̽��ֱ�� of Cambridge - Ben Underwood

Dementia patients and their carers to be asked about direction of drug research

cjb250 — Wed, 19 Mar 2025 07:00:07 +0000

Today sees the launch of the POrtal for Patient and Public Engagement in Dementia Research (POPPED) website, where anyone can give their feedback on dementia research projects.

Dementia affects 50 million people worldwide and 1 million people in the UK. Current treatments are limited, but research has led to some significant recent advances. For example, the first drugs which slow down the disease are now licensed in the UK and potential dementia blood tests are being trialled.

Scientists are also turning to existing drugs to see if they may be repurposed to treat dementia. As the safety profile of these drugs is already known, the move to clinical trials can be accelerated significantly. Researchers want to ask members of the public which drugs they would like to see prioritised for these clinical trials.

Dr Ben Underwood, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust, said: “One thing that always improves research into medical conditions is the involvement of people with experience of them – in many respects, you are the experts, rather than us.

“As dementia is common, almost everyone has some experience of it, either through family, friends, work or meeting people with dementia in general life. It’s a problem across society and we want a wide range of opinions for the best way to tackle it.”

Dr Underwood has teamed up with Linda Pointon, a Programme Manager at the Department of Psychiatry, to create a website where everyone can give their feedback on dementia research projects. Linda herself has experience of caring for her mother-in-law, who had frontotemporal dementia and passed away in 2020.

Linda said: “We’re launching our website because we want as many people as possible to share their views and help us guide the direction of our research. It’s a great opportunity for all of us who have been affected by dementia, either directly or caring for a friend or relative, to help researchers understand what aspects of these potential treatments are important and meaningful, both in terms of benefits and side-effects.”

̽��ֱ��information collected by the POPPED team will be used to help inform AD-SMART, a trial to be led by Imperial College London, which will test several existing drugs alongside a placebo to quickly determine if any can slow early Alzheimer’s progression.

Dr Underwood added: “Instead of asking a few people what might be helpful, our website gives us the opportunity to ask thousands of people. ̽��ֱ��more people who use it, the more powerful it will be, so I’d encourage everyone to visit the site and tell us what they think. We can use it to work together to beat dementia, a condition whose effects I see in my clinic every day.”

Cambridge researchers are seeking the views of people with lived experience of dementia – patients and their friends and families – on which existing drugs should be repurposed for clinical trials to see whether they can slow or halt the progress of dementia.

One thing that always improves research into medical conditions is the involvement of people with experience of them – in many ways, they are the experts, not us

Ben Underwood

Toa55 (Getty Images)

Elderly woman putting pills into pill box for the week - stock photo

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Antibiotics, vaccinations and anti-inflammatory medication linked to reduced risk of dementia

cjb250 — Tue, 21 Jan 2025 12:00:03 +0000

̽��ֱ��study, led by researchers from the universities of Cambridge and Exeter, identified several drugs already licensed and in use that have the potential to be repurposed to treat dementia.

Dementia is a leading cause of death in the UK and can lead to profound distress in the individual and among those caring for them. It has been estimated to have a worldwide economic cost in excess of US$1 trillion dollars.

Despite intensive efforts, progress in identifying drugs that can slow or even prevent dementia has been disappointing. Until recently, dementia drugs were effective only for symptoms and have a modest effect. Recently, lecanemab and donanemab have been shown to reduce the build-up in the brain of amyloid plaques – a key characteristic of Alzheimer’s disease – and to slow down progression of the disease, but the National Institute for Health and Care Excellence (NICE) concluded that the benefits were insufficient to justify approval for use within the NHS.

Scientists are increasingly turning to existing drugs to see if they may be repurposed to treat dementia. As the safety profile of these drugs is already known, the move to clinical trials can be accelerated significantly.

Dr Ben Underwood, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust, said: “We urgently need new treatments to slow the progress of dementia, if not to prevent it. If we can find drugs that are already licensed for other conditions, then we can get them into trials and – crucially – may be able to make them available to patients much, much faster than we could do for an entirely new drug. ̽��ֱ��fact they are already available is likely to reduce cost and therefore make them more likely to be approved for use in the NHS.”

In a study published today in Alzheimer’s and Dementia: Translational Research & Clinical Interventions, Dr Underwood, together with Dr Ilianna Lourida from the ̽��ֱ�� of Exeter, led a systematic review of existing scientific literature to look for evidence of prescription drugs that altered the risk of dementia. Systematic reviews allow researchers to pool several studies where evidence may be weak, or even contradictory, to arrive at more robust conclusions.

