̽��ֱ�� of Cambridge - Department Clinical Neurosciences

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

̽��ֱ��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.

Yes

Rare disease research at Cambridge receives major boost with launch of two new centres

cjb250 — Mon, 22 Apr 2024 23:34:17 +0000

̽��ֱ��virtual centres, supported by the charity LifeArc, will focus on areas where there are significant unmet needs. They will tackle barriers that ordinarily prevent new tests and treatments reaching patients with rare diseases and speed up the delivery of rare disease treatment trials.

̽��ֱ��centres will bring together leading scientists and rare disease clinical specialists from across the UK for the first time, encouraging new collaborations across different research disciplines and providing improved access to facilities and training.

LifeArc Centre for Rare Mitochondrial Diseases

Professor Patrick Chinnery will lead the LifeArc Centre for Rare Mitochondrial Diseases, a national partnership with the Lily Foundation and Muscular Dystrophy UK, together with key partners at UCL, Newcastle ̽��ֱ�� and three other centres (Oxford, Birmingham and Manchester).

Mitochondrial diseases are genetic disorders affecting 1 in 5,000 people. They often cause progressive damage to the brain, eyes, muscles, heart and liver, leading to severe disability and a shorter life. There is currently have no cure for most conditions, however, new opportunities to treat mitochondrial diseases have been identified in the last five years, meaning that it’s a critical time for research development. ̽��ֱ��£7.5M centre will establish a national platform that will connect patient groups, knowledge and infrastructure in order to accelerate new treatments getting to clinical trial.

Professor Chinnery said: “ ̽��ֱ��new LifeArc centre unites scientific and clinical strengths from across the UK. For the first time we will form a single team, focussed on developing new treatments for mitochondrial diseases which currently have no cure.”

Adam Harraway has Mitochondrial Disease and says he lives in constant fear of what might go wrong next with his condition. “With rare diseases such as these, it can feel like the questions always outweigh the answers. ̽��ֱ��news of this investment from LifeArc fills me with hope for the future. To know that there are so many wonderful people and organisations working towards treatments and cures makes me feel seen and heard. It gives a voice to people who often have to suffer in silence, and I'm excited to see how this project can help Mito patients in the future."

LifeArc Centre for Rare Respiratory Diseases

Professor Stefan Marciniak will co-lead the LifeArc Centre for Rare Respiratory Diseases, a UK wide collaborative centre co-created in partnership with patients and charities. This Centre is a partnership between Universities and NHS Trusts across the UK, co-led by Edinburgh with Nottingham, Dundee, Cambridge, Southampton, ̽��ֱ�� College London and supported by six other centres (Belfast, Cardiff, Leeds, Leicester, Manchester and Royal Brompton).

For the first time ever, it will provide a single ‘go to’ centre that will connect children and adults with rare respiratory disease with clinical experts, researchers, investors and industry leaders across the UK. ̽��ֱ��£9.4M centre will create a UK-wide biobank of patient samples and models of disease that will allow researchers to advance pioneering therapies and engage with industry and regulatory partners to develop innovative human clinical studies.

Professor Marciniak said: “There are many rare lung diseases, and together those affected constitute a larger underserved group of patients. ̽��ֱ��National Translational Centre for Rare Respiratory Diseases brings together expertise from across the UK to find effective treatments and train the next generation of rare disease researchers.”

Former BBC News journalist and presenter, Philippa Thomas, has the rare incurable lung disease, Lymphangioleiomyomatosis (LAM). Her condition has stabilised but for many people, the disease can be severely life-limiting. Philippa said: “There is so little research funding for rare respiratory diseases, that getting treatment - let alone an accurate diagnosis - really does feel like a lottery. It is also terrifying being diagnosed with something your GP will never have heard of.”

Globally, there are more than 300 million people living with rare diseases. However, rare disease research can be fragmented. Researchers can lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management, which are vital in getting new innovations to patients.

Dr Catriona Crombie, Head of Rare Disease at LifeArc, says: “We’re extremely proud to be launching four new LifeArc Translational Centres for Rare Diseases. Each centre has been awarded funding because it holds real promise for delivering change for people living with rare diseases. These centres also have the potential to create a blueprint for accelerating improvements across other disease areas, including common diseases.”

Adapted from a press release from LifeArc

Cambridge researchers will play key roles in two new centres dedicated to developing improved tests, treatments and potentially cures for thousands of people living with rare medical conditions.

