A major hurdle to developing new treatments for dementias and other neurodegenerative disorders is the practical and ethical barriers to undertaking brain research in people. However, it is now possible to turn cells from skin biopsies or blood samples into stem cells, which can be grown in a dish in the lab. In turn, the stem cells can be differentiated into any cell type, including brain cells. This allows study of the cell processes affected in dementia and other neurodegenerative diseases in human cells, and has potential in identifying and testing new therapies. This proposal brings together six UK stem cell Centres recently supported by the MRC Dementias Platform UK (Cambridge, Cardiff, Edinburgh, Manchester, Oxford and University College London). This Dementia Stem Cell Network will provide a step change in UK dementia stem cell research and feed into drug discovery initiatives to find novel dementia treatments. Our proposed Partnership will significantly increase the capacity, competitiveness and effective use of resources of UK dementia stem cell research by helping us work together as a coordinated stem cell network. The technology involved in producing brain cells from stem cells is relatively new and evolving at a rapid pace. The Partnership will create a unique, deeply studied collection of cells donated by volunteers with dementia, plus from healthy individuals to compare them against. These cells can be grown in the lab indefinitely, and will form a global and powerful stem cell research resource. Critically, the Partnership will develop and validate protocols that will be harmonised across the network. In this way we can work together using state-of-the-art automated and large-scale technology to understand the biology of dementia. Our goal is to find new markers and develop robust tests for dementia that will accelerate the search for new drug treatments by pharmaceutical companies. This proposal will deliver this programme of research and resources by appointing and training four highly skilled Network Technical Scientists. Each will be dedicated to specific scientific techniques and goals, but share expertise and findings across the Partnership and beyond. The Partnership will also produce a training programme for PhD students, who will work across at least two Centres to address important questions about dementia/neurodegenerative disease. These two programmes will future-proof the Dementia Stem Cell Network and MRC investment by equipping the UK with researchers highly skilled in stem cell technologies who will participate in multi-site interdisciplinary research. Through the Network Technical Scientists and PhD students, we will reach out to other researchers in the UK with regular meetings to involve new sites in this collaborative venture. In summary, the Partnership will create unique shared resources and expertise to drive joined-up UK-wide dementia research with the goal of identifying new disease modifying treatments.

The word dementia refers to groups of disease processes that involve a range of cognitive impairment symptoms, including memory loss and problems with reasoning, perception and communication skills. There are around 50 million people living with dementia in the world today and this is expected to triple by 2050. The most common type of dementia is Alzheimer's Disease. Because there is presently no cure for it, dementia is a chronic condition - people who are diagnosed with dementia live with it for the rest of their lives. In the UK alone there are currently estimated to be around 850,000 people living with dementia, a figure that is anticipated to increase in the future due to the country's ageing population. Dementia is major public health challenge in the UK, where the costs of care are estimated to be around £13.5 billion, with the costs of 'unpaid' care in the country understood to be even higher. As the incidence of dementia increases in the UK, it is anticipated that these costs will increase too. People receiving a dementia diagnosis not only live with dementia, but many must also live with the stigma that surrounds it. Dementia stigma can negatively impact the lives of people living with dementia and their families in a wide range of ways, such as creating feelings of shame and making them less likely to seek medical support and take part in research. In the UK, dementia stigma has also been found to distort service standards at all levels of healthcare, from funding decisions to service commissioning and frontline care. In other words, dementia stigma is harmful not only for the quality of life of people with dementia but also, potentially, for their life chances too. Dementia stigma is also likely to have implications for the British public more generally, as it has been found to create fear and misunderstanding of the syndrome, as well as negative attitudes towards people living with it. The harm done by dementia stigma is thus widespread and deep, having implications not only for the health and quality of life of those most affected by the syndrome, but for society as a whole. The way we talk and communicate about dementia, including our use of language and imagery, has the power to shape our attitudes towards it and, for people diagnosed with dementia, how it is experienced. Unfortunately, much communication about dementia in the public domain, such as in the media, is negative and sensationalistic, foregrounding its threat and presenting dementia diagnosis as an effective death sentence. People living with dementia, meanwhile, are presented as hazardous and lesser versions of their past selves. Such portrayals have been found to have harmful effects on people living with dementia and their families, to create fear and misunderstanding in the public, and are more likely to add to dementia stigma than to challenge it. This research will thus challenge dementia stigma by changing the ways in which dementia is discussed in the public domain in the UK, focusing in particular on the mainstream media, public health bodies, charities, social media and online dementia support groups. Understanding how the language and imagery associated with communication about dementia in these contexts relate to, but also vary between, one another can help us to assess the potential effects of dementia representation in one situation on another. In light of its findings, the researchers on this project will work closely with people with dementia, charities, advocacy groups and the mainstream media to implement changes to communicative practices around dementia in ways that challenge stigma and promote personhood, through the development of communication guidelines and the delivery of training to these stakeholders. Crucially, the research team is collaborating closely with people with dementia to ensure that their voices are heard and valued not only in future public discourse but also in the research process itself.

