探花直播 of Cambridge - James Rowe

Ultra-powered MRI scans show damage to brain鈥檚鈥榗ontrol centre鈥� is behind long-lasting Covid-19 symptoms

sc604 — Tue, 08 Oct 2024 01:28:45 +0000

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford were able to observe the damaging effects Covid-19 can have on the brain.

探花直播study team scanned the brains of 30 people who had been admitted to hospital with severe Covid-19 early in the pandemic, before vaccines were available. 探花直播researchers found that Covid-19 infection damages the region of the brainstem associated with breathlessness, fatigue and anxiety.

探花直播powerful MRI scanners used for the study, known as 7-Tesla or 7T scanners, can measure inflammation in the brain. Their results, published in the journal Brain, will help scientists and clinicians understand the long-term effects of Covid-19 on the brain and the rest of the body. Although the study was started before the long-term effects of Covid were recognised, it will help to better understand this condition.

探花直播brainstem, which connects the brain to the spinal cord, is the control centre for many basic life functions and reflexes. Clusters of nerve cells in the brainstem, known as nuclei, regulate and process essential bodily functions such as breathing, heart rate, pain and blood pressure.

鈥淭hings happening in and around the brainstem are vital for quality of life, but it had been impossible to scan the inflammation of the brainstem nuclei in living people, because of their tiny size and difficult position.鈥� said first author Dr Catarina Rua, from the Department of Clinical Neurosciences. 鈥淯sually, scientists only get a good look at the brainstem during post-mortem examinations.鈥�

鈥� 探花直播brainstem is the critical junction box between our conscious selves and what is happening in our bodies,鈥� said Professor James Rowe, also from the Department of Clinical Neurosciences, who co-led the research. 鈥� 探花直播ability to see and understand how the brainstem changes in response to Covid-19 will help explain and treat the long-term effects more effectively.鈥�

In the early days of the Covid-19 pandemic, before effective vaccines were available, post-mortem studies of patients who had died from severe Covid-19 infections showed changes in their brainstems, including inflammation. Many of these changes were thought to result from a post-infection immune response, rather than direct virus invasion of the brain. 聽

鈥淧eople who were very sick early in the pandemic showed long-lasting brain changes, likely caused by an immune response to the virus. But measuring that immune response is difficult in living people,鈥� said Rowe. 鈥淣ormal hospital-type MRI scanners can鈥檛 see inside the brain with the kind of chemical and physical detail we need.鈥�

鈥淏ut with 7T scanners, we can now measure these details. 探花直播active immune cells interfere with the ultra-high magnetic field, so that we鈥檙e able to detect how they are behaving,鈥� said Rua. 鈥淐ambridge was special because we were able to scan even the sickest and infectious patients, early in the pandemic.鈥�

Many of the patients admitted to hospital early in the pandemic reported fatigue, breathlessness and chest pain as troubling long-lasting symptoms. 探花直播researchers hypothesised these symptoms were in part the result of damage to key brainstem nuclei, damage which persists long after Covid-19 infection has passed.

探花直播researchers saw that multiple regions of the brainstem, in particular the medulla oblongata, pons and midbrain, showed abnormalities consistent with a neuroinflammatory response. 探花直播abnormalities appeared several weeks after hospital admission, and in regions of the brain responsible for controlling breathing.

鈥� 探花直播fact that we see abnormalities in the parts of the brain associated with breathing strongly suggests that long-lasting symptoms are an effect of inflammation in the brainstem following Covid-19 infection,鈥� said Rua. 鈥淭hese effects are over and above the effects of age and gender, and are more pronounced in those who had had severe Covid-19.鈥�

In addition to the physical effects of Covid-19, the 7T scanners provided evidence of some of the psychiatric effects of the disease. 探花直播brainstem monitors breathlessness, as well as fatigue and anxiety. 鈥淢ental health is intimately connected to brain health, and patients with the most marked immune response also showed higher levels of depression and anxiety,鈥� said Rowe. 鈥淐hanges in the brainstem caused by Covid-19 infection could also lead to poor mental health outcomes, because of the tight connection between physical and mental health.鈥�

探花直播researchers say the results could aid in the understanding of other conditions associated with inflammation of the brainstem, like MS and dementia. 探花直播7T scanners could also be used to monitor the effectiveness of different treatments for brain diseases.