In total, the team examined 14 studies that used large clinical datasets and medical records, capturing data from more than 130 million individuals and 1 million dementia cases. Although they found a lack of consistency between studies in identifying individual drugs that affect the risk of dementia, they identified several drug classes associated with altered risk.

One unexpected finding was an association between antibiotics, antivirals and vaccines, and a reduced risk of dementia. This finding supports the hypothesis that common dementias may be triggered by viral or bacterial infections, and supports recent interest in vaccines, such as the BCG vaccine for tuberculosis, and decreased risk of dementia.

Anti-inflammatory drugs such as ibuprofen were also found to be associated with reduced risk. Inflammation is increasingly being seen to be a significant contributor to a wide range of diseases, and its role in dementia is supported by the fact that some genes that increase the risk of dementia are part of inflammatory pathways.

̽��ֱ��team found conflicting evidence for several classes of drugs, with some blood pressure medications and anti-depressants and, to a lesser extent, diabetes medication associated with a decreased risk of dementia and others associated with increased risk.

Dr Ilianna Lourida from the National Institute for Health and Care Research Applied Research Collaboration South West Peninsula (PenARC), ̽��ֱ�� of Exeter, said: “Because a particular drug is associated with an altered risk of dementia, it doesn’t necessarily mean that it causes or indeed helps in dementia. We know that diabetes increases your risk of dementia, for example, so anyone on medication to manage their glucose levels would naturally also be at a higher risk of dementia – but that doesn’t mean the drug increases your risk.

“It’s important to remember that all drugs have benefits and risks. You should never change your medicine without discussing this first with your doctor, and you should speak to them if you have any concerns.”

̽��ֱ��conflicting evidence may also reflect differences in how particular studies were conducted and how data was collected, as well as the fact that different medications even within the same class often target different biological mechanisms.

̽��ֱ��UK government is supporting the development of an Alzheimer’s trial platform to evaluate drugs rapidly and efficiently, including repurposed drugs currently used for other conditions.

“Pooling these massive health data sets provides one source of evidence which we can use to help us focus on which drugs we should try first,” said Dr Underwood. “We’re hopeful this will mean we can find some much-needed new treatments for dementia and speed up the process of getting them to patients.”

Reference
Underwood, BU & Lourida, I et al. Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review. Alz & Dem; 21 Jan 2025; DOI: 10.1002/trc2.70037

Antibiotics, antivirals, vaccinations and anti-inflammatory medication are associated with reduced risk of dementia, according to new research that looked at health data from over 130 million individuals.

We urgently need new treatments to slow the progress of dementia, if not to prevent it. If we can find drugs that are already licensed for other conditions, then we can get them into trials much faster than we could do for an entirely new drug

Ben Underwood

Andrzej Rostek (Getty Images)

Elderly Woman's Hands and Orange Pills

Yes

Cambridge joins forces with ARIA to fast-track radical new technologies to revolutionise brain health

Anonymous — Wed, 09 Oct 2024 12:57:22 +0000

̽��ֱ��collaboration, which includes researchers from the ̽��ֱ�� of Cambridge, aims to accelerate progress on new neuro-technologies, including miniaturised brain implants designed to treat depression, dementia, chronic pain, epilepsy and injuries to the nervous system.

Neurological and mental health disorders will affect four in every five people in their lifetimes, and present a greater overall health burden than cancer and cardiovascular disease combined. For example, 28 million people in the UK are living with chronic pain and 1.3 million people with traumatic brain injury.

Neuro-technology – where technology is used to control the nervous system - has the potential to deliver new treatments for these disorders, in much the same way that heart pacemakers, cochlear implants and spinal implants have transformed medicine in recent decades.

̽��ֱ��technology can be in the form of electronic brain implants that reset abnormal brain activity or help deliver targeted drugs more effectively, brain-computer interfaces that control prosthetic limbs, or technologies that train the patient’s own cells to fight disease. ARIA’s Scalable Neural Interfaces opportunity space is exploring ways to make the technology more precise, less invasive, and applicable to a broader range of diseases.

Currently, an implant can only interact with large groups of neurons, the cells that transmit information around the brain. Building devices that interact with single neurons will mean a more accurate treatment. Neuro-technologies also have the potential to treat autoimmune disorders, including rheumatoid arthritis, Crohn’s disease and type-1 diabetes.

