Category: News

• The AMYPAD consortium, in its partnership with Aridhia and AD Data Initiative, is delighted to announce the external release of its PNHS dataset.
• The integrated dataset represents the largest European PET dataset phenotyping longitudinally individuals at risk of AD-related progression.
• The public dataset has been incorporated into the AD Workbench to provide even greater value to the global neuroscience research community.

Supported by the Innovative Medicines Initiative (IMI) through the Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) project, the Prognostic and Natural History Study (PNHS) was an open-label, prospective, multicentre, cohort study aiming to understand the role of amyloid positron emission tomography (PET) imaging in the earliest stages of Alzheimer’s disease (AD). The study was established to collect amyloid PET scans in a large-scale population and included participants from 11 European parent cohorts of similar characteristics in a predementia phase. The first external data-release of the AMYPAD PNHS study has been made in June 2023. Data from the multiple data sources have been integrated using the Aridhia Workspaces infrastructure and are now available to the research community through the AD Workbench of the Alzheimer’s Disease Data Initiative (AD Data Initiative), which is an open, global and free cloud-based platform for scientists to accelerate discoveries and innovations for AD and related dementias. To access the data, you will need to make an online request via the AD Workbench.

“We are proud to partner with the AD Data Initiative to help further our understanding of the early stages of AD to accelerate scientific progress. This partnership powers global open access to project’s data. The PNHS dataset will be maintained and improved over the next years thanks to the close collaboration with the AD Data Initiative.”, said Frederik Barkhof (Amsterdam UMC) and Gill Farrar (GE HealthCare), AMYPAD Project Coordinators.

For more information about the AMYPAD PNHS, you can download the study design paper published in the journal Alzheimer’s & Dementia here.

For more information about AMYPAD, please visit: https://amypad.eu/

For more information about the AD Data Initiative, please visit: https://www.alzheimersdata.org/

For more information about Aridhia, please visit: https://www.aridhia.com/

About the AMYPAD PNHS Data

The AMYPAD PNHS data collection is a combination of prospective and historical data from multiple European sites in Belgium, France, Germany, Spain, Sweden, Switzerland, The Netherlands and The United Kingdom. These sites have provided information through 11 parent cohorts, including EPAD LCS, EMIF-AD (60++ and 90+), ALFA+, FACEHBI, FPACK, UCL-2010-412, Microbiota, DELCODE, H70 and AMYPAD Diagnostic and Patient Management Study (DPMS).

The current dataset includes a total of 3,368 participants. Of them, 1,620 underwent a baseline amyloid PET that includes the visual read and the Centiloid quantification (1,476 subjects), among other metrics. Moreover, 888 participants have (at least) one follow-up PET scan, 763 of them with Centiloid quantification. The participant’s clinical outcomes (e.g., cognition), disease (imaging) biomarkers, risk factors (e.g., genetics and environmental), and other relevant variables are included in the dataset. The dataset is planned to be further expanded, both in terms of parent cohorts and in available data (e.g. quantification of advanced MRI sequences, genetics, blood biomarkers, etc.).

How to access the AMYPAD PNHS data?

AMYPAD offers a way of accessing the data to academic researchers, institutions and companies from all over the world. This is shared through secure online Workspaces and you will need to make a formal request to access the imaging, clinical, and biomarker data for scientific research investigation and/or educational activities. The application can be performed via the FAIR Data Service of the AD Data Initiative.

You can find the data access request procedure for the AMYPAD PNHS here.

If you are requesting access to the AMYPAD PNHS, you should accept the responsible use of the data under the terms described here.

Requirements for publishing results

AMYPAD encourage the publication of any research arising from the AMYPAD PNHS. If results are published that were generated using the AMYPAD PNHS data, it is mandatory to acknowledge the AMYPAD Consortium and the grants that supported this IMI project. More details are provided in the document here, which outlines the policies for publication and the publication credits for those who use the AMYPAD PNHS data.

Acknowledgements and disclaimer

The AMYPAD project received funding from the Innovative Medicines Initiative 2 Joint undertaking under grant agreement No 115952. This Joint Undertaking received support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This communication reflects the views of the consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.

A new article entitled “Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort” has recently been published in the journal Alzheimer’s Research and Therapy.

