European Prevention of Alzheimer’s Dementia Consortium

The secondary prevention of Alzheimer’s dementia (AD) is achievable if we can identify individuals at risk of disease progression defined by biomarker evidence of AD pathology and no or only minimal clinical symptoms and engage them in a standing adaptive clinical trial, of the highest quality, testing multiple interventions.

To achieve this, EPAD will also provide the analytical infrastructure to make correct observations regarding an intervention’s value as an agent for secondary prevention. All this must exist in the right ethical, legal and social context. It must also be sustainable by being of value to numerous partners and stakeholders in the long term. The EPAD Consortium has been carefully designed to achieve the aim of secondary prevention of Alzheimer’s dementia. Current and recent drug development programmes in AD have been limited through the collection of heterogeneous samples of patients with advanced brain disease and an inability to measure effectively an index of disease course modification. Recruiting participants from clinics and the community for AD prevention trials with limited clinical background is both a risky and cost-inefficient strategy. Creating a disease register of people consented to enter secondary prevention trials delivers a degree of readiness that ensures better knowledge of a participants suitability and a more rapid throughput of screening for the trials.

The EPAD Consortium has the necessary reach and influence from its partners to develop such a ‘readiness’ cohort. By delivering an earlier, risk stratified population with run-in data in the EPAD Cohort across both clinical and biological domains; we can ensure a more homogenous population for study. We can also track changes in disease status as the basis for deciding on an intervention or combination of interventions likelihood of success in larger Phase 3 confirmatory trials. Most of the scientific community still consider Ab dysregulation as central to AD so targeting this pathological process is a rational first step in what will be a standing trial. Other disease processes can be targeted when candidate interventions and intermediate phenotypes to reflect success are available.

EPAD High Level Structure: The IMI-EPAD Consortium will form the third part to a proposed IMI–AD Platform (with IMI-EMIF-AD and IMI-Aetionomy) to produce a globally important superstructure for the secondary prevention of Alzheimer’s dementia. IMI-EPAD brings together all the major cohorts in Europe purposed for the exploration of disease processes and risks for dementia. In drawing from over 40 cohorts with almost 250,000 participants in 11 countries we have the basis for the EPAD Register from which we can draw the EPAD Cohort. Expertise in basic neurodegenerative sciences, epidemiology, statistics and trial design ensures that the standing proof of concept adaptive trial will have the optimal chance of delivering meaningful and definitive answers on an interventions likely success in confirmatory trials. In establishing the International Scientific Synergy Group (ISSG) we have ensured that our work is visible to similar international initiatives and vice versa hence, through pooling know how and sharing data we can collectively overcome this devastating global disease.

EPAD Work Packages and National Leadership:

We have created 8 work packages with 4 of these bound together in the EPAD Delivery Cluster which includes the scientific bedrock (WP1), the statistical engine room (WP2), the aggregation of suitable subjects (WP3) and trial delivery (WP4). These trial delivery activities are supported by project management (WP5), dissemination (WP6), business model and sustainability (WP7) and ethics, legal and social implications (WP8). All WPs are tightly integrated with the EPAD Steering Committee with inter-dependencies tightly managed.

This structure will ensure optimal candidate selection and trial delivery by way of creating