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Genetic risk of Alzheimer's disease: advising relatives

Department of Psychological Medicine, University of Wales College of Medicine, Cardiff

S. LOVESTONE, MRCPsych

Institute of Psychiatry, London

M. J. OWEN, FRCPsych

Department of Psychological Medicine, University of Wales College of Medicine, Cardiff

Correspondence: Dr M. B. Liddell, Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff CF14 4xN, UK. E-mail: liddellmb{at}cardiff.ac.uk

Declaration of interest None.

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.

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