鈥淭his was an incredible collaboration, right at the peak of the pandemic, when testing was very difficult, and I was amazed how well the 7T scanners worked,鈥� said Rua. 鈥淚 was really impressed with how, in the heat of the moment, the collaboration between lots of different researchers came together so effectively.鈥�

探花直播research was supported in part by the NIHR Cambridge Biomedical Research Centre, the NIHR Oxford Biomedical Research Centre, and the 探花直播 of Oxford COVID Medical Sciences Division Rapid Response Fund.

聽

Reference:
Catarina Rua et al. 鈥�7-Tesla quantitative susceptibility mapping in COVID-19: brainstem effects and outcome associations.鈥� Brain (2024). DOI: 10.1093/brain/awae215

Damage to the brainstem 鈥� the brain鈥檚鈥榗ontrol centre鈥� 鈥� is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

探花直播 of Cambridge

3D projections of QSM maps on the rendered brainstem

探花直播text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways 鈥� 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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UK-wide trials to begin on blood tests for diagnosing dementia

cjb250 — Thu, 04 Apr 2024 12:15:22 +0000

Professor James Rowe from the Department of Clinical Neurosciences at Cambridge will co-lead a team that will test multiple existing and novel blood tests, looking at a range of types of dementia.

探花直播trials will capitalise on recent breakthroughs in potential dementia blood tests, and generate the evidence needed for them to be validated for use in the NHS within the next 5聽years.

探花直播teams from Dementias Platform UK (which includes the Universities of Cambridge and Oxford) and UCL make up the Blood Biomarker Challenge - a multi-million pound award given by Alzheimer鈥檚 Society, Alzheimer鈥檚 Research UK and the National Institute for Health and Care Research and Gates Ventures including 拢5m raised by players of People鈥檚 Postcode Lottery. 探花直播project aims to revolutionise dementia diagnosis.

Both teams will recruit participants from sites spread across the country, to ensure their findings are applicable to the whole of the UK鈥檚 diverse population.

Timely and accurate diagnosis of the diseases that cause dementia, such as Alzheimer鈥檚 disease, is crucial as it means people can access vital care and support and take part in medical research. This will be even more imperative if new treatments are approved for use in the NHS, as these work best for people in the earliest stage of their disease.

Currently, people are usually diagnosed using memory tests and brain scans. These are less accurate than 鈥榞old standard鈥� tests like PET scans or lumbar punctures, which can confirm what type of dementia they have. However, only 2% of people can access these specialist tests.

In recent years, a number of different blood tests that can diagnose Alzheimer鈥檚 disease and other causes of dementia have shown very promising results in research settings. But they have yet to be tested widely in clinical settings in the UK.

探花直播READ-OUT team (REAl World Dementia OUTcomes) will be led by Professor James Rowe from Cambridge and Drs Vanessa Raymont and Ivan Koychev from Oxford, who are part of Dementias Platform UK. They will test multiple existing and novel blood tests, looking at a range of types of dementia, including Alzheimer鈥檚 disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. 探花直播researchers will also look at whether the blood tests can help detect these diseases at various stages.

Professor Rowe said: 鈥淭his is a ground-breaking study, to discover the best blood tests for dementia, not just Alzheimer鈥檚 but any type of dementia and for anyone, whatever their background age and other health problems. An early accurate diagnosis opens the way to better treatment, support and care. Cambridge researchers will lead the analysis pipeline, and the vital input from patients and families throughout the study.鈥澛�

For the first 3 years, READ-OUT will run a fact-finding study that will take blood tests in around 20 Dementias Platform UK sites across the UK, involving 3000 people from diverse populations. In the final 2 years, they will run a clinical trial with 880 people to explore how having a blood test for dementia affects diagnosis and quality of life, patients and carers, impact on care and how the results should be communicated to patients.

Dr Raymont聽said: 鈥淪ince I first stepped into a memory clinic 30 years ago there has thankfully been a shift in the way society thinks about dementia. There was previously a feeling that this was just another part of aging, but now we鈥檙e seeing that people want to know more about their condition and they want a diagnosis as it helps them access the support they need. Both my parents lived with dementia so I know firsthand the devastation this disease causes, and how a timely and accurate diagnosis can benefit people and their families.鈥�

A second team, ADAPT, will be led by Professor Jonathan Schott and Dr Ashvini Keshavan at UCL and will focus on the most promising biomarker for Alzheimer鈥檚 disease, called p-tau217. This reflects levels of two hallmark proteins found inside the brain in Alzheimer鈥檚 disease 鈥� amyloid and tau. 探花直播researchers will carry out a clinical trial to see whether measuring p-tau217 in the blood increases the rate of diagnosis for Alzheimer鈥檚 disease both in people with early dementia, but also in those with mild, progressive problems with memory.

