The impact of genetic research on our understanding of normal cognitive ageing: 1995 to 2009.

Identifying the risk factors for individual differences in age-related cognitive ability and decline is amongst the greatest challenges facing the healthcare of older people. Cognitive impairment caused by "normal ageing" is a major contributor towards overall cognitive deficit in the elderly and a process that exhibits substantial inter- and intra-individual differences. Both cognitive ability and its decline with age are influenced by genetic variation that may act independently or via epistasis/gene-environment interaction. Over the past fourteen years genetic research has aimed to identify the polymorphisms responsible for high cognitive functioning and successful cognitive ageing. Unfortunately, during this period a bewildering array of contrasting reports have appeared in the literature that have implicated over 50 genes with effect sizes ranging from 0.1 to 21%. This review will provide a comprehensive account of the studies performed on cognitively healthy individuals, from the first study conducted in 1995 to present. Based on current knowledge the strong and weak methodologies will be identified and suggestions for future study design will be presented.