Annual Report 2015 - Dementias Platform UK

Annual Report 2015
Beating Dementia Together
The Dementias Platform UK (DPUK), funded by the Medical Research Council, is a multi-million
pound public-private partnership aiming to accelerate progress in, and open up, dementias research.
It began in June 2014 and was officially launched in October 2014. The project is directed by Professor John Gallacher from the University of Oxford supported by an Executive Team of investigators.
The universities currently within DPUK are Cambridge, Cardiff, Edinburgh, Imperial College London,
Oxford, Newcastle, University College London (UCL) and Swansea, including the UCL-based MRC
Unit for Lifelong Health and Ageing. The Clinical Research Infrastructure award links DPUK with further
An-
nual
2
Contents
1. Foreword
4
2. Introduction
6
3. The DPUK Research Infrastructure
7
3.1 Informatics
8
3.2 Dementias Resources
10
3.3 Methods Development
11
3.4 Research Networks
- Imaging Network
12
- Informatics Network
14
- Stem Cells Network
16
3.5 Experimental Medicine
18
- Theme 1 - Synaptic Health
19
- Theme 2 - Innate and Adaptive Immunity
20
- Theme 3 - Vascular Disease Mechanisms
21
4. Raising the DPUK Profile
22
5. Wider Connections
25
6. Director’s Overview of the 1st Year
27
7. Funder’s View
28
8. Industry Perspective
29
9. Looking Forward
30
10. Appendices
31
3
1. Foreword
This first annual report of the MRC Dementias Platform UK provides an overview of our research
and public engagement activities.
The Platform is a response to the need to understand more fully the causes of dementia and the
need for a new generation of early phase dementia trials, in which cellular and molecular mechanisms are more closely linked to patient selection and response. The UK, through its high-level technologies and portfolio of rigorously maintained population studies is uniquely positioned to address
these needs.
Through academic and industry partnership, the Platform is building the infrastructure to enable rapid data analysis at scale, highly stratified participant selection, and streamlined multi-centre data collection. This involves working closely with the scientific community to address structural and technological barriers, and public engagement to understand the issues surrounding the recruitment to, and
conduct of, early intervention studies.
2014-15 has been an exciting year. A growing number of population studies have joined the Platform and world-class scientific networks have been established for molecular and structural imaging,
induced pluripotent stem cells, and bio-informatics. In addition a nascent scientific programme has
begun. This success, is due to the significant engagement of both academic and industry partners to
the collaborative ethos of the Platform. The breadth and depth of collaborative activity across disciplines across the UK has been remarkable and reflects a strength of commitment to beating dementia.
Director, Dementias Platform UK, Professor John Gallacher, PhD AFBPsS CPsychol FFPF
4
Five Year Vision
Our vision is to provide an integrated research environment enabling a new generation of highly
targeted and highly informative clinical trials linking more closely cellular and molecular changes to
patient selection and response. Within five years we will establish world leading data sharing facilities,
world leading research networks for Imaging, Stem Cells and Informatics, and systematic Experimental Medicine programmes focussing on Synaptic Health, Innate and Adaptive Immunity and Vascular Disease Mechanisms.
Platform Objectives

To create an optimal environment for dementias research, where the scientific community can
access data to aid understanding of the disease.

To integrate data from multiple cohorts to enable rapid and extensive evidence synthesis.

To develop a single-point data access portal for accessing and analysing data across cohorts.

To use more efficient methods for conducting Experimental Medicine studies.

To create dedicated dementia research resources by re-purposing strategically selected cohorts
for dementia mechanisms discovery and trials readiness.

To develop an integrated and systematic programme of Experimental Medicine, in partnership
with industry focusing on the early detection of decline and treatment of dementia.

To demonstrate the value of collaborative working to generate further funding.

To establish an Imaging Network across the UK, with state of the art MRI-PET capabilities, coordinated research activity and a common data repository.

To establish an Informatics Network supporting researchers by enabling them to search for and
analyse data, including scan images and tissue samples.

