A life-course approach to the aetiology of late-onset dementias

SummarySubstantial progress has been made in the understanding of the neurobiology of dementias, but comprehensive causal models are not available. Genetic and environmental factors probably interact to determine vulnerability to the dementias. The life-course approach to age-related diseases, when systematically applied to the dementias, provides opportunities to identify the nature and timing of environmental contributions. We discuss the relevance of the fetal origins of adult disease hypothesis to the dementias. Associations between the dementias (most often described as Alzheimer's disease) and ischaemic heart disease, obesity, hypertension, hyperlipidaemia, and non-insulin-dependent diabetes mellitus are set against associations between dementias and childhood intelligence, low educational attainments, low socioeconomic status, occupation, and lifetime dietary history. Biological mechanisms that explain how fetal development might influence the risk of adult disease may be relevant to many age-related diseases including the dementias and, possibly, to the biology of ageing.