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World Young Leaders in Dementia (WYLD), a network for emerging leaders in the field, grew out of the legacy meetings that followed the 2013 G8 (now G7) dementia summit: Together with JPND, the UK Science & Innovation Network identified young leaders to convene to draft a set of proposals and present them at the WHO’s First Ministerial Conference on Global Action Against Dementia in March 2015. This process sparked a number of new research collaborations and indeed the creation of the WYLD network itself.

Now with more than 130 members across six continents, WYLD is mobilising to drive forward creative new solutions for people with dementia, their caregivers, and their communities. JPND spoke with Laura Booi, William Hu, Anja Leist, Kristine Newman, and Clare Walton from the WYLD Steering Committee to learn more about what the group wants to accomplish and how they plan to do it.

Accelerating solutions to tackle dementia
To help lay the groundwork for the future of dementia care, cure, research, and advocacy, the members of WYLD are working to foster new, interdisciplinary collaborations among the next generation of leaders. “WYLD members come from the broad fields of basic, clinical, health, social and care,” said Anja Leist, a research associate at the PEARL Institute for Research on Socio-Economic Inequality at the University of Luxembourg. “Most members, however, are not only researchers,” added Kristine Newman, an assistant professor at the Daphne Cockwell School of Nursing at Ryerson University. “They’re also advocates and, in many cases, care providers.”

The young leaders aim to identify ethical and daring models of inquiry and then translate them across disciplinary and national borders. Their end goal: to advance new dementia strategies that incorporate the latest innovations in technology and methods and that are global in scope. “We want to develop compelling strategies that meet the needs of a rapidly changing world,” said William Hu, Assistant Professor of Neurology and Director of the Neurodegenerative Biomarkers Laboratory at Emory University. “Dementia is a global challenge and it will require global solutions.” Hu himself has promoted scientific exchange by establishing new collaborations with young clinicians and scientists from Bulgaria, Italy, the Netherlands, Taiwan, and the U.S.

European young leaders meeting, London, February 2015

A new take from the ‘Think different’ generation
According to the young leaders, many of whom qualify as so-called millennials (those born roughly between the years 1982-2000), theirs is a generation marked by a rejection of conformity and a confidence in thinking outside the box. It’s this ethos that the young leaders say allows them to bring creative brainstorming, fresh perspectives, and novel solutions to the dementia field. In short: this is a group of young people who aren’t afraid to put forward challenging new ideas.

First WHO Ministerial Conference on Global Action Against Dementia, Geneva, March 2015

As the first generation of dementia researchers who grew up with home computers, the young leaders also bring technological fluency to the field. One advantage of being a digital native, they say, is that they’re able to utilise, uncover, and recommend the most advanced tools, trends, and technologies, such as content management systems and social media, for dementia-related initiatives. For this reason, WYLD incorporates a technology and dementia element into each international workshop.

Ready, set, assume the mantle
WYLD’s ongoing activities include regular meetings at international dementia conferences and participation in the World Dementia Council, with one young leader contributing to each of the five Global Teams (Research, Open Science & Data, Care, Integrated Development, Risk Reduction, and Finance). In order to develop into a truly international network, the young leaders are taking steps to implement their governance structures, formalise their communication channels and create a membership directory to facilitate connecting from both within and outside of the network. “We want to rapidly ramp up our collaborations,” said Laura Booi, Doctoral Candidate in Gerontology at Simon Fraser University in Vancouver, Canada. “That’s how we believe that we can most quickly make progress toward a world that cares for and values people with dementia.”

Japanese young leaders meeting, Tokyo, November 2014

Researchers from across Europe team up to decode the interplay between genetics and environment

For scientists studying the origins and pathways of Alzheimer’s disease, experimental animal and cell models are a critical tool. These models mimic the processes thought to be at play in human patients and allow researchers to assess possible treatments before moving into clinical trials. Yet most models of Alzheimer’s disease are unable to take into account the complex genetic and environmental factors involved in what’s known as late-onset ‘sporadic’ Alzheimer’s disease, which is the most common type of the disease.

