Early-onset Alzheimer's disease in Scotland: Environmental and familial factors

Abstract

Background: Alzheimer's disease(AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important. Aims: To integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model. Method: Disease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD. Results: Informative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life. Conclusions: The studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (≥600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms. Declaration of interest: The author has received consultancy fees from Bristol-Myers Squibb, Novartis, Esai, Hoechst Marion Roussel and Bayer. He was principal UK investigator in clinical trials of rivastigmine.