These complementary research approaches will maximise the chances of providing the evidence needed to prove that blood tests are ready for use in the NHS. They will pave the way for them to be made available to all who might benefit within the next 5 years.

Fiona Carragher, Director of Research and Influencing at Alzheimer鈥檚 Society, said: 鈥淎t the moment only 2% of people with dementia can access the specialised tests needed to demonstrate eligibility for new treatments, leading to unnecessary delays, worry and uncertainty. Blood tests are part of the answer to this problem 鈥� they鈥檙e quick, easy to administer and cheaper than current, more complex tests. I鈥檝e spent decades working in research and the NHS and, after years of slow progress, it feels like we鈥檙e on the cusp of a new chapter on how we treat dementia in this country.鈥�

Dr Sheona Scales, Director of Research at Alzheimer鈥檚 Research UK, said: 鈥淚t鈥檚 fantastic that through collaborating with the leading experts in the dementia community, we can look to bring cutting-edge blood tests for diagnosing dementia within the NHS. And this will be key to widening access to groundbreaking new treatments that are on the horizon.鈥�

For more information about the Blood Biomarker Challenge and how to take part, please visit the Dementia Platforms UK website.

Adapted from a press release from Alzheimer鈥檚 Research UK

Cambridge researchers are helping lead countrywide trials to identify accurate and quick blood tests that can diagnose dementia, in a bid to improve the UK鈥檚 shocking diagnosis rate.

This is a ground-breaking study, to discover the best blood tests for dementia, not just Alzheimer鈥檚 but any type of dementia and for anyone, whatever their background age and other health problems. An early accurate diagnosis opens the way to better treatment, support and care

James Rowe

micheile henderson

Elderly couple taking a walk through the park

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Cambridge researchers elected to Academy of Medical Sciences Fellowship 2023

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

探花直播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鈥檚 work. This includes providing career support to the next generation of researchers and contributing to the Academy鈥檚 influential policy work to improve health in the UK and globally.

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

鈥淭his year, we are celebrating our 25th anniversary. 探花直播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.鈥�

探花直播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.

鈥淚t鈥檚 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鈥檇 like to thank these wonderful colleagues, especially patient advocates,鈥� said Coles.

鈥淚 hope to contribute to the Academy鈥檚 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.鈥�

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鈥檚 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.

鈥淚 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,鈥� said Di Angelantonio.

鈥淩esearch excellence across medical sciences and translation to health improvements has been at the centre of the Academy鈥檚 mission and I am very pleased to now be able to contribute to fulfilling this aim as a Fellow.鈥�

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.

鈥淚 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,鈥� said Horvath.

鈥淎s 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.鈥�

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鈥檚 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.

鈥淲onderful recognition of the work of an amazing team of researchers I have the pleasure to work with,鈥� said Miska. 鈥淢ost of our research has been done using the roundworm C. elegans. As Friedrich Nietzsche wrote in Thus Spoke Zarathustra: 鈥榊ou have evolved from worm to man, but much within you is still worm鈥�.鈥�

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鈥檚 research is focused on investigating the vast number of mutations that occur in human DNA from birth, causing patterns called 鈥榤utational signatures鈥�, 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.聽

鈥淲hat an honour it is to be elected to the Fellowship. This is a wonderful recognition of the work from my team,鈥� said Nik-Zainal. 鈥淲e 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.鈥�

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鈥檚 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.

鈥淢alaria 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鈥檓 enormously honoured by this announcement, which reflects not my work but the work of all the talented people I鈥檝e been lucky enough to host in my lab, and collaborations with friends and colleagues across the world,鈥� said Rayner.

鈥淚鈥檓 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.鈥�

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.

鈥淚 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,鈥� said Rowe.

鈥淩esearch 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.鈥�

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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 探花直播 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

探花直播text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified.聽 All rights reserved. We make our image and video content available in a number of ways 鈥� 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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Ultra-powerful brain scanners offer hope for Parkinson鈥檚 disease patients

cjb250 — Tue, 17 May 2022 08:00:09 +0000

7T MRI scanners could be used to help identify those patients with Parkinson鈥檚 disease and similar conditions most likely to benefit from new treatments for previously-untreatable symptoms, say scientists.