̽��ֱ��new LifeArc centre unites scientific and clinical strengths from across the UK

Patrick Chinnery

Alexander_Safonov (Getty)

Woman inhaling from a mask nebulizer

Yes

Cambridge researchers elected to Academy of Medical Sciences Fellowship 2023

lw355 — Thu, 18 May 2023 08:00:52 +0000

̽��ֱ��new Fellows have been elected to the Academy in recognition of their exceptional contributions to the advancement of biomedical and health science, cutting-edge research discoveries and translating developments into benefits for patients and wider society.

They join a prestigious Fellowship of 1,400 esteemed researchers who are central to the Academy’s work. This includes providing career support to the next generation of researchers and contributing to the Academy’s influential policy work to improve health in the UK and globally.

Professor Dame Anne Johnson PMedSci, President of the Academy of Medical Sciences, said: “These new Fellows are pioneering biomedical research and driving life-saving improvements in healthcare. It’s a pleasure to recognise and celebrate their exceptional talent by welcoming them to the Fellowship.

“This year, we are celebrating our 25th anniversary. ̽��ֱ��Fellowship is our greatest asset, and their broad expertise and dynamic ability has shaped the Academy to become the influential, expert voice of health. As we look to the future, the collective wisdom our new Fellows bring will be pivotal in achieving our mission to create an open and progressive research sector to improve the health of people everywhere.”

̽��ֱ��new Cambridge Fellows are:

Professor Charlotte Coles FMedSci

Professor of Breast Cancer Clinical Oncology, Department of Oncology, NIHR Research Professor and Director of Cancer Research UK RadNet Cambridge

Professor Coles leads practice-changing breast radiotherapy trials, has influenced international hypofractionation policy and is addressing global health, gender and equity challenges within the Lancet Breast Cancer Commission.

“It’s an honour to be elected as a new Fellow of the Academy of Medical Sciences. This is a result of research collaborations in Cambridge, the UK and internationally and I’d like to thank these wonderful colleagues, especially patient advocates,” said Coles.

“I hope to contribute to the Academy’s work to increase equity, diversity and inclusion within leadership roles, including lower- and middle-income countries, to enrich research and improve the culture in Medical Sciences.”

Professor Emanuele Di Angelantonio FMedSci

Professor of Clinical Epidemiology and Donor Health, Department of Public Health and Primary Care, and Head of Health Data Science Centre, Human Technopole (Milan)

Professor Di Angelantonio’s research has focused on addressing major clinical and public health priorities in cardiovascular disease (CVD) and transfusion medicine. His election recognises his many contributions both in helping resolve important controversies in CVD prevention strategies and in improving the safety and efficiency of blood donation.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences, which I recognise is an outcome of the collaborations with many colleagues in UK and worldwide,” said Di Angelantonio.

“Research excellence across medical sciences and translation to health improvements has been at the centre of the Academy’s mission and I am very pleased to now be able to contribute to fulfilling this aim as a Fellow.”

Dr Rita Horvath FMedSci

Director of Research in Genetics of Rare Neurological Disorders in the Department of Clinical Neurosciences and Honorary Consultant in Neurology

Dr Horvath is an academic neurologist using genomics and biochemistry to diagnose rare, inherited neurological disorders, with a focus on mitochondrial diseases. Throughout her career she has combined fundamental experimental work with clinical studies. She pioneered the development and implementation of next generation sequencing in the diagnosis of rare neurogenetic diseases in the UK, leading to precision genetic approaches. She has established extensive international collaborations, having impact in Europe, but also for underserved groups in countries where such expertise is lacking.

“I am delighted and honoured to be elected to this Fellowship, which recognises the impact of my work. I would not have achieved it without the support of my excellent colleagues and research team, for which I give my sincere thanks,” said Horvath.

“As a Hungarian woman working in different countries before I arrived in the UK in 2007, I feel particularly proud of this award, which I recognise is an outcome of the open and fair research environment in Cambridge. This Fellowship enables me to further expand my research to develop effective treatments for patients with rare inherited neurological diseases.”

Professor Eric Miska FMedSci

Herchel Smith Chair of Molecular Genetics and Head of Department of Biochemistry, Affiliated Senior Group Leader at the Gurdon Institute, Associate Faculty at the Wellcome Sanger Institute and Fellow of St John’s College

Professor Miska is a molecular geneticist who has carried out pioneering work on RNA biology. His work led to fundamentally new insights into how small RNA molecules control our genes and protect organisms from selfish genes and viruses, and how RNA can carry heritable information across generations. Miska is Founder and Director of STORM Therapeutics Ltd, which creates novel therapies that inhibit RNA modifying enzymes for use in oncology and other diseases.

