Alzheimer's may be detectable before symptoms appear

Healthy people with an inherited risk of Alzheimer's disease show structural brain differences before the onset of symptoms.

Researchers at the University of Glasgow assessed genetic variations in over 32,000 healthy adults. Using data collected by the UK Biobank, they determined a polygenic risk score to estimate an individual's risk of developing Alzheimer's disease.

'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,' said Rachana Tank, lead author of the study. '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.'

Individuals with a high polygenic risk score for Alzheimer's disease displayed reductions in hippocampal volume, the brain region involved in learning and memory. The hippocampus is one of the first regions to deteriorate following the onset of dementia. A high polygenic risk score also correlated with poorer scores on cognitive tests relating to reasoning and attention, in the study.

Published in Neuropsychopharmacology, this is the largest study to date investigating the risk of late-onset Alzheimer's disease in healthy people. The scale of the study means that other factors, such as diet or socioeconomic background, are less likely to influence the results.

Although other factors play a role, Alzheimer's has a strong genetic component. Having a parent or sibling with Alzheimer's makes you more likely to develop the disease. Genes such as APOE-ε4 have been identified as risk factors, but the cumulative effect of weaker genetic variants is also believed to contribute.

However, individuals with a high polygenic risk score were not followed up so it is unclear what proportion went on to develop dementia. Additional long-term studies are needed to determine whether polygenic risk scores can reliably determine health outcomes.

'The overall genetic risk of developing late onset Alzheimer's disease, as reflected in the polygenic risk score, has the potential to identify individuals at high risk of developing late onset Alzheimer's disease long before clinical symptoms emerge.' Professor Paul Morgan from Cardiff University, who was not involved in the study, said 'Although therapeutic options for late-onset Alzheimer's disease remain limited, early risk prediction might encourage individuals to adopt lifestyle changes reported to delay disease progression.'

Drug trials for Alzheimer's disease have a 99 percent fail rate, which some scientists attribute to cohorts consisting of patients already in the later stages of the disease, by which point irreversible degeneration has occurred. Identification of pre-symptomatic individuals for trials may increase the number of treatments that successfully make their way through clinical trials.