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On 17 February, we were pleased to hold the first local EPAD community meeting among the Scottish research sites, collaborators, academics and scientists who have been involved in the EPAD Longitudinal Cohort Study (LCS) throughout the IMI funded period and now continue to contribute to the study locally.

The first local EPAD community meeting focused on carrying on data collection within the established EPAD LCS network in Scotland, follow-on studies and open access for the large EPAD data including biosamples and imaging data. The community meeting also marked the launch of the first post-IMI EPAD local initiative which we hope will be one of many across Europe to carry on collecting longitudinal data from the participants who have already contributed valuable data over several years, as well as for the research community to share ideas.

The lead of the EPAD project Prof Craig Ritchie gave an overview of the post-IMI period including work already published and encouraging the research community to apply for the EPAD LCS data now freely available. We also got an overview from the other speakers on how to access the biosamples, the collaboration between EPAD and GAP and many of the follow-on studies. Some of the follow-on studies include a limited version of the original EPAD study protocol as well as studies using retinal imaging and speech analysis.

The EPAD Participant Panel is continuing to be active and has contributed to many projects during a challenging year, whether by getting involved in online-courses by Brain Health Scotland in Future Learn or providing valuable feedback on several study protocols for various Scottish studies. It was decided to organise local community meetings quarterly with support from the Scottish Dementia Research Consortium and keep hopeful for a face-to-face conference at the end of summer.

On 1 February, the members of the Neuronet (Efficiently Networking European Neurodegeneration Research) programme announced the launch of a pan-European Knowledge Base which brings together key information about the 18 projects of the Innovative Medicines Initiative (IMI) neurodegeneration (ND) portfolio, including the EPAD project.

This comprehensive resource is an integral part of Neuronet’s endeavour to boost collaboration across the research portfolio by assisting in identifying gaps, multiplying the portfolio’s impact, and enhancing its visibility with related initiatives in Europe and worldwide.

“The Neuronet Knowledge Base tool intends to bring the “better together” team concept to life and overcome the inherent fragmentation often found in a project-based research landscape,” said Carlos Díaz, CEO SYNAPSE and Neuronet Coordinator.

Programme overview

As well as providing a summary overview of the IMI neurodegeneration research programme through its interactive dashboard, the Neuronet Knowledge Base includes links to over 380 publications and more than 350 publishable deliverable reports, acting as a one-stop shop to explore the diverse projects and outputs of the programme.

Knowledge Base tools

An “Asset Map” gives a comprehensive view of the different assets resulting from the projects, such as genetic datasets, clinical cohorts, and data platforms. The interactive map allows users to obtain more detailed information about the specific assets of each project. Furthermore, the Knowledge Base offers access to a regulatory, health technology assessment & payer engagement Decision Tool to help researchers identify the key processes and procedures for engagement with these stakeholders at key points in the development of an asset.

Staying up to date on scientific progress and activities

In addition to project and programme-related information, users can also access an agenda listing key upcoming scientific conferences and view a feed with the latest project-related activities.

“This newly developed platform is key in Neuronet’s effort to centralize and integrate the vast amount of knowledge generated within the ND IMI portfolio,” said Lennert Steukers, Associate Director, Clinical Scientist, Janssen Pharmaceutica NV, and Neuronet Leader. “The Knowledge Base sets the stage for future research tools to inform and shape the next generation of research and advancements in the neurodegeneration field.”

The Knowledge Base can be accessed here: https://kb.imi-neuronet.org/

The European Prevention of Alzheimer’s Dementia (EPAD) project is very pleased to announce the external release of its final dataset for all researchers from over the world. The final dataset is called Version.IMI (V.IMI) as it represents all the data collected and processed during the IMI period of EPAD.

A key achievement of the EPAD project was the establishment of a Longitudinal Cohort Study (LCS) that has screened a total of 2,096 participants, collecting a wide range of cognitive, clinical, neuroimaging and biomarker data to help further our understanding of the early stages of Alzheimer’s disease.  The LCS was initiated and the first participant screened in May 2016. Screening into the LCS was stopped on 29 February 2020. The 2096 participants who consented and were entered into the eCRF during the IMI-period of funding are included in the V.IMI data release.

EPAD has made this database open access and publicly available to the research community. To access the data, you will need to make an online request via EPAD LCS Research Access Process. To find how to apply and learn what data is available in the EPAD data releases before your apply, visit the EPAD website here.

