Every year, the number of people with dementia increases, with estimates suggesting more than 1 million people in the UK will be living with the condition by 2030. As this figure increases, there is an even greater need for breakthroughs in developing treatments and improving lives.

So how close are we to new therapeutics? And what innovations will help us get there? This World Alzheimer's Day, we asked UK DRI researchers for their predictions on what we can expect over the next decade, and where they see the most promising advances.

A blood test for Alzheimer’s will revolutionise diagnosis

Currently, there is no single diagnostic test for Alzheimer’s disease. A diagnosis is usually based on memory assessments and brain scans, and can be a lengthy process. These tests are costly and by no means fool-proof. Often, a definitive diagnosis is reached at an advanced stage of disease when someone is already experiencing symptoms, at which point any intervention would be less likely to be effective and it may be too late to join a clinical trial.

Many see the goal as a simple blood test that could detect disease at a very early stage and be performed at your local GP. For this to be achieved, researchers must identify and validate new biomarkers. Short for ‘biological markers’, these are a measure – or a flag – of a biological state, helping to identify and monitor biological processes and, crucially, harmful changes occurring in disease.

Currently most biomarker research is performed on a sample of cerebrospinal fluid (CSF, the substance that flows in and around the brain and spinal cord) and tests run to determine the levels of molecules known to be hallmarks of Alzheimer’s.

Dr Amanda Heslegrave, Senior Research Fellow at the UK DRI at UCL, who leads the UK DRI Biomarker Factory with Prof Henrik Zetterberg, explains issues with this approach:

“To take a sample of CSF for biomarker analysis, you have to do a lumbar puncture. In this country it’s not done routinely, so it wouldn’t be performed at your GP, for example. And it can be quite an invasive procedure.

“If we could replace this with a blood test, it would be much more routinely available and accessible, and the whole process would be far quicker and easier. People are much less worried about a blood test than a lumbar puncture.”

The main challenge faced by researchers is the tiny amount of biomarker, typically a protein, that makes it into the blood from the brain. Until just a few years ago, the technology wasn’t sensitive enough to detect such low quantities. Now, Dr Heslegrave’s team have a piece of equipment that can do just that.

Currently the researchers are determining which blood biomarkers are important and what levels represent cause for concern. With the Biomarker Factory established last year, they are set to transform research in this area and bring blood biomarkers into a clinical setting. Not only will this technology improve the process of diagnosing the condition, but it also has the potential to revolutionise early detection of disease, before symptoms of dementia become apparent. This will be invaluable in trial recruitment too – enabling more people with dementia to join targeted trials and take part in vital research to find new treatments.

Treatments will be tailored based on your genetics

The more we learn about Alzheimer’s disease, the more we appreciate how complex a condition it is. In the past decade, large-scale genetic studies have helped us identify many of the genes associated with the condition, and we are now at a point where we can predict the development of Alzheimer’s in the general population to an accuracy of around 80%. This will be crucial for knowing where to target interventions.

Prof Julie Williams, Centre Director of the UK DRI at Cardiff, and world-leading dementia geneticist explains the impact of this research: “When we do start to see successful treatments emerge for Alzheimer’s over the next decade, we will be able to match them with people who are most likely to benefit, identifying those at greatest susceptibility based on their genetic profiles and therefore the dominant biological mechanism or cause of their disease.

“With even greater knowledge of people’s genetics, we’ll also be able to reduce risk long before symptoms start, so we can hopefully delay the onset of symptoms, and eventually eliminate the disease altogether.”

‘Smart’er trials to improve access to research

The number of dementia clinical trials is rising, yet the figure is still dwarfed by the number of cancer clinical trials. This means many people with cancer have the opportunity to participate in research. To accelerate the identification of disease modifying treatments for dementias and related conditions, there is a need for many more patient led studies; from observational studies to clinical trials. If we are to reach the ultimate goal of identifying new treatments, broader access to trials is paramount as it will bring understanding of how these treatments affect the entire population.

Inspired by innovations in the cancer field, Prof Siddharthan Chandran, Group Leader at the UK DRI at Edinburgh, is pioneering a new ‘SMART’ trial for people with motor neuron disease (MND). From his perspective, “If there is a gain to be made, placing people at the heart of the discovery and trials journey is key.”

SMART stands for ‘Systematic Multi-arm Adaptive Randomised Trial’. He describes the trial as ‘an effort to learn from cancer medicine’ and improve access to trials for people with MND. The trial’s innovative design means that it is time, cost, and resource efficient. Unlike typical trials which test a single treatment, MND-SMART is monitoring more than one at the same time. It also benefits from being adaptive, so researchers can change the drugs being tested in response to new emerging results.

Randomised trials are also a major opportunity for discovery research through reverse translation. “Discovery and translational research can’t be sequential; they are inseparable,” Prof Chandran says.“We need to have the same level of imagination and investment in the designs of tomorrow's clinical trials as we do with fundamental discovery science".

Importantly, the trial, which now has nearly 20 sites across the UK, is designed with inclusion in mind, so that as many people with MND as possible can participate in response to the demands of the patient groups. The pioneering design of MND-SMART, if adopted by other neurodegenerative disease trials, could help achieve a future where as many people as possible can participate in research.