Apathy could predict onset of dementia years before other symptoms

cjb250 — Tue, 15 Dec 2020 00:01:21 +0000

Frontotemporal dementia is a significant cause of dementia among younger people. It is often diagnosed between the ages of 45 and 65. It changes behaviour, language and personality, leading to impulsivity, socially inappropriate behaviour, and repetitive or compulsive behaviours.

A common feature of frontotemporal dementia is apathy, with a loss of motivation, initiative and interest in things. It is not depression, or laziness, but it can be mistaken for them. Brain-scanning studies have shown that in people with frontotemporal dementia it is caused by shrinkage in special parts at the front of the brain 鈥� and the more severe the shrinkage, the worse the apathy. But, apathy can begin decades before other symptoms, and be a sign of problems to come.

鈥淎pathy is one of the most common symptoms in patients with frontotemporal dementia. It is linked to functional decline, decreased quality of life, loss of independence and poorer survival,鈥� said Maura Malpetti, a cognitive scientist at the Department of Clinical Neurosciences, 探花直播 of Cambridge.

鈥� 探花直播more we discover about the earliest effects of frontotemporal dementia, when people still feel well in themselves, the better we can treat symptoms and delay or even prevent the dementia.鈥�

Frontotemporal dementia can be genetic. About a third of patients have a family history of the condition. 探花直播new discovery about the importance of early apathy comes from the Genetic Frontotemporal dementia Initiative (GENFI), a collaboration between scientists across Europe and Canada. Over 1,000 people are taking part in GENFI, from families where there is a genetic cause of Frontotemporal dementia.聽

Now, in a study published today in Alzheimer's & Dementia: 探花直播Journal of the Alzheimer's Association, Professor Rowe and colleagues have shown how apathy predicts cognitive decline even before the dementia symptoms emerge.聽

探花直播new study involved 304 healthy people who carry a faulty gene that causes frontotemporal dementia, and 296 of their relatives who have normal genes. 探花直播participants were followed over several years. None had dementia, and most people in the study did not know whether they carry a faulty gene or not. 探花直播researchers looked for changes in apathy, memory tests and MRI scans of the brain.聽

鈥淏y studying people over time, rather than just taking a snapshot, we revealed how even subtle changes in apathy predicted a change in cognition, but not the other way around,鈥� explained Malpetti, the study鈥檚 first author. "We also saw local brain shrinkage in areas that support motivation and initiative, many years before the expected onset of symptoms.鈥�

People with the genetic mutations had more apathy than other members of their family, which over two years increased much more than in people with normal genetics. 聽探花直播apathy predicted cognitive decline, and this accelerated as they approached the estimated age of onset of symptoms.

Professor Rogier Kievit from the Donders Institute, Radboud 探花直播 Medical Center at Nijmegen聽and MRC Cognition and Brain Sciences Unit at Cambridge, said: 鈥淎pathy progresses much faster for those individuals who we know are at greater risk of developing frontotemporal dementia, and this is linked to greater atrophy in the brain. At the start, even though the participants with a genetic mutation felt well and had no symptoms, they were showing greater levels of apathy. 探花直播amount of apathy predicted cognitive problems in the years ahead.鈥�

鈥淔rom other research, we know that in patients with frontotemporal dementia, apathy is a bad sign in terms of independent living and survival. Here we show its importance in the decades before symptoms begin,鈥� said Professor James Rowe from the Department of Clinical Neurosciences, joint senior author.聽

Professor Rowe said the study highlights the importance of investigating why someone has apathy. 鈥淭here are many reasons why someone feels apathetic. It may well be an easy to treat medical condition, such as low levels of thyroid hormone, or a psychiatric illness such as depression. But doctors need to keep in mind the possibility of apathy heralding a dementia, and increasing the chance of dementia if left unaddressed, particularly if someone has a family history of dementia.

鈥淭reating dementia is a challenge, but the sooner we can diagnose the disease, the greater our window of opportunity to try and intervene and slow or stop its progress.鈥�

探花直播research was largely funded by the Medical Research Council, Wellcome, and the National Institute for Health Research.

