Lifebrain aims to establish a solid foundation of knowledge for understanding how brain health and cognitive function can be optimized in response to the enormous societal challenges with the ageing of the European population. Our main objective is to ide ntify and validate trends and determinants of cognitive decline by creating a large database of detailed information about health, cognitive function, genetics and brain imaging. This is central to understanding health, ageing and disease, as called for i n Horizon 2020 and PHC1-2014. We will achieve our objective by integration and standardization of four major longitudinal European studies ? Betula (Sweden), Whitehall II (UK), the Berlin Aging Study (Germany) and Cognition and plasticity through the life span (Norway) ? yielding a total number of participants approaching 10.000. By linking this information to additional national databases and biobanks, including birth registries, national and city archives and conscription data, we will be able to address life-long risk and protective factors, mediators and moderators, of brain health and cognitive ageing throughout the life span. Brain imaging measures are central to all studies. We will study both cross-sectional differences and longitudinal changes, to identify and validate pathways through which these risk and protective factors work in affecting cognitive function. The final part of the study will be to test pathways and mechanisms for brain health and cognitive changes experimentally in specific sub -samples. This approach of pooling large and unique datasets from different countries will increase the validity and generalizability of the findings, and lay a foundation for earlier diagnosis of brain disorders and cognitive decline, as well as future p reventive and therapeutic strategies. This project cannot be realized without close collaborations involving both small and medium-sized enterprise