Submitted Abstract
Curative drugs for dementia and Alzheimer disease (AD) are not yet available, and prevention has been identified as a global priority. Only 10-30% of clinical AD cases have pure AD pathology, and vascular pathology is the most common comorbidity. Thus, targeting a single proteinopathy (e.g. amyloid), will not be sufficient to prevent dementia. Large European pioneer trials showed that improvement of vascular and lifestyle-based risk factors can benefit cognition in older adults, but highlighted also the crucial need for better-defined, stratified, at-risk groups for achieving intervention response. EURO-FINGERS proposes a novel multimodal precision prevention toolbox to address the complex and heterogeneous nature of dementia in AD, based on (i) a successful multimodal lifestyle/vascular prevention model, FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability: so far the only large, longer-term trial to show significant cognitive benefits in at-risk elderly); and (ii) a precision prevention and early detection (PPED) approach adapted from cancer research. Specific aims are: (1) Developing disease models and accurate tools for prediction and stratification based on risk and prevention potential; (2) Real-life testing to assess response to preventive interventions and cost-benefit aspects; (3) Designing the first multimodal prevention trial combining lifestyle intervention with disease-modifying drugs, based on the JPND-funded MIND-AD model; (4) Assessing patient-reported outcomes in the context of early AD detection and precision prevention; and (5) Setting up the EURO-FINGERS online registry (based on models successfully tested by Consortium partners) for developing better-phenotyped cohorts for AD/dementia precision prevention research and streamlining recruitment into clinical trials. The project will align multinational cohorts from observational studies and recent landmark multimodal dementia prevention trials, with new unique long-term within- and post-trial data (up to 7 years). The entire continuum from at-risk and preclinical to prodromal disease stages will be covered, with deep comprehensive clinical, functional and biological assessments. Biomarkers based on e.g. microbiome, metabolomics, GWAS will be tested for the first time in real-life clinical trial data. A novel machine learning method will be used, with transparent visualization of risk signatures and prevention potential. The EURO-FINGERS Toolbox will include the full range of tools needed to start the next generation of AD dementia prevention trials, within the framework of precision medicine. The aim is to deliver targeted and timely interventions to effectively prevent/delay dementia. The Toolbox will also provide a common framework and align main European cohorts in the AD research field, to deliver results easily implementable in Europe. This large-scale multimodal precision prevention approach is completely new in the AD field.