EPAD

European prevention of Alzheimer’s dementia consortium

Summary

There is an urgent need for new treatments for Alzheimer’s disease. The number of people affected worldwide is expected to reach over 100 million by 2050, yet despite intensive efforts over many years, there is still no cure for Alzheimer’s and little in the way of treatments. Today, research increasingly focuses on ways to prevent the onset of Alzheimer’s in the first place. The EPAD project is pioneering a novel, more flexible approach to clinical trials of drugs designed to prevent Alzheimer’s dementia. Using an ‘adaptive’ trial design should deliver better results faster and at lower cost.

Dementia – focus on prevention

Dementia primarily affects older people, and symptoms include memory loss, confusion, difficulties with communication and everyday tasks, and personality changes. According to the World Health Organization (WHO), an estimated 36 million people globally have dementia, and by 2050 this figure is set to rise to 115 million. A progressive disease that currently has no cure, Alzheimer’s places a huge burden on families, carers and health systems. The total annual costs of Alzheimer’s disease are estimated at around €515 billion, similar to the annual gross domestic product (GDP) of Belgium.

Considerable effort has gone into the search for a cure for Alzheimer’s. However, it is now well known that signs of Alzheimer’s disease can be found in the brain decades before the first symptoms appear. Researchers are therefore increasingly focusing their efforts on finding ways of stopping the disease in its tracks during this pre-symptomatic phase to prevent the disease entirely or at least delay the onset of symptoms.

Challenges here include the difficulty of identifying people who are likely to develop Alzheimer’s dementia, our poor understanding of these earliest stages of the disease, and a lack of flexibility in the way clinical trials are carried out.

The EPAD project is addressing these problems in a number of ways. Firstly, it will draw on existing national and regional registers of people at risk of developing Alzheimer’s dementia to create a single, pan-European EPAD register of around 24 000 people. Of these, the 6 000 deemed to be at greatest risk of Alzheimer’s dementia will be invited to join an EPAD cohort of at risk subjects. This group will undergo standardised tests and follow-up. Finally, the project will select around 1 500 people from this EPAD cohort to take part in early stage ‘adaptive’ clinical trials of drugs designed to prevent Alzheimer’s dementia.

Trialling adaptive trials for Alzheimer’s prevention

In traditional clinical trials, half of the people participating in the trial receive the drug under investigation, and half receive a placebo. Trials may last years and cost a lot of money. In adaptive clinical trials, several candidate drugs are simultaneously compared to each other and to a placebo, meaning that a greater proportion of patients benefit from a potentially active treatment. Furthermore, in an adaptive trial, researchers can adapt the trial design in response to emerging results. For example, if a candidate medicine appears to be particularly effective in only certain groups of people, that medicine can be preferentially given to those people in order to confirm the finding. Similarly, new candidate drugs can be added to the trial and medicines that prove ineffective can be dropped. In addition, adaptive trials allow researchers to test both individual drugs and combinations of different medicines.

This innovative trial design has already proven effective for testing new treatments for breast cancer. The EPAD project is pioneering this approach in Alzheimer’s disease. By adopting this approach, the project expects to be able to identify ineffective medicines earlier in drug development and so avoid failures in more advanced (Phase III) trials. By setting up a cohort of patients ready to enter trials and creating a pan-European network of trial sites, EPAD will also make clinical trials more efficient.

Patients are well represented in the project; this will ensure the project responds to the needs of people with dementia and their families.

The EPAD project does not operate alone. Together with IMI’s EMIF-AD and AETIONOMY projects, it forms the IMI Alzheimer’s disease platform. It is also working closely with other, similar initiatives worldwide, including the US-based Global Alzheimer’s Platform.

In addition, all data collected from the EPAD cohort and trial will be made publicly available for analysis to help researchers everywhere improve their understanding of the early, pre-dementia phase of Alzheimer’s disease.