A conference blog about the 13th Clinical Trials on Alzheimer’s Disease (CTAD) conference which took online, from 4-7 November 2020, has been published on the AlzForum website. The article mentions EPAD and can be read below:

EPAD had been supported for five years by the Innovative Medicines Initiative (IMI), which is funded jointly by the European Union and the European pharmaceutical industry.

EPAD aimed to recruit, and deeply phenotype, thousands of potential clinical trial participants across Europe, and then to run side-by-side Phase 2 trials with a shared placebo group and a Bayesian adaptive design. By the time the five-year funding period ended, the cohort had more than 2,000 participants, each phenotyped for multiple cognitive measures, genetics, and CSF biomarkers, but, alas, no drug sponsors to run trials. “We had everything but a drug,” said Craig Ritchie of the University of Edinburgh, who headed EPAD.

Why did no would-be trial sponsor take the plunge? Failed Phase 1 trials were one reason, lack of internal funding another, plus companies hesitated to be the first to take a risk on this innovative platform design, Ritchie said. That there was no funding to maintain the trial-ready cohort as trials took off may have also given sponsors cold feet.

After the loss of IMI funding at the end of 2019, EPAD secured some funds from philanthropic sources to wrap up final study visits and to maintain the massive dataset for the cohort. Then COVID-19 hit, and follow-up visits were halted, too.

But all is not lost. The more than 2,000 participants enrolled in EPAD are “desperately keen” to join a clinical trial, Ritchie said. Around 300 of them are cognitively normal but have amyloid, making them perfect subjects for secondary prevention trials. To help them join trials, Ritchie said EPAD is partnering with organizations such as the Global Alzheimer’s Platform Network (GAP-Net), a U.S.-centered network of study sites that aims to boost the efficiency and quality of AD clinical trials. GAP-Net coordinates with TRC-PAD. And of course, participants will be eligible to join trials conducted within their own countries.

While EPAD will not realize its dream of running head-to-head proof-of-concept trials with multiple drugs, Richie hopes that the cohort will nevertheless find its way into clinical trials. Last but not least, the rich EPAD dataset is available to the neurodegenerative disease research community for analysis.

The article can be found here: https://www.alzforum.org/news/conference-coverage/trc-pad-funnel-finally-touches-down

A key achievement of the EPAD project was the establishment of a Longitudinal Cohort Study (LCS) that has screened over 2,000 participants and collected a wide range of cognitive, clinical, neuroimaging and biomarker data to help further our understanding of the early stages of Alzheimer’s disease.

“We aim to ensure that this precious collection of samples is put to the very best use towards the prevention of Alzheimer’s dementia.”, said Jean Manson, PI of the EPAD Bioresource and Chair of the Sample Access Committee.

EPAD offers a way of accessing the data, samples and image data collected during the EPAD LCS to academic researchers, institutions and companies from all over the world. The current EPAD database, provided by Aridhia, is open-access, ensuring the use of the data for the Alzheimer’s disease research community worldwide. Data access is free to all researchers. Three databases have been released:

1. EPAD LCS V500.0, which includes baseline data from the first 500 people to enter the cohort;
2. EPAD LCS V1500.0, which includes baseline data from the first 1,500 people to enter the cohort; and
3. EPAD LCS V500.1, which includes updated data from the first 500 participants, including one-year follow-up data

To access the data, you will need to make an online request via the EPAD LCS Research Access Process (ERAP).
For more information about the EPAD data and samples and how to apply, visit the new webpage: https://alzheimer.noemi.lu/open-access-data/overview/

“Our data team generate the published snapshots of the analytical database, and publish snapshots and metadata. Researchers can discover the data through publications, Internet searches and go through a partially automated process to request access.”, said Rodrigo Barnes from Aridhia

The Alzheimer’s Disease Data Initiative (AD Data Initiative) has launched its Alzheimer’s disease (AD) Workbench, a cloud-based platform for scientists to accelerate discoveries and innovations for AD and related dementias. The AD Data Initiative is a new global effort that aims to advance AD innovation by connecting researchers with the data needed to generate insights and inform the development of improved treatments and diagnostic tools. The AD Data Initiative was created by a coalition of partners to increase sharing of dementia-related data among researchers and provide new ways to experiment with the most trusted datasets.

We are pleased that the AD Data Initiative platform will be the host (via Aridhia) of the EPAD data.