To establish a strategic UK-wide Stem Cell Network enabling coordinated research
programmes.
5
2. Introduction
The MRC Dementias Platform UK (DPUK) has been established to address the structural and technological challenges associated with accelerating the development of new interventions for the dementias. These challenges include the rapid analysis of complex and diverse data to generate and
test hypotheses, the recruitment of well-characterised participants to early phase trials and discovery
studies, and the development of technologies to facilitate the conduct of multi-centre studies.
DPUK is funded by the MRC in partnership with industry. It has received a core award over five
years of £12M from MRC with a further £4M contribution from industry partners. In addition, it has
been awarded £36M by MRC to establish three high-technology research networks comprising a 7site molecular and structural Imaging Network, a 6-site induced pluripotent Stem Cell (iPSC) Network and a 5-site Bio-Informatics Network.
The key resource on which the Platform is predicated is the large number and diversity of population
studies (cohorts) available within the UK. Many of these studies have followed the cognitive performance of their participants, often for decades, allowing cognitive change to be associated with genetic, lifestyle and environmental factors. This allows individuals of particular scientific interest to be
identified for more detailed study. Data from two million cohort members will be accessible for analysis. More detailed data will be available for 100,000 members of UK Biobank who will have 3T brain
imaging with concurrent cognitive testing. Finally, two year repeat scanning and testing will identify
10,000 individuals with biomarker change data who are willing to participate in more detailed studies.
A key concept in the design of DPUK is integration (figure 1). Bringing together well-characterised
participants from our cohorts and high-technology research networks, provides an unusually rich environment for understanding the dementias. We can investigate the broader impact of early and late
exposure to risk factors, and provide a context for a new generation of early phase trials, in which
cellular and molecular mechanisms are more closely linked to patient selection and response. In exploiting these resources our Experimental Medicine programme is focussed on Synaptic Health, Innate and Adaptive Immunity, and Vascular Disease Mechanisms, although other interests are welcome. DPUK is delighted to be working alongside other national and international initiatives in the
drive to beat dementia, and welcomes further opportunities for collaboration.
Figure 1: The DPUK Integrated Research Environment
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3. The DPUK Research Infrastructure
To deliver this research environment the DPUK programme is organised into five work streams comprising Informatics, Dementia Resources, Methods Development, Research Networks and Experimental Medicine (figure 2). To assist in the delivery of DPUK, funding has been provided for a range
of roles. An outline of appointments is shown in Appendix 2.
The Informatics work stream involves collating cohort data and building a secure ‘one-stop-shop’
analytic environment for data storage and analysis.
The Dementia Resources work stream is strategically enhancing several cohorts according to scientific need; developing a trials ready cohort, comparing amyloid deposition between late and early onset dementia, and an intensive wet biomarker study.
To exploit this wealth of opportunity the Methods Development work stream is developing techniques
for more informative biostatistical analysis, reducing loss-to-follow-up for dementia outcomes, cognitive assessment at scale, understanding dementia trials recruitment with asymptomatic participants,
exploring the wider Ethical, Legal and Social Issues (ELSI) surrounding trials recruitment from cohort
participants, and developing protocols for brain donation in a fast moving scientific environment.
The Research Networks promote the sharing of best practice suitable for use in a fast moving environment and the streamlining of scientific activity in key areas. The Molecular and Structural Imaging
network enables multi-centre studies benefitting from shared specialist radiochemistry, standardised
protocols and streamlined governance. The iPSC Network brings together centres with expertise in
high throughput genome editing, cell differentiation, and cell immortalisation. The Informatics Network brings a range of technologies to DPUK from record linkage, through image processing, to
wearables.
Although challenging, Experimental Medicine remains the key to progress in dementia as it can deliver the evidence necessary for introducing new treatments. DPUK has four initiatives focussing on
Synaptic Health, Innate and Adaptive Immunity, Vascular Health Mechanisms and a Deep and Frequent Phenotyping study.
Achieving an integrated research environment capable of delivering an Experimental Medicine programme in dementia is a strategic objective which will be delivered incrementally over the course of
the programme. Over the five years of this award there will be a process of identifying and addressing barriers to dementia research.
Figure 2: Overview of DPUK Infrastructure
7
3.1 Informatics
DPUK brings together over 30 case-rich population cohorts, genetic-at-risk clinical cohorts, and premorbid population cohorts to deliver a unique resource enabling the triangulation of different types of
evidence for the rapid identification of promising targets and the testing of hypotheses. Collaboration
will occur at three levels comprising the sharing of existing data, the sharing of biosamples, and access to cohort participants for additional assessment or recruitment to Experimental Medicine studies.
Different levels of collaboration will be appropriate for different cohorts depending upon cohort size,
legacy consents and the research question. Collating information on all cohorts and populating the
meta-data catalogue is DPUK Work Package 1. Constructing and managing the informatics portal is
DPUK Work Package 2. These work packages are featured on page 9.
Interviews Completed by June 2015
Cohort Name
Estimated number
of participants
Start Date
Age at
Recruitment
Aberdeen Children of the 1950's (ACONF)
AMyloid imaging for Phenotyping LEwy body
dementia (AMPLE)
12,150
1962 (1999)
6-12 (43-49)
80
2013
60+
UK BIOBANK
503,316
2006-2010
40-69
3,200
2009
65+
159
2000
30+
CFAS I (Cognitive Function in Ageing Study I)
18,000+
1989
65+
CFAS II (Cognitive Function in Ageing Study II)
European Prospective Investigation of Cancer
Norfolk (EPIC – Norfolk)
Generation Scotland: Scottish Family Health
Study (GS:SFHS)
7,524
2008
65+
25,639
1993-1997
40-79
24,090
2006
18-100
100
2013
60+
1,091
1947 (2004)
11 (70-72)
5,362
1946
Birth
The PREVENT Research Programme
210
2014
40-59
Southall And Brent Revisited (SABRE)
4,858
1988
40-69
366
2008
18-65
Brains for Dementia Research (BDR)
Cambridgeshire Parkinson's Incidence from
GP to Neurologist (CamPaIGN)
Lewy Pro
Lothian Birth Cohort 1936 (LBC 1936)
MRC National Survey for Health and Development
(MRC NSHD)
TrackHD
Members of the Lothian Birth
Cohort 1936, age 78.
8
In Focus
Work Package 1: Cohort Profiling
Professor Craig Ritchie, University of Edinburgh
The aim of Work Package 1 (WP1) is to integrate existing UK cohorts into
the Dementias Platform. The primary goal is to compile a profile of each
cohort, outlining what types of information have been collected in the
study, the key researchers involved and the people included in the study.
“The existing
cohorts in the UK are Cohort integration has been achieved by meeting with the study teams
and developing an online tool in which to capture the cohort profiles.
an unparalleled
resource for
advancing
research. Engaging
with cohorts will be a
key
strength
of
DPUK and
fundamental to its
success.”
Thus far, we have identified over 30 cohorts that are engaged with DPUK,
and by October 2015, we will have interviewed all but two of them. In addition, we have created a Cohort Directory and Cohort Matrix which will
outline on our website the nature of cohorts and the broad types of cohorts involved in DPUK. In addition, WP1 also manages the relationships
with cohorts and are the link between DPUK staff and the cohort teams. A
key objective of the remainder of WP1 is to assess the value of the existing cohorts and is highlighting strengths and identifying the areas in which
current research could be expanded or improved. An example from the
DPUK Cohort Directory is shown in Appendix 1).
Work Package 2: Informatics Platform
Ronan Lyons, Swansea University
A key aim for DPUK is to enable secure but rapid access to cohort data allowing the analysis of multiple independent datasets. To achieve this Work
Package 2 is creating a ‘one-stop-shop’ Data Portal. Through this portal researchers will be able to identify which cohorts have data of interest to them,
and for how many participants. The Portal will also act as a communications
hub between researchers and cohort research teams to streamline proposal
development and data-access permissions. Finally, the Portal will enable
data to be transferred to a secure space within DPUK servers for statistical
analysis and report writing. This space may be accessed remotely by researchers from their desks. Data will not be downloadable from DPUK servers.
“Providing access
to complex data to
a research team
distributed across
multiple universities
will really bring
team science to Data security is paramount and will be achieved by using the Farr Institute’s
life.”
UKSeRP analytics platform which has triple encryption, trusted third party de
-identification, and two-factor user authentication.
The data portal build is nearing completion and we anticipate adding the first
data by Q4 2015.
9
3.2 Dementias Resources
Trials Readiness Cohort
We are working with UK Biobank to establish a cohort of 100,000 largely premorbid middle-aged (4069 years) adults with extensive genotyping, and concurrent 3T brain imaging, biosampling and cognitive phenotyping. This will establish the world's largest cohort specifically characterised for dementia.
From within this group DPUK will recruit 10,000 participants who are willing to be re-contacted for experimental studies for two year repeat assessment. This will create the world’s largest trials register
with detailed biomarker change data. Progress in year 1 includes agreement with UK Biobank regarding the enhancement of cognitive testing and biosampling at imaging baseline, and beginning pilot
work to assess the acceptability of repeat imaging and brain donation. Delivering the DPUK trials
readiness cohort is DPUK Work Package 3.
UK Biobank samples
Amyloid Marker Discovery Cohort
Amyloid and Tau pathology is strongly indicated in Alzheimer’s disease (AD). To identify non-invasive
markers for these pathologies 500 members of the MRC NSHD with known brain Aβ status will undergo PET/MR imaging and biosampling, including where possible cerebrospinal fluid (CSF). Progress in
year 1 includes finalising recruitment and data acquisition protocols, obtaining ethical approval and
beginning recruitment. Recruitment is on course with 11 cohort members having completed amyloid
and structural imaging. It has been decided to establish the acceptability of amyloid imaging with cohort participants before extending the study to include Tau imaging and CSF sampling. Identifying amyloid and Tau biomarkers is DPUK Work Package 4.
Familial Disease Cohort
The familial disease cohort is designed to replicate and determine the longitudinal pattern of biomarkers of disease identified in sporadic cohorts. By comparing markers from different diseases i.e.
FAD, FTD and HD we hope to identify common and unique mechanisms associated with these conditions. This Work Package has recently achieved collateral funding, staff are being appointed, and liaison with the amyloid discovery cohort team has begun. A further aim is to use the FTD cohort to explore PET tau tracers and the time course of tau deposition in pre manifest tau mutation cases. This
can then be extended to other tauopathies including AD. The familial disease cohort is DPUK Work
Package 5.
Biomarker Discovery Cohort
Work looking at biomarkers in genetically risk stratified populations is due to begin in year 2 (20152016). Meanwhile, as biomarkers for dementia is a fast moving area, the emergence of new data is
being monitored to inform finalising the protocol prior to sample draw down. The biomarker discovery
cohort is DPUK Work Package 6.
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3.3 Methods Development
Cognitive Assessment at Scale
A major challenge to dementia science is identifying early cognitive change at scale. This requires cost
-effective repeated assessment of a multiple domains in the normal range of cognitive performance.
Auto-mated methods, suitable for use in population studies, and methods for reducing non-compliance
at repeat assessment, are being developed for use in UK Biobank with a view to wider application.
Progress in year 1 includes reviewing the cognitive testing landscape, and agreeing cognitive testing
enhancement with UK Biobank. Computerisation of the enhanced test battery for use in the Biobank
imaging assessment has begun. Cognitive assessment is DPUK Work Package 10.
Brain Donation
Working with large numbers of rigorously maintained cohorts provides an unprecedented opportunity
for collecting highly characterised brains for research. In a fast moving Experimental Medicine environment this involves flexible brain donation consent procedures that do not necessarily require the collection of all brains for which consent has been given. Progress in year 1 includes the development of materials and agreement with UK Biobank to conduct a pilot study into the acceptability to research participants of more flexible brain donation procedures. Developing flexible brain donation consent procedures is DPUK Work Package 13.
Ethical Legal and Social Issues
Re-purposing cohorts for Experimental Medicine Ethical, Legal and Social Issues (ELSI) studies is not
limited to UK Biobank. Other studies within the collaboration such as PREVENT (a cohort study) and
CFAS (Cognitive Function and Ageing Studies, a cohort study) are either trials ready or working towards trials readiness. Nevertheless, the re-purposing of cohorts involves the coming together of many
Ethical, Legal and Social Issues. Ethical legal and Social Issues are in Work Package 12.
Trials Recruitment
To pilot recruitment to trials from cohorts a small scale recruitment process will be conducted from
within the PREVENT cohort. This process is dependent on the outcome of the Ethical Legal and Social
Issues Work Package and is anticipated to begin in year 2. Trials recruitment is DPUK Work Package
11.
Outcome Adjudication
Adjudicating dementia related outcomes, at scale using routinely collected data, provides a means of
assessing dementia in a wide range of population studies. Using UK Biobank as a model, a staged approach going from the ascertainment of suspected cases to confirming and sub-classifying cases will
be adopted. Progress in year 1 includes starting systematic reviews for dementias and other neurodegenerative conditions diagnosis and the design of prototype diagnostic algorithms. Outcome adjudication is DPUK Work Package 9.
Biostatistics
To make best use of the breadth and depth of data available to DPUK, statistical methods for improved
cross-sectional and longitudinal analyses are being developed. Progress in year 1 includes staff appointments and initial work on polygenic scores, with a first publication in press. Biostatistics is DPUK
Work Package 14.
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Imaging Network
Network Lead: Paul Matthews, Imperial College London
Who is involved in the network?
Franklin Aigbirho, Cambridge (Co-Chair and Radiotracer
access & development)
Nick Fox, University College London (Co-Chair)
Geoff Parker, Manchester (Procurement & set up)
Edwin Van Beek, Edinburgh (Procurement & set up)
Jan Passchier, Imanova (Radiotracer access & development)
Karl Herholz, Manchester (Clinical Governance for multicentre studies)
John-Paul Taylor, Newcastle (Clinical Governance for multicentre studies)
Roger Gunn, Imperial College London (Analysis pipelines & QC)
Tim Fryer, Cambridge (Analysis pipelines & QC)
Clare Mackay, Oxford (IT)
Sebastien Ourselin, UCL (IT)
What is the Network aiming to achieve?
Over 2014-15, the DPUK Neuroimaging Network was created. The Network links neuroimaging for
neurodegenerative disease across eight major UK research institutions (Cambridge, UCL, Kings, Imperial, Cardiff, Manchester, Newcastle, and Edinburgh).
A governance structure for the Network was developed with Paul Matthews (Imperial) Chairing and
Nick Fox (UCL) and Franklin Aigbirho (Cambridge) as co-Chairs. The primary task for the Network
were to pursue a major procurement (funded by the MRC Clinical Research Infrastructure (CRI) monies) to equip five of the centres with state-of-the-art MRI-PET imaging, complementing facilities already in place at UCL and Kings. Other tasks were defined around work packages intending to:




