Signs of Alzheimer’s ‘could be detected before worse symptoms show,’ study suggests

By Lamiat Sabin
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Signs of Alzheimer's disease (AD) could be detected early before significant symptoms become obvious, a new study suggests.

Healthy people with a higher genetic risk of dementia may show earlier changes in their brain structure, and declining scores in cognitive tests relating to reasoning and attention, researchers at the University of Glasgow found.

But some experts have said that the study’s findings are “too weak” to yet be useful in the early diagnosis and treatment of the disease.

AD is a neurodegenerative disorder that tends to get worse with time, and is the main cause of dementia.

The disease affects several parts of the brain, but among the earliest to be affected is the hippocampus – a region responsible for processing memory and learning that is found deep in the brain.

Scientists found that early decline of the hippocampus is linked to a higher genetic risk of AD.

Doctors typically assess a person’s risk of AD by looking at their age, whether there is a family history of the disorder, lifestyle, and comorbidites such as heart disease, and untreated depression. The NHS says depression can also be one of the symptoms of AD.

The researchers in their study used polygenic risk scoring (PRS) to estimate an individual’s genetic risk of developing the disease.

PRS – which analyses a person’s risk of certain diseases using their genetic data – is a cheaper and less laborious method of possible disease detection than brain imaging or cognitive testing.

The study, which is the largest of its kind, saw scientists calculate scores based on a large number of genetic mutations for 32,790 generally-healthy adults without dementia.

They found that the people’s lifetime genetic risk of developing the disease was linked to the 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 Susan Kohlhaas, Director of Research from Alzheimer's Research UK, said that the “research was not able to tell if these brain changes underly the development of dementia.”

She suggested that further research in future finds new ways of spotting early signs of dementia.

Her concerns were shared by Prof Derek Hill, Professor of Medical Imaging Science at UCL, who said that the scale of the study is “impressive” but that the “results do not demonstrate that the polygenic risk score could be used reliably to detect and – when suitable treatments are available – treat people at risk of AD.”

Prof Hill added: “For that a very different study would be needed.

“It would be necessary to study people over time and see how well the risk score can predict people who actually develop and rapidly decline due to AD.

“And it would be necessary to show that the polygenic risk score works better than other tests like blood tests and brain imaging which are also promising approaches.”

Prof David Curtis, Honorary Professor, UCL Genetics Institute, said that the study “reports a weak association” between a genetic risk score for AD and some aspects of brain anatomy and function.

He suggested that there may have been some people involved in the study – who had an average age of 64 – who had “ some degree of dementia”.

Prof Curtis said that the researchers did not take “rigorous measures” to exclude data of those with dementia.

He added: “The study does not demonstrate that these brain abnormalities exist in people who will go on to develop Alzheimer’s disease in the future.

“Nor does it show that the genetic risk score has any clinical utility in predicting who will develop Alzheimer’s disease because the association is simply too weak to be helpful.”

The study has been published in Neuropsychopharmacology.


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