To create an efficient research environment the DPUK programme is organised into five work streams comprising
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.
Experimental Medicine remains the key to progress in dementia as it can deliver the evidence necessary for introducing new treatments. 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.
As DPUK becomes more established and collaboration in the research community gathers momentum, new DPUK-linked projects will emerge. These will add to the value of DPUK and utilise the resources that have been created through the core research programme.
Descriptions of the cohorts will be gathered in one place and sustainable plans for accessing the data will be made. This will make it quicker and easier for researchers to see what’s available, spot any gaps in evidence and rapidly test out their ideas.
The huge volumes of precious data generated by the DPUK project will be collected, integrated, curated and analysed and linked with UK-wide data into a single, efficient ‘informatics portal’ for researchers.
10,000 people already participating in the UK Biobank cohort study will have their relevant essential characteristics (phenotypes) re-analysed two years on from when they first signed up to UK Biobank, including having new brain scans. This will create a ‘ready to use’ cohort primed for clinical trials in dementia research.
Amyloid Discovery Cohort – led by Dr Jonathan Schott, Prof Nick Fox and Prof Marcus Richards
500 men and women who have been followed in a cohort study since their births in 1946 will be newly assessed in relation to amyloid – a brain protein linked with dementia – using PET and structural MRI imaging, blood and urine samples and (in a proportion of the group) cerebro-spinal fluid. This will ‘re-purpose’ an existing cohort for new use in studies of the role of amyloid in neurodegenerative disease.
A cohort centred on finding biomarkers (molecules in our tissues) which are either specific to certain neurodegenerative diseases or common to all will be created. This will be done by bringing together data from four established cohorts of people with the inherited diseases fronto-temporal dementia, familial Alzheimer’s diseases, Huntington’s disease and Parkinson’s disease.
Samples taken from 1500 DPUK cohort participants divided up according to their risk of developing different diseases will be extensively analysed at the molecular level for insights into their genetics, metabolism, and other physiological traits that might be involved in disease. This work will be linked with other research internationally. Completion is dependent on data analysis provided by Work Package 14.
Experimental medicine research on synapses, the connections between nerve cells, will be coordinated across the UK. The aim is to get a picture of the current state of knowledge and spot the key questions that need to be asked in this area of research to make the process more efficient, therefore aiding early detection and treatment of dementia.
Experimental medicine studies relating to how the immune system is involved in dementia will be carried out, led by a network of experts who will identify the best research ideas and take them forward, ultimately aiding early detection and treatment.
Experimental medicine research on Epidemiological, genetic, neuroimaging and clinic-pathological data indicate vascular mechanisms as fundamental risk factors for Dementia.
It will build on the existing UK Biobank follow-up and outcomes adjudication strategy to develop methods for dementia case identification at scale using linked routine health care data available to UKB and other population-based cohorts in DPUK. It also aims to produce an online system for remote case classification for use by UKB and other DPUK cohorts.
100,000 healthy people who are already part of the UK Biobank cohort will be tested for cognitive abilities at the same time as having their brains scanned. This will measure abilities that can change during normal ageing as well as in dementia, creating a large sample of people that will be useful for dementias research.
An ethnographic study and the development of governance structures for dementia experimental medicine, helping to ‘repurpose’ existing cohort studies for dementia experimental medicine research.
This will put the best methods and processes in place for the donation of both human brains and a type of stem cell that can be created from adult cells (induced Pluripotent Stem Cells, or iPSCs) – a crucial resource for DPUK experimental medicine research studies.
Sophisticated methods will be developed for dividing up people and data in the DPUK cohorts according to different characteristics, symptoms, genetic traits and a variety of other factors in order to study them. Data from the cohorts will be integrated to allow scientists to gather research evidence quickly and efficiently, through a single point of access.
There are three networks within Dementias Platform UK striving to raise standards, reduce costs and deliver innovative and coordinated research, making the UK an internationally unique place to study dementia. Bringing researchers and resources together will encourage, facilitate and develop a fully integrated dementia dedicated UK research environment.
Imaging Network – led by Prof Paul Matthews
The Network links neuroimaging for neurodegenerative disease across eight major UK research institutions (Cambridge, UCL, Kings, Imperial, Cardiff, Manchester, Newcastle, and Edinburgh).
Informatics Network – led by Prof Simon Lovestone
The Informatics Network is aiming to enhance the ability of researchers to find and then use data and information collected in DPUK.
Stem Cells Network – led by Prof Richard Wade-Martins
Contributing to a systematic and coordinated programme of stem-cell research, the iPSC network will also support the development of iPSC-based enhancement of strategic DPUK cohorts.
A new £6.9m research project that is designed to identify measureable characteristics, known as biomarkers, which can detect the occurrence of Alzheimer’s disease very early on in the progression of the disease – when a person may have no obvious symptoms. The study will include the most thorough and rigorous series of tests to detect Alzheimer’s disease ever performed on volunteers.