Researchers in the US have shown that genes associated with the risk of Alzheimer’s disease could be exerting an effect on the brain well before people develop symptoms of the disease. According to the study, published today in the journal Neurology, some effects may even be detectable in young adults.
The researchers analysed data from two large studies to calculate an Alzheimer’s risk score based on a person’s genetic makeup. There are more than 20 genes that have been shown to influence a person’s risk of developing Alzheimer’s and many hundreds more that may play a small role but haven’t yet been conclusively shown to do so. The researchers in this study quantified the risk associated with established risk genes as well as suspected risk genes, and combined this data to produce a way to calculate an overall genetic risk score for an individual.
Working with data collected from people with an average age of 75, 166 who had dementia and 1,026 who didn’t, the team investigated how strongly the risk scores were associated with different indicators of Alzheimer’s disease.
In people without dementia, a higher genetic risk score was associated with worse memory, a smaller hippocampus (an area of the brain involved in memory), and brain scans that showed more of an Alzheimer’s protein called amyloid. Over the three years of the study, a higher score was linked to a greater decline in memory and thinking skills, a greater reduction in the size of the hippocampus and an increased risk of participants developing Alzheimer’s disease or early memory and thinking problems known as mild cognitive impairment. These associations were small, accounting for around 1-3% of the difference between older individuals without dementia, but did reach a level of statistical significance that suggests the observations did not happen by chance.
The researchers also looked at data from a group of 1,322 18-30 year olds. In this younger group, a higher risk score was shown to be weakly associated with a smaller hippocampus. The researchers suggest that this could show that the effect of genetic risk factors might be detectable long before people begin to experience symptoms of the disease and not just influence biological processes in later life but also in early adulthood.
Dr Laura Phipps of Alzheimer’s Research UK, said:
“A person’s risk of developing Alzheimer’s is down to a complex mix of age, genetic and environmental factors. It’s important that we better understand the risk factors for Alzheimer’s and how they affect the brain throughout life, as this will help to identify people at the greatest risk of the disease who may benefit the most from new preventions and treatments. The genetic risk score used in this study is not able to reliably predict who will develop dementia but the findings raise some interesting areas for future research into how genetic risk factors exert their effect on the brain and make someone more susceptible to Alzheimer’s. These findings will now need to be taken forward in studies involving larger numbers of participants and Alzheimer’s Research UK is already funding scientists in the UK who are using complex genetic risk scores to advance dementia research.”
“While we can’t do anything to alter our genetic risk for Alzheimer’s there are a number of lifestyle changes that people can adopt to help maintain brain health into later life. Current evidence suggests not smoking, eating a balanced diet, keeping blood pressure and cholesterol in check and staying physically and mentally active can all help to reduce our dementia risk as we age.”