I thank Dr Shamas-Ud-Din for showing interest in my paper and would have to concur with the general criticism that Down's syndrome should have been mentioned. I would like to say, in my defence, that the article was written within the remit of ‘advances in old age psychiatry’. A large number of old age psychiatric services see patients with Alzheimer's disease regardless of their age of onset and hence there was a need to cover some of the aspects of the genetics of early-onset Alzheimer's disease. However, I am unaware of any old age psychiatric service within the UK that routinely sees patients with Down's syndrome and Alzheimer's disease. This defence does not, however, excuse a restricted view that is damaging both to patient management and basic research.

Clearly, no patient should be excluded from expert dementia services because of their learning disability. In addition, there is much to learn about the genetic influences on the development of Alzheimer's disease in patients with Down's syndrome and on its clinical phenotype. Thus, as well as the effects of triplication of the amyloid precursor gene, the presence of theAPOEϵ4 allele also appears to be associated with an increased risk of developing Alzheimer's disease (Debet al, 2000). The effect of the presence of theAPOEϵ4 allele on age of onset is still unclear but, unlike in those with no learning disability, the presence of APOEϵ4 appears to be associated with an earlier age of death (Hardy et al, 1994). At post-mortem the brain lesions and cholinergic losses seen in individuals with Down's syndrome are the same as those seen in both early— and late-onset Alzheimer's disease. However, despite these neuropathological findings, the evidence for the beneficial effects of cholinesterase inhibitors in patients with Down's syndrome and Alzheimer's disease is still largely anecdotal (Kishani et al, 1999). It is clear that the two specialities, old age psychiatry and learning disabilities, have much to learn from each other.