̽��ֱ��science of building technology small enough, precise enough and cheap enough to make a global impact requires an environment where the best minds from across the UK can collaborate, dream up radical, risky ideas and test them without fear of failure.

Professor George Malliaras from the ̽��ֱ�� of Cambridge’s Department of Engineering is one of the project leaders. “Miniaturised devices have the potential to change the lives of millions of people currently suffering from neurological conditions and diseases where drugs have no effect,” he said. “But we are working at the very edge of what is possible in medicine, and it is hard to find the support and funding to try radical, new things. That is why the partnership with ARIA is so exhilarating, because it is giving brilliant people the tools to turn their original ideas into commercially viable devices that are cheap enough to have a global impact.”

Cambridge’s partnership with ARIA will create a home for original thinkers who are struggling to find the funding, space and mentoring needed to stress-test their radical ideas. ̽��ֱ��three-year partnership is made up of two programmes:

̽��ֱ��Fellowship Programme (up to 18 fellowships)

Blue Sky Fellows – a UK-wide offer - we will search the UK for people from any background, with a radical idea in this field and the plan and personal skills to develop it. ̽��ֱ��best people will be offered a fellowship with the funding to test their ideas in Cambridge rapidly. These Blue Sky Fellows will receive mentorship from our best medical, scientific and business experts and potentially be offered accommodation at a Cambridge college. We will be looking for a specific type of person to be a Blue Sky Fellow. They must be the kind of character who thinks at the very edge of the possible, who doesn’t fear failure, and whose ideas have the potential to change billions of lives, yet would struggle to find funding from existing sources. Not people who think outside the box, more people who don’t see a box at all.

Activator Fellows - a UK-wide offer - those who have already proved that their idea can work, yet need support to turn it into a business, will be invited to become Activator Fellows. They will be offered training in entrepreneurial skills including grant writing, IP management and clinical validation, so their innovation can be ready for investment.

̽��ֱ��Ecosystem Programme

̽��ֱ��Ecosystem Programme is about creating a vibrant, UK-wide neurotechnology community where leaders from business, science, engineering, academia and the NHS can meet, spark ideas and form collaborations. This will involve quarterly events in Cambridge, road trip events across the UK and access to the thriving online Cambridge network, Connect: Health Tech.

“This unique partnership is all about turning radical ideas into practical, low-cost solutions that change lives,” said Kristin-Anne Rutter, Executive Director of Cambridge ̽��ֱ�� Health Partners. “Cambridge is fielding its best team to make this work and using its networks to bring in the best people from all over the UK. From brilliant scientists to world-leading institutes, hospitals and business experts, everyone in this collaboration is committed to the ARIA partnership because, by working together, we all see an unprecedented opportunity to make a real difference in the world.”

“Physical and mental illnesses and diseases that affect the brain such as dementia are some of the biggest challenges we face both as individuals and as a society,” said Dr Ben Underwood, Associate Professor of Psychiatry at the ̽��ֱ�� of Cambridge and Honorary Consultant Psychiatrist at Cambridgeshire and Peterborough NHS Foundation Trust. “This funding will bring together different experts doing things at the very limits of science and developing new technology to improve healthcare. We hope this new partnership with the NHS will lead to better care and treatment for people experiencing health conditions.”

Cambridge partners in the project include the Departments of Engineering and Psychiatry, Cambridge Neuroscience, the Milner Therapeutics Institute, the Maxwell Centre, Cambridge ̽��ֱ�� Health Partners (CUHP), Cambridge Network, the Babraham Research Campus, Cambridgeshire and Peterborough NHS Foundation Trust, and Vellos.

A team from across the Cambridge life sciences, technology and business worlds has announced a multi-million-pound, three-year collaboration with the Advanced Research and Invention Agency (ARIA), the UK government’s new research funding agency.

Science Photo Library via Getty Images

Illustration of human brain

Yes

Artificial intelligence outperforms clinical tests at predicting progress of Alzheimer’s disease

cjb250 — Fri, 12 Jul 2024 22:30:52 +0000

̽��ֱ��team say this new approach could reduce the need for invasive and costly diagnostic tests while improving treatment outcomes early when interventions such as lifestyle changes or new medicines may have a chance to work best.

Dementia poses a significant global healthcare challenge, affecting over 55 million people worldwide at an estimated annual cost of $820 billion. ̽��ֱ��number of cases is expected to almost treble over the next 50 years.

