The role of ApoE in outcome after
Traumatic Brain Injury

Detailed Project Description

The gene responsible for the expression of apolipoprotein E (ApoE ) has been shown to be a powerful predictor of outcome following traumatic brain injury (Friedman et.al. 1999, Teasdale et.al 1997). ApoE is implicated in metabolic processes, which occur in the brain after damage. The four common alleles of ApoE are e2, e3 and e4. ApoE e4 allele is associated with poor outcome after traumatic brain injury, as well as a greater incidence of mortality (Nicol et.al. 1995). This allele has also been found to be an important determinant of susceptibility of risk for Alzheimer's disease, and this has been shown to act synergistically with a history of prior head injury (Mayeux et.al. 1995).

The e3 allele is that most commonly found in the population - about 50% of the general Caucasian population is homozygous for this allele. The e2 and e4 alleles are rarer, with the e4 allele being more common than the e2 allele. It has been found that the presence of the e2 allele is associated with a substantially lower risk of developing Alzheimer's disease (Talbot et.al. 1994). It is not known whether its presence is associated with a more positive outcome after head injury.

In this study we propose to record the ApoE genotype of each participant, analysing this data in conjunction with other data that is routinely obtained during a patient's rehabilitation at the unit. This research will be innovative in that it will look a the association of outcome after traumatic brain injury and ApoE genotype in an ethnically diverse sample, which has not been previously examined, and it will examine whether there is association between ApoE e 2 genotype and good outcome following traumatic brain injury. There will be an opportunity to sample data from a wider diversity of outcome measures than has been reported previously in the literature.

To measure outcome, we propose to measure the following data for our study.

  1. Duration of post traumatic amnesia. This is the best known basic indicator of severity of injury.
  2. The Functional Independence Measure (FIM) on admission and discharge. This is a measure of the severity of disability.
  3. The Sydney Psychosocial Reintegration Scale. This is a measure of psychosocial disability.
  4. The Glasgow Outcome Scale. This is a simple measure of outcome developed specifically for use with traumatic brain injury survivors.
  5. A variety of neuropsychological test results relating to recall memory from the initial inpatient evaluation and from the 6 to 9 month follow up assessment.
  6. A brief neurological evaluation, at admission and at discharge from the inpatient unit.
  7. A questionnaire to examine the severity of post-concussion symptoms for each patient at discharge from the inpatient unit, or admission to the community programme, and at the 6 to 9 month follow-up assessment.

The first 6 instruments are routinely administered to patients throughout their admission and follow-up at the Liverpool Hospital Brain Injury Rehabilitation Unit, and have been selected to get an indication of the severity of brain injury, and to provide sensitive measures of different aspects of recovery after brain damage. The seventh instrument takes 5 to 10 minutes to administer. We will specifically be investigating whether clients' ApoE status has any effect on the initial severity of their injury, and secondly, whether their ApoE status is associated with improvements that they make in the course of their rehabilitation

References

Friedman, G, Froon P, Sazbrok L, et.al. 1999 Apolipoprotein e4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology 52: 244 - 248

Mayeux R, Ottman R, Maestre G et.al 1995 Synergistic effects of traumatic head injury and apolipoprotein-e4 in patients with Alzheimer's disease. Neurology 45: 555-557

Nicoll J.A.R. Roberts G.W. Graham D.I 1995 Apolipoprotein E e4 allele is associated with deposition of amloyid b protein following head injury. Nature Medicine 1: 135-137

Teasdale G.M. Nicoll J.A.R., Murray G, Fiddes M. 1997 Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350: 1069-1071

Talbot C, Lendon C, Craddock N, et.al 1994 Protection against Alzheimer's disease with apoE e2. Lancet 343: 1432 - 1433

Last modified: Thursday, 20 April 2006