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A study published in Nature Mental Health looks at the possibility of early dementia prediction from brain scans.
Dr Julia Dudley, Head of Strategic Research Programmes at Alzheimer’s Research UK, said:
“One in three people with dementia never receive a formal diagnosis, so there’s an urgent need to improve the way people with the condition are diagnosed. This will be even more important as dementia becomes a treatable condition.
“This study provides intriguing insights into early signs that someone might be at greater risk of developing dementia. While this technique will need to be validated in further studies, if it is, it could be a promising addition to the toolkit of methods to detect the diseases that cause dementia as early as possible. An earlier and accurate diagnosis is key to unlocking personalised care and support, and, soon, to accessing first-of-a-kind treatments that are on the horizon.”
Dr Sebastian Walsh, NIHR Doctoral Fellow in Public Health Medicine, University of Cambridge, said:
“These results are potentially exciting, and there are some really good things about the way the team have conducted this study. However, there are a couple of important caveats.
“Most significantly, the sample was small (only 100 people with dementia) and the time between brain scan and diagnosis was up to 9 years, but actually an average of 3.7 years. Given delays in the way diagnoses appear in the UK biobank cohort, it is not surprising that the ’new’ cases of dementia actually had cognitive impairment at the time of the scans. So before we can be truly confident that this technology can predict dementia onset (rather than just be an early indicator it is present), it will be really important to see these findings demonstrated in bigger samples with a much longer delay between scan and onset of cognitive symptoms.
“Importantly, the Biobank cohort is quite unrepresentative of the population, and the average age in this study was 70, whereas the average age that people develop dementia in the UK is mid to late 80s, so we need to see these results repeated for more diverse and older samples.
“Lastly, the logistics of MRI scans which are expensive and this particular approach needs a high-quality scan which requires people to keep their head still.”
Dr Eugene Duff, Advanced Research Fellow at the UK Dementia Research Institute at Imperial College London, said:
“This work shows how advanced analysis of brain activity measured using MRI can predict future dementia diagnosis. Early diagnosis of dementia is valuable for many reasons, particularly as improved pharmaceutical treatments become available. Brain activity measures may be complementary to cognitive, blood and other markers for identifying those at risk for dementia. The brain modelling approach they use has the benefit of potentially clarifying the brain processes affected in the early stages of disease. However, the study cohort of diagnosed patients was relatively small (103 cases). Further validation and head-to-head comparisons of predictive markers is needed.”
Prof Tara Spires-Jones, FMedSci, President of the British Neuroscience Association and Professor in the UK Dementia Research Institute at the University of Edinburgh, said:
“This study from Ereira and colleagues found that brain scans looking at functional connections between brain regions can detect early brain changes in people who go on to develop dementia. 81 people had brain scans between 5 months and 8.5 years before being diagnosed with dementia. Their brain scans showed less connectivity in a brain network called the default mode network than those from over 1000 people who did not go on to develop dementia. This is a well-conducted study that adds to the existing substantial data showing that the default mode network is disrupted early in dementia. While this type of resting state functional MRI scan is useful for research and identifying people who might be in the early stages of dementia, it is important to note that that these scans are not widely available nor are they perfect at predicting who will go on to develop dementia.”
Prof Andrew Doig, Professor of Biochemistry, University of Manchester, said:
“Dementia, for which Alzheimer’s Disease is the most important type, is now one of our biggest killers, bringing misery and immense cost to millions around the world. Despite intense efforts, we still lack effective drugs that can halt or even reverse the disease. Key to achieving this goal is likely to be identifying people who are starting to undergo changes in their brains before they get any symptoms. These earliest stages of dementia are expected to be easier to treat than the full-blown disease, when severe memory problems are obvious.
“To tackle this problem of detecting dementia as early as possible, Eirera et al. have used brain MRI images, collected as part of the UK Biobank project. By measuring the use of oxygen by MRI in different brain regions, they can see how parts of the brain are connected to each other, and which parts are active or inactive at the same time. They looked at one brain state in particular, called the Default Mode Network, which is functioning when we are thinking about ourselves or other people.
“The authors compared brain connection patterns from 103 people who had been diagnosed with dementia to 1030 people who were healthy. They convincingly found several changes in connections, often linking brain regions that are involved with the processing of emotions, decisions and memory. After applying artificial intelligence to their data, they were able to tell the difference between the brains of people on their way to dementia and those who are healthy, with good accuracy. MRI imaging data therefore shows promise as a way to diagnose dementia at its earliest stages. The results matched well to known genetic risks for dementia and to social isolation, also known to be a risk factor for dementia.
