Healthy people with a higher genetic risk of Alzheimer’s disease may show differences in brain structure and in cognitive test scores relating to reasoning and attention, a new study has revealed.
The research suggests that, although the association between these differences in people with a higher genetic risk of Alzheimer’s disease were small, signs of the neurodegenerative disease may be detectable before significant symptoms are obvious.
The study, from the University of Glasgow, is the largest study to date investigating the genetic risk for late-onset Alzheimer’s disease and non-demented structural brain MRI and cognition phenotypes.
Its findings have been hailed as a potential “real game changer” by the Alzheimer’s Society.
Alzheimer’s disease (AD) affects several brain regions, but among the earliest includes the hippocampus, which is vital for processing memory and learning.
Genetic factors are known to play a role in developing AD dementia, and researchers can use polygenic risk scoring – a method used to estimate an individual’s genetic risk of developing a particular disease, such as AD.
In this study, the researchers calculated a polygenic genetic risk score based on a large number of mutations for 32,790 generally-healthy adults without dementia from the UK Biobank, a large-scale biomedical database and research resource, to see if their lifetime genetic risk of AD was associated with average differences in brain structure and cognitive performance.
Rachana Tank, a lead author on the study, said: “Our findings are novel because they show the effects of genetic risk may, to a certain extent, be apparent long before a clinical dementia diagnosis. Although we cannot say for certain that these differences are early signs of dementia per se, it is important that we do further research in this area.
Dr Donald Lyall, from the University’s Institute of Health and Wellbeing, said: “These findings could lead to a better, more meaningfully informative way of gauging Alzheimer’s disease risk than current methods of inquiring about a family history of dementia, as being able to identify individuals at risk of worse cognitive abilities and potentially accelerated decline could greatly improve diagnosis and treatment options in future.”
Fiona Carragher, director of research and influencing at Alzheimer’s Society, said: “If we can accurately identify people at risk of developing Alzheimer’s disease later in life, it could be a real gamechanger.
“Early detection of those at a higher risk has the potential to pave the way for new treatments in the future and help researchers understand what causes diseases like Alzheimer’s to develop.
“The scale of this study is significant. It adds further evidence to the theory that some brain changes associated with Alzheimer’s disease can start many years before symptoms such as memory loss.
“However, it only looked at people from a white European background – we need to better understand whether there are associations between different genetic risk factors and changes in the brain in people from other ethnic communities.
“Research will beat dementia, but we need more funding. The Government must honour their commitment to double dementia research funding to provide hope for future generations. We owe to the 850,000 people in the UK currently living with dementia.”
