EMIF

EMIF’s datasets helped researchers identify plasma proteins that changed in the presence of traditional Alzheimer’s markers, opening new avenues of research.###

A major output of EMIF is the Multimodal Biomarker Discovery (MBD) study, which brought together hundreds of samples from three groups of people: cognitively normal controls, those with mild cognitive impairment and those with confirmed Alzheimer’s disease. That study, which concluded that the presence of amyloid and APOE ε4 status play central roles in the disease, was intended to help other researchers in the hunt for diagnostic and prognostic biomarkers by allowing any researcher to access them via the EMIF-AD Catalogue.

Now, a team led by the University of Oxford has analysed the samples and data from the EMIF-AD MBD cohort and found that certain blood proteins can predict the presence of Alzheimer’s pathology without the need for invasive lumbar punctures, accurately discriminating between people with mild cognitive impairment and people with Alzheimer's disease.

The study, published in the journal Alzheimer's and Dementia, compared the blood plasma of 600 people with mild cognitive impairment or Alzheimer’s with over 370 of their unaffected peers. Using a technology called SOMAscan, which can measure over 4 000 different blood proteins in a single plasma sample, the researchers identified groups of proteins that changed in correlation with traditional markers of amyloid plaque, tau tangles and neurodegeneration. These proteins point to potential targets for further studies on the molecular basis of Alzheimer’s.

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Europe’s vast collection of electronic patient health records and medical research data holds important clues for battling major illnesses affecting millions. But this important resource is scattered and difficult to search, hampering efforts to make the most of it. IMI’s EMIF project addresses this problem by creating a secure online platform that consolidates metadata from a wide variety of sources, creating a one-stop shop – or ‘catalogue’ – to browse and compare what is available. ###The effort has already led to promising findings linked to Alzheimer's and obesity. For example, EMIF researchers have used the platform to probe whether drugs prescribed for certain conditions also lower a patient’s risk of developing dementia, the aim being to potentially repurpose – or reuse – such medications. Project coordinator, Simon Lovestone of the University of Oxford, noted that a “promising” initial analysis shows that some drugs do seem to do just that, adding to similar evidence from other studies. EMIF also enabled Lovestone and his team to rapidly locate 1 200 blood samples for research into developing a blood test to determine whether someone has Alzheimer’s before they develop symptoms so as to make clinical trials of anti-dementia drugs more effective by involving such individuals. Lovestone says EMIF saved about a decade of work. ‘Now we may or may not have a blood test at the end of it, but we will have done this super quickly and super cheaply compared to the alternative,’ he adds. ‘And if it turns out we do have a blood test that could help, then it could save huge amounts of money in clinical trials. And if those clinical trials lead to a new drug – well, that’s what we’re all working towards.’

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According to the ‘obesity paradox’, it is possible to be overweight or even obese yet not have an increased risk of heart disease. Now, a study in the European Heart Journal shows that in fact the risk of heart and blood vessel problems such as heart attacks, strokes, and high blood pressure, rises as body mass index (BMI) increases beyond 22-23 kg/m². The research was funded in part by IMI through the EMIF project. ###The team followed 300 000 people in the UK over a number of years; all were healthy when they joined the study. Analyses of the data revealed that people with a BMI of 22-23 kg/m² had the lowest risk of heart disease. The risk rises by 13% for every 5.2 kg/m² increase in BMI in women and 4.3 kg/m² in men. The risk also rises with an increase in waist circumference. While some studies have suggested that the obesity paradox is true, the researchers say this could be due to factors such as smoking (which suppresses appetites) and undiagnosed diseases (which could cause weight loss). ‘This is the largest study that provides evidence against the obesity paradox in healthy people,’ said first author Stamatina Iliodromiti of the University of Glasgow in the UK. ‘By maintaining a healthy BMI of around 22-23 kg/m², healthy people can minimise their risk of developing or dying from heart disease.’ Acknowledging that this target may be difficult for some people to achieve and maintain, co-author Naveed Sattar added: ‘We know many cannot get to such low BMIs so the message is, whatever your BMI, especially when in the overweight or obese range, losing a few kilograms or more if possible, will only improve your health. There are no downsides to losing weight intentionally and the health professions need to get better at helping people lose weight.’

Read the University of Glasgow’s press release

IMI’s EMIF project will hold a public symposium entitled ‘Liberating evidence from European health data – the achievements and challenges of a five year IMI project: EMIF’ on 18 April in Brussels, Belgium. ###The meeting will bring together a large variety of stakeholders to discuss issues such as the value of re-using healthcare data, how the new General Data Protection Regulation (GDPR) will affect the re-use of healthcare data, how to better involve patients, and how the healthcare data ecosystem will evolve. The day will also feature ample opportunities for networking.

Registration is free but obligatory – to sign up, fill in this form by 1 April.

More information can be found on the EMIF homepage and in this document.

The European Institute for Innovation through Health Data (i~HD) and IMI’s EMIF project will hold a joint conference on ‘Realising the Value from Health Data - Improving Care and Research’ in Madrid, Spain, on 21-22 September 2017. There will be a strong focus on progressing towards value based healthcare, comparing health ministry, health insurer, policy experts, pharmaceutical industry, and health technology assessment (HTA) perspectives. ### Through presentations and panel discussions, participants will find out how hospitals are successfully reusing patient data as learning health systems, and improving their data quality. The conference will also showcase the state of the art in clinical research using big data, presenting research findings that could only have been discovered using large scale data, showcasing the latest in analysing high dimensional data. A major part of the conference will be dedicated to patients’ perspectives on reusing their health data for research. Speakers come from the Spanish Ministry, European Commission, patient associations, health insurers, policymakers, clinical research and the pharmaceutical industry. i~HD is a not-for-profit European institute, with a mission to guide and catalyse the quality, interoperability and trustworthy uses of health data, for optimising health and knowledge discovery. It was born out of the IMI project EHR4CR. IMI’s EMIF project is developing a technology and governance framework for the identification, assessment and (re)use of data for health research, and it will showcase progress in its final year at the event.