Reference
Malpetti, M et al. Apathy in pre-symptomatic genetic frontotemporal dementia predicts cognitive decline and is driven by structural brain changes. Alzheimer's & Dementia; 14 Dec 2020; DOI: 10.1002/alz.12252

Apathy 鈥� a lack of interest or motivation 鈥� could predict the onset of some forms of dementia many years before symptoms start, offering a 鈥榳indow of opportunity鈥� to treat the disease at an early stage, according to new research from a team of scientists led by Professor James Rowe at the 探花直播 of Cambridge.

探花直播more we discover about the earliest effects of frontotemporal dementia, when people still feel well in themselves, the better we can treat symptoms and delay or even prevent the dementia

Maura Malpetti

Zohre Nemati

Woman sleeping

探花直播text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright 漏探花直播 of Cambridge and licensors/contributors as identified.聽 All rights reserved. We make our image and video content available in a number of ways 鈥� 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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Inflammation in the brain linked to several forms of dementia

cjb250 — Tue, 17 Mar 2020 00:14:10 +0000

Inflammation is usually the body鈥檚 response to injury and stress 鈥� such as the redness and swelling that accompanies an injury or infection. However, inflammation in the brain 鈥� known as neuroinflammation 鈥� has been recognised and linked to many disorders including depression, psychosis and multiple sclerosis. It has also recently been linked to the risk of Alzheimer鈥檚 disease.

In a study published today in the journal Brain, a team of researchers at the 探花直播 of Cambridge set out to examine whether neuroinflammation also occurs in other forms of dementia, which would imply that it is common to many neurodegenerative diseases.

探花直播team recruited 31 patients with three different types of frontotemporal dementia (FTD). FTD is a family of different conditions resulting from the build-up of several abnormal 鈥榡unk鈥� proteins in the brain.

Patients underwent brain scans to detect inflammation and the junk proteins. Two Positron Emission Tomography (PET) scans each used an injection with a chemical 鈥榙ye鈥�, which lights up special molecules that reveal either the brain鈥檚 inflammatory cells or the junk proteins.

In the first scan, the dye lit up the cells causing neuroinflammation. These indicate ongoing damage to the brain cells and their connections. In the second scan, the dye binds to the different types of 鈥榡unk鈥� proteins found in FTD.

探花直播researchers showed that across the brain, and in all three types of FTD, the more inflammation in each part of the brain, the more harmful build-up of the junk proteins there is. To prove the dyes were picking up the inflammation and harmful proteins, they went on to analyse under the microscope 12 brains donated after death to the Cambridge Brain Bank.

鈥淲e predicted the link between inflammation in the brain and the build-up of damaging proteins, but even we were surprised by how tightly these two problems mapped on to each other,鈥� said Dr Thomas Cope from the Department of Clinical Neurosciences at Cambridge.

Dr Richard Bevan Jones added, 鈥淭here may be a vicious circle where cell damage triggers inflammation, which in turn leads to further cell damage.鈥�

探花直播team stress that further research is needed to translate this knowledge of inflammation in dementia into testable treatments. But, this new study shows that neuroinflammation is a significant factor in more types of dementia than was previously thought.

鈥淚t is an important discovery that all three types of frontotemporal dementia have inflammation, linked to the build-up of harmful abnormal proteins in different parts of the brain. 探花直播illnesses are in other ways very different from each other, but we have found a role for inflammation in all of them,鈥� says Professor James Rowe from the Cambridge Centre for Frontotemporal Dementia and a Fellow of Darwin College聽.

鈥淭his, together with the fact that it is known to play a role in Alzheimer鈥檚, suggests that inflammation is part of many other neurodegenerative diseases, including Parkinson鈥檚 disease and Huntington鈥檚 disease. This offers hope that immune-based treatments might help slow or prevent these conditions.鈥�

探花直播research was supported by Wellcome, the Medical Research Council, National Institute for Health Research Cambridge Biomedical Research Centre, Association of British Neurologists, Patrick Berthoud Charitable Trust, and the Lundbeck Foundation.

Reference
Bevan-Jones, WR & Cope, TE et al. Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum. Brain; 17 Mar 2020; DOI: 10.1093/brain/awaa033

Inflammation in the brain may be more widely implicated in dementias than was previously thought, suggests new research from the 探花直播 of Cambridge. 探花直播researchers say it offers hope for potential new treatments for several types of dementia.

