Age-related cognitive changes in healthy humans: influences from genetic variation in genes related to oxidative stress

This project successfully identified genes associated with age-related cognitive changes. A number of individual candidate genes—related to free radical defense—were screened during the early stages of the project and several of them were significantly associated with age-related cognitive decline. These include the prion protein gene, previously shown to be involved in Creutzfeldt-Jakob Disease. The length of a person’s telomeres—the structures that protect the ends of our chromosomes—was also shown possibly to influence the executive function aspect of cognitive ability and ischaemic heart disease in later life. The effect size of any one genetic factor is small. Our results now must be replicated in other samples of older people.
We have also used recently-developed, larger scale screening technologies to screen three times as many candidate genes as originally planned. This led to the identification of a gene previously associated with Alzheimer’s disease, APP, as candidate gene for normal cognitive ageing. A genome-wide study that looked at genetic variants spread throughout the entire human genome, identified a number of regions that are potentially involved in human intelligence, which are themselves candidates for influencing age-related cognitive decline. This also means that in a sub-set of our subjects 500 times more variants than were originally planned were screened.