Ultimately, the hope is that this project will reinvigorate the development of treatments for one of the most challenging diseases facing our ageing societies.

Achievements & News

Data suggest four categories of trajectories in people at risk of dementia

The EPAD project has used computational models, working on geographically-diverse, high-quality datasets, to help identify subgroups in cognitive function evolution.### Writing in Frontiers in Big Data, the team describes its work on teasing out the different trajectories of people at risk of developing dementia.

The modelling suggests four distinct trajectories, from class zero, characterised by individuals having the highest levels of cognitive functioning with no signs of impairment at the beginning of the study and no decline throughout the course of the study, to class three, which describes individuals who showed the most obvious signs of early cognitive and/or functional impairment in the beginning of the study and continued to show impairment upon follow-up.

The ultimate aim of this work is to establish whether cognitive tests and biomarkers can be used to figure out who is likely to develop dementia, because early intervention offers the best chance of better outcomes.

Find out more

Alzheimer’s project EPAD releases first wave of data to research community

IMI’s EPAD project is recruiting people across Europe aged 50 and over to participate in a long-term study that will help to improve our understanding of the very earliest stages of Alzheimer’s dementia – before people have any symptoms. Participants undergo multiple assessments including regular health checks, standardised tests and brain scans over several years.

Now, the project is making data from the first visit of the first 500 participants available to the scientific community. ###The data has been de-identified to protect participants’ privacy, and quality controlled. Access is provided via secure online tools; researchers who want to use it have to apply via the EPAD website.

According to project coordinator Craig Ritchie of the University of Edinburgh, the research participants are enthusiastic about the move to make their data available to researchers. ‘Research participants love and expect it - they want as much knowledge to be gained as possible from their contribution,’ he says. So far, EPAD has recruited almost 2,000 people through 28 study sites in 8 European countries. As the project progresses, further data will be made available to the wider research community.

Read more

EPAD project launches academy

IMI dementia project EPAD has launched the EPAD Academy with the goal of efficiently leveraging the project’s resources ‘to foster and develop academic research capacity and output in AD [Alzheimer’s disease] across Europe for maximum global impact’. According to the project, among other things the academy will be a space where the next generation of AD researchers and thought leaders can advance their careers. ###This is the focus of the first action of the academy, namely the creation of the register of EPAD fellows;. These early career pre-doc and post-doc researchers will be eligible for academy activities such as stays in other centres, webinars, online forums for brainstorming, competitions around specific challenges, and support for funding applications, among other things. So far, 23 EPAD Fellows have been confirmed from academia, industry and patient organisations in the consortium. In the longer term, the academy will also help in the creation of procedures that will make it easier for research teams both within and outside EPAD to access the project’s data, samples and participants with a view to deepening our understanding of AD onset and progression. Finally, the academy aims to support EPAD’s academic output in terms of scientific publications, participation in conferences and the development of guidelines and studies, and to maximise their visibility and impact. For more information on the academy, contact academy@ep-ad.org.

Revolutionising clinical trials for dementia – an interview with the EPAD project leaders

Despite considerable efforts and investments over the past decades, there is still no disease-modifying treatment for Alzheimer’s disease. This is probably due in part to the fact that efforts to develop treatments have traditionally focused on those who already have very advanced disease.### However, scientists now know that the earliest signs of Alzheimer’s disease start to appear in people’s brains years and even decades before the first symptoms of dementia appear. The ambitious goal of the EPAD project is to revolutionise the way we carry out clinical trials for treatments designed to prevent Alzheimer’s dementia. ‘What that means is taking people who show evidence of Alzheimer’s disease, but don’t yet have dementia, and trying to prevent that from happening,’ explains project coordinators Craig Ritchie of the University of Edinburgh in an interview with the IMI Programme Office. Together with fellow coordinator Serge Van der Geyten of Janssen Pharmaceutica, he explained what the project has achieved so far and why the project team is like a family.