The published study showed that Hormone Replacement Therapy (HRT) use is associated with better memory, cognition and larger brain volumes in later life among women carrying the APOE4 gene – the strongest risk factor gene for Alzheimer’s disease. The research team found that HRT was most effective when introduced early in the menopause journey during perimenopause.

Prof Anne-Marie Minihane, from UEA’s Norwich Medical School and director of the Norwich Institute for Healthy Aging at the University of East Anglia (UEA), led the study in collaboration with Prof Craig Ritchie at the University of Edinburgh.

The research team studied data from 1,178 women participating in the European Prevention of Alzheimer’s Dementia (EPAD) initiative to analyse the impact of HRT on women carrying the APOE4 genotype.

Prof Minihane said: “We know that 25 per cent of women in the UK are carriers of the APOE4 gene and that almost two thirds of Alzheimer’s patients are women. In addition to living longer, the reason behind the higher female prevalence is thought to be related to the effects of menopause and the impact of the APOE4 genetic risk factor being greater in women.We wanted to find out whether HRT could prevent cognitive decline in at-risk APOE4 carriers.”

Prof Craig Ritchie, said: “This important finding from the EPAD Cohort highlights the need to challenge many assumptions about early Alzheimer’s disease and its treatment, especially when considering women’s brain health. An effect on both cognition and brain changes on MRI supports the notion that HRT has tangible benefit. These initial findings need replication however in other populations.”

Congratulations to all authors: Rasha N. M. Saleh, Michael Hornberger, Craig W. Ritchie and Anne Marie Minihane.

You can read the press release from the University of East Anglia here: https://www.uea.ac.uk/news/-/article/HRT-could-ward-off-Alzheimers-among-at-risk-women

You can read the published paper here: https://doi.org/10.1186/s13195-022-01121-5

To access the EPAD data, you will need to make an online request via the Alzheimer’s Disease Workbench of the Alzheimer’s Disease Data Initiative.

For more information or to request an interview, please contact the UEA communications office on +44 (0)1603 593496 or email communications@uea.ac.uk.

The EPAD BioRepository team successfully sent 3,000 samples for RNA analyses in Germany. These samples were collected annually from research participants throughout their participation in the EPAD Longitudinal Cohort Study.

The samples have been sent to Hummingbird Diagnostics, a German Biotech. We caught up with Dr. Bruno Steinkraus, Chief Scientific Officer (CSO) at Hummingbird Diagnostics, and asked him a few questions about his work and our collaboration.

Could you tell us a bit about you and the company you work for?

My name is Bruno Steinkraus and my background is in RNA biochemistry. I currently serve as CSO of Hummingbird Diagnostics, a clinical stage liquid biopsy company located in Heidelberg, Germany. Hummingbird detects small RNA signatures in blood for early disease detection and personalised clinical decisions. Small RNAs – ~20-30 nucleotide short ‘snips’ of RNA – can be thought of as molecular rheostats of virtually all developmental, physiological and pathological processes. We have used lung cancer as a pathfinder indication for our technology but more recently became interested in expanding our approach to address the pressing needs in Alzheimer’s disease. We are currently developing an ADDF-funded Diagnostics Accelerator program to evaluate the use of small RNAs to augment and complement the AT(N) framework currently employed in the diagnosis and management of Alzheimer’s patients.

Could you please tell us more about your work and the research done using the EPAD samples?

We are delighted to have been introduced to the EPAD consortium. As part of their extensive biological material collection, EPAD has included stabilised whole blood. Hummingbird has built a robust small RNA biomarker engine that uses whole blood as input. This perhaps slightly unconventional approach differs from the typically used cell-free plasma or serum analyses and offers two components:
1. Since whole blood includes plasma we do capture cell-free small RNAs that are released from the diseased organ of interest (classical “liquid biopsy”). However,
2. whole blood also includes the small RNA profiles of cells of the peripheral immune system. We believe that the relative constellation of the peripheral immune system and its intracellular small RNA expression levels can be surrogate markers of (neuro)inflammation as well as vascular involvement and thus complement the liquid biopsy component of a blood test. Because small RNAs can capture all of these components we believe they are well suited as biomarkers for Alzheimer’s disease.

