Apolipoprotein E-ε4 genotype predicts a poor outcome in survivors of traumatic brain injury

TLDR

Traumatic brain injury is linked to neuropsychological deficits and functional disability, and recent evidence suggests APOE influences CNS response to injury. The study aimed to assess whether APOE genotypes predict duration of unconsciousness and functional outcome in TBI survivors. In a prospective cohort of 69 TBI survivors followed for at least six months, APOE genotypes were determined and evaluated for their predictive value on days of unconsciousness and functional outcome, with good outcome defined by absence of speech, behavioral, cognitive deficits and independent living. Results showed that ε4 carriers had a 5.69‑fold higher odds of remaining unconscious for more than seven days, a 13.93‑fold higher odds of a suboptimal outcome, and were far less likely to achieve a good functional outcome (3.7% vs 31.0%).

Abstract

<b><i>Objective:</i></b> To determine the ability of apolipoprotein E (<i>APOE</i>) genotypes to predict days of unconsciousness and a suboptimal functional outcome in traumatic brain injury (TBI) survivors. <b><i>Background:</i></b> TBI is known to be associated with neuropsychological deficits and functional disability. Recent evidence indicates that <i>APOE</i> plays a pivotal role in CNS response to injury. <b><i>Methods:</i></b> In this prospective study the authors determined the <i>APOE</i> genotypes and tested their ability to predict days of unconsciousness and functional outcome after at least 6 months in 69 survivors of TBI. A good functional outcome was defined as no dysarthria, behavioral abnormalities, or dysphasia; no severe cognitive abnormalities; and the ability to live independently. <b><i>Results:</i></b> The odds ratio of more than 7 days of unconsciousness was 5.69 in those with the <i>APOE</i>-ε4 allele compared with those without the ε4 allele (95% CI, 1.69 to 20.0; <i>p</i> = 0.001). Only 1 of 27 subjects (3.7%) with the ε4 allele had a good functional outcome compared with 13 of 42 (31.0%) of those without the ε4 allele (<i>p</i> = 0.006). The OR of a suboptimal outcome (fair or unfavorable) was 13.93 for those with the ε4 allele compared with those without the allele after controlling for age and time of unconsciousness (95% CI, 1.45 to 133.97; <i>p</i> = 0.02). <b><i>Conclusion:</i></b> The results demonstrate a strong association between the <i>APOE</i>-ε4 allele and a poor clinical outcome, implying genetic susceptibility to the effect of brain injury. Additional studies of TBI patients are warranted to confirm their findings.