For decades, scientists have made limited progress in Alzheimer’s research and therapeutics, even though Alzheimer’s disease is a leading cause of death around the world with care estimated to cost more than $1 trillion annually. Now more than ever, greater data sharing is needed to spark innovative discoveries in AD research. Advancement is possible—limited access to data should not be a barrier.

The idea for the AD Data Initiative was initiated in 2018, after Bill Gates brought together a coalition of partners interested in improving AD and related dementias data sharing with the aim of moving innovation further and faster toward better treatments and diagnostic tools.

“The need for new and more effective treatments for Alzheimer’s disease has never been greater. A better understanding of the disease will help us detect and diagnose it earlier. It should be easier for people to find, enroll and stay in clinical trials, and we must accelerate the pace of discovery and innovation. Data can play a critical role in breakthroughs,” said Bill Gates. “Data is a tremendously powerful tool that can be better harnessed to understand and reduce the impact of AD. It’s what the AD Workbench is designed to do.”

The AD Workbench will facilitate interoperability across data platforms and enable researchers to work with multiple datasets. With a federated model of data sharing, the AD Workbench allows permissioned researchers to import their datasets, access, and transfer data from other platforms. It also allows them to work securely with anonymized datasets that are unable to be transferred due to data privacy, regulation and local laws. Within the platform, users have a personalized workspace where they can ensure quality control, harmonize data, and analyze data within the platform. Soon the AD Workbench will provide researchers and data scientists with the ability to share code and crowdsource ideas.

“There are no limits to the innovation that can arise from researchers working together with more data than ever before,” said the AD Data Initiative Executive Director Tetsu Maruyama. “That’s what makes the Workbench so exciting – and it’s just the beginning. The Workbench will continue to evolve with input and data from the research community, allowing scientists to work with new tools and more data.”

The Workbench will increase access to many types of data that will both speed our basic understanding of AD and related dementias and progress toward new treatments by:

• Allowing scientists to combine data from multiple studies to strengthen understanding beyond what could be learned from a single study;
• Enabling researchers to revisit existing datasets with new analytical methods and technologies; and
• Accelerating future research by breaking down traditional research barriers.

“There is tremendous power in data sharing and the ability to harmonize data across multiple groups,” said Dr. Reisa Sperling, Director, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital. “The AD Workbench will make it easier to access and explore data in new ways and expand collaboration opportunities.”

The AD Data Initiative will foster an environment that supports and facilitates researchers’ abilities to share data by providing resources. In addition to the AD Workbench, the AD Data Initiative has collated existing tools and created new tools that will help researchers navigate regulatory frameworks and policies that are often barriers to data sharing. The AD Data Initiative will also provide grants to fund researchers and organizations that seek to expand data access and sharing using the AD Workbench. Increasing access to the best and most trusted datasets is one of the most effective ways to accelerate progress toward more effective treatments, and the diagnostics that can help physicians and people with dementia. Together, these breakthroughs will drastically reduce the impact of AD on patients, their families, and the healthcare system.

For more information please visit: www.Alzheimersdata.org

The 30^th Alzheimer Europe Conference (#30AEC) “Dementia in a changing world” was held online from 20-22 October 2020. Almost 800 participants, from 42 countries, attended the conference, which boasted 260 speakers and 100 poster presentations, sharing their research, projects and experiences in an atmosphere of collaboration and solidarity, against the backdrop of the global COVID-19 pandemic. The three-day conference featured 24 parallel sessions and 6 special symposia on diverse topics for delegates to choose from.

Four Neuronet parallel sessions were held as part of the conference to showcase the work of IMI neurodegenerative diseases (ND) projects in key areas, stimulating discussion on major issues and how to address them. The first session, chaired by Neuronet’s Coordinator Carlos Díaz, was entitled “Efficient data sharing: a must for science to respond to societal needs”. During this session, Nigel Hughes, Rodrigo Barnes and Colin Veal from the EHDEN and EPAD projects discussed technical solutions that are being developed by IMI projects to overcome key obstacles to effective sharing of health data, including data harmonisation, federated networks, digital data discovery tools and research environments.

In addition, the EPAD Fellow Natassia Brenman presented the findings of the SPEAR study in the form of a quick-oral presentation entitled “Jumping into the research: insights from the SPEAR study into motivations and expectations of participation in Alzheimer’s disease research”.

For further details on the Neuronet sessions, please check out the Neuronet Sessions brochure and read the news piece here.