Simon Lovestone of IMI’s EMIF and EPAD projects awarded knighthood

Simon Lovestone of IMI’s dementia projects EMIF and EPAD has been awarded a knighthood in the Queen’s birthday honours ‘for services to neuroscience research’. Professor Lovestone is the coordinator of IMI’s EMIF project, which is developing a common information framework of patient-level data that will link up and facilitate access to diverse medical and research data sources, opening up new avenues of research for scientists.### He also leads the work package on scientific challenges in IMI’s EPAD project, which is revolutionising the way we carry out clinical trials for treatments designed to prevent dementia. Professor Lovestone described himself as ‘thrilled and delighted’ by the honour. ‘The past 25 years working in dementia research has been, and continues to be, the most fulfilling and rewarding experience and it has been the greatest of pleasures to work with superb scientists and students in my group and through collaboration; I am humbled by the excellence of their work and their dedication,’ he said. ‘We are making progress towards therapies and tests for Alzheimer's disease and this award only spurs me on to redouble our efforts and defeat this disease that causes so much unhappiness to so many people. I remain convinced that we will succeed; and such success cannot come soon enough.'

IMI scientist wins Alzheimer’s research award

Miia Kivipelto, a scientist in IMI’s Alzheimer’s disease project EPAD, has received a MetLife Foundation Award for Medical Research in Alzheimer’s Disease at the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada. Dr Kivipelto was one of two scientists to win a ‘Major Award’, the other going to Guojun Bu of the Mayo Clinic in the US.### ‘MetLife Foundation is proud to present the Major Awards to Dr Bu and Dr Kivipelto for their exceptional scientific research contributions, which help bring us closer to finding a cure for Alzheimer’s disease and related dementias,’ said MetLife Foundation President and Chief Executive Officer Dennis White. ‘Their outstanding contributions, recognised around the world, have helped us better understand this devastating illness, and both awardees have laid the groundwork leading to effective treatments.’ Now in their 30th year, the MetLife Foundation awards are administered by the American Federation for Aging Research. Awardees are selected by an expert advisory committee. The Major Award comes with a USD 100 000 (approx. EUR 88 300) institutional grant and a personal prize of USD 25 000 (approx. EUR 22 100). Dr Kivipelto works at Karolinska Institutet in Sweden and at the University of Eastern Finland. In EPAD, she co-leads the team responsible for setting up the EPAD cohort of 6 000 people who will undergo a range of tests that will help scientists identify early warning signs of dementia before symptoms appear.

EPAD recruits first volunteer in major study on preventing dementia

IMI Alzheimer’s project EPAD has recruited its first volunteer in a major study that aims to add to our understanding of the earliest stages of dementia, before symptoms appear, and open up new avenues to prevent it. Julie Duffus from Scotland was inspired to take part in the project by her parents, both of whom had dementia.### ‘My mum and dad both had Alzheimer’s disease so I’ve seen first-hand the devastating effects it has on patients’ lives and those around them,’ she said. ‘I hope that my contribution will in some way help scientists to find better ways of diagnosing the disease and potentially, one day, to prevent it.’ The project aims to recruit a total of 6 000 people from across Europe to take part in the project. Participants will have regular health checks including blood tests and brain scans. Researchers will also track their thinking skills over time using tests of mental agility. The team hopes to develop tests to identify early signs of Alzheimer’s disease that may indicate when a person is at risk of dementia before symptoms appear. They will then invite these people to take part in clinical trials aimed at testing interventions that could delay, or even prevent, the onset of dementia.

Read EPAD’s press release.

EPAD and EU Lead Factory websites get a make-over

IMI Alzheimer’s disease project EPAD launched a new website on World Alzheimer’s Day, 21 September 2015. The website aims to inform different audiences, including the scientific community, companies, people with dementia, families and carers, Alzheimer associations and the general public, about the project’s existence, its progress and its achievements.### ’EPAD wants to contribute to raising awareness on Alzheimer’s disease and more specifically on the importance of the prevention of Alzheimer’s dementia,’ asserts Alzheimer Europe Executive Director Jean Georges.

