With multiple clinical trials in dementia failing over the past years, attention has recently shifted to subjects with Alzheimer’s disease (AD) who have not reached the stage of dementia yet (i.e., ‘pre-dementia’). Since these subjects have limited brain damage and are suggested to be more likely responsive to treatment than subjects with full-blown dementia, they are an important target group for future treatment studies.
Trial design in pre-dementia AD, however, is challenging because subjects with pre-dementia AD are difficult to identify and limited information is available on their outcome. The lack of reliable diagnostic and prognostic markers for pre-dementia AD can be explained by the availability of only small-scale ongoing biomarker studies and longitudinal cohorts including these subjects. EMIF has linked this information and unlocked the true potential of these studies.
By connecting relevant cohort studies across Europe, EMIF-AD has set up a pan-European platform for large-scale research on biomarkers and risk factors for neurodegenerative disorders. The biomarker discovery activities in EMIF-AD were driven by an extreme phenotype approach, in which decline or biomarker status was used as the end point for biomarker discovery, rather than a clinical diagnosis. Doing so, EMIF-AD has developed new treatment targets, multimodality/omics diagnostic tools and qualification level biomarker datasets suitable for presentation to regulatory authorities prior to approval for use in clinical trials and practice.
Finally, prediction rules for cognitive decline in presymptomatic and prodromal AD were developed which will not only improve clinical diagnosis and prognosis, but equally support subject selection and stratification in future clinical trials. These achievements have been possible because EMIF-AD combined both large-scale patient cohorts, linkage with EHR data, and cutting edge biomarker discovery expertise.