All delegates were invited to mark the dates of the next Alzheimer Europe Conference (#31AEC) in their calendars. “Building bridges” will take place in Bucharest, Romania from 29 November to 1 December 2021.

Could you tell us a bit about you and your work?

My background lies in the fields of neurobiology and neuropsychology, and I am currently a PhD student at Barcelonabeta Brain Research Center. My research focuses on the study of fluid biomarker profiles in preclinical Alzheimer’s disease, as well as on the effect of modifiable and non-modifiable risk factors on these biomarkers in the early stage of the disease. I have a special interest in studying whether there are sex differences in fluid biomarkers reflecting different pathophysiological pathways, and on the effect of risk and protective factors on brain pathology. I think this research can provide very valuable knowledge to better understand the disease development and potentially contribute in the design of effective preventive and therapeutic strategies.

Besides my work as a researcher, I have also been involved in the coordination of EPAD WP1: “Scientific challenges”.

You are a member of the EPAD WP1 “Scientific challenges”. Could you please tell us more about its work and main achievements?

EPAD WP1 was created to address scientific challenges related to the design and execution of the study throughout its duration. The main challenges included the definition of a risk spectrum of research participants suitable for secondary prevention, the development of evaluation criteria for inclusion to the project based on biomarker and clinical endpoints, and the assessment and selection of potential trial mechanisms and compounds.

To address these objectives, WP1 was informed and advised through the creation of five different Scientific Advisory Groups (SAGs), which provided key scientific input and support. These were the Imaging SAG, the Clinical and Cognitive outcomes SAG, the Genetics SAG, the Fluid biomarkers SAG and, finally, the Lifestyle and non-pharmacological interventions SAG.

Each of these SAGs has crucially contributed providing evidence and recommendations in relation to the study inclusion criteria, assessments and endpoints. Importantly, their recommendations and white papers resulted in publications in high impact scientific journals.

Besides this, WP1 has also been involved in research access procedures, giving support in the creation of research access committees and processes to receive and manage research applications and to grant access to EPAD data and samples to EPAD partners and also to external researchers. The creation of these processes has allowed the provision of high-quality research data open for the research community through a systematized and overseen research access process.

What value do you see in public-private collaboration and networking with related initiatives?

From my perspective, the public-private collaboration has represented an advantage in the context of the design and execution of EPAD.

Experts in the field from Academy have been key providing scientific input and addressing the challenging questions and decisions to design a high quality and scientifically valuable trial-ready observational cohort such as EPAD. On the other hand, industry partners are crucial for their expertise on study protocols design and implementation. They have also been key for the management of the different trial delivery centres across Europe, and for the development of tools allowing efficient data collection and access processes.

What are the most prominent challenges you see in Alzheimer’s disease research?

Recent research in Alzheimer’s disease is showing very promising evidence on potential therapeutic candidates which, if proved to be effective, might represent a breakthrough advancement towards the possibility to control or prevent the disease progression in Alzheimer’s patients.

Also, many efforts are being put at understanding the physiopathology of the disease in its preclinical phase, years before clinical manifestations arise. A better understanding of the pathophysiological cascade occurring in this early stage would help to identify potential intervention targets. Also, besides seeking pharmacological intervention candidates, non-pharmacological interventions are getting growing interest among the research community, with the aim to find preventive strategies that avoid or delay the onset of dementia.

The heterogeneity in terms of pathological mechanisms and trajectories between individuals is a prominent challenge in the field. The development of the disease is influenced by multiple factors such as sex, gender, race, or lifestyle. Therefore, in my opinion, this is a highly relevant topic that should be further addressed, in order to progress towards precision medicine approaches that enable prevention and therapeutic strategies suitable and effective for each particular risk group.

The EPAD Registry was set up as an innovative framework to find participants for the EPAD studies from Parent Cohorts (PCs) across Europe. Making this work in practise has required the creation and optimisation of an array of software tools including the SEEPAD tool for monitoring the EPAD Registry workflows and recruitment (‘Subject Enrolment in EPAD’ or SEEPAD).

The University of Leicester developed this online graphic too, so that EPAD partners could visualise and flexibly explore many aspects of the whole enrolment process from the start of the project to the present time, using semi-real time information derived from the Current Status table. SEEPAD was built progressively from late 2017 onwards, but officially released online to the whole EPAD consortium in May 2018.