Integrate complementary technical expertise and resources across centres to enable rapid “set
up” of new centres;
Ensure access to major radiotracers for dementia research across the Network, develop a path
for more rapid access to newly developed ligands and create an environment to foster the discovering and development of novel ligands;
Coordinate research and development for other technical innovations (multi-modal integration,
new imaging sequences, analytical techniques, artefact resolution); and
Encourage harmonisation of operating procedures and provide a single portal for engagement
across the Network for multi-centre clinical studies.
Tangible progress already has been made. A common procurement framework for new instrumentation was put in place and competitions run in a coordinated fashion across all partners. Final preferences will be declared by all sites by the end of September 2015, allowing installations to progress
within timelines agreed with the MRC for the CRI spend. It already is clear that the national network
will include state of the art systems from both of the major vendors. This will leverage lessons from
the better-established platform in the context of newer technology. The two platforms will help in validation of robust acquisition harmonisation methodologies. It also contributes substantially to allowing
research to be translated from research towards clinical applications in the longer term. With its implementation, there will be a geographically well-distributed range of facilities across the UK to enhance
opportunities for deriving value for experimental medicine from cohorts within DPUK:
12
Working in concert with the DPUK IT group, a common platform for image management was
defined and is being brought to the DPUK Executive Team for endorsement in September
2015. A first Network support grant has been outlined and will be submitted to the MRC in October 2015. A first PET Experimental Medicine study that will move towards validation of a
novel radioligand for dementia studies within the Platform was developed jointly across partners and endorsed by the DPUK Executive in July. Ethics approval is anticipated in October
2015. Additional, multi-centre MRI-PET studies to be conducted using resources of the Network are under discussion and will be confirmed over 2015/16.
Specific research plans are in place to address important methodological problems underlying
the use of MRI-PET for the brain. These include:

Improved registration of MRI and PET to enhance precision of integrated, regionally specific outcome measures. This work of particular importance in dementia patients for
whom normal brain anatomy is individually variable and may be altered substantially.

Dynamic 3D motion correction of PET scans based on simultaneous MRI to enhance
effective sensitivity and further improve spatial resolution. This is expected to realise
particular benefits for tau radioligands, which assess an intrinsically low abundance
signal.

Reduced radiation exposure relative to MRI/CT. Optimisation of MRI-informed attenuation corrections will contribute to the potential to obtain greater numbers of PET scans
(relative to PET/CT) for longitudinal or multi-tracer studies (e.g., an inflammatory marker
and mis-folded protein probes), especially in younger, prodromal subjects.
Additional funding already has been secured by members of the collaboration to pursue these
and related problems, e.g., by Kris Thielemans (UCL, EPSRC) and Roger Gunn (Imperial,
MRC DPFS).
Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses influence pathology development, synapse health and neurodegeneration in AD. Functions can be
modulated in vitro and in animal models by a broad range of molecules, many of which are directed against well precedented targets, suggesting the potential for astrocyte-directed, repurposed or novel therapeutics. A first DPUK supported Experimental Medicine study already
is moving forward to evaluate a novel radioligand, [11C]BU99008, selective for I2-imidazoline
binding sites, developed by Prof. David Nutt (Imperial) and his colleagues that may provide an
in vivo index of astrocyte activation with dementia. First subjects with dementia are expected
to be scanned in early 2016.
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Informatics Network
Network Lead: Simon Lovestone, University of Oxford
Who is involved in the Network?
Mike Denis, Oxford (CRIS for DPUK)
Clare Mackay, Oxford (Imaging Informatics)
Iain Buchan, Manchester (Connected devices)
Ronan Lyons, Swansea (DPUK Portal)
Julie Williams, Cardiff (Genomics Informatics)
Seth Love, Bristol (Brain Banking Informatics)
What is the Network aiming to achieve?
The Informatics Network is aiming to enhance the ability of
researchers to find and then use data and information collected
in DPUK. This involves first making that data ‘visible’ – what is
available, where is it and how is it accessed. Then the Informatics Network is establishing a set of
platforms that will improve researchers’ ability to access the data within a safe and secure environment that respects data-privacy and the Information Governance agreements including consent and
approvals of the parent cohorts in DPUK. Finally, the Informatics Network will enhance, through the
provision of analytical tools and the building of a strong and open collaborative grouping, the ability
of researchers to turn the data in DPUK cohorts into information that will increase our understanding
of dementia and lead to improved therapies.
The platforms that the Network is establishing are described below and include the Data Portal that
serves Work Package 2, a system for accessing information in the Clinical Record Interactive
Search (CRIS), a development of the use of peripheral devices for dementia research and platforms
for data sharing in neuroimaging and genetics and infrastructure for digital archiving of brain bank
material.
The objectives for the Informatics Network are:
1.
2.
3.
4.
5.
6.
Extending CRIS from three to 10 NHS regions to complement the existing cohort research
generated datasets with the re-utilisation of routine care data from secondary and tertiary
health care for dementia outcomes (Oxford).
Creating a remote data collection platform using mobile devices in the collection of dementia
relevant objective data (Manchester).
Designing and building a national image sharing and analysis platform and increase storage
capacity for DPUK imaging across clinical and research datasets (Oxford)
Establishing the infrastructure to underpin genetic analyses across DPUK.
Providing digital archiving to improve accessibility of samples for pathological examination
and Experimental Medicine (Bristol).
Increasing DPUK Data Portal processing speed and capacity to meet the additional
requirements of the proposed Informatics Networks (Swansea).
14
How is the Network achieving these aims?
Informatics Data Portal development: The DPUK Portal is described in Work Package 2. The basic
analytical Data Portal has been developed and is in the process of being upgraded with the additional
high performance computer, funded by the MRC capital development. The DPUK Data Portal is
based on an extension of the UK Secure eResearch Platform (UKSeRP), a facility operated by
Swansea University for the Farr Institute. UKSeRP is a federated solution to data sharing in which cohort custodians are provided with their own remotely managed section to upload and remove data and
benefit from the facilities the Portal offers. These include data documentation, data quality measurement, automation of processes, probabilistic matching engine, some natural language processing capability, a variety of new technologies including clusters of SQL Server 2014, HADOOP, R as well as
XNAT and TranSmart, a security model with two factor authentication if required. Documentation on
data sharing and information governance have been produced and presentations made to cohort custodians in meetings in London, Cambridge and Edinburgh. The Portal is now ready to receive data
once data access agreements are signed with cohort custodians.
UK-CRIS: CRIS is an innovative research solution that retrieves data from an NHS Trust’s Electronic Medical Record system, pseudonimises it to protect patient identities and then loads it in to a
database. This database can then be queried to perform a detailed range of research queries. UKCRIS will build and expand on successful projects and will deploy the Clinical Record Interactive
Search solution (CRIS) to an additional 10 Mental Health Trusts across the UK. UK-CRIS will implement ‘Federated Querying’ (the ability to run research queries across data sourced from multiple Trust
organisations) thus creating a potential research cohort of up to two million subjects. In addition, UKCRIS will seek to establish a linkage between CRIS data and UK-Biobank.
Remote data collection: DPUK represents an ideal opportunity to develop and test the use of
remote data collection through peripherals, wearables and other uses of pervasive or mobile computing technologies. In preparation for this anticipated substantial change in the way research and ultimately clinical, data is collected, the Informatics Network will establish a platform for secure data management and analysis and test devices of relevance to dementia data collection.
Neuroimaging sharing and analysis platform: The objective with the DPUK Imaging Informatics
work stream is to establish a national image sharing and analysis platform for dementia research as
part of the Dementias Platform UK. We will develop and implement a platform for management, sharing and analysis of multimodal imaging data associated with DPUK cohorts. The programme will deliver 1) A catalogue of existing DPUK imaging data with a search and data request capability, 2) A Data
Management System (DMS) designed and implemented at multiple sites using a generic data model
and 3) A central instance of the DMS with a capability to search for subjects across distributed sites,
and to receive data from local sites for central data analysis. We will deliver the capability (but not the
implementation) of automated pipelines for image analysis.
Genetic data sharing and analysis platform: The genetics component of the informatics work
stream will provide the tools and software to share genomic data collected within the cohorts of DPUK
and facilitate analysis of these rich datasets. A key component of the Platform will be a simple, but
powerful, secure online workspace for analysis relevant to dementia genetics. Another key component
will be a results database, an online workspace for searching and identifying genes, Single Nucleotide
Polymorphism (SNPs), and genomic locations of interest or with special relevance to dementia, integrating summary data from different study cohorts for the purposes of aggregate data meta-analysis.
Digital archiving for brain banking: Through DPUK a network of brain banks are being enhanced with facilities for digital archiving including the use of barcode infrastructure to enable tracking
of samples donated for research.
15
Stem Cell Network
Network Lead: Richard Wade-Martins, The University of Oxford
Who is involved in the Network?
Sally Cowley, StemBANCC & Oxford (Cellular reprogramming)
Tom Warner, University College London (Cellular phenotyping)
Nicholas Allen, Cardiff (Neuronal physiology)
Siddharthan Chandran, Edinburgh (Glial biology)
Frederick Livesey, Cambridge (Genetics)
Nigel Hooper, Manchester (Proteomics)
What is the Network aiming to achieve?
Contributing to a systematic and coordinated programme of stem-cell
research, the Induced Pluripotent Stem Cells (iPSC) Network will also support the development of iPSCbased enhancement of strategic DPUK cohorts.
Collaboration and coordination

UK-wide coordination of iPSC technology to study dementia

Expertise sharing, protocol harmonisation, innovation, increased capacity
Preserve DPUK cohorts

Collection and preservation of primary cells suitable for reprogramming

Deep clinical phenotyping will identify DPUK patients for iPSCs
Provide cellular component of clinical phenotype