“Wonderful recognition of the work of an amazing team of researchers I have the pleasure to work with,” said Miska. “Most of our research has been done using the roundworm C. elegans. As Friedrich Nietzsche wrote in Thus Spoke Zarathustra: ‘You have evolved from worm to man, but much within you is still worm’.”

Professor Serena Nik-Zainal FMedSci

NIHR Research Professor, Professor of Genomic Medicine and Bioinformatics, Department of Medical Genetics and Early Cancer Institute, and Honorary Fellow of Murray Edwards College

Professor Nik-Zainal’s research is focused on investigating the vast number of mutations that occur in human DNA from birth, causing patterns called ‘mutational signatures’, and the associated physiological changes to cellular function, in progressive diseases such as cancer and neurodegeneration. She uses a combination of experimental and computational methods to understand biology and to develop clinical tests for early detection and precision diagnostics. Her team also builds computational tools to enable genomic advances become more accessible across the NHS.

“What an honour it is to be elected to the Fellowship. This is a wonderful recognition of the work from my team,” said Nik-Zainal. “We are thrilled and hugely indebted to all our inspiring collaborators, supporters and patients, who have shared in our passion and joined us on our path, exploring biomedical science and translating insights into patient benefit.”

Professor Julian Rayner FMedSci

Director of the Cambridge Institute for Medical Research, School of Clinical Medicine, Honorary Faculty at the Wellcome Sanger Institute, and Director of Wellcome Connecting Science

Professor Rayner’s research has made significant contributions to our understanding of how malaria parasites recognise and invade human red blood cells to cause disease. His work has helped to identify new vaccine targets, such as a protein essential for red blood cell invasion that is now in early stage human vaccine testing, and inform antimalarial drug development, through co-leading the first ever genome-scale functional screens in malaria parasites. He collaborates closely with researchers in malaria-endemic countries and is strongly committed to engaging public audiences with the process and outcomes of science.

“Malaria is a devastating and too often forgotten disease that still kills more than half a million children every year. Tackling it requires deep collaboration and working across disciplines. I’m enormously honoured by this announcement, which reflects not my work but the work of all the talented people I’ve been lucky enough to host in my lab, and collaborations with friends and colleagues across the world,” said Rayner.

“I’m excited to become a Fellow of the Academy of Medical Sciences because I strongly share their conviction that science is not just for scientists. I believe that dialogue, learning and public engagement are all fundamental and essential parts of the research process, and I look forward to contributing to their leading role in these areas.”

Professor James Rowe FMedSci

Professor of Cognitive Neurology, Department of Clinical Neurosciences, and MRC Cognition and Brain Sciences Unit

Professor Rowe leads a highly interdisciplinary research team at the Cambridge Centre for Frontotemporal Dementia and at Dementias Platform UK to improve the diagnosis and treatment of people affected by dementia. His work integrates cognitive neuroscience, brain imaging, fluidic biomarkers, computational models and neuropathology for experimental medicine studies and clinical trials. He is motivated by his busy clinical practice and the need for better diversity and inclusivity throughout medical research.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences. It is a testament to the many wonderful colleagues and students I have been fortunate to work with, and to inspirational mentors,” said Rowe.

“Research excellence, and translation of research for direct human benefit, comes from innovation and collaboration in diverse cross-disciplinary teams. I believe in the vision and values of the Academy as the route to better health for all.”

In addition, two researchers from the wider community have also been elected:

Dr Trevor Lawley FMedSci, Senior Group Leader, Wellcome Sanger Institute and Chief Scientific Officer, Microbiotica

Professor Ben Lehner FRS FMedSci, Senior Group Leader, Human Genetics Programme, Wellcome Sanger Institute

Seven Cambridge ̽��ֱ�� researchers are among the 59 biomedical and health researchers elected to the Academy of Medical Sciences Fellowship.

As we look to the future, the collective wisdom our new Fellows bring will be pivotal in achieving our mission to create an open and progressive research sector to improve the health of people everywhere

Professor Dame Anne Johnson, President of the Academy of Medical Sciences

Clockwise from top left: E. Di Angelantonio, J. Rayner, J. Rowe, R. Horvath, S. Nik-Zainal, E. Miska, C. Coles

̽��ֱ��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 – 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.

Yes

From sick-care to health-care

skbf2 — Wed, 09 Feb 2022 18:23:18 +0000

Meet the young biotech entrepreneur with two companies to her name and a plan to revolutionise the way we manage our health.