An international research collaboration called DACAPO-AD is trying to change this. Led by Gabor Petzold, a professor at the German Center for Neurodegenerative Diseases (DZNE), DACAPO-AD (short for ‘Deciphering Interactions of Acquired Risk Factors and ApoE-mediated Pathways in Alzheimer’s Disease’), aims to elucidate the complex interactions between known genetic and environmental risk factors, with the goal of establishing the reliable new models of Alzheimer’s disease that scientists need to identify potential treatments.

At the intersection of genetics and environment
Researchers classify Alzheimer’s disease in different groups according to the age at onset. Early-onset inherited (or ‘familial’) Alzheimer’s disease is very rare, but half of the cases have a genetic cause that is relatively well understood. Then there’s what is known as late-onset sporadic Alzheimer’s disease. This type is far more common — accounting for more than 98% of cases — but the pathways leading to sporadic Alzheimer’s disease are much less well understood and look far more complex. The most important known genetic risk factor for sporadic Alzheimer’s disease is a gene called APOE-ε4, although not everyone with sporadic Alzheimer’s disease carries the gene, and some people who do carry the APOE-ε4 gene ultimately die without ever developing Alzheimer’s disease. Indeed, around a third of sporadic Alzheimer’s patients are APOE-ε4 -negative.

For the DACAPO-AD project, the challenge is to better understand the reasons for this heterogeneity, and the researchers are focusing on the role of environmental (or ‘acquired’) risk factors. They’re trying to uncover how a range of these different factors — such as a high-fat diet, cardiovascular disease, traumatic brain injury, systemic inflammation and sleep problems — interact with the APOE-ε4 gene to result in an increased risk of Alzheimer’s disease. “It would be a real breakthrough in the field if we could understand, on a cellular or molecular level, how these risk factors trigger the onset and contribute to the progression of sporadic Alzheimer’s disease,” Petzold explained from his lab in Bonn, Germany. “Our hope is that this research will ultimately lead to better preventive strategies and novel treatment options.”

Pooling resources to speed up discovery
The high-level skills and technologies needed to approach these questions meant that international collaboration was not just beneficial but necessary. DACAPO-AD, which was selected for support in the 2015 JPco-fuND call, brings together research teams from four countries: in addition to Germany, researchers in Denmark, France and Sweden are bringing different expertise to the project. “We are a team of five labs from four different countries that are sharing technologies and data to more rapidly address the same common goals,” Petzold said.
The project partners were selectively identified to ensure that the combination of each lab’s unique skill set would enable the collaborators to work on questions that the individual labs wouldn’t have been able to take on alone. Moreover, all of the partners have agreed to share preliminary findings and technological developments freely within the team, with one of the consortium’s explicit goals being knowledge transfer. “We will give young researchers from each lab the possibility to travel to partner labs, Petzold explained. “This will allow our teams to learn new techniques, exchange data and get to know other researchers.”

Calling young researchers!
The Alzheimer’s field is quickly evolving and offers scientists and clinicians a host of exciting challenges. To early-career researchers who are considering specializing in Alzheimer’s disease, Petzold recommends surveying a broad range of researchers, including PIs and postdocs as well as students, to see what they think the most pressing questions are facing the field and where it’s headed. “In other words,” he explained, “what novel research finding would be a real breakthrough, and how do we get there?” He advises joining a lab with a hands-on PI who has the technological and financial resources to tackle these big questions. From there, a mix of perseverance and openness, he says, is most likely to yield success: “It’s important be diligent and work hard, but also to stay flexible for new research avenues and technologies that may emerge in the future.”

By analyzing brainstem tissue and testing their findings in ongoing aging cohorts, EPI-AD, a JPND-supported project run by a young PI from the Netherlands, aims to uncover the stress-related epigenetic mechanisms linked to Alzheimer’s disease.

A few years ago, Daniel van den Hove, a neurobiologist who has long been interested in studying the connections between stress and brain function, began to think about a new question: what if stress associated with disorders such as anxiety and depression was causally linked to Alzheimer’s disease?

“We already have some evidence that a history of depression may speed up cognitive decline related to Alzheimer’s disease,” van den Hove explained from his office at Maastricht University in the Netherlands, where he is an Assistant Professor in the Department of Neuroscience. “What we want to do now is to look at the brainstem, where the regions critically involved in stress regulation and affected by depression are also affected early in Alzheimer’s disease, and see if we find any causality.”