Cellular basis of disease stratification

Molecular mechanisms to support biomarker discovery
Interrogate key dementia pathogenic pathways

Understand disease mechanisms

Rationale for target identification

Collaborative automated high content imaging analysis
The objectives for the Stem Cell Network are to:
1.
2.
3.
4.
5.
6.
Immortalise highly valuable DPUK clinical cohorts through collection and preservation of primary
cells suitable for reprogramming
Use deep clinical phenotyping, including imaging data, to select high priority informative patients
from DPUK cohorts for primary cell reprogramming into iPSC lines using a standardised consortium
protocol
Build capacity for genome editing and high-content cellular phenotyping of iPSC neuronal and glial
models to better understand disease mechanisms to provide rationale for target identification;
Develop a collaborative programme of automated high content imaging analysis of iPSC neurons to
identify key dementia pathogenic pathways
Use iPSC models to provide cell biological support for risk stratification and biomarker discovery in
DPUK cohorts
Optimise and implement phenotype screening assays for target discovery and drug development.
How is the Network achieving these aims?
This Network will enable UK-wide coordination of iPSC technology in the study of dementia facilitating
expertise sharing, harmonisation, innovation, and increased capacity.
16
Progress so far
iPSC Cell lines
We are building a valuable legacy resource of iPSC lines through the preservation of primary cell types
(both blood and fibroblasts) from extensive and exceptionally-well characterised DPUK cohorts of patients with dementia to include Alzheimer’s Disease, Frontotemporal Dementia, Parkinson’s Disease and
Motor Neurone Disease.
Cowley (Oxford) is co-ordinating with the major EU iPSC programmes (StemBANCC, EBiSC and HipSci)
to ensure the cataloguing, distribution and open access of DPUK iPSC lines to facilitate research into
dementia both within and beyond the DPUK network. The EU-wide StemBANCC reprogramming work
has been running for three years and lines are being made available. The Oxford Parkinson’s Disease
Centre (OPDC) has generated over 100 iPSC lines from patients and controls.
Exceptional DPUK cohorts have been identified as a priority for iPSC reprogramming. Edinburgh will use
DPUK DSCN resources to reprogram the highly informative, deeply phenotyped cognitive and brain ageing 1936 Lothian Birth Cohort (LBC).
The DSCN has applied for a DPUK Experimental Medicine Pilot Award (Lead Wade-Martins; June 2015)
to fund iPSC reprogramming, neuronal differentiation and disease phenotyping of the MRC Deep and
Frequent Cohort (in collaboration with Lovestone).
Network building
We are building UK capacity for iPSC work through collaboration, shared equipment platforms, shared
methods, shared expertise driven by regular communication. The Dementias Platform UK Dementia
Stem Cell Network (DPUK DSCN) holds regular monthly meetings of all six Centres to ensure close cooperation and collaboration. DPUK DSCN members already actively collaborate exchanging iPSC lines,
protocols and expertise. A face-to-face meeting took place in London at the MRC offices in January 2015
to plan the initial phase of the Network. A further meeting of PIs is planned for Autumn 2015, and a scientific meeting for Principal Investigators, post-docs and students for the first half of 2016.
Equipment procurement is well underway. UCL is leading on a tender process to purchase three highthroughput scanning confocal microscopes. The tender is open, site visits are underway and bids are
expected in early September. Cambridge is near completion on a tender and purchase of a 2-photon microscope. Smaller equipment items have been purchased. Laboratory refurbishment is underway.
Harmonisation of protocols is already underway. For example, Cambridge has previously held workshops on cortical neuronal differentiation and Cowley has made places available on the upcoming Oxford Stem Cell Workshop to DSCN members (Dec 7th-9th, 2015).
The DPUK DSCN applied for an MRC Partnership award in June 2015 (Lead Chandra). Our Partnership
Award will (1) establish a UK community of Network Technical Scientists who will (2) use standardised
operating protocols (SOPs) to generate functional neurons and glia from already available prototypic disease (and isogenic control) lines plus newly generated control lines from the Lothian Birth Cohort (LBC)
that will then be (3) systematically phenotyped using the DPUK newly established technical platforms to
deliver (4) a master reference publicly available data set of normal and “dementia” disease variability
plus gold-standard lines that will be incorporated into (5) a Dementia-UK CellPlate to enable multi-site
working, high-throughput screening, drug discovery and engagement with industry.
DSCN Engagement
The formation of the DPUK DSCN will enable the UK dementia community to engage with iPSC technology by lowering the barrier to entry to groups with no prior experience of this work through collaborative
opportunities. This capital award will establish six Dementia Stem Cell Centres across the UK to provide
sites where iPSC lines, essential equipment and expertise can be shared and training provided for visiting collaborating scientists. The DSCNs are integrating with other ongoing related programs. For example, DSCN PIs at Oxford, Cambridge and London are working closely with Alzheimer’s Research UK
(ARUK) through the new ARUK Drug Discovery Institutes and the new ARUK Stem Cell Research Centre , a collaborative effort between Cambridge and UCL (Lead: Livesey). The input of StemBANCC lines
will be essential to the DPUK DSCN.
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3.5 Experimental Medicine
Background
The vision of DPUK is to provide an integrated research environment for dementias research to accelerate the development of new interventions, focussing on utilising cohorts to support Experimental
Medicine (EM) programmes.
Introduction
The DPUK definition of EM is broad to encourage innovation and collaboration, but is human focussed. A guidance note has been written to provide information for researchers wishing to submit
proposals to DPUK for support with EM projects. This is available on the website to download.
DPUK EM strategy is to facilitate synergy across disciplines and technologies establishing expert
working groups for specific research themes. The focus of the DPUK EM programme is to accelerate
the development of interventions through identifying neuropathologic and neuroprotective pathways
and mechanisms.
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Theme 1: Synaptic Health
Lead: James Rowe, University of Cambridge
Facilitator: Declan Jones (Janssen Research & Development and
DPUK Executive Team)
Synaptic loss and regeneration is a highly dynamic process that persists
throughout adulthood, and unlike neuronal loss, which is irreversible, synaptic
regeneration can be promoted. A greater understanding of synapse function,
loss and repair, would enable therapies to be developed to retard synapse
degeneration and enhance synapse repair.
Progress highlights:






A shared understanding of the state-of-the-art in Synaptic Health (SH), and the readiness for
translating the current evidence from animal models and healthy humans into clinical cohorts
Consensus on the contribution from genetic models and cellular models, while keeping the future
DPUK-SH focus on human studies and clinical pull-through.
Knowledge sharing in terms of technologies and analyses available to manipulate synaptic function, assess cognitive impact, and potential for early diagnosis
Establishing common ground between partners on the mutual priorities for robust deliverables in a
cost-effective and timely research programme:
SH will focus on human observational and interventional studies, with disease modification
(including immunotherapies and BACE inhibition) as a priority over pharmacological symptom alleviation.
Magnetoencephalography (MEG) and Electroencephalography (EEG) with advanced modelling of
the human neurophysiology, are the major methods in the forthcoming applications, but not to the
exclusion of other contributory methods
Following the DPUK launch, two SH related Expression of Interest forms (EOIs) were submitted to the
first call for EM project proposals: one proposing a strategic approach to clinical measurement of SH
and one using APOε4 and Brain-derived neurotrophic factor (BDNF) status to assess cognitive risk.
Strategy Group (see Appendix 3):
There is a huge opportunity to leverage the expertise and infrastructure that exists within the UK, the
DPUK investment in the Imaging and Stem Cell Networks, and the desire by the commercial partners to
support this work. Preliminary scoping suggests there is room for improved coordination between existing UK research teams, improved coordination between academic and industry groups, and that key
questions have not yet been fully addressed.
Given the immediate Experimental Medicine needs of the Industry Partners, and the available technologies, expertise, and infrastructure, Declan Jones (Janssen Research & Development) agreed to programme manage the development of the Network for the SH theme, with the aim of developing
an overall strategy, early experimental plans, and longer term funding strategy for a discrete clinical SH
sub-theme.
The initial meeting of the SH team was held in January in preparation for a workshop in February which
defined the strategy and short-medium term experimental plans. Subsequently meeting at the DPUK
Scientific Symposium in May 2015, and with regular teleconferences, the SH theme has been active in
building a strong programme with both scientific consensus and clear industrial-academic engagement.
A copy of the May Symposium presentation is available to download from the DPUK website.
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Theme 2: Innate and Adaptive Immunity
Lead: Paul Morgan, Cardiff University
Introduction
Evidence implicating the immune system and inflammation in dementia is
growing. A convergence of mechanisms has been observed in Alzheimer’s
disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis
(ALS), in which neuronal damage promotes neurotoxic microglial hyperactivity. Targeted ant-inflammatory therapies to regulate glial related inflammatory response may have broad application across neurodegeneration.
Four inflammation related Expression of Interest forms (EOIs) have been
submitted to the DPUK calls for Experimental Medicine (EM) project proposals. Of these, three have been invited to submit full proposals: one using PET and MR imaging to ascertain neuroinflammatory status and link with cognitive function; one using low dose, one using PET to investigate astrocyte activity and cognitive performance; one completing
a Mandelian Randomisation study – Inflammation, cognitive function and dementia.
Strategy Group (see Appendix 3):
Preliminary scoping has identified an existing expert community that has formed around a recently funded Wellcome Strategic Award. Professor Paul Morgan, who is a co-applicant on the award, will liaise
with the consortium to establish a DPUK expert strategy group, including consortium members, who will
identify preferred hypotheses then develop and submit proposals to the Platform.
Early discussions of the group will focus on:
Translating evidence from animal models into human models
Translating evidence from genetic models to cellular models
Challenging underpinning assumptions:
- Inflammation is an early event in the genesis of dementias
- Systemic inflammation is a trigger to central damage
- Inflammation and Immune biomarkers may predict disease.
Identifying core themes within the Immunology and Inflammation framework:
- Markers of inflammation and immune cell activation
- Signalling pathways and immune cell activation
- Imaging inflammation in dementias
To initiate discussion within a newly forming group a presentation was given at the DPUK Scientific Symposium in May 2015. A copy of the presentation is available to download from the DPUK website.
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Theme 3: Vascular Disease Mechanisms (VDMs)
Lead: Joanna Wardlaw, University of Edinburgh
Facilitator: Paul Wren (GlaxoSmithKline & DPUK Executive Team)
Introduction:
Epidemiological, genetic, neuroimaging and clinico-pathological data
indicate vascular mechanisms as fundamental risk factors for Dementia. These are intrinsic in Vascular Dementia with an extensive overlap
between neurodegenerative and vascular factors defining significant
mixed dementia populations. Considering that mixed dementia is the
most common cause of dementia in the elderly, it has become increasingly important to harmonise basic science, translational, and
clinical approaches that includes the integration of a deeper understanding of the contribution of peripheral and central vascular disease
mechanisms in diverse dementia populations.
The high level aims of this theme:
‘General’
‘Specific’