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.'

Omega-3 and omega-6 unsaturated fatty acids play a role in the progression of Alzheimer’s disease, according to research published in the journal PLOS Medicine and supported in part by IMI’s EMIF project. Currently it is thought that the main reason for developing memory problems in dementia is the presence of two big molecules in the brain called tau and amyloid proteins.### These proteins have been extensively studied and have been shown to start accumulating in the brain up to 20 years before the disease onset. In the new study, researchers from King’s College London and the National Institute on Aging in the USA, looked at concentrations of thousands of metabolites in brain tissue samples of 43 people: 14 people with healthy brains, 15 that had high levels of tau and amyloid but didn’t show memory problems, and 14 clinically diagnosed Alzheimer’s patients. They found that six unsaturated fatty acids, including omegas, were significantly different in Alzheimer’s brains when compared to brains from healthy patients. Overall, their levels were lower than in the healthy patients and one omega, DHA, was increased. As this study was observational, it is not clear whether decreased levels of unsaturated fatty acids drive the progression of Alzheimer’s or they are a result of the disease. As one of the co-leaders of the study, Cristina Legido Quigley of King’s College London said: ‘While this was a small study, our results show a potentially crucial and unexpected role for fats in the onset of dementia. It is now important for us to build on and replicate these findings in a larger study and see whether it corroborates our findings’.

The EMIF project has announced that it is extending access to the EMIF Data Catalogue to the wider research community. The online catalogue currently includes 14 population-based data sources (e.g. electronic health records, regional databases) and 46 cohorts (mainly in the Alzheimer’s field) where the project partners have consented to providing information to bona fide researchers who want to explore potential data partners for their own work.### At the moment, the catalogue provides basic information to help users investigate the data sources, but further developments are planned. ‘This is the first tool of the EMIF platform to have wider access, and in the coming final year we plan to have deployed platforms for researchers to be able to go beyond the Catalogue phase right through suitability evaluation and ultimately conducting studies with data source collaborators,’ the project leaders write. ‘On behalf of EMIF we hope that this wider access to the first tool of the EMIF platform will be a significant asset to the EU research community, and very much look forward to its continued development and use, eventually within a broader research platform and communities.’

• Find out how to access the catalogue

The inaugural conference of the European Institute for Innovation through Health Data (i~HD) will be held in Paris, France on 10 March 2016. i~HD is a non-profit institute that was born out of the IMI electronic health records project EHR4CR and other related projects. Its mission is to guide and catalyse the quality, interoperability and trustworthy uses of health data, for optimising health and knowledge discovery.###

This inaugural conference will mark the launch of a novel European platform to support multi-centre clinical research. This operational platform, the result of EHR4CR, can connect securely to the data within multiple hospital electronic health record (HER) systems and clinical data warehouses across Europe, to enable a trial sponsor to predict the number of eligible patients for a candidate clinical trial protocol, to assess its feasibility and to locate the most relevant hospital sites. Also on the agenda is IMI’s EMIF, Europe’s largest ‘big data’ project in health. The conference will also spotlight the challenges and state-of-the-art approaches to improving the quality and interoperability of clinical data. i~HD will play an important future role in the development and quality labelling of interoperability standards, bringing together clinical and research domain experts, with patients, to help ensure that future standards support patient care, learning health systems and clinical research.

The event is invitation only; those who wish to attend should express their interest via this form.

Scientists from IMI’s EMIF project were part of a major study that paves the way for a simple test of how well a person is ageing. The findings, published in Genome Biology, could help to identify people at greatest risk of diseases associated with ageing, such as Alzheimer’s disease.### The scientists studied the extent to which various genes were activated in thousands of human tissue samples. They found that the activation of some 150 genes in the blood, brain and muscle tissue represented a good marker of health in people who were 65 years old. The scientists were then able to turn this information into a simple formula to assess how well someone is ageing compared to other people of the same age. People with a poor score showed signs of cognitive impairment, suggesting that the research could be turned into a simple blood test to identify people who could be at risk of Alzheimer’s disease or other dementias. This is a major goal of the EMIF project.

• Read a press release on the research from the Medical Research Council.

Two new papers in the Journal of the American Medical Association add to our understanding of the factors that increase people’s risk of developing Alzheimer’s disease. The research was supported in part by IMI’s EMIF project. The first study assessed the prevalence of amyloid plaques (clumps of protein commonly associated with Alzheimer’s disease) in both healthy people and people with varying levels of cognitive impairment.### The second study reviewed the prevalence of amyloid plaques on positron emission tomography (PET) imaging scans of people with difference kinds of dementia. The findings highlight the impact of the APOE gene on the formation of amyloid plaques and on the risk of developing Alzheimer’s disease. They also underline the fact that amyloid plaques may start appearing 20-30 years before the onset of dementia symptoms (although not everyone with amyloid plaques will develop dementia, and not everyone with dementia has amyloid plaques). An accompanying editorial explains the importance of the new research. ‘These reports are the largest and most detailed to date and are critical assessments that help define the role of amyloid in the causation of cognitive impairment and dementia.’ Looking to the future, questions raised by the research include the role of other genetic factors (besides APOE) in amyloid formation, and the links between genetic risks and lifestyle factors such as smoking and high blood pressure.