Embracing data and putting our trust in machines

Data science is a broad and fast-evolving area of research, accelerating as technology advances.

Prof Caleb Webber, the new UK DRI Director of Informatics, explains:

“I’ve often thought that, in the past, the biggest problem of biology was that it was limited by the imagination of the biologist. Excitingly, we now have an ability to test everything using data-led science, rather than question- or hypothesis-led science. This accelerates our research understanding, as you get answers to questions you never even thought to ask.”

Hand in hand with data science, artificial intelligence (AI) and machine learning is used to build predictive statistical models, analyse data sets, and even run experiments.

“It’s a fascinating area of research,” Prof Webber says. “Closed-loop systems have been developed, where an experiment is run, the results are collected automatically and fed into a machine learning engine. The engine then adjusts the process based on the results and starts the experiment again. It’s removing the person from the process altogether.”

AI is becoming ubiquitous to our everyday lives, such as the chat bots we’ve all become accustomed to communicating with online. But how far off are we from allowing it to take on a more prominent role within science and healthcare?

“Initially, I think it will be a case of supporting our decisions with the machine,” Prof Webber says. “After that, maybe we will hand it over. There is a real trust process involved, I don’t know how comfortable I am with that at the moment! But ultimately, we’re here to fix folk, and if that’s the best way to do it, I find morally it’s difficult to deny. I think we will have to learn to share the intellectual leadership in science with AI as there is so much to be gained.”

Harnessing technology to help people living with dementia

New treatments are becoming closer to reality, but we can’t ignore the immense need to help people living with dementia now; a dementia diagnosis can be immensely challenging for both the person being diagnosed and their loved ones, and there is a lack of support for those in this situation. In the UK, the estimated cost of dementia to our economy is £35bn per year, equivalent to nearly a quarter of the NHS budget.

Prof Payam Barnaghi, Group Leader at the UK DRI Care Research & Technology centre, leads the UK DRI ‘Healthy Homes’ programme, which brings together scientists from a range of backgrounds, including medicine, engineering, computer science and synthetic biology to develop innovative technologies – from AI to sleep monitoring – to enable people affected by dementia to live safely and independently in their own homes for as long as possible.

“We can see how behaviour and physiology evolves over time, compared with how a person’s symptoms are progressing,” Prof Barnaghi says. “Putting this information together will give us a picture of how the cognitive symptoms associated with dementia relate to all these behavioural and activity changes. You can also look at this the other way around and think, if I see changes in behaviour, what can I infer about what is happening in someone’s brain? Can I use these changes as a digital biomarker to look for early signs of cognitive impairment?”

The technology is already being tested in the homes of over 100 people with dementia, with plans to expand further soon.

“In 10 years, my feeling is that we will have better, more accurate devices and cheaper technologies that will allow us to collect more effective data and make huge progress in diagnosis, monitoring and care for those living with dementia,” predicts Prof Barnaghi.

In addition to using the technology to validate new digital biomarkers and improve diagnosis of dementia, a key goal of the programme is to provide better care and support, to allow clinicians to intervene at an earlier stage and prevent the crises that lead to hospital stays, and to improve the day-to-day life of people living with dementia and their carers.

Effective treatments around the corner if we act now

Over recent years, hundreds of drugs have been tested in clinical trials, but sadly no effective treatments have emerged. So where does the Director of the UK DRI, Prof Bart De Strooper, see the great promise for dementia therapeutics?

“I think the biggest chances of a breakthrough is through targeting amyloid protein which we know shows abnormal changes early in disease, and is the cause of many of the familial cases of Alzheimer’s. There has also been exciting developments in the neuroinflammation field, and I believe gene therapy shows real promise.”

And how far are we from the first treatments for dementia? Prof De Strooper argues that we still need more focus on the fundamental science before we can expect effective therapies to materialise.

“Back in the 80s, everyone was convinced a mutation in a specific gene was the cause of cancer, but it started to become clear that the story was much more complicated than that,” Prof De Strooper recalls. “The knowledge that was acquired then was used to pursue deeper understanding of the mechanisms involved. Now, progress is accelerating because we understand the disease process. If we are to fully understand what drives dementia, we need a drastic increase in investment in fundamental research over the next 10 years.”

On track to treatments

Launched in 2017, the UK DRI aims to fill the knowledge gap in the diseases that lead to dementia. By bringing together world-leading expertise across the UK and collaborating internationally, we are laying the vital groundwork for tomorrow’s treatments.

With innovations transforming diagnosis, trials expanding access to many more people living with dementia, and advances in genetics and data science readying us to deliver targeted treatments as soon as they’re available, there are certainly many reasons to be excited and hopeful. To make this reality however, momentum must be maintained with long-term investment and ambitious targets set for the dementia research field over the next 10 years. We look forward to playing our role in that.

To stay up to date on the latest advances in dementia research from the UK DRI, sign up to receive our monthly newsletter, ‘Inside Eye on UK DRI’.

Image credits: Better Ageing, Shutterstock: Andrey Popov, Thomas Angus, Imperial College London
Article published: 21 September 2022