Raise awareness of vascular disease


Enhance protocols to ensure vascular
relevance
Early markers of vascular
dysfunction

Integrate with other UK and international
initiatives

Vascular dysfunction risk factors

Identify interventions
The Strategy Group (see Appendix 3):
An expert group has been established including senior clinical and pre-clinical researchers, expertise
in large multicentre clinical trials, observational mechanistic studies, imaging including analysis, neuropathology, experimental models, stem cells, regulatory processes, and evidence synthesis, that will
use early studies to identify barriers and facilitators to developing a coordinated programme of work on
how VDMs contribute to risk of, and decline in, Dementia. The vision is that this will help determine
how interventional studies may be conducted inclusive of the employment of diverse endpoints to
identify cost-effective, predictive and sensitive early biomarkers of vascular disease mechanisms in
humans that may be back translated into animals/stems cells in the future.
The group are currently focussing on developing three strategies:

Initiating: through approved DPUK seed funding, explore the potential linkage of lipid profiles (with the NPC) from banked blood plasma samples with established neuroimaging correlates of cerebro-vascular disease with cognitive decline in the Lothian Birth Cohort 1936.

Building: to evolve a range of EM proposals that introduces vascular concepts into tissue banking, compares cardiac to brain vascular phenotypes and explores vascular imaging correlates of various vascular phenotypes including e.g. cerebral amyloid angiopathy.

Enabling: to gather vascular information from the DPUK cohorts; standard vascular disease risk factors, cardiac, systemic and cerebro-vascular disease burdens to understand the
variance and gaps in data to help inform future EM proposals.
There have been five meetings of the VDM group, who are also supporting other scientists to help define and develop a range of project ideas, and avenues for future funding opportunities. A presentation
of the outputs given at the DPUK Scientific Symposium is available to download from the website.
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4. Raising the DPUK Profile
Launch Events
Two successful launch events were held in October 2014.
Ministerial Reception:
On 27 October 2014, a Ministerial Reception was held at the Royal Society, London. Attended by
around 60 VIPs, including MPs and industry experts, the event was a great success, with a rousing
speech from George Freeman, Minister for Life Sciences, who described the Platform as “genuinely pioneering”. There was also enthusiastic support from the President of GlaxoSmithKline, Dr Patrick Vallance.
Scientific Launch Conference:
On 28 October 2014 we held a scientific launch conference at the Royal Society, London, attended by
around 200 people from across the scientific community, charities and members of the public. Fiona
Phillips, TV Presenter and Journalist, gave a moving speech about her personal experience of both her
parents having dementia. The conference outlined the future plans for the project and generated interesting questions from the audience, which were debated with the DPUK panel. The conference generated much excitement around the launch of the Dementias Platform UK, with a flourish of Twitter activity
and new followers. One person tweeted: “@DementiasUK In years to come I'll be able to look back on
today and say 'I was there'.”
Communication Channels
During the first year DPUK has set out its communication strategy and plans for the five year project.
Significant progress has been made in the first year, with DPUK establishing its brand and identity, as
well as a number of communication channels for conveying messages to stakeholders. Our promotional
brochure was produced and issued at the launch conference and this is used at events and
conferences to explain more about who we are and what we are trying to achieve.
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Website
A three page micro-site was developed in October 2014 and moved to a full, seven section website
in Spring 2015. The website aims to reach out to both the public and scientific community, conveying
information about the project aims and developments. It is an evolving site, which will grow with the
project. For example, new cohort details are being added as we receive them, and events and news
stories are continually updated. As we develop new collaborations and partnerships we will add details of them to the site. A file share system is being created where DPUK members can upload and
download relevant papers, which will support internal communications. We are recruiting a website
user group who will gather in Autumn 2015 to develop future plans for the site.
www.dementiasplatform.co.uk
External Events
DPUK representatives have attended around 20 conferences and events to speak about or represent
the Platform. The majority of events were research conferences aimed at a scientific audience. A few
of the events were more public facing – notably, FORGETWest, the Cheltenham Science Festival
and the Alzheimer’s Society Annual Research Conference.
A summary of events attended and a selection of abstracts are included in Appendices 4 & 5.
Internal Events
Partners Seminar, February 2015
The aim of this event was to bring together colleagues from Industry (Company Partner Forum) and
those contributing to the Work Packages. We welcomed colleagues working on the wider delivery of
the Platform and Work Packages. This event assisted in colleagues understanding the context of
DPUK activities and how parts of the programme fit together. The Partners Seminar was attended by
about 40 partners from Industry and HEIs. Presentations were delivered by Industry Partners and
about Experimental Medicine.
DPUK Scientific Symposium, May 2015
The purpose of the Symposium was for all members of DPUK to come together to discuss and learn
more about the scientific activity of the Platform, specifically looking at the main themes of Cohorts,
Networks and Experimental Medicine. This event was attended by around 90 people from DPUK
Work Packages, Networks and Industry Partners.
23
Cohort Seminars, June / July 2015
Three Cohort Seminars were held to bring together Cohort Principal Investigators. The purpose of
these was to provide an overview of the Dementias Platform UK, build relationships with cohorts
and formally invite them to be part of DPUK. 20 people attended the London event, 11 in Cambridge
and 9 in Edinburgh.
Digital Media Tools
All statistics provided are for year one of the project, up to July 2015.
Twitter
(220 tweets)
Created
August
2014
Communication of DPUK and relevant dementia news stories, including conferences and events.
506 followers
4504 profile visits
59,793 impressions
Vimeo
(22 videos)
Created
December
2014
Promotional and informative videos produced and published to illustrate the work and role of DPUK.
209 plays (7019 loads)
Over 6,000 people visited the vimeo page directly from the
DPUK website.
Countries where the video was played: USA, Canada, Argentina, South Africa, Australia, New Zealand, India, Sweden, Norway, Ireland, Spain, Switzerland, Italy, Greece,
Romania, Poland, Germany, France.
Flickr
(164 photos)
Created
December
2014
Flickr has been set up to share photos with the public from
our conferences and events.
107 Views
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5. Wider Connections
Central to the success of the DPUK mission is a collaborative and collegiate ethos. We believe that
progress can be most rapidly achieved by widespread collaboration and liaison with experts from the
UK and around the world in designing and executing the programme of work. This involves access to
Platform generated data and access to Platform infrastructure and expertise. The motivational model
underlying the DPUK collaboration is to incentivise self-organised coordination of scientific activity by
reducing the transaction costs of research, and increasing the rewards of collaboration.
As a public-private-partnership DPUK is committed to exploiting the benefits of bringing academic and
industry partners together in pre-competitive space, to create synergy and develop Experimental
Medicine programmes which facilitate bringing new interventions to market.
DPUK is committed to working in partnership with other UK based infrastructures. Within the emerging UK dementias research infrastructure translational pipeline, DPUK is positioned between the discovery of new molecules by the Alzheimer’s Research UK (ARUK) Drug Discovery Alliance (DDA),
and the conduct of phase 3 trials through Join Dementia Research (JDR). DPUK will work in partnership with these and other infrastructures such as the NIHR Dementia Translational Research Collaboration (TRC-D) to develop an efficient, flexible, and responsive UK dementia research environment.
DPUK will also work with other centres of excellence such as the National Phenome Centre and the
Clinical Proteomics Centre to encourage greater interest in the metabolomics and proteomics of the
dementias.


