Advancing imaging’s role in understanding Alzheimer’s disease
Not only is Alzheimer’s disease (AD) the most common cause of dementia, it’s also proven to be one of the most difficult to treat. In fact, despite nearly a century of research, all clinical trials of potential therapies have failed. Believing that the key to managing AD is to better understand its cause, research initiatives like the EU and industry-funded AMYPAD project are working to improve our ability to diagnose the disease. “The overarching goal of this project was to evaluate the effectiveness of using amyloid PET imaging to diagnose – and prevent – the development of Alzheimer’s disease,” says Frederik Barkhof, a researcher at the Amsterdam University Medical Centers (UMC) and AMYPAD project coordinator. Positron emission tomography (PET) is a minimally invasive diagnostic imaging procedure used to distinguish normal from diseased tissue in a number of conditions, including some neurological disorders. Amyloid PET imaging uses a class of radiopharmaceuticals that detect levels of amyloid in the human brain.
A large European study
The project was a large European study consisting of two clinical sub-studies: a Diagnostic and Patient Management Study (DPMS) and a Prognostic and Natural History Study (PNHS). The aim of the former was to determine the usefulness and cost-effectiveness of amyloid imaging as a diagnostic marker. The PNHS, on the other hand, investigated the added value of the amyloid PET imaging technique in assessing a patient’s risk of developing cognitive decline due to AD. Both components put a significant amount of effort into optimising the use of amyloid PET in the clinical setting – to much effect. “The DPMS study showed that visual assessment of amyloid PET early in the diagnostic work-up markedly increases diagnostic confidence,” explains Barkhof. Researchers also demonstrated the usefulness of quantification for clinical routine. “The AMYPAD team investigated the robustness of the Centiloid quantification method, its feasibility in detecting early Aβ pathology – one of two hallmark pathologies required for diagnosing AD – and its ability to detect changes over time,” adds Barkhof. This work led to the submission of a Biomarker Qualification Opinion procedure for the Centiloid measure, which is currently being assessed by the European Medicines Agency.
The importance of collaboration
The AMYPAD project was a joint collaboration between a number of academic centres and headed by the Amsterdam Medical Center and European Federation of Pharmaceutical Industries and Associations (EFPIA) partners GE Healthcare and Life Molecular Imaging. “We have had a very fruitful partnership between the industry and academic partners and we are very proud that both of these large clinical studies were completed within the project timeframe and are now yielding results that could directly impact patients in the clinic,” says Gill Farrar, EFPIA lead for the project. While the project may be finished, the consortium’s work continues. For example, together with the Alzheimer’s Disease Data Initiative, AMYPAD’s data set of over 3 500 amyloid PET scans covering the entire AD continuum will become available to the global research community. “We are finalising procedures to further unlock the wealth of the data we generated,” concludes Barkhof. “We hope that the AMYPAD data will be a significant asset to worldwide research in the dementia field.” The project is also joining forces with other European cohorts to better integrate all available data – a process that Barkhof says will further our understanding of AD and lay the groundwork for developing an effective approach to treating the disease.
Keywords
AMYPAD, dementia, imaging, Alzheimer’s disease, diagnostic imaging, amyloid PET imaging, European Medicines Agency