The Association between Apolipoprotein E and Traumatic Brain Injury Severity and Functional Outcome in a Rehabilitation Sample

Abstract

Traumatic brain injury (TBI) can result in significant disability, but outcome is variable. The impact of known predictors accounts for a limited proportion of the variance in outcomes. Apolipoprotein E (ApoE) genotype has been investigated as an additional source of variability in injury severity and outcome, with mixed findings reflecting variable methodology and generally limited sample sizes. This study aimed to examine whether possession of the ApoE ɛ4 allele was associated with greater acute injury severity and poorer long-term outcome in patients referred for rehabilitation following TBI. ApoE genotype was determined for 648 patients with TBI, who were prospectively followed up a mean of 1.9 years post-injury. Hypotheses that ɛ4 carriers would have lower Glasgow Coma Scale (GCS) scores and longer post-traumatic amnesia (PTA) duration were not supported. Prediction of worse Glasgow Outcome Scale-Extended (GOSE) scores for ɛ4 carriers was supported with greater susceptibility seen in females. These results indicate the ApoE ɛ4 allele may be associated with poorer long-term outcome, but not acute injury severity. Possible mechanisms include differential effects of the ɛ4 allele on inflammatory and cellular repair processes, and/or amyloid deposition.

The Glasgow Outcome Scale — 40 years of application and refinement

“…Results of these longitudinal studies indicate that some outcomes remain unchanged, but others are dynamic and can improve or deteriorate even ten years or more after injury 4,35,45,74,75 .…”

“…The GOS and GOSE have been used extensively in Australian studies that assessed early interventions [76][77][78][79][80] and examined the effects of genetic status 75,81 , psychiatric disorders 82,83 , demographics, injury severity and rehabilitation 74,84-88 on outcome. The Victorian State Trauma Registry also involves use of the GOSE to assess outcome in general trauma victims, including those with TBI 89 .…”

“…In many studies, the scale has been dichotomized, leading to reduced sensitivity. The point of dichotomization has varied: in some studies of medical interventions, a GOSE ranking of 5-8 has indicated a good outcome [76][77][78]80 , whereas in some studies of rehabilitation , rankings of 7-8 were good outcomes 74,75 . Not all of these dichotomizations are necessarily sensible:…”

Long-Term Cognitive Correlates of Traumatic Brain Injury across Adulthood and Interactions with APOE Genotype, Sex, and Age Cohorts

“…Compared to TBI patients who carry only the ε2 and ε3 isoforms of the APOE gene, carriers of the ε4 isoform are more likely to die post-injury (Teasdale et al, 1997), have a longer length of coma (Sorbi et al, 1995), greater neurological deficits (Friedman et al, 1999), as well as poorer functional outcome several years following rehabilitation (Ponsford et al, 2011). The mechanisms underpinning the effect of APOE genotype are not well understood, but may influence the degree of Aβ plaque deposition within the brain (Johnson, Stewart, & Smith, 2010).…”

“…Some findings suggest that sex may also interact with genotype in predicting outcome of TBI. For example Ponsford et al (2011) reported that negative outcomes in APOE ε4 + patients were more apparent in females than males, and particularly in patients aged over 55…”