Genetic risk of Alzheimer's disease: Advising relatives

Background: Clinicians are increasingly asked by relatives of patients with Alzheimer's disease to advise on their genetic risk of developing Alzheimer's disease in later life. Many clinicians find this a difficult question to answer. Aims: To provide information for old age psychiatrists wishing to advise relatives of their risk of developing Alzheimer's disease. Method: A selective review of the key literature on the genetic epidemiology of Alzheimer's disease. Results: Currently a DNA diagnosis is attainable in some 70% of families with autosomal dominant Alzheimer's disease. In first-degree relatives of most cases, risk is increased some three- or four-fold relative to controls, but only one-third of this is realised in the average life span. Apolipoprotein E genotyping cannot be used as a predictive test and confers only minimal diagnostic benefit. Conclusions: Pedigrees with familial Alzheimer's disease should be referred to a Regional Centre for Medical Genetics. Accurate risk prediction is not possible in the vast majority of pedigrees with Alzheimer's disease, although it is possible for the psychiatrist to give a rough estimate of the risk, which can reasonably the couched in reassuring terms.