Major Finding: At 2 years after suffering a TBI, significantly more APOE e4 carriers had severe disability than did noncarriers (27% vs. 15%), and significantly fewer e4 carriers had good recovery (30% vs. 39%).
Data Source: A long-term follow-up study of 648 patients with traumatic brain injury.
Disclosures: Dr. Ponsford reported that she had no financial disclosures.
WASHINGTON – Apolipoprotein E e4 genetic status appears to affect long-term recovery from traumatic brain injury significantly, particularly in those who carry two copies of the e4 allele.
At 2 years post injury, apolipoprotein E (APOE) e4 carriers were significantly more likely than noncarriers to have moderate or severe disabilities, and significantly less likely to have a good functional recovery, Jennie Ponsford, Ph.D., said at the World Congress on Brain Injury.
“We know that the APOE e4 allele has an impact on a number of processes involved in recovery, including increased inflammation, diminished cholesterol synthesis, and reduced neurite outgrowth,” she said in an interview. “These effects seem to go on for a long period of time, so it makes sense that their biggest impact would be seen when recovery is almost complete.”
The observation of poorer recovery in e4 carriers suggests the possibility of targeted rehabilitation, suggested Dr. Ponsford, a neuropsychologist at Monash University, Melbourne, Australia. “If you know at the beginning of treatment, that this 25% of your population is going to have a poorer prognosis, you might be able to put more or a different kind of rehabilitation into effect early on.”
Dr. Ponsford presented a long-term follow-up study of 648 patients who were admitted to a regional rehabilitation center between 2000 and 2007. Most of the subjects were male (67%); their mean age was 35 years. The study examined the relationship between APOE e4 status and the initial Glasgow Coma Scale (GCS) score, days of posttraumatic amnesia (PTA), and the Glasgow Outcome Scale–Extended (GOS-E). The GOS-E rates long-term recovery on an 8-point scale, in which good recovery is a score of 7 or 8. All of the subjects gave a saliva sample for APOE genotyping.
Genotyping showed that 166 (26%) patients carried the e4 allele. Of these, 6 were homozygous (e4/e4) and 160 were heterozygous (152 with e3/e4 and 8 with e2/e4). Of the remaining 482, 404 were e3/e3; 75 were e2/e3; and three were e2/e2.
Overall, the mean GCS score was 8, and did not vary significantly between the groups. APOE e4 had no significant effect on the mean length of PTA (31 days).
Recovery was assessed at 1, 2, and 3 or 5 years post injury; the mean time between injury and assessment was 1.9 years. After controlling for age and sex, Dr. Ponsford found that APOE e4 carriers had significantly poorer outcomes than noncarriers. Significantly more e4 carriers had severe disability than did noncarriers (27% vs. 15%), and significantly fewer e4 carriers had good recovery (30% vs. 39%).
“There also appeared to be somewhat of a dose-response effect, with homozygous e4 carriers having a tendency to have much worse outcomes,” she said. The median GOS-E score for this group was 4.8, which was significantly lower than the median score of 6 in the e4 noncarriers and lower (but not significantly so) than those who were heterozygous for the allele.
However, she noted that the very low number of homozygous e4 patients made it impossible to draw any strong conclusions.
In addition to increasing inflammation and interfering with cell repair, the APOE e4 gene is involved in the binding and deposition of amyloid beta (Abeta), the protein thought to be involved in the development of Alzheimer's disease. Dr. Ponsford said there are no data to indicate that a traumatic brain injury predisposes a person to develop Alzheimer's. However, the gene's interaction with Abeta may impair recovery from a brain injury.
There appeared to be a dose-response effect, with homozygous e4 carriers having much worse outcomes.
Source DR. PONSFORD