DPUK is a public-private partnership to accelerate the development of new treatments for dementia. Since inception (2014) DPUK has increased the UK capacity for dementia research through infrastructure development and strategic data collection, leveraging a further £74.4m for dementia research. The second phase of DPUK (DPUK2) focuses on developing UK capacity for dementia experimental medicine. A major challenge in developing new treatments is understanding the mechanisms through which a drug might operate. This involves precision studies where individuals of known vulnerability to specific causes of dementia are recruited to studies of cause-specific mechanistic pathways. These studies are very difficult to do as they require detailed assessment of volunteers before the study begins and standardising all the procedures in centres across the UK. These studies are also high risk in that there is no guarantee of success. DPUK2 addresses these issues head-on at two levels. First it uses the UK's rich legacy in population cohort studies to identify suitable volunteers by using and enhancing existing cohort data. Second it creates a pre-competitive environment that brings together industry, academic and third-sector entities into partnership. This not only shares the costs and risks of experimental medicine (EM) studies, it also shares the benefits amongst a wider spread of stakeholders, each able to exploit the findings. DPUK2 does this through 3 inter-dependent work-streams. 1. The Data Portal (DP): The DP is a world leading end-to-end dementia focused data management solution. It enables large and complex datasets to be accessed remotely from around the globe without compromising data security. The DP is being developed in partnership with Health Data Research UK (HDR UK) so that we can maximise the data available to dementia research. The DP is used to manage all the data and information systems necessary for conducting precision studies. It brings large and complex datasets together in order to test new ideas; it manages personal information securely to enable recruitment to precision studies; it manages many types of data so that genetics, brain imaging, cognitive performance; and questionnaire data can all be analysed together. 2. The Trials Delivery Framework (TDF): The TDF is the vehicle that enables the DPUK2 experimental medicine programme to be efficient. The TDF organises our Clinical Studies Register (CSR) through which cohort members can volunteer for experimental medicine studies. The CSR allows us to contact members to enrich their data in terms of background information, cognitive testing, and where necessary genetics. As part of the CSR, and in partnership with the Alzheimer's Society, we have a PPI programme to understand what best practice is in terms if recruitment to experimental medicine studies. The TDF also enables us to identify centres of excellence across the UK for conducting experimental studies rigorously. This not only assures data quality, but also means that volunteers do not have to travel too far to participate. 3. The EM Incubator: The incubator is where our partners meet to plan and execute the experimental medicine programme. It has three themes; the first is Vascular Health. This is important because so many factors that affect the heart also affect the brain. If any area is likely to have drugs that already exist and could be re-purposed for dementia, this is it.The second theme is Synaptic Health. Here we investigate factors that affect the loss of neuron synapses. This is important because unlike neurons, synapses (the connections between neurons), can be generated, which is critical to learning and maintaining memory. The third area is Neuroimmunology. This is important as inflammation is a systemic problem that is known to affect the brain and might have systemic solutions, and so represents a promising area for new treatments.