What value to you see with this collaboration? Can you share some of the insights that may have emerged?

EPAD provides a one-of-its-kind resource of the earliest stages of disease while offering deep neurochemical and neuropsychological characterisation of each individual participant. A solid reference such as EPAD is extremely important when developing and establishing novel markers as one otherwise might have two moving targets. We have only just begun to analyse the EPAD data and are exploring small RNAs for different use cases, for example i) amyloid detection, ii) cognitive impairment detection (by biomarkers) as well as iii) the detection of different cognitive levels within patients with similar amyloid burden. The latter might have consequences for patient stratification in clinical trials. We will share a first glimpse of these interesting results at the CTAD conference in November 2022 (Poster LP48: “Early Detection of Alzheimer’s Disease using microRNAs”).

How do you think the EPAD samples can contribute to the future of Alzheimer’s disease research?

As noted above, the EPAD samples are a remarkable collection offering insight into the earliest stages of disease with deep interdisciplinary phenotyping, including biomarkers, imaging and neuropsychology. It is expected that any strategy stopping or preventing Alzheimer’s has to rely on multipronged approaches and engage the disease as early as possible. EPAD is a vantage point offering these fascinating perspectives.

“The EPAD samples are a remarkable collection offering insight into the earliest stages of disease with deep interdisciplinary phenotyping, including biomarkers, imaging and neuropsychology.”, said Dr. Bruno Steinkraus, Chief Scientific Officer (CSO) at Hummingbird Diagnostics.

The Alzheimer’s Association International Conference is the largest and most influential international meeting dedicated to advancing dementia science. Each year, AAIC convenes the world’s leading basic science and clinical researchers, next-generation investigators, clinicians and the care research community to share research discoveries that’ll lead to methods of prevention and treatment and improvements in the diagnosis of Alzheimer’s disease. This year, the conference took place from 31st July to 4th August as a hybrid event (online and in San Diego, US) and attracted over 10,000 attendees.

We were pleased that several EPAD researchers presented their respective work at the Alzheimer’s Association International Conference:
– Sarah Gregory (UEDIN): “Does adherence to the Mediterranean diet have differential effects on brain health for those living within and outside of the Mediterranean region?” ORAL
– Luigi Lorenzini (VUmc): “Concerted alterations of functional connectivity and WM integrity in relationship to early amyloid deposition” POSTER
– Luigi Lorenzini (VUmc): “Functional eigenvector centrality dynamics are related to amyloid deposition in preclinical Alzheimer’s Disease.” POSTER
– Gonzalo Sánchez-Benavides (BBRC) “Re-examining the impact of adjusting for education and sex the RBANS delayed memory score: Implications on the cut-offs used to detect cognitive impairment in prodromal Alzheimer’s disease. Data from the EPAD-LCS study.” POSTER
– Irene Cumplido-Mayora (BBRC) “Biological Brain Age Prediction Using Machine Learning on Structural Neuroimaging Data: Multi-Cohort Validation Against Biomarkers of Alzheimer’s Disease and Neurodegeneration. POSTER

If you are interested to learn more about our dataset and samples, you can download the EPAD flyers that we distributed at the AD Data Initiative booth here.

In addition, winners of the AD Data Initiative NeuroToolKit (NTK) Data Hackathon have been anncounced live at the AD Data Initiative’s symposium during the conference. The AD Data Initiative NTK Hackathon was a virtual event, bringing together researchers, biostatisticians, data scientists, and clinicians to investigate the potential clinical utility of different biomarkers in Alzheimer’s disease. Self-selected teams used a beta version of the NTKApp, EPAD datasets, and statistical analysis tools available on the AD Workbench.

Save the date for the next Alzheimer’s Association International Conference to be held on 16-23 July 2023 in Amsterdam (Netherlands).

Edinburgh Dementia Prevention are hosting a brain health summer school on Monday 26 September – Thursday 29 September 2022, at St Leonard’s Hall, Edinburgh. It is is a 4-day interactive course designed principally for trainee and qualified clinicians, nurses and allied health professionals working in (or with an aim to work in) brain health and Alzheimer’s disease services. Post-graduate students with an interest in pursuing research in brain health and Alzheimer’s disease will also be welcome, as are those interested in increasing their general knowledge of research in this area (for example public health workers).

