genetic model was used in this study based on the available literature. [7][8][9][10][11] It is possible that other APOE alleles might correlate with cognitive outcome in a more robust fashion, although post hoc analyses did not suggest that this is the case. A more expansive evaluation of genetic factors, as we had conducted in the cardiac surgical population, may have yielded a significant association.…”

“…While cognitive function tends to improve over months to years postoperatively in affected individuals, some proportion have seemingly permanent cognitive injury. 4,5,6 Apolipoprotein E4 (APOE4) genotype has been shown to be a risk factor for worse cerebral injury and poor neurologic outcome from a variety of insults, including traumatic brain injury 7 and intracranial hemorrhage, 8 and is a risk factor for Alzheimer's Disease 9 and atherosclerosis. 10 It is therefore conceivable that APOE4 genotype may influence susceptibility to POCD.…”