We propose to create the EPSRC Centre for Doctoral Training (CDT) in intelligent integrated imaging in healthcare (i4health) at University College London (UCL). Our aim is to nurture the UK's future leaders in next-generation medical imaging research, development and enterprise, equipping them to produce future disruptive healthcare innovations either focused on or including imaging. Building on the success of our current CDT in Medical Imaging, the new CDT will focus on an exciting new vision: to unlock the full potential of medical imaging by harnessing new associated transformative technologies enabling us to consider medical imaging as a component within integrated healthcare systems. We retain a focus on medical imaging technology - from basic imaging technologies (devices and hardware, imaging physics, acquisition and reconstruction), through image computing (image analysis and computational modeling), to integrated image-based systems (diagnostic and interventional systems) - topics we have developed world-leading capability and expertise on over the last decade. Beyond this, the new initiative in i4health is to capitalise on UCL's unique combination of strengths in four complementary areas: 1) machine learning and AI; 2) data science and health informatics; 3) robotics and sensing; 4) human-computer interaction (HCI). Furthermore, we frame this research training and development in a range of clinical areas including areas in which UCL is internationally leading, as well as areas where we have up-and-coming capability that the i4health CDT can help bring to fruition: cancer imaging, cardiovascular imaging, imaging infection and inflammation, neuroimaging, ophthalmology imaging, pediatric and perinatal imaging. This unique combination of engineering and clinical skills and context will provide trainees with the essential capabilities for realizing future image-based technologies. That will rely on joint modelling of imaging and non-imaging data to integrate diverse sources of information, understanding of hardware the produces or uses images, consideration of user interaction with image-based information, and a deep understanding of clinical and biomedical aims and requirements, as well as an ability to consider research and development from the perspective of responsible innovation. Building on our proven track record, we will attract the very best aspiring young minds, equipping them with essential training in imaging and computational sciences as well as clinical context and entrepreneurship. We will provide a world-class research environment and mentorship producing a critical mass of future scientists and engineers poised to develop and translate cutting-edge engineering solutions to the most pressing healthcare challenges.

Medical imaging has transformed clinical medicine in the last 40 years. Diagnostic imaging provides the means to probe the structure and function of the human body without having to cut open the body to see disease or injury. Imaging is sensitive to changes associated with the early stages of cancer allowing detection of disease at a sufficient early stage to have a major impact on long-term survival. Combining imaging with therapy delivery and surgery enables 3D imaging to be used for guidance, i.e. minimising harm to surrounding tissue and increasing the likelihood of a successful outcome. The UK has consistently been at the forefront of many of these developments. Despite these advances we still do not know the most basic mechanisms and aetiology of many of the most disabling and dangerous diseases. Cancer survival remains stubbornly low for many of the most common cancers such as lung, head and neck, liver, pancreas. Some of the most distressing neurological disorders such as the dementias, multiple sclerosis, epilepsy and some of the more common brain cancers, still have woefully poor long term cure rates. Imaging is the primary means of diagnosis and for studying disease progression and response to treatment. To fully achieve its potential imaging needs to be coupled with computational modelling of biological function and its relationship to tissue structure at multiple scales. The advent of powerful computing has opened up exciting opportunities to better understand disease initiation and progression and to guide and assess the effectiveness of therapies. Meanwhile novel imaging methods, such as photoacoustics, and combinations of technologies such as simultaneous PET and MRI, have created entirely new ways of looking at healthy function and disturbances to normal function associated with early and late disease progression. It is becoming increasingly clear that a multi-parameter, multi-scale and multi-sensor approach combining advanced sensor design with advanced computational methods in image formation and biological systems modelling is the way forward. The EPSRC Centre for Doctoral Training in Medical Imaging will provide comprehensive and integrative doctoral training in imaging sciences and methods. The programme has a strong focus on new image acquisition technologies, novel data analysis methods and integration with computational modelling. This will be a 4-year PhD programme designed to prepare students for successful careers in academia, industry and the healthcare sector. It comprises an MRes year in which the student will gain core competencies in this rapidly developing field, plus the skills to innovate both with imaging devices and with computational methods. During the PhD (years 2 to 4) the student will undertake an in-depth study of an aspect of medical imaging and its application to healthcare and will seek innovative solutions to challenging problems. Most projects will be strongly multi-disciplinary with a principle supervisor being a computer scientist, physicist, mathematician or engineer, a second supervisor from a clinical or life science background, and an industrial supervisor when required. Each project will lie in the EPSRC's remit. The Centre will comprise 72 students at its peak after 4 years and will be obtaining dedicated space and facilities. The participating departments are strongly supportive of this initiative and will encourage new academic appointees to actively participate in its delivery. The Centre will fill a significant skills gap that has been identified and our graduates will have a major impact in academic research in his area, industrial developments including attracting inward investment and driving forward start-ups, and in advocacy of this important and expanding area of medical engineering.