An important aim of the course is to introduce students to approaches outside their current discipline with a view to developing multi-disciplinary practice and research. The course will provide an overview of brain health clinical services and an exploration of the evidence base underpinning these. There will be a blend of lectures and interactive activities throughout the summer school to enhance learning.

The cost of the event is £275 (plus £25 for dinner – optional).

Admission will be limited to 30 participants to maximise learning and networking opportunities.

For more information, visit https://www.sdrc.scot/summer-school or contact Sarah Gregory Sarah.Gregory@ed.ac.uk

The Alzheimer’s Association International Conference is the largest and most influential international meeting dedicated to advancing dementia science. Each year, AAIC convenes the world’s leading basic science and clinical researchers, next-generation investigators, clinicians and the care research community to share research discoveries that’ll lead to methods of prevention and treatment and improvements in the diagnosis of Alzheimer’s disease. This year, the conference will be held in San Diego (US) and online from 31st July to 4th August 2022.

Several EPAD researchers will be presenting their respective work at the upcoming Alzheimer’s Association International Conference. We are very much looking forward to the conference and discussing our work!

ORAL
– Tuesday, August 2nd (Ballroom 20BC, 9:25am Pacific / 6:25pm CET) Sarah Gregory (UEDIN)
“Does adherence to the Mediterranean diet have differential effects on brain health for those living within and outside of the Mediterranean region?”

POSTERS
– Monday, August 1st (P2-09) Gonzalo Sánchez-Benavides (BBRC)
“Re-examining the impact of adjusting for education and sex the RBANS delayed memory score: Implications on the cut-offs used to detect cognitive impairment in prodromal Alzheimer’s disease. Data from the EPAD-LCS study.”

– Tuesday, August 2nd (P3-07) Luigi Lorenzini (VUmc)
“Concerted alterations of functional connectivity and WM integrity in relationship to early amyloid deposition”.

– Wednesday, August 3rd (P4-07)
Luigi Lorenzini (VUmc) “Functional eigenvector centrality dynamics are related to amyloid deposition in preclinical Alzheimer’s Disease.”

Irene Cumplido-Mayora (BBRC) “Biological Brain Age Prediction Using Machine Learning on Structural Neuroimaging Data: Multi-Cohort Validation Against Biomarkers of Alzheimer’s Disease and Neurodegeneration.”

The Alzheimer’s Disease Data Initiative (AD Data Initiative) is calling on experts from around the world to join them in a two-week virtual Data Hackathon. In self-selected teams of two to four people, participants will be investigating the potential of different biomarkers in Alzheimer’s disease.

Teams will be using the new NeuroToolKit (NTK) app, developed by Roche in partnership with leading academic collaborators, and work with datasets from the EPAD project by utilizing the AD Data Initiative resources. Participants will also be able to collaborate with other participants in the new AD Data Initiative online community.

Specifically, teams will:
– Perform exploratory data analysis
– Execute standardized descriptive analysis
– Conduct standardized hypothesis-related analysis
– Create their own standardized analysis
– Share and validate the customization analysis in different datasets.

Interested in participating? Space is limited and registration will close on June 24, 2022 (or when spaces are full).

For more information, visit the website.

On 9 May, the members of the Neuronet (Efficiently Networking European Neurodegeneration Research) programme were pleased to announce the launch of an updated version of their Decision Tool to support engagement with Regulatory and Health Technology Assessment (HTA) bodies. The Decision Tool now provides a clickable overview of the processes and procedures for HTA and regulatory interactions at different stages of the development pipeline. This will help ensure that the outputs being developed by projects are relevant for regulatory and HTA settings, where applicable.

Neuronet is a Coordination and Support Action aiming to support and better integrate projects of the Innovative Medicines Initiative’s (IMI) neurodegeneration (ND) research portfolio including the EPAD project. One of Neuronet’s workstreams aims to develop tools and services to support IMI ND projects in areas where unmet needs have been identified, which include the need for further support for interactions with HTA and regulatory agencies.

Representatives of the Neuronet project partner, NICE (UK National Institute for Health and Care Excellence) have performed a general update of the Decision Tool that went live on 9 May. This involved updating the signposting information and text to include any changes to organisations and processes and providing case studies from projects within the Neuronet portfolio that have been through HTA or regulatory processes and procedures. Additional signposting information on relevant agencies, organisations, tools and projects was also incorporated.