“Current research on finding a diagnostic method for dementia most often either measures the levels of proteins in cerebrospinal fluid or blood, or looks at protein deposits in the brain by imaging. The work here reveals another approach. At present, analysing protein levels in blood is probably the most accurate method. However, the connectivity method described here is new, so could well add value to other tests or be developed further to improve its accuracy. We do need to test the method on a larger group of people, however, to confirm its validity. In particular, we should see how well it generalises beyond the affluent, white British people who were the main participants in the Biobank project. The paper also groups different kinds of dementia together, so specific tests for different disease types, notably Alzheimer’s Disease, might well work better.
“Dementia is a complex condition, and it is unlikely that we will ever find one simple test that can accurately diagnose it. Within a few years, however, there is good reason to believe that we will be routinely testing for dementia in middle aged people, using a combination of methods, such as a blood test, followed by imaging. The MRI connectivity method described here could form part of this diagnostic platform. We will then have an excellent understanding of which people are likely to benefit most from the new generation of dementia drugs.”
Prof Paresh Malhotra, Professor of Clinical Neurology, Imperial College London, said:
“This is a very interesting study that utilises MRI scan data from the UK Biobank cohort. The researchers have examined patterns of connections between brain regions in groups of 103 participants with dementia, of whom 81 developed dementia after being scanned, and over 1000 volunteers without dementia. They developed a model that was able to detect, on the basis of the brain connectivity patterns, which people in this cohort would go on to be diagnosed with dementia.
“This work adds to our understanding of brain changes prior to development of clinical dementia. As the authors note themselves, because it is in a specific research cohort it may not be fully generalisable to the whole population. Further, because it was looking at ‘all-cause’ dementia, rather than any specific type (e.g., Alzheimer’s Disease), we cannot be certain of exactly how these changes reflect underlying disease processes. The study does provide further valuable evidence of changes in the brain before symptoms and diagnosis of dementia. As the researchers suggest, combining tests such as new brain scanning and analysis techniques with recently developed blood tests and assessments of cognition, is likely to prove to be the most effective way of predicting who is at most risk of developing dementia.”
Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said:
“Getting an early and accurate diagnosis is vital to help improve the care and quality of life of people living with dementia.
“This new research has identified, for the first-time, structural changes in the brain before dementia symptoms appear using a novel model and MRI scan.
“This could be a non-invasive way of identifying people at risk of developing dementia, when they are most likely to benefit from lifestyle changes which could potentially reduce their risk. While we have new disease modifying treatments for Alzheimer’s disease on the horizon, they are only suitable for people in the early stages of the disease, so early and accurate diagnosis through tools such as this are vital.
“We need further research involving diverse groups of people of different ages and ethnicities to fully understand the benefits and limitations of this MRI scan as a diagnostic tool.
“On a practical level, the NHS does not yet have capacity to roll out early diagnostic tools such as this. MRI scanners are expensive, require specialised staff, and can be difficult to access for many people in the UK. With one in three people born today going on to develop dementia, we need to see urgent investment in the NHS to improve dementia diagnosis.”
‘Early detection of dementia with default mode network effective connectivity’ by Sam Ereira et al. was published in Nature Mental Health at 10.00am UK time Thursday 6 June 2024.
DOI: 10.1038/s44220-024-00259-5
Declared interests
Dr Eugene Duff: no conflicts.
Prof Andrew Doig: He is a founder, shareholder and consultant for PharmaKure Limited, which is developing new diagnostics for neurogenerative diseases using blood biomarkers.
Prof Tara Spires-Jones: I have no conflicts with this study.
Dr Paresh Malhotra: I have received research funding from NIHR, MRC, Dementia Platforms UK, Alzheimer’s Research UK, British Heart Foundation and Alzheimer’s Society. I am lead for an NIHR-funded trial with drug/placebo provided by Takeda. I sit on the Alzheimer’s Society Research Strategy Council, am an Associate Member of the UK DRI, and am the National Specialty Lead for Dementia and Neurodegeneration in the NIHR Research Delivery Network. I also sit on two NHS England policy working groups.
For all other experts, no reply to our request for DOIs was received.