This is the question that van den Hove and his colleagues from across Europe will explore in a new project supported by the EU Joint Programme for Neurodegenerative Disease Research (JPND). The consortium, called EPI-AD (short for “Targeting epigenetic dysregulation in the brainstem in Alzheimer’s disease”), brings together research teams from five countries: in addition to the Netherlands, researchers from Germany, Luxembourg, Spain, and the United Kingdom will collaborate on EPI-AD. The project was selected for support under the 2015 JPco-fuND call, which was co-funded with the European Commission under Horizon2020.

Zeroing in on the brainstem
Although EPI-AD won’t officially launch until July 2016, the research teams have spent the last several months planning via email, and they held their first face-to-face meeting in March. “I think we’re all really excited to get started on this project, which we believe represents an important shift in research focus,” van den Hove says. Although much of Alzheimer’s disease research is currently concentrated on brain regions like the hippocampus, which is affected in the later stages of the disease, van den Hove and his colleagues are looking somewhere else: the brainstem. “We suspect that the changes seen in the hippocampus are more likely to be the consequence of what’s already happened than causally involved,” van den Hove explains. “We want to shift our focus to the earlier stages — we’re looking for causal factors — and we think the best places to look are the the locus coeruleus and the dorsal raphe nucleus in the brainstem, which is where these early changes are seen.”

EPI-AD researchers will have a rich collection of tools at their disposal, starting with unique, well-defined brain tissue samples for patients and controls. The samples are banked an average of 2.8 hours postmortem, and subjects were followed for eight years on average, offering the researchers a trove of valuable new information. In addition, they’ll have access to three ongoing aging cohorts in the Netherlands and Germany, which will allow the researchers to immediately test what they find in the brain to see whether it has any predictive value in living subjects. In parallel, they will be able to directly compare their findings with other biomarkers – they’ll have access to imaging data and amyloid beta and tau as well as cognitive data – resulting in a multi-level and multi-disciplinary project. Finally, the Spanish partner, led by Manel Esteller and Raul Delgado at the Bellvitge Biomedical Research Institute, will manipulate the identified genes in stem cells of Alzheimer’s disease patients to see if they’re changed in terms of structure and function. The key question: Can these cells be made ‘healthier’ by intervening in epigenetic processes? “We’re combining a lot of recently developed knowledge in different fields and integrating it into one concept,” van den Hove says. “But what’s the use of finding something very interesting and then stopping there? Our goal is to uncover critical findings and then find a way to add value by translating this new knowledge as efficiently as possible to the clinic.”

If at first you don’t succeed, try, try again

Dr. Daniel van den Hove

For van den Hove, the path to the JPND grant wasn’t necessarily quick or easy. “When I came up with this hypothesis I was incredibly enthusiastic — I thought that this might mean something, that I could really make a difference, even in a relatively short period of time,” he explained. But his first grant application was turned down. Then another one was declined, although the scientific excellence of the project proposal was underscored by all of the reviewers. One of his mentors, Professor Klaus-Peter Lesch, urged him to be persistent. “Fail better next time,” he kept telling him. “When I saw the JPND grant opportunity, we’d already been fine-tuning this concept, working on extending our network a little more and thinking about the most interesting angles, so we were ready to apply,” he said. Ultimately, the researchers’ persistence paid off. “It’s important to keep believing in your ideas and never give up,” van den Hove says. “It’s also important as a young researcher to find mentors who will assist you in navigating the grant application process and who will help you seize new opportunities. At 37, I’m still relatively young to coordinate such a large project, but I’m lucky in that my mentors encouraged me to step forward and apply for this grant. My mentors’ support, on matters small and large, has helped me enormously, and I hope I can now more and more fulfill such a supportive mentoring role. Of course, science, in all its aspects, should never be seen as an individual effort, although many funding schemes are aimed at the individual.”

Joining forces to accelerate research progress
Research collaborations that developed as EPI-AD came together have been amplified and extended since the project was selected for the JPND grant, with the partners securing funding from other outside sources to hire additional students to work on the project. “What’s wonderful about getting this grant is not just the money the grant brings in but the extra opportunities it brings along with it,” van den Hove says, explaining that over the lifecycle of the project he and his partners hope to apply for more funding and continue to expand their research collaboration. “Since a single lab can’t be experts in everything, international collaboration helps us bring together the broad range of expertise we need to make real strides in this area of research,” he says. “At the same time, as we send students and researchers back and forth between labs, we’re able to bring new knowledge and expertise from one country to another and integrate this new expertise into our own labs as well. So we aren’t just making use of each other’s expertise. We’re also bringing new knowledge back home.”