The European Lead Factory has also recently given its website make over and has now a new, user-friendly look, that will make it easier for scientists to find out how they can take advantage of the project’s resources.

Participants

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EFPIA companies
  • Ac Immune SA, Lausanne, Switzerland
  • Amgen, Brussels, Belgium
  • Biogen Idec Limited, Maidenhead, Berkshire, United Kingdom
  • Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
  • Eli Lilly And Company LTD, Basingstoke, United Kingdom
  • F. Hoffmann-La Roche AG, Basel, Switzerland
  • H. Lundbeck As, Valby, Denmark
  • Janssen Pharmaceutica Nv, Beerse, Belgium
  • Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States
  • Novartis Pharma AG, Basel, Switzerland
  • Pfizer Limited, Sandwich, Kent , United Kingdom
  • Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
  • Takeda Pharmaceuticals International AG, Glattpark-Opfikon (Zurich), Switzerland
  • UCB Biopharma, Brussels, Belgium
Universities, research organisations, public bodies, non-profit groups
  • Assistance Publique Hopitaux De Paris, Paris, France
  • Cardiff University, Cardiff, United Kingdom
  • Centre Hospitalier Universitaire De Toulouse, Toulouse Cedex 09, France
  • Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, Netherlands
  • Fraunhofer Gesellschaft Zur Forderung Der Angewandten Forschung Ev, München, Germany
  • Fundacio Barcelonabeta Brain Research Center, Barcelona, Spain
  • Institut National De La Sante Et De La Recherche Medicale, Paris, France
  • Karolinska Institutet, Stockholm, Sweden
  • Klinikum Der Universitaet Zu Koeln, Cologne, Germany
  • Medical Research Council, Swindon, United Kingdom
  • Stichting Radboud Universiteit, Nijmegen, Netherlands
  • Stichting Vumc, Amsterdam, Netherlands
  • The University Of Edinburgh, Edinburgh, United Kingdom
  • Universite De Geneve, Genève 4, Switzerland
  • University Of Leicester, Leicester, United Kingdom
  • University of Cambridge, Cambridge, United Kingdom
  • University of Oxford, Oxford, United Kingdom
Small and medium-sized enterprises (SMEs)
  • Aridhia Informatics Limited, Glasgow, United Kingdom
  • Berry Consultants Llp, London, United Kingdom
  • Ixico Technologies Limited, London, United Kingdom
  • Synapse Research Management Partners SL, Barcelona, Spain
Patient organisations
  • Alzheimer Europe, Luxembourg, Luxembourg
Third parties
  • Region Stockholm, Stockholm, Sweden
Non EFPIA companies
  • Araclon Biotech S.L., Zaragoza, Spain
  • Quintiles Limited, Reading, United Kingdom

Participants
NameIHI funding in €
Alzheimer Europe321 556
Assistance Publique Hopitaux De Paris681 100
Berry Consultants Llp219 000
Cardiff University141 100
Centre Hospitalier Universitaire De Toulouse2 084 650
Erasmus Universitair Medisch Centrum Rotterdam337 922
Fraunhofer Gesellschaft Zur Forderung Der Angewandten Forschung Ev340 475
Fundacio Barcelonabeta Brain Research Center3 258 316
Institut National De La Sante Et De La Recherche Medicale223 600
Ixico Technologies Limited528 355
Karolinska Institutet567 000
Klinikum Der Universitaet Zu Koeln336 014
Medical Research Council134 120
Stichting Radboud Universiteit84 464
Stichting Vumc2 236 543
Synapse Research Management Partners SL1 543 976
The University Of Edinburgh7 631 711
Universite De Geneve1 479 626
University of Cambridge892 859
University Of Leicester479 800
University of Oxford1 894 313
 
Third parties
NameFunding in €
Region Stockholm463 500
 
Total Cost25 880 000