̽��ֱ��main cause of dementia is Alzheimer’s disease, which accounts for 60-80% of cases. Early detection is crucial as this is when treatments are likely to be most effective, yet early dementia diagnosis and prognosis may not be accurate without the use of invasive or expensive tests such as positron emission tomography (PET) scans or lumbar puncture, which are not available in all memory clinics. As a result, up to a third of patients may be misdiagnosed and others diagnosed too late for treatment to be effective.

A team led by scientists from the Department of Psychology at the ̽��ֱ�� of Cambridge has developed a machine learning model able to predict whether and how fast an individual with mild memory and thinking problems will progress to developing Alzheimer’s disease. In research published today in eClinical Medicine, they show that it is more accurate than current clinical diagnostic tools.

To build their model, the researchers used routinely-collected, non-invasive, and low-cost patient data – cognitive tests and structural MRI scans showing grey matter atrophy – from over 400 individuals who were part of a research cohort in the USA.

They then tested the model using real-world patient data from a further 600 participants from the US cohort and – importantly – longitudinal data from 900 people from memory clinics in the UK and Singapore.

̽��ֱ��algorithm was able to distinguish between people with stable mild cognitive impairment and those who progressed to Alzheimer’s disease within a three-year period. It was able to correctly identify individuals who went on to develop Alzheimer’s in 82% of cases and correctly identify those who didn’t in 81% of cases from cognitive tests and an MRI scan alone.

̽��ֱ��algorithm was around three times more accurate at predicting the progression to Alzheimer’s than the current standard of care; that is, standard clinical markers (such as grey matter atrophy or cognitive scores) or clinical diagnosis. This shows that the model could significantly reduce misdiagnosis.

̽��ֱ��model also allowed the researchers to stratify people with Alzheimer’s disease using data from each person’s first visit at the memory clinic into three groups: those whose symptoms would remain stable (around 50% of participants), those who would progress to Alzheimer’s slowly (around 35%) and those who would progress more rapidly (the remaining 15%). These predictions were validated when looking at follow-up data over 6 years. This is important as it could help identify those people at an early enough stage that they may benefit from new treatments, while also identifying those people who need close monitoring as their condition is likely to deteriorate rapidly.

Importantly, those 50% of people who have symptoms such as memory loss but remain stable, would be better directed to a different clinical pathway as their symptoms may be due to other causes rather than dementia, such as anxiety or depression.

Senior author Professor Zoe Kourtzi from the Department of Psychology at the ̽��ֱ�� of Cambridge said: “We’ve created a tool which, despite using only data from cognitive tests and MRI scans, is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s – and if so, whether this progress will be fast or slow.

“This has the potential to significantly improve patient wellbeing, showing us which people need closest care, while removing the anxiety for those patients we predict will remain stable. At a time of intense pressure on healthcare resources, this will also help remove the need for unnecessary invasive and costly diagnostic tests.”

While the researchers tested the algorithm on data from a research cohort, it was validated using independent data that included almost 900 individuals who attended memory clinics in the UK and Singapore. In the UK, patients were recruited through the Quantiative MRI in NHS Memory Clinics Study (QMIN-MC) led by study co-author Dr Timothy Rittman at Cambridge ̽��ֱ�� Hospitals NHS Trust and Cambridgeshire and Peterborough NHS Foundation Trusts (CPFT).

̽��ֱ��researchers say this shows it should be applicable in a real-world patient, clinical setting.

Dr Ben Underwood, Honorary Consultant Psychiatrist at CPFT and assistant professor at the Department of Psychiatry, ̽��ֱ�� of Cambridge, said: “Memory problems are common as we get older. In clinic I see how uncertainty about whether these might be the first signs of dementia can cause a lot of worry for people and their families, as well as being frustrating for doctors who would much prefer to give definitive answers. ̽��ֱ��fact that we might be able to reduce this uncertainty with information we already have is exciting and is likely to become even more important as new treatments emerge.”

Professor Kourtzi said: “AI models are only as good as the data they are trained on. To make sure ours has the potential to be adopted in a healthcare setting, we trained and tested it on routinely-collected data not just from research cohorts, but from patients in actual memory clinics. This shows it will be generalisable to a real-world setting.”

̽��ֱ��team now hope to extend their model to other forms of dementia, such as vascular dementia and frontotemporal dementia, and using different types of data, such as markers from blood tests.

Professor Kourtzi added: “If we’re going to tackle the growing health challenge presented by dementia, we will need better tools for identifying and intervening at the earliest possible stage. Our vision is to scale up our AI tool to help clinicians assign the right person at the right time to the right diagnostic and treatment pathway. Our tool can help match the right patients to clinical trials, accelerating new drug discovery for disease modifying treatments.”