We predicted the link between inflammation in the brain and the build-up of damaging proteins, but even we were surprised by how tightly these two problems mapped on to each other

Thomas Cope

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Advances in brain imaging settle debate over spread of key protein in Alzheimer鈥檚

cjb250 — Fri, 05 Jan 2018 00:05:06 +0000

An estimated 44 million people worldwide are living with Alzheimer鈥檚 disease, a disease whose symptoms include memory problems, changes in behaviour and progressive loss of independence. These symptoms are caused by the build-up in the brain of two abnormal proteins: amyloid beta and tau. It is thought that amyloid beta occurs first, encouraging the appearance and spread of tau 鈥� and it is this latter protein that destroys the nerve cells, eating away at our memories and cognitive functions.

Until a few years ago, it was only possible to look at the build-up of these proteins by examining the brains of Alzheimer鈥檚 patients who had died, post mortem. However, recent developments in positron emission tomography (PET) scanning have enabled scientists to begin imaging their build-up in patients who are still alive: a patient is injected with a radioactive ligand, a tracer molecule that binds to the target (tau) and can be detected using a PET scanner.

In a study published today in the journal Brain, a team led by scientists at the 探花直播 of Cambridge describe using a combination of imaging techniques to examine how patterns of tau relate to the wiring of the brain in 17 patients with Alzheimer鈥檚 disease, compared to controls.

Quite how tau appears throughout the brain has been the subject of speculation among scientists. One hypothesis is that harmful tau starts in one place and then spreads to other regions, setting off a chain reaction. This idea 鈥� known as 鈥榯ransneuronal spread鈥� 鈥� is supported by studies in mice. When a mouse is injected with abnormal human tau, the protein spreads rapidly throughout the brain; however, this evidence is controversial as the amount of tau injected is much higher relative to brain size compared to levels of tau observed in human brains, and the protein spreads rapidly throughout a mouse鈥檚 brain whereas it spreads slowly throughout a human brain.

There are also two other competing hypotheses. 探花直播鈥榤etabolic vulnerability鈥� hypothesis says that tau is made locally in nerve cells, but that some regions have higher metabolic demands and hence are more vulnerable to the protein. In these cases tau is a marker of distress in cells.

探花直播third hypothesis, 鈥榯rophic support鈥�, also suggests that some brain regions are more vulnerable than others, but that this is less to do with metabolic demand and more to do with a lack of nutrition to the region or with gene expression patterns.

Thanks to the developments in PET scanning, it is now possible to compare these hypotheses.

鈥淔ive years ago, this type of study would not have been possible, but thanks to recent advances in imaging, we can test which of these hypotheses best agrees with what we observe,鈥� says Dr Thomas Cope from the Department of Clinical Neurosciences at the 探花直播 of Cambridge, the study鈥檚 first author.

Dr Cope and colleagues looked at the functional connections within the brains of the Alzheimer鈥檚 patients 鈥� in other words, how their brains were wired up 鈥� and compared this against levels of tau. Their findings supported the idea of transneuronal spread, that tau starts in one place and spreads, but were counter to predictions from the other two hypotheses.

鈥淚f the idea of transneuronal spread is correct, then the areas of the brain that are most highly connected should have the largest build-up of tau and will pass it on to their connections. It鈥檚 the same as we might see in a flu epidemic, for example 鈥� the people with the largest networks are most likely to catch flu and then to pass it on to others. And this is exactly what we saw.鈥�

Professor James Rowe, senior author on the study, adds: 鈥淚n Alzheimer鈥檚 disease, the most common brain region for tau to first appear is the entorhinal cortex area, which is next to the hippocampus, the 鈥榤emory region鈥�. This is why the earliest symptoms in Alzheimer鈥檚 tend to be memory problems. But our study suggests that tau then spreads across the brain, infecting and destroying nerve cells as it goes, causing the patient鈥檚 symptoms to get progressively worse.鈥�

Confirmation of the transneuronal spread hypothesis is important because it suggests that we might slow down or halt the progression of Alzheimer鈥檚 disease by developing drugs to stop tau from moving along neurons.

Image:聽Artist's illustration of the spread of tau filaments (red) throughout the brain. Credit: Thomas Cope

探花直播same team also looked at 17 patients affected by another form of dementia, known as progressive supranuclear palsy (PSP), a rare condition that affects balance, vision and speech, but not memory. In PSP patients, tau tends to be found at the base of the brain rather than throughout. 探花直播researchers found that the pattern of tau build-up in these patients supported the second two hypotheses, metabolic vulnerability and trophic support, but not the idea that tau spreads across the brain.

