• APOE status
• cognition
• head injury

The possibility of late mental deterioration after head injury has been raised for many years, although infrequently until recently. It is now becoming quite a hot topic, with three separate and interacting strands of research and ideas. The first of the three interrelated topics is the work on genetic factors in recovery after head injury. The second is the possible relation between head injury and later onset of Alzheimer’s disease. The third is the possible relation between head injury and (much) later cognitive deterioration.

There is certainly evidence to draw on in all three areas, although probably it is the former in which information is the least ambiguous, with evidence of a relation between genetic factors (APOE status) and early recovery/outcome after head injury. One problem with all these areas of research is the practical difficulty of obtaining good research data. To do so demands a prolonged longitudinal follow up of the kind that is very rarely seen; when it is seen, it is often in a military context (for example, the long term follow up of British World War II injuries reported by Newcombe¹ and the American long term follow up of World War II injuries reported by Walker and others.²

Evidence from those sources is ambiguous and conflicting. On the one hand, Corkin et al found mental deterioration very late after head injury in World War II missile injury survivors, reporting that the survivors in their 50s and 60s became simply less mentally “sharp”, and this was also reflected on tests of mental function.³ Plassman et al reported a raised prevalence of Alzheimer’s disease in World War II brain injured veterans many years after injury compared with controls.⁴ However, Newcombe,¹ in an English follow up, found no evidence of mental deterioration, and was particularly impressed with the mental acuity of the brain injured soldiers whom she followed up for many years. Of course, the mental testing procedure used in those studies would now, inevitably, be thought of as relatively unsophisticated and perhaps not very sensitive.

The paper by Millar et al in this issue (pp 1047–1052)⁵ is something of a first. It is a long term follow up of cognitive status in civilians who have suffered a head injury and in whom APOE status is known. The results are, to a degree, ambiguous, showing that there is a possibility of late decline, although any decline is clearly not major and arguably it may not have been identified fully by the neuropsychological procedures employed by the authors. Furthermore, there was no clear relation to an APOE genotype. Despite the fact that the authors followed patients up for 15 to 25 years, they were very careful to point out that their cohort is still “too young” (with a mean age of 42.1 years) to assess the risk of Alzheimer’s disease. Coming up with good data in this area is going to take dedicated research teams with very long term perspective. Given the exigencies of research funding, is this likely to happen?