This work was in collaboration with a cross-disciplinary team including Professor Peter Tino at the ̽��ֱ�� of Birmingham and Professor Christopher Chen at the National ̽��ֱ�� of Singapore. It was funded by Wellcome, the Royal Society, Alzheimer’s Research UK, the Alzheimer’s Drug Discovery Foundation Diagnostics Accelerator, the Alan Turing Institute, and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference
Lee, LY & Vaghari, D et al. Robust and interpretable AI-guided marker for early dementia prediction in real-world clinical settings. eClinMed; 12 July 2024; DOI: 10.1016/j.eclinm.2024.102725

Cambridge scientists have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease.

We’ve created a tool which is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s

Zoe Kourtzi

Yuichiro Chino (Getty Images)

Brain on molecular structure, circuitry, and programming code background

Yes

Tackling COVID-19: Dr Ben Underwood

jg533 — Mon, 04 Jan 2021 09:20:32 +0000

Like many clinical researchers, my latest work has focused on urgent public health studies in response to the pandemic. Normally I have three roles: as a Consultant Psychiatrist and Deputy Medical Director at Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Clinical Director of CPFT’s Windsor Research Unit in Fulbourn, and Dementia Lead for the National Institute for Health Research (NIHR) Clinical Research Network Eastern. Most of my research until recently has been in dementia, and in particular trialling potential treatments with the Gnodde Goldman Sachs Translational Neuroscience Unit. I still do that, but 2020 has also thrown me into the world of viral pandemics in a completely unexpected way.

̽��ֱ��Windsor Research Unit team and I are supporting delivery of coronavirus vaccine trials in Cambridge, including the Oxford/AstraZeneca (ChAdOx) vaccine. ̽��ֱ��way that CPFT, the ̽��ֱ��, NIHR Cambridge Clinical Research Facility, Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) and Royal Papworth Hospital NHS Foundation Trust (RPH) pulled together to rapidly deliver a vaccine trial was extraordinary to see, and an honour to be part of. It’s a milestone partnership for research in this region, and we are lucky to have the support and infrastructure of the NIHR across the UK.

We couldn’t have hoped for a better result in terms of overall vaccine efficacy, and I'm delighted to hear the vaccine has now been approved for use. ̽��ֱ��fact we had such a clear and important goal really galvanised us and there was a great spirit in the team. There are too many people to name for their outstanding efforts, and this research would not have been possible without the entire team behind it, and all the health and care workers across Cambridgeshire and Peterborough who volunteered. I cannot thank everyone involved enough! I hope I have made new friendships that endure, and I have such great respect for many of the people involved.

̽��ֱ��next challenge is delivering effective vaccines to a global population as quickly as possible. ̽��ֱ��creation and testing of COVID-19 vaccines within a year has been one of the greatest scientific and medical achievements of our time, made possible through new partnerships, with researchers all over the world working together and sharing data. We need to get effective vaccines out to people as soon as they are approved, starting with the most vulnerable and at risk.

̽��ֱ��pandemic has posed crucial questions for our clinical services. My team also collaborated to publish papers addressing some of these including: the role of community services in dealing with COVID-19, the impact of the virus on community and mental health services and the risk factors for mortality, the provision of memory assessments during the pandemic, and mathematical modelling of rates of spread in community healthcare settings.

We must now question whether we have got the balance of governance and delivery right on clinical trials. We have demonstrated that we can safely and accurately deliver trials in a year - this previously might have taken ten years, largely due to governance processes. How can we capture what we have learned, to deliver clinical trials just as safely in a much shorter timeframe in future?

We have learned so much from this experience, and our research team are now determined to transfer knowledge and skills for testing vaccines into developing new effective treatments for dementia, which is still the leading cause of death in the UK.

When the pandemic is over I just want to lie down with a wet towel over my face! Professionally, I’m looking forward to finding better treatments for dementia. Personally I love playing music in my spare time but haven’t been able to play with others since the pandemic began, so I can’t wait to be back in a band rehearsal room.

Ben Underwood is a Visiting Researcher in the ̽��ֱ�� of Cambridge’s Department of Psychiatry, where he will become ̽��ֱ�� Lecturer in Older People’s Health from April 2021.

How you can support Cambridge’s COVID-19 research

Ben Underwood’s expertise in delivering clinical trials became highly prized last year, as he worked on a vaccine trial the whole world was watching.

Ben Underwood with the COVID-19 vaccine research team

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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