MRC Dementias Platform
Lead Research Organisation:
CARDIFF UNIVERSITY
Department Name: School of Medicine
Abstract
Dementia is one of the biggest health issues that we face and is a major concern for governments around the world. Recent studies have shown that the disease processes which underlie dementia begin in middle age if not before. This suggests that it is better to develop treatments that can be used long before dementia begins to affect daily life. However, identifying these early changes is very difficult.
To make detecting early changes easier, we want to create a 'one-stop-shop' for dementia researchers. We think this will help in several ways:
1. It will bring scientists and industry together in partnership. This will direct our scientific efforts in ways that will help develop new treatments more efficiently.
2. It will reduce the risk of failure. A major problem in studying the early stages of dementia is finding the right people to study. It's too late if a person has dementia and it's a waste of time if they won't ever get it. To overcome this problem we will measure in detail large numbers of apparently healthy people to identify those who are showing signs of early change.
3. It will enable quicker discovery. We will bring together and share results and insights from all the major dementia related studies in the UK so that we know have a better idea of where to put our effort. For example, we will be able to rapidly identify target mechanisms in, for example, a cohort of older people with many dementia cases, and see if we find the same mechanisms operating in younger persons with early changes found in a newly recruited cohort.
Combining all the information available to us in order to achieve these goals is not easy and so we will develop a powerful computing and information integration infrastructure to ensure that data and the ability to analyse it is available and accessible to a wide range of scientists representing many specialist disciplines.
This project raises some difficult ethical issues. For example, what should you tell someone if they show early changes? However, these issues have to be faced if we are going to solve the dementia problem.
Using these methods we think that the impact of dementia can be much reduced. Even if we are unable to stop the underlying mechanisms that produce dementia completely, by finding ways of slowing them down, and by applying these treatments as early as possible, it may be that most of us need never actually suffer the indignity of dementia, even if our 'mental arithmetic' is not what it once was.
To make detecting early changes easier, we want to create a 'one-stop-shop' for dementia researchers. We think this will help in several ways:
1. It will bring scientists and industry together in partnership. This will direct our scientific efforts in ways that will help develop new treatments more efficiently.
2. It will reduce the risk of failure. A major problem in studying the early stages of dementia is finding the right people to study. It's too late if a person has dementia and it's a waste of time if they won't ever get it. To overcome this problem we will measure in detail large numbers of apparently healthy people to identify those who are showing signs of early change.
3. It will enable quicker discovery. We will bring together and share results and insights from all the major dementia related studies in the UK so that we know have a better idea of where to put our effort. For example, we will be able to rapidly identify target mechanisms in, for example, a cohort of older people with many dementia cases, and see if we find the same mechanisms operating in younger persons with early changes found in a newly recruited cohort.
Combining all the information available to us in order to achieve these goals is not easy and so we will develop a powerful computing and information integration infrastructure to ensure that data and the ability to analyse it is available and accessible to a wide range of scientists representing many specialist disciplines.
This project raises some difficult ethical issues. For example, what should you tell someone if they show early changes? However, these issues have to be faced if we are going to solve the dementia problem.
Using these methods we think that the impact of dementia can be much reduced. Even if we are unable to stop the underlying mechanisms that produce dementia completely, by finding ways of slowing them down, and by applying these treatments as early as possible, it may be that most of us need never actually suffer the indignity of dementia, even if our 'mental arithmetic' is not what it once was.
Technical Summary
The main aim of the dementias platform is to identify phenotypic markers and their change from the earliest prodromal stages of dementia and to facilitate the translation of this knowledge into the development of new therapeutic and public health interventions intended to delay or prevent the common late life dementias.
Our strategy is to develop synergy between molecular and population science by embedding experimental and translational programmes within case-rich population cohorts, pre-morbid population cohorts, and genetic-at-risk clinical cohorts.
We aim to work closely with industry partners to accelerate the translation of basic science to public benefit.
Our objectives over the next five years are to:
1. Integrate multiple cohorts to provide a comprehensive epidemiologic research platform for dementia.
2. Develop bio-informatics methods to support a large-scale experimental medicine platform.
3. Fill methodological gaps for the characterisation of dementia and its earliest detection in large population cohorts.
4. Create a dedicated dementia research cohort of 100,000, and a dementia discovery cohort of 10,000 participants that will also serve as a pre-dementia registry.
5. Build a systematic programme of experimental studies focussing on the early detection and treatment of dementia.
Objective 5 will involve methodological innovation in biostatistics (data integration, risk stratification, efficient trial design), public engagement, biomarker discovery efficient trial design, as well as a flexible and evolving programme of hypothesis testing that is responsive to emerging hypotheses and concepts.
Our strategy is to develop synergy between molecular and population science by embedding experimental and translational programmes within case-rich population cohorts, pre-morbid population cohorts, and genetic-at-risk clinical cohorts.
We aim to work closely with industry partners to accelerate the translation of basic science to public benefit.
Our objectives over the next five years are to:
1. Integrate multiple cohorts to provide a comprehensive epidemiologic research platform for dementia.
2. Develop bio-informatics methods to support a large-scale experimental medicine platform.
3. Fill methodological gaps for the characterisation of dementia and its earliest detection in large population cohorts.
4. Create a dedicated dementia research cohort of 100,000, and a dementia discovery cohort of 10,000 participants that will also serve as a pre-dementia registry.