The project is expected to span three years, but the researchers expect the new information they gather could give them enough material to work with for many more. “EPI-AD gives us the infrastructure we need to generate an enormous quantity of data,” van den Hove says. “What we can do with that in the years to come is almost endless — and incredibly exciting.”

Prof. Gunhild Waldemar of Rigshospitalet and Copenhagen University participated in BIOMARKAPD, a JPND project on biomarkers for Alzheimer’s disease and Parkinson’s disease that ran from 2012-2015.

She spoke with JPND about the importance of biomarkers for research into neurodegenerative diseases, her hopes for the field, and advice she would give to early-career researchers.

Dr. Charlotte Teunissen of the VU University Medical Center in Amsterdam was a work package leader for BIOMARKAPD, a JPND project on biomarkers for Alzheimer’s disease and Parkinson’s disease that ran from 2012-2015.

In an interview with JPND, she reflects on the project and discusses the importance of biomarkers for research into neurodegenerative diseases:

Professor Judes Poirier of McGill University and the Douglas Institute in Montreal, Canada, was a participant in BIOMARKAPD, a JPND project on biomarkers for Alzheimer’s disease and Parkinson’s disease that ran from 2012-2015.

In an interview with JPND, he expounds on how advancements in the biomarkers field, combined with genetics, is bringing tremendous change to the study of Alzheimer’s disease and Parkinson’s disease.

“From my own perspective, participating in JPND projects has been a very good experience. You meet different people from different disciplines, you learn how to do things differently, you get different perspectives on things, and I think that enriches the field.”

What impact do you think JPND is having?
I think JPND is having a fairly significant impact. The profile of JPND-sponsored programmes has increased significantly in recent years. Researchers are now very aware of the benefits that synergies created through JPND-supported multi-national research brings. This has made researchers very motivated to participate in JPND-supported calls. I believe that this transnational synergistic approach to research is the right one. JPND has identified that by tackling the big challenges in the field of neurodegenerative disorders in a coordinated manner, the impact of research outputs can be maximised.

JPND has also succeeded in bringing researchers into the field of neurodegenerative disease research who might otherwise have found it difficult to break into areas beyond their own expertise. I am currently collaborating with a group of exercise physiologists on a JPND project that examines the benefits of exercise intervention for people with cognitive impairment. I think that this type of collaborative approach is a great opportunity for us going forward to refresh the field and expand its boundaries while facilitating the growth and exchange of interdisciplinary knowledge.

What is your experience of JPND-supported projects?
What I really like about multi-national projects, such as the JPND ones I’m involved in, is the added value they afford our research. Ireland’s population base does not allow us access to a large number of patients compared to other research groups in Europe, but by working with them, everyone benefits from what we can adopt from each other’s experiences, exploit in terms of resources and learn from new perspectives.

Do you have any general aspirations for this field of research?
Human capital development is very important right now in the field of neurodegenerative disease research, and no less so in dementia research, which I have a particular interest in. At the moment the approach to research is siloed, with basic scientists, clinicians, service providers and policy makers often working independently from one another. This approach needs changing so that the neuroscience research we are doing is rapidly translated into clinical fields and then into policy and practice. The only way to achieve this is through human capital, by educating people from all these areas together – that’s the future and it is so important.

There are a number of initiatives that we are working on in Ireland to achieve consensus and address the siloed approach to research. The next step will be to create human capital-type programmes that are integrated, applied and inter-disciplinary. Even in the event of the development of a very effective disease-modifying treatment for Alzheimer’s disease, patients will still require quality care and informed clinical practice – all this is only achievable with sympathetic, well-considered policy implementation.

“We need to get the best value we can from existing resources and we can do that by doing really good quality research. I think JPND is contributing by trying to meet the big economic challenge, as well as the clinical and biological challenges.”