A visit to Hong Kong took place to investigate collaborative opportunities.
A visit to the US (Mt Zion, New York City) was made to develop links with the Synaptic Health
researchers.
Internationally, the dementias research landscape is increasingly coordinated and DPUK is well positioned to develop a range of collaborations. By making Platform resources available internationally,
we anticipate being instrumental in developing a global network of scientific engagement and a stepchange in global dementia research capacity.
Dementias Platform UK forms a central pillar in the delivery of the UK Prime Minister’s Dementia
Challenge. DPUK is developing an integrated research environment enabling rapid data analyses and
a new generation of highly targeted, highly informative discovery studies and early phase trials; positioning the UK as world leading location for dementia research.
DPUK has a strong global voice, connected and integrated within the dementia research ecosystem
in Europe and beyond. DPUK facilitates data integration and harmonisation across studies to support
data sharing, DPUK supports the development of standardised cognitive assessment suitable for use
in large-scale population studies and trials. DPUK welcomes opportunities for international collaboration.
Global Alzheimer’s Association Interactive Network (GAAIN)
GAAIN is a data gateway facilitating access to a wide range of population
and clinical datasets. DPUK is complementary to GAAIN in also enabling
access to multiple independent datasets. In addition, DPUK offers a
secure data analysis space to make it easier to allow researchers to
interrogate these data. DPUK looks forward to working with GAAIN to
promote international data sharing.
25
European Medical Information Framework (EMIF)
EMIF is a European initiative that aims to develop a common information framework
of patient data to open up new avenues of research for scientists. DPUK works alongside EMIF, helping to advance statistical analyses of information across population
studies (cohorts). DPUK has based its meta-data catalogue on the EMIF Alzheimer’s
Disease fingerprint. MRC, on behalf of DPUK are negotiating a MoU with EMIF in
relation to data sharing.
Innovative Medicines Initiative (IMI)
IMI is one of Europe’s largest public-private initiatives which aims to speed up
the development of better and safer medicines for patients. DPUK is a strong
contributor to the IMI European Prevention of Alzheimer’s Dementia Initiative
(EPAD), which will establish a European-wide register of 24,000 study participants, of which 1,500 will be invited to participate in trials to test new treatments for prevention of
Alzheimer’s.
Organisation for Economic Co-operation and Development (OECD)
OECD promotes policies that will improve the economic and social well-being of people around the world. DPUK is plugged into OECD global Open Science and Big Data
initiatives. DPUK has signed a transatlantic collaboration agreement with the Canadian Collaboration for Neurodegeneration and Aging (CCNA) to share data and research expertise in the fight to better understand, treat and prevent dementia.
World Dementia Council (WDC)
The World Dementia Council emerged following the G8 Dementia
Summit in December 2013. The Council aims to stimulate global innovation, development and commercialisation of life enhancing
drugs, treatments and care for people with dementia, or at risk of dementia, within a generation. As an innovative partnership between academics and industry, DPUK’s
own mission chimes with the ambitions of the Council, with our programme of discovery studies and
early phase trials and goals to accelerate the development of new compounds for dementia. Dr Dennis Gillings, the World Dementia Envoy recorded a message of support for DPUK’s official launch
conference in October 2014.
Network of Centres of Excellence in Neurodegeneration (CoEN)
CoEN is an international initiative involving research funders in the UK, Canada,
Germany, Belgium, Ireland, Italy, Slovakia and Spain. The aim of the initiative is to
encourage collaborative research between recognised National Centres of Excellence in Neurodegeneration in order to accelerate progress in understanding the
disease as well as the identification of new therapeutic approaches. DPUK population studies and researchers are active participants in CoEn programmes and the recipients of several CoEN awards.
EU Joint Programme – Neurodegenerative Disease Research (JPND)
JPND is the largest global research initiative aimed at tackling the challenge
of neurodegenerative diseases. JPND aims to increase coordinated investment between participating countries in research aimed at finding causes,
developing cures, and identifying appropriate ways to care for those with
neurodegenerative diseases. DPUK cohort studies and researchers are active participants in JPND
programmes and the recipients of several JPND awards. DPUK strongly supports the cross-border
collaborative goals of the JPND and CoEN initiatives.
26
6. Director’s Overview of the First Year
DPUK has broken new ground on many fronts during its first year. The
building of a closely integrated multi-disciplinary dementia research community, the sharing of diverse broad and deep data, and the development of systems facilitating Experimental Medicine are being attempted
on an unprecedented level and this first year has shown major progress
in each. The scale and complexity of the enterprise has grown substantially with the award of infrastructure funding for Imaging, iPSC and Informatics Networks. These exciting developments have stimulated much
collaborative activity as well as producing many administrative and operational challenges. However, due to the enthusiasm and flexibility of our
Partners, collaborators and staff, I am delighted to report all our overarching goals for the year have been met and DPUK is on course to fulfil
its mission.
The Executive Team has melded and provided an enthusiastic and supportive environment for decision
making. Our Industry Partners have been particularly active in supporting the Experimental Medicine
Strategy Groups, and in developing the process of adding new Company Partners. Academic Partners
have led in the development of Research Networks, engagement with cohorts, and informatics. This is a
talented and generous team and it is a pleasure to work with them. The relocation of the Director to Oxford necessitated an Executive ‘reshuffle‘ to ensure UK-wide representation, which occurred smoothly.
With the advent of the Experimental Medicine strategy groups the role of the Steering Group became
less clear, therefore this has now been expanded to include work programme review.
The growth in complexity of DPUK, particularly through the Imaging, iPSC and Informatics Networks has
placed considerable additional administrative demand on the Operations Team, who have responded
well. Project management and governance documentation have been put in place alongside reporting
systems. A communications strategy and plan have been created and implementation of events and
marketing activities are ongoing. We appreciate the additional support from MRC to enhance our project
management capability to meet this increased demand.
Any enterprise of this size and complexity entails risk, particularly those related to buy-in from a large
and diverse range of stakeholders and those due to dependencies between components of the work
programme. Many of the major risks have ameliorated over the last 12 months. Although several high
level dependencies continue to operate regarding data sharing and the resourcing of Experimental Medicine programmes, these do not give cause for concern as flexibility and resourcefulness has been
shown by all parties in addressing issues as they arise. An example is the procurement of PET/MR
scanners. All the institutions involved have shown scientific maturity in a complex process of marrying
local and national aspirations to deliver a sustainable world-class molecular and structural imaging
environment.
The scientific programme has been initiated. To date 16 EOIs have been received with two reaching the
award stage and a further under independent peer review. Resourcing scientific activity beyond DPUK
funding has been a priority. The iPSC Network submitted a partnership grant proposal in June and the
Imaging Network is preparing a partnership grant proposal for submission in October. The Innate and
Adaptive Immunity Strategy Group is preparing several proposals for the MRC Experimental Medicine
challenge. The Experimental Medicine Strategy Group structure has matured with academic leads being
appointed and Industry Partners providing strong support. Each group is developing programmes of
work. DPUK has limited resources to support this activity and the time given by busy senior academics
to this should be acknowledged. Scoping of the Experimental Medicine landscape for neurodegeneration
has revealed a highly diverse landscape with, genetics apart, strategic collaboration across Higher Education Institutions being unusual. DPUK has responded with a more positive approach to strategic network building than was anticipated. DPUK has engaged with the international dementia community at
several levels with presentations at both ADPD (Nice) and AAIC (Washington), a Memorandum of Understanding on data sharing being signed with CCNA, and for technology sharing on our behalf by MRC
with EMIF.
27
7. Funder’s View – Rob Buckle
It has been a full and fruitful year for the Dementias Platform UK. Born from
the need to expedite real progress in dementia research, DPUK has already
shown capacity for leadership, innovation and agility, even in its relative infancy. Additionally, its collaborative ethos has already begun to open doors,
nationally and internationally. By joining together networks of world class researchers, with state of the art technology and an exciting research framework, DPUK has set out its stall well. The momentum DPUK has developed
over this first year stands it in good stead for achieving its ambitious goals, to
better understand, treat and eventually prevent dementia.
Tackling dementia is a key priority for the UK Government, and the Prime
Minister has spearheaded a campaign amongst G7 Nations to find a cure or
disease modifying treatment by 2025. MRC is fully committed to the promotion of neurodegeneration research and, in response to the Prime Minister's
Dementia Challenge, is leading the development of the UK's research agenda, making significant contributions at the European and global level to address this growing public health burden.
To catalyse the concerted effort needed to address the Challenge, we have invested £53M to build a
coherent UK-wide programme that connects capabilities in the academic and commercial sectors to
drive research that can lead to improved management of dementia symptoms to improve the quality of
life for patients, as well as provide a basis for developing new therapies and preventive strategies.
DPUK has been designed to capitalise upon the UK’s wealth in population-based research, where it is
anticipated that the analysis of whole-body data on large numbers of people will provide enormous statistical power to study what happens to our bodies as we age and enter the early stages of neurodegenerative disease. In order to develop this opportunity, the funding of DPUK has been directed towards establishing a series of interconnected Research Networks with access to state-of the art equipment in brain imaging, stem cell modelling of disease and informatics, which importantly has engaged
