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Title: Apolipoprotein E4 polymorphism and outcomes from traumatic brain injury : a living systematic review and meta-analysis
Authors: McFadyen, Charles A.
Zeiler, Frederick A.
Newcombe, Virginia
Synnot, Anneliese
Steyerberg, Ewout
Gruen, Russel Lindsay
Rosand, Jonathan
Palotie, Aarno
Maas, Andrew I. R.
Menon, David K.
Keywords: Science::Medicine
Issue Date: 2019
Source: McFadyen, C. A., Zeiler, F. A., Newcombe, V., Synnot, A., Steyerberg, E., Gruen, R. L., . . . Menon, D. K. (2019). Apolipoprotein E4 polymorphism and outcomes from traumatic brain injury : a living systematic review and meta-analysis. Journal of Neurotrauma, 36, 1-13. doi:10.1089/neu.2018.6052
Journal: Journal of Neurotrauma 
Abstract: The mortality of traumatic brain injury (TBI) has been largely static despite advances in monitoring and imaging techniques. Substantial variance exists in outcome, not fully accounted for by baseline characteristics or injury severity, and genetic factors likely play a role in this variance. The aims of this systematic review were to examine the evidence for a link between the apolipoprotein E4 (APOE4) polymorphism and TBI outcomes and where possible, to quantify the effect size via meta-analysis. We searched EMBASE, MEDLINE, CINAHL, and gray literature in December 2017. We included studies of APOE genotype in relation to functional adult TBI outcomes. Methodological quality was assessed using the Quality in Prognostic Studies Risk of Bias Assessment Instrument and the prognostic studies adaptation of the Grading of Recommendations Assessment, Development and Evaluation tool. In addition, we contacted investigators and included an additional 160 patients whose data had not been made available for previous analyses, giving a total sample size of 2593 patients. Meta-analysis demonstrated higher odds of a favorable outcome following TBI in those not possessing an ApoE ɛ4 allele compared with ɛ4 carriers and homozygotes (odds ratio 1.39, 95% confidence interval 1.05 to 1.84; p = 0.02). The influence of APOE4 on neuropsychological functioning following TBI remained uncertain, with multiple conflicting studies. We conclude that the ApoE ɛ4 allele confers a small risk of poor outcome following TBI, with analysis by TBI severity not possible based on the currently available published data. Further research into the long-term neuropsychological impact and risk of dementia is warranted.
ISSN: 0897-7151
DOI: 10.1089/neu.2018.6052
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: NTU Institute for Health Technologies
Rights: © 2019 Charles A. McFadyen et al.,; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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