探花直播researchers also took patients at different stages of disease and looked at how tau build-up affected the connections in their brains.

In Alzheimer鈥檚 patients, they showed that as tau builds up and damages networks, the connections become more random, possibly explaining the confusion and muddled memories typical of such patients.

In PSP, the 鈥榟ighways鈥� that carry most information in healthy individuals receives the most damage, meaning that information needs to travel around the brain along a more indirect route. This may explain why, when asked a question, PSP patients may be slow to respond but will eventually arrive at the correct answer.

探花直播study was funded by the NIHR Cambridge Biomedical Research Centre, the PSP Association, Wellcome, the Medical Research Council, the Patrick Berthoud Charitable Trust and the Association of British Neurologists.

Reference
Cope, TE et al. Tau Burden and the Functional Connectome in Alzheimer's Disease and Progressive Supranuclear Palsy. Brain; 5 Jan 2018; DOI: 10.1093/brain/awx347

Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer鈥檚 disease 鈥� and hence that blocking its spread may prevent the disease from taking hold.

Global Panorama

Alzheimer's patients & carers

探花直播text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Cambridge extends world leading role for medical imaging with powerful new brain and body scanners

cjb250 — Mon, 24 Oct 2016 07:22:25 +0000

探花直播equipment, funded by the Medical Research Council (MRC), Wellcome Trust and Cancer Research UK, sits within the newly-refurbished Wolfson Brain Imaging Centre (WBIC), which today celebrates two decades at the forefront of medical imaging.

At the heart of the refurbishment are three cutting-edge scanners, of which only a very small handful exist at institutions outside Cambridge 鈥� and no institution other than the 探花直播 of Cambridge has all three. These are:

a Siemens 7T Terra Magnetic Resonance Imaging (MRI) scanner, which will allow researchers to see detail in the brain as tiny as a grain of sand
a GE Healthcare PET/MR scanner that will enable researchers to collect critical data to help understand how cancers grow, spread and respond to treatment, and how dementia progresses
a GE Healthcare hyperpolarizer that enables researchers to study real-time metabolism of cancers and other body tissues, including whether a cancer therapy is effective or not

These scanners, together with refurbished PRISMA and Skyra 3T MRI scanners at the WBIC and at the Medical Research Council Cognition and Brain Sciences Unit, will make the Cambridge Biomedical Campus the best-equipped medical imaging centre in Europe.

Professor Ed Bullmore, Co-Chair of Cambridge Neuroscience and Scientific Director of the WBIC, says: 鈥淭his is an exciting day for us as these new scanners will hopefully provide answers to questions that we have been asking for some time, as well as opening up new areas for us to explore in neuroscience, mental health research and cancer medicine.

鈥淏y bringing together these scanners, the research expertise in Cambridge, and the latest in 鈥榖ig data鈥� informatics, we will be able to do sophisticated analyses that could revolutionise our understanding of the brain 鈥� and how mental health disorders and dementias arise 鈥� as well of cancers and how we treat them. This will be a powerful research tool and represents a big step in the direction of personalised treatments.鈥�

Dr Rob Buckle, Director of Science Programmes at the MRC, adds: 鈥� 探花直播MRC is proud to sponsor this exciting suite of new technologies at the 探花直播 of Cambridge. They will play an important role in advancing our strategy in stratified medicine, ultimately ensuring that the right patient gets the right treatment at the right time.鈥�

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Slide show: Click on images to expand

7T Medical Resonance Imaging (MRI) scanner

探花直播Siemens 7T Terra scanner 鈥� which refers to the ultrahigh strength of its magnetic field at 7 Tesla 鈥� will allow researchers to study at unprecedented levels of detail the workings of the brain and how it encodes information such as individual memories. Current 3T MRI scanners can image structures 2-3mm in size, whereas the new scanner has a resolution of just 0.5mm, the size of a coarse grain of sand.

鈥淥ften, the early stages of diseases of the brain, such as Alzheimer鈥檚 and Parkinson鈥檚, occur in very small structures 鈥� until now too small for us to see,鈥� explains Professor James Rowe, who will be leading research using the new 7T scanner. 鈥� 探花直播early seeds of dementia for example, which are often sown in middle age, have until now been hidden to less powerful MRI scanners.鈥�

探花直播scanner will also be able to pick up unique signatures of neurotransmitters in the brain, the chemicals that allow its cells to communicate with each other. Changes in the amount of these neurotransmitters affect how the brain functions and can underpin mental health disorders such as depression and schizophrenia.