expertise from research teams that had not been previously focussed on dementia. DPUK also provides a significant example of how exciting new science can be progressed through leveraging existing
infrastructures and investments, such as UK Biobank and other large population cohorts, the Farr Institute for e-health informatics, the MRC-NIHR National Phenome Centre and the UK Brain Banks Network.
A key goal in the establishment of the Platform has been to create a new dynamic with committed partners from the biopharmaceutical sector, to spark innovative ideas, de-risk the drug-development pipeline, and unlock capabilities that could add new impetus to the research agenda. This approach is
working well, and has already provided additional benefit through helping attract inward investment.
For example, DPUK is a key player in the major new EC-funded IMI EPOC-AD programme to undertake clinical trials in Alzheimer's Disease. DPUK acts as a major focal point for international connectivity, and has a number of links to two major international collaborative programmes - the Joint Programming in Neurodegenerative Disease (JPND) and the Centres of Excellence Network (CoEN) – which
MRC has helped to develop over the past five years. For example, DPUK has integrated the Genetic
Frontotemporal dementia Initiative (GENFI), established under CoEN and recently provided with new
MRC funding. DPUK is also central to our effort to progress global ‘big data’ developments in the dementia area, and has established formal collaborative links with the Canadian Collaboration on Neurodegeneration in Aging (CCNA), as well as connectivity with the IMI European Medical Informatics
Framework (EMIF).
The establishment of DPUK heralds a significant gear shift in the approach to dementia research. Key
academic groups and biopharma partners are engaged together in a dynamic, goal-oriented and nationally coordinated research programme. As it develops, DPUK will enhance its existing relationships
and engage additional capabilities. The future of DPUK is bright, its ambitions are challenging but the
rewards will be great.
28
8. Industry Perspective – Derek Hill
The launch of the Dementias Platform UK followed several years of
negative clinical trial results for dementia treatments - especially of
experimental treatments of Alzheimer’s Disease (AD) targeting Amyloid. There was a strong feeling in industry that the risks of dementia
drug development were becoming too great and new approaches to
discovery and development of dementia treatments were needed. At
the end of 2014, soon after the DPUK launch, another major phase III
clinical trial of an AD therapy (known as SCarlet RoAD) was terminated following a futility analysis, delivering a further blow to both drug
developers and patients.
It has long been recognised that developing treatments for the diseases that cause dementia is tough.
As a consequence, there are numerous collaborations and consortia that over recent years have
brought together academic and industry scientists with the aim of de-risking, or accelerating the development of treatments for the diseases that cause dementia. Many in the industry are talking of consortium fatigue – with industry scientists struggling to engage constructively in them all, and many consortia not generating the value initially hoped for.
But the Dementias Platform UK was designed around a very different philosophy, and the first year
has illustrated how this works. Unlike many other consortia, DPUK wasn’t built around a particular clinical study protocol, a proposed disease target, or a regulatory agenda. DPUK is a Platform to facilitate innovative collaborative research. There is no predefined research plan, nor are there any implicit
assumptions about which diseases causing dementia should be the focus, nor which molecular targets
are of interest. The Experimental Medicine themes that have emerged illustrate how the Partners in
DPUK have chosen to focus on innovative areas like Innate and Adaptive Immunity, Synaptic Health
and Vascular Disease Mechanisms, rather traditional targets like Amyloid or Tau.
The participants from large companies, small companies, and academia have the opportunity to work
as equal partners to come up with genuinely innovative research ideas that can leverage the cohorts,
expertise and infrastructure of the Platform. This does give the Platform a bit of a “build it as you fly it”
flavour, but given the uncertainty in the path to success in dementia treatments, it feels like a refreshing change. It is, of course, critical to industry participants that DPUK is productive. There are many
other consortia and to continue to maintain the attention of current Platform members and attract new
companies to join, DPUK will need to maintain its momentum and demonstrate the ability to make
timely progress of major strategic themes.
It is worth noting that the last few months have seen green shoots of good news from some of the current AD therapies in development. This is providing some grounds for an increase in optimism in industry, while also further emphasising that finding the right patients to treat is critical to success. DPUK
has an opportunity to benefit from this increase in optimism to make some genuinely transformational
contributions to the field, and take a step closer to getting effective treatments for patient suffering from
these diseases.
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9. Looking forward
The next 12 months will be challenging, as we transition from infrastructure build to use.
The informatics challenge is to see the DPUK Data Portal become operational and populated with
data from a growing number of cohorts. We are confident that the timetable is realistic and that the
portal will be open for business by the end of 2015, although initially with data from a limited number
of cohorts.
The dementia resources challenge is to continue working closely with UK Biobank and the other
resource cohorts. The synergy between UK Biobank and DPUK is widely recognised, as is the
synergy between our late and early onset amyloid studies.
Our methods development programme is diverse, but establishing acceptable and straightforward
procedures for recruitment to experimental studies is a priority.
The challenge to the Research Networks is progression from procurement and installation to developing integrated programmes of activity. This is a particularly exciting prospect as it offers intriguing
opportunities for increased scientific rigour and innovative hypothesis testing.
For Experimental Medicine the priority is to accelerate the programme of work. Issues to be
addressed include reducing per review cycle times, increasing added value, and reducing costs.
Creative solutions are required.
All said, continued engagement with stakeholders is our main priority. Data sharing and coordinated
activity on this scale are unprecedented, and rely for success on solutions generated by each specialist community. Our cohort Principal Investigators will be critical in helping to develop efficient data
access procedures, as will our imagers in developing multi-centre data acquisition protocols, and our
Informaticians in providing secure data access. However, it is the continued constructive exchange of
ideas between academic and industry partners, focusing in year 2 on how best to deploy industry
partner contributions, that will fundamentally shape much Platform activity.
30
10. Appendices - Contents Page
1. Example of one of our Cohorts
32
2. DPUK Funded Researchers
33
3. Experimental Medicine Strategy Groups
34
4. DPUK Event Summary
35
5. Sample of Conference Abstracts
36
31
1. Example of one of our Cohorts
MRC National Survey of Health and Development/ 1946 Birth Cohort (NSHD/1946BC)
The NSHD has informed UK health care, education and social policy for more than 50 years and is the
oldest and longest running of the British birth cohort studies. Today, with study members in their sixties,
the NSHD offers a unique opportunity to explore the long-term biological and social processes of ageing
and how ageing is affected by factors acting across the whole of life and this started in 1946.
PI: Professor Diana Kuh
Sample size at recruitment: 5,362
The NSHD has informed UK health care, education and social policy for more than 50 years and is the
oldest and longest running of the British birth cohort studies. Today, with study members in their sixties,
the NSHD offers a unique opportunity to explore the long-term biological and social processes of ageing
and how ageing is affected by factors acting across the whole of life. From an initial maternity survey of
13,687 of all births recorded in England, Scotland and Wales during one week of March, 1946, a socially
stratified sample of 5,362 singleton babies born to married parents was selected for follow-up. This sample comprises the NSHD cohort and participants have been studied 23 times throughout their life.
During their childhood, the main aim of the NSHD was to investigate how the environment at home and
at school affected physical and mental development and educational attainment. During adulthood, the
main aim was to investigate how childhood health and development and lifetime social circumstances
affected their adult health and function and how these change with age.
Now, as participants reach retirement, the research team is developing the NSHD into a life course study
of ageing. Study members attended a clinic at age 60-64 and more recently completed a postal questionnaire in 2014. They will be invited to participate in a home visit in 2015, collecting data on health,
lifestyle and life circumstances as well as obtaining repeat physical and cognitive measurements. Over
the next two years, a subset of 500 study members will also be invited to participate in a neuroimaging
sub-study. ‘ This stud will be conducted in collaboration with the Institute of Neurology, UCL with cofunding from Alzheimer’s Research UK and the Wolfson Foundation
MCS is part of CLOSER (Cohort & Longitudinal Studies Enhancement Resources) which aims to maximise the use, value and impact of the UK’s longitudinal studies.
Website: http://www.nshd.mrc.ac.uk
Contact details: MRC Unit for Lifelong Health and Ageing at UCL, 33 Bedford Place, London, WC1B 5JU
General enquiries: [email protected]
Data access:[email protected]
Gender: MF
Variables Collected:
Anthropometric: Height, Weight, Blood pressure / Physical: Respiratory, Reproductive / Cognitive: Cognitive function / Lifestyle: Smoking, Alcohol / Socio-Economic: Occupation and Employment,
Income and Finances, Family circumstances, Housing and accommodation, Education, Martial Status /
Biological Samples: Blood, Urine, Saliva, Other
32
2. DPUK Funded Researchers
Work Package 1
Kate McAllister
Edinburgh
Work Package 2
Karen Tingay
Swansea
Justin Biddle
Swansea
Chi Hun Kim
Oxford
No staff funded
Work Package 3
Work Package 4
Work Package 5
Chris Lane
Sept 14 – Aug 17
Heidi Murray-Smith
Sept 14 – Aug 17
Justin Kinsella
Jul 15 – Jul 18
Claire Bloomsfield
Jul 15 - Jul 18
UCL
UCL
Work Package 6
No staff funded
Work Package 7
No staff funded
Work Package 8
No staff funded
Christian Schnier
July 15 – Jan 19
Tim Wilkinson