5. Build a systematic programme of experimental studies focussing on the early detection and treatment of dementia.
Objective 5 will involve methodological innovation in biostatistics (data integration, risk stratification, efficient trial design), public engagement, biomarker discovery efficient trial design, as well as a flexible and evolving programme of hypothesis testing that is responsive to emerging hypotheses and concepts.
Planned Impact
The main aim of the platform is to identify phenotypic markers and their change from the earliest prodromal stages of dementia and to facilitate the translation of this knowledge into the development of new therapeutic and public health interventions intended to delay or prevent the common late life dementias. The personal and economic burden of dementia is growing and is a major concern to governments around the world. By facilitating the cost-effective development of therapies to delay the onset and progression of cognitive decline leading to dementia, our work will impact global health and wellbeing. There will thus be many beneficiaries of our work including sufferers, their families and the wider population upon which much of the economic burden falls. Here we focus on the most immediate areas of non-academic impact for the platform as a whole.
Academic sector
The need for new models to improve the rate of advance in dementia research is evident. By bringing together international specialists under one virtual roof, and by focussing resources systematically on the challenges associated with early intervention, we expect to deliver a step-change in the research environment resulting in the rapid discovery of promising targets whether they be genes, molecules, proteins or cellular mechanisms. The full exploitation of data generated by the platform is an important principle. To facilitate this we are developing an informatics infrastructure that will enable widespread access and analysis of very large and complex datasets.
Commercial and Private Sector
The identification of pathological mechanisms underlying cognitive deterioration is of profound interest to molecular, cellular and systems neuroscientists working in the pharmaceutical industry to identify novel drug targets. The platform is structured to facilitate close collaboration with the private sector. To this end industry partners will have direct input to the development of the platform's programme of work. We believe that such direct engagement is essential for meaningful translation of basic research findings and in reducing the risk of failure in late stage trials. The platform brings experience of existing of institution specific collaborative arrangements with industry in this area, however, a more closely integrated and systematic programme of public-private-partnership is required to generate and focus resources for making more rapid discovery and translation.
Public sector, policy and practice.
We will raise the profile of contemporary debate about dementia and its treatment. We wish to encourage a culture of commitment to solving this problem. By increasing awareness at all levels of society we intend to leverage resources for the platform and for dementia research in general, to increase awareness of the need for earlier interventions and better targeted treatment in general by health service providers and the public alike.
Wider public engagement
Engagement with the general public and with patients and carers is a very important part of our mission. This serves not only to communicate our research findings and their relevance but also to address such issues as stigma in society and the research culture in the NHS in relation to dementia and older people. Our commitment to this is based upon our belief that instead of regarding the dementias as essentially an incurable and inevitable disease of (usually) old-age, for which the therapeutic focus should be largely palliative, we should regard these disorders as lifecourse related disorders which are increasingly tractable to research in genetics, molecular and neuroscience, and epidemiology, and for which treatments can be effective for delaying onset and progression sufficiently to avoid dementia if not prevent pathology.
Academic sector
The need for new models to improve the rate of advance in dementia research is evident. By bringing together international specialists under one virtual roof, and by focussing resources systematically on the challenges associated with early intervention, we expect to deliver a step-change in the research environment resulting in the rapid discovery of promising targets whether they be genes, molecules, proteins or cellular mechanisms. The full exploitation of data generated by the platform is an important principle. To facilitate this we are developing an informatics infrastructure that will enable widespread access and analysis of very large and complex datasets.
Commercial and Private Sector
The identification of pathological mechanisms underlying cognitive deterioration is of profound interest to molecular, cellular and systems neuroscientists working in the pharmaceutical industry to identify novel drug targets. The platform is structured to facilitate close collaboration with the private sector. To this end industry partners will have direct input to the development of the platform's programme of work. We believe that such direct engagement is essential for meaningful translation of basic research findings and in reducing the risk of failure in late stage trials. The platform brings experience of existing of institution specific collaborative arrangements with industry in this area, however, a more closely integrated and systematic programme of public-private-partnership is required to generate and focus resources for making more rapid discovery and translation.
Public sector, policy and practice.
We will raise the profile of contemporary debate about dementia and its treatment. We wish to encourage a culture of commitment to solving this problem. By increasing awareness at all levels of society we intend to leverage resources for the platform and for dementia research in general, to increase awareness of the need for earlier interventions and better targeted treatment in general by health service providers and the public alike.
Wider public engagement
Engagement with the general public and with patients and carers is a very important part of our mission. This serves not only to communicate our research findings and their relevance but also to address such issues as stigma in society and the research culture in the NHS in relation to dementia and older people. Our commitment to this is based upon our belief that instead of regarding the dementias as essentially an incurable and inevitable disease of (usually) old-age, for which the therapeutic focus should be largely palliative, we should regard these disorders as lifecourse related disorders which are increasingly tractable to research in genetics, molecular and neuroscience, and epidemiology, and for which treatments can be effective for delaying onset and progression sufficiently to avoid dementia if not prevent pathology.