鈥淗ow a patient responds to a particular drug may depend on how much of a particular neurotransmitter present is currently present,鈥� says Professor Rowe. 鈥淲e will be looking at whether this new scanner can help provide this information and so help us tailor treatments to individual patients.鈥�

探花直播scanner will begin operating at the start of December, with research projects lined up to look at dementias caused by changes to the brain almost undetectable by conventional scanners, and to look at how visual and sound information is converted to mental representations in the brain.

PET/MR scanner

探花直播new GE Healthcare PET/MR scanner brings together two existing technologies: positron emission tomography (PET), which enables researchers to visualise cellular activity and metabolism, and magnetic resonance (MR), which is used to image soft tissue for structural and functional details.

Purchased as part of the Dementias Platform UK, a network of imaging centres across the UK, the scanner will enable researchers to simultaneously collect information on physiological and disease-related processes in the body, reducing the need for patients to return for multiple scans. This will be particularly important for dementia patients.

Professor Fiona Gilbert, who will lead research on the PET/MR scanner, explains: 鈥淒ementia patients are often frail, which can present challenges when they need separate PET and MR scanners. So, not only will this new scanner provide us with valuable information to help improve understanding and diagnosis of dementia, it will also be much more patient-friendly.鈥�

PET/MR聽 will allow researchers to see early molecular changes in the brain, accurately map them onto structural brain images and follow their progression as disease develops or worsens. This could enable researchers to diagnose dementia before any symptoms have arisen and to understand which treatments may best halt or slow the disease.

As well as being used for dementia research, the scanner will also be applied to cancer research, says Professor Gilbert.

鈥淎t the moment, we have to make lots of assumptions about what鈥檚 going on in tumour cells. We can take biopsies and look at the different cell types, how aggressive they are, their genetic structure and so on, but we can only guess what鈥檚 happening to a tumour at a functional level. Functional information is important for helping us determine how best to treat the cancer 鈥� and hence how we can personalise treatment for a particular patient. Using PET/MR, we can get real-time information for that patient鈥檚 specific tumour and not have to assume it is behaving in the same way as the last hundred tumours we鈥檝e seen.鈥�

探花直播PET/MR scanner will begin operation at the start of November, when it will initially be used to study oxygen levels and blood flow in the tumours of breast cancer patients and in studies of brain inflammation in patients with Alzheimer鈥檚 disease and depression.

Hyperpolarizer

探花直播third new piece of imaging equipment to be installed is a GE Healthcare hyperpolarizer, which is already up and running at the facility.

MRI relies on the interaction of strong magnetic fields with a property of atomic nuclei known as 鈥榮pin鈥�. By looking at how these spins differ in the presence of magnetic field gradients applied across the body, scientists are able to build up three-dimensional images of tissues. 探花直播hyperpolarizer boosts the 鈥榮pin鈥� signal from tracers injected into the tissue, making the MRI measurement much more sensitive and allowing imaging of the biochemistry of the tissue as well as its anatomy.

鈥淏ecause of underlying genetic changes in a tumour, not all patients respond in the same way to the same treatment,鈥� explains Professor Kevin Brindle, who leads research using the hyperpolarizer. 鈥淯sing hyperpolarisation and MRI, we can potentially tell whether a drug is working, from changes in the tumour鈥檚 biochemistry, within a few hours of starting treatment. If it鈥檚 working you continue, if not you change the treatment.鈥�

探花直播next generation of imaging technology, newly installed at the 探花直播 of Cambridge, will give researchers an unprecedented view of the human body 鈥� in particular of the myriad connections within our brains and of tumours as they grow and respond to treatment 鈥� and could pave the way for development of treatments personalised for individual patients.

By bringing together these scanners, the research expertise in Cambridge, and the latest in 鈥榖ig data鈥� informatics, we will be able to do sophisticated analyses that could revolutionise our understanding of the brain 鈥� and how mental health disorders and dementias arise 鈥� as well of cancers and how we treat them

Ed Bullmore

探花直播text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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探花直播 of Cambridge - James Rowe

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7T Medical Resonance Imaging (MRI) scanner

PET/MR scanner

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