What impact do you think JPND is having?
I think it is having a big impact as a focal point. I think it has managed to bring together discussions and thinking around this set of conditions, and the research that is needed to tackle them. I think it has helped to generate more funding for this endeavor, too. I think it has also helped to bring together researchers to communicate what they are doing. So lots and lots of ways: I’m very positive about it. I came in as a social scientist into what is an area dominated by biomedical science, but am very positive about what JPND is doing in my area of Health and Social Research.

Did you always want to work in the area of health and social care research?
I started off doing a Masters degree in Econometrics and Mathematical Economics, which I loved intellectually, but I got bored with doing something that felt too removed from the real world. I have always worked in Health and Social Care Research, and I absolutely love it. And I particularly like the dementia field, as I think it brings enormous intellectual challenges. I have a parent with dementia – indeed, almost everyone knows someone with dementia, so it’s a real-world problem today, and I like working in an area that is that challenging.

What is the best piece of advice you have received in your own career?
I’ve been very fortunate to work with people who are strong on the science of research and I hugely value that. I have also been very fortunate in my job to work with people whose main priorities are changing policy or putting policy into practice, and they constantly remind me that university-based researchers need to be aware that there is a real world out there, and we need to be serving that real world – so it is about balancing the scientific robustness with what we can do for today’s populations.
And what would your advice be to younger researchers?
My advice would be “come into this field and stay in it”. This is an interesting field partly because there are no simple solutions. There are huge challenges, so from that point of view, it is very good. It is important that researchers keep a broad profile and that they look to do good, solid scientific research. In my field, I would want them to do research that will have an impact on the real world and to do that quite quickly, so that’s again balancing the robustness of science with the relevance to today’s challenges.

How can we better involve patients in research?
As a research community, we have not involved patients enough, and I think we’ve just assumed that they are not able to participate – that’s clearly not the case. We need to understand what they see as important, both in the short- and long-term. They are not the only people whose views need to be taken into account, but we need to include them more in research, in terms of how we plan it and how we interpret it. Doing so will generate better value for our research.

Click here to read Martin Knapp’s biography.

“Research is all about increasing quality of life and cannot happen without public participation.”

“Never be afraid to ask questions, even though we, as scientists, don’t have all the answers.”

“Take care of your brain by embracing a lifestyle that promotes its overall health.”

What in your opinion are the most pressing issues in research into neurodegenerative diseases?
Neurodegenerative diseases present us with several paradoxes: A number of conditions share several features in common, and yet even within a particular disease, a subset of patients display dissimilar symptomatic profiles and pathological features. In conditions like Huntington’s disease, there is a clear genetic cause, whereas in others, such as Alzheimer’s disease, genetic mutations are only present in a small subcategory of individuals. Unfortunately, there is also a lack of models that really work, and this makes it difficult to understand the complex pathophysiological mechanisms involved. The identification of biomarkers that potentially predict neurodegenerative diseases in the pre-symptomatic stage will not only help in diagnosis but will also enhance our understanding of the underlying pathological mechanisms.

What advice would you give to young researchers who want to build a career in this field of research?
Work hard, be passionate and never shy away from asking questions. Neuroscience is a challenging field, so expect the unexpected.

How can research into healthcare and social care be better supported to build up its capacity?
Countries that have committed themselves to enhancing the level of research in health and social care are increasing, as can be testified to by the various national dementia strategies that have been launched in recent years. Although research may be seen as an element of risk in terms of return on investment, it is essential for the promotion of well being and modernisation of health and social services. High-quality research that promotes innovation and good practice while ensuring scientific collaboration, public involvement and effective transfer of knowledge will have a positive impact on the lives of people living with neurodegenerative conditions.

What impact do you think JPND is having on neurodegenerative disease research?
The challenges that neurodegenerative diseases present to us are far too many, and thus coordinating our efforts is a major prerequisite in responding to this. Besides, joining forces is also essential in promoting high-quality scientific research. There is no doubt that JPND’s Research Strategy is reaping its fruits, as can be attested to by the level of response to the scientific calls.

In your opinion, what is the benefit of JPND for patients and/or patient organisations?
JPND is already benefiting the lives of people living with neurodegenerative diseases and their caregivers. Just by taking a look at the supported research projects under the JPND 2012 translational call, which focused on themes evaluating health care policies, strategies and interventions for neurodegenerative diseases, one can appreciate the impact that such research will have on areas such as timely diagnosis and access to care.

Click here to read Charles Scerri’s biography.