The Decision Tool can be accessed through the Neuronet Knowledge Base, here: https://kb.imi-neuronet.org/

“The timing of engagement with regulators and which procedures to follow are important considerations to maximize the value of feedback received for research strategies. Neuronet’s interactive tool can help in making such fit-for-purpose decisions”, Dr Lennert Steukers, Neuronet Project Leader and Associate Director, Clinical Scientist, Janssen Pharmaceutica NV, a member of the Neuronet Project.

Acknowledgement

The Neuronet project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821513. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Parkinson’s UK.

Disclaimer

This communication reflects the views of the Neuronet Consortium and neither IMI nor the European Union and EFPIA or any Associated Partners are liable for any use that may be made of the information contained herein.

Contact info@imi-neuronet.org for further information.

We are delighted to announce that the first study participant for the EPAD Scotland study was seen today at the University of Edinburgh in the UK. The EPAD Scotland study is the first follow-on study to the large pan-European EPAD Longitudinal Cohort Study (LCS) which finished study visits in 2020.

The European Prevention of Alzheimer’s Dementia (EPAD) LCS was a pan-European study with an aim to identify the very earliest signs of Alzheimer’s disease years before any clinical symptoms manifest. As part of the EPAD LCS, over 2,000 participants were screened and a wide range of cognitive, clinical, neuroimaging and biomarker data collected.

Since the end of the overall Innovative Medicine’s Initiative funding of EPAD LCS, there are follow-on studies to the EPAD LCS being set up locally within each host country in order to continue collecting longitudinal data on early risk factor for dementia. EPAD LCS continues to be one of the largest cohorts of participants in the pre-dementia stages and will be further enhanced with local follow-on studies inviting the same participants back to continue building up longitudinal data over many years. The EPAD Scotland study is the first national initiative to have started study recruitment.

The primary investigator for the EPAD Scotland study is Prof Craig Ritchie and the study is funded by the Alzheimer’s Disease Discovery Fund.

The European Prevention of Alzheimer’s Dementia (EPAD) consortium, in their partnership with Aridhia and Alzheimer’s Disease Data Initiative (AD Data Initiative), are delighted to announce that the EPAD genomic data has been incorporated into the Alzheimer’s Disease (AD) Workbench to provide even greater value to the global neuroscience research community.

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. EPAD has made this database open access and publicly available to the research community through the AD Workbench, which is an open, global and free cloud-based platform for scientists to accelerate discoveries and innovations for AD and related dementias.

This incredibly rich data source has now been enriched with the EPAD genomic data. It is an important step in continuing to share the EPAD LCS data in the long-term and ensuring that this valuable resource is used by the research community to generate as much knowledge as possible.

“At the heart of the EPAD Programme was an explicit commitment, responsibility and obligation to ensure that the time and effort of research participants and researchers yielded the highest quality outputs of knowledge. The global visibility and ease of access and research which the AD Data Initiative provides helps us to achieve our objective. This most recent release with genomic data from the EPAD LCS will provide new knowledge to the global research community and marks another major milestone for EPAD. We expect that in the months ahead, new data being collected from further research/analysis of EPAD samples and other programmes run within the Edinburgh Dementia Prevention will utilise the AD workbench making AD data findable, accessible, interoperable and reusable (according to the FAIR principles)”, said Craig Ritchie, Project Coordinator of the EPAD project.

About the EPAD LCS data
The final EPAD dataset (V.IMI) went into open access to all researchers from over the world in November 2020. This contains the final longitudinal data from over 2,000 participants of the EPAD LCS. Screening for the first participant in the LCS occurred in May 2016 and finished in early 2020. A total of 2,096 participants were screened. From these 2,096 participants, EPAD followed up with 1,225 after one year, 421 after two years and 121 after three years.

How to access the EPAD data and samples?
EPAD offers a way of accessing the data, samples and image data collected during the EPAD Longitudinal Cohort Study to academic researchers, institutions and companies from all over the world. This is shared through secure online Workspaces and you will need to make an online request via the Alzheimer’s Disease Workbench. For more information, click here.