July 15 - Jan 19
Robin Flaig
Jan 15 – Jan 19
To be appointed
Sept 15 – Jan 19
Work Package 10
To be appointed
Chloe Fawns-Ritchie
Jun 16 – Jan 19
Aug 15 – July 16
Edinburgh
Work Package 11
Katie Wells
Sept 15 – Aug 16
Imperial
Work Package 12
Sally Atkinson
Feb 15 – Feb 17
Cambridge
Work Package 13
Helen Costello
Dec 14 – Nov 15
Kings College London
Work Package 14
Christian Bannister
Jan 15 – Dec 17
Cardiff
Elise Majounie
Jan 15 – Dec 17
Cardiff
To be appointed
Sept 15 – Aug 18
Cambridge x2
No staff funded
Work Package 9
Work Package 15
Edinburgh
33
3. Experimental Medicine Strategy Groups
Synaptic Health
Innate and Adaptive Immunity
1. James Rowe (lead)
Paul Morgan (lead)
2. Declan Jones (facilitator)
Simon Lovestone
3. Nicholas Allen
Siddharthan Chandran
4. Gerry Dawson
5. Robert Neal
6. Giacomo Salvadore
7. Hartmuth Kolb
John Iredale
Tracy Hussell
Janet Lord
Joanna Wardlaw
8. John Kemp
9. Kevin Fox
10. Krishna Singh
11. Mark Schmidt
12. Michael Perkinton
13. Roy Twyman
14. Serge Van Der Geyten
15. Paul Matthews
16. Darrel Pemberton
17. Luc Truyen
18. Keith Tan
19. Nathan Pradeep
Vascular Disease Mechanisms
Joanna Wardlaw (lead)
Paul Wren (facilitator)
Mike O’Sullivan
Paul Ince
Steve Williams
David Werring
John O’Brien
Zameel Cader
Karen Horsborough
Phillip Bath
Hugh Markus
John Gallacher
Derek Hill
Andy Lockhart
Somalogic
34
4. DPUK Event summary 2014/15
DATE
CONFERENCE / EVENT
LOCATION
DPUK REPRESENTATIN
19th Jan
GW4 Ageing & Dementia
Conference 2015
Digital Health Assembly
Bristol
Presentation delivered by John Gallacher about DPUK.
Cardiff
Presentation delivered by John Gallacher about DPUK
and Big Data.
Paper given by Simon Lovestone: Clinical Informatics &
Dementia Research in the UK
10-12th
February
13th February
American Association for
the Advancement of Science.
10th-11th
March
Alzheimer’s
Research
UK Conference.
London
DPUK Poster presentation: The MRC UK Dementias
Platform: Accelerating Dementia Research
18th-22nd
March
Alzheimer’s & Parkinson’s Disease Congress
2015
Nice,
France
Paper and poster presentation by John Gallacher:
DPUK: a global resource for the dementias
Paper by Simon Lovestone: “The IMI-European Medical
Information Framework; repurposing and connecting
data for Alzheimer’s disease and beyond”.
Joint IMI session
26th
March
Dementia Conference
Cheltenham
31st
March
FORGETwest
A
conference
where
members of the public
can meet with expert scientists,
Promoting Statistical Insight Conference
Bristol
15-19th
May
4th June
A number of Academic
lectures.
Cheltenham
Science
Festival (in partnership
with Alzheimer’s Research UK).
Hong Kong
29-30th
June
Alzheimer’s Society Annual Research Conference
Manchester
10-13th
May
London
Cheltenham
Paper by Craig Ritchie: "The European Prevention of
Alzheimer’s Dementia (EPAD) Programme: Clinical and
Scientific Need and Early Progress."
Paper by Karl Herholz: “New Clinical Imaging Techniques for dementias”
DPUK brochures included in packs to 100 delegates.
Paper by John Gallacher: “A Powerhouse for dementias
research: The MRC Dementias Platform”.
Information stand to explain more about DPUK to the
public. Around 150 people attended.
Paper delivered by Paul Wren:
“Progress in Public Private Partnerships engaged in the
Dementia Challenge”
John Gallacher delivered a number of Academic lectures about DPUK.
Sponsored event - How your life affects your brain
Can the way you live reduce your chance of developing
Alzheimer’s? By monitoring groups of people over their
lifetimes, and with genetic data, brain scans and medical histories researchers are building as complete a picture as possible of how dementia develops. John Gallacher and Nick Fox join us to show how these studies can uncover the risks involved in developing forms
of dementia, and how they can be avoided.
About 100 people attended.
Paper delivered: ‘What DPUK can do for you’. Talk attended by around 20 researchers and members of the
public.
Poster Presentation for DPUKs cohorts. Around 300 at
the conference.
Exhibition stand and brochures in delegate packs.
35
5. Sample of Conference Abstracts
Further Abstract and poster information can be found on the website.
Conference: Alzheimer’s Disease Research Summit 2015:
Path to Treatment and Prevention [http://www.nia.nih.gov/about/events/2014/alzheimers-diseaseresearch-summit-2015]
Date: Friday, 13 February 2015
Location: Washington, USA
Session
Title:
Dementia:
Research
Milestones
Talk title: Clinical Informatics and Dementia Research in the UK
Speaker: Simon Lovestone
and
Policy
Priorities
Abstract: Everyday in every clinical contact between doctors, nurses and other health workers and
their patients data is collected, stored and used for decision making about healthcare. But until now
using that information for research has been relatively limited. Today with the increasing use of
electronic medical records that information can be used – to evaluate treatments, to investigate risk
factors and, at least potentially, to help in the recruitment to investigational studies to test new therapies. However, in order to utilize this data – for dementia research and other indications - there
are challenges, both technical and those of governance.
I will describe a system that has met these challenges in the UK, the Case Records Interactive
Search system, that enables access to substantial numbers of case records for research. With
deep anonymisation of data, access to both encoded and narrative data and the use of natural language processing to enable data recovery from the narrative data together with a service user led
governance structure, the CRIS system is not only delivering larger data sets than can be realistically generated from research but is increasingly being used to audit and improve health care delivery. The CRIS system is being linked to one of the world’s largest longitudinal cohort studies
through the UK Dementias Platform.
In Europe more generally the IMI European Medical Information Framework has similar ambitions
but includes aggregation of and access to huge data sets from epidemiological cohort studies,
through cohort studies to clinical databases. Aggregating data through access to meta-data as well
as individual-level data the EMIF programme together with the UK Dementias Platform will link to,
indeed are both essential components of, the European Prevention of Alzheimer’s Disease platform; an ambitious plan to develop preventative therapies for Alzheimer’s.
Such ambitious plans for large scale multi-national trials can only be achieved at scale and at realizable cost through public-private partnership and with the utilization of existing clinical information
currently all too often underutilized in parent cohorts and clinical datasets.
36
Conference: 12th International Conference on Alzheimer's & Parkinson's Diseases
Date:18-22,March,2015
Location: Nice, France
Talk Title: DPUK: A Global resource for the Dementias
Speaker: John Gallacher:
Poster Presentation title: The MRC Dementias Platform UK (DPUK): accelerating dementia research
Attendance: Carol Brayne (Cambridge), Iain Chessel (AZNeuro), Ian Deary (Edinburgh), John Gallacher (Cardiff), Derek Hill (IXICO), Declan Jones (JnJ), Simon Lovestone (Oxford), Martin Rossor
(UCL), Paul Wren (GSK),
Introduction:
DPUK is a £53m dementia dedicated ‘big-data’ platform created to provide closer synergy between
epidemiology and experimental medicine.
Materials and methods:
Data from 2 million intensively phenotyped participants from 22 cohorts will be used for the rapid
testing of complex hypotheses across multiple independent datasets. Population and familial disease cohorts will enable the identification of unique and common mechanisms across the dementias. Data access will be through a single informatics portal. DPUK is a public private partnership
bringing together a broad range of scientific and industry expertise. Linking molecular pathology at
the cellular level with biological systems impact and in-depth phenotyping of outcomes will powerfully enable new therapeutics development. Readiness cohorts will include 10,000 UK Biobank participants with 2 year repeat 3T brain MRI, cognitive phenotyping and bio-sampling; providing a stepchange in the size and phenotypic detail of trials ready cohorts.
Infrastructure:
Integration of the research environment, linking strategic resource cohorts and methods development programs to specialist PET/MR, informatics and iPSC networks will support an in-depth experimental medicine programme of discovery studies and early phase trials. Initial experimental medicine foci include innate and acquired immunity, synaptic function, and vascular risk factors with other programmes to be developed
Conclusions:
DPUK brings many opportunities for accelerating dementia research and the development of new
treatments. DPUK has a growing programme of international collaboration and welcomes further
collaborative proposals.
37
Conference: PSI: Relevant Applications in a Changing Environment
[http://www.psiweb.org/events/annual-conference]
Date: 10-13 May 2015
Location: The Millennium Gloucester Hotel, London.
Title: Progress in Public Private Partnerships engaged in the Dementia Challenge
Speaker: Dr Paul Wren, Director, GSK Neuroscience & member of DPUK Executive Team
Abstract: Working through partnership across public private sectors enables the sharing of ideas,
data and resources to provide open science platforms for advances in Medical Research. The recently initiated Dementias Platform UK will be used as one example of how academia and industry
are working together to increase the understanding of the Dementias to accelerate the delivery of
medicines to patients. A holistic view of the early development of the platform will be shared from
an Industry perspective with a specific focus on the establishment of core infrastructure and methodologies to enable secure data collation and analysis from across multiple large diverse clinical
cohorts across the spectrum of Dementias. Using a range of methodologies including neuroimaging, genetics, fluid and physiological biomarkers, cognitive testing and clinical outcomes, innovative
experimental hypothesis testing and collation of longitudinal data will help to enhance our
knowledge and probabilities to ultimately deliver disease modifying medicines.
Biography: Dr Paul Wren is a Director of Clinical Development in the GSK Neuroscience
Therapy Area Unit with over 20 years experience in Neurology & Psychiatry R&D. He has worked
for a range of large pharma companies with increasing responsibilities starting as a lab technician to
significant leadership roles across diverse geographical territories across the discovery, translational and clinical interfaces. He has led multiple disease areas including GSK strategies in Alzheimer’s
disease and is a member of the Dementias Platform DPUK Executive team. His interests are in understanding human pharmacology and translatable bridges that may facilitate drug discovery and
development and in working with multidisciplinary teams across sectors to accelerate the understanding of disease mechanisms.
38
Photographer credits
Photographs supplied by:
Steve Cagnoni, CCACE: Douglas Robertson, Wellcome Trust Images, Imperial College London:
Tom Whipps, The University of Edinburgh, Norma Silva, Cheltenham Science Festival.
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www.dementiasplatform.uk | [email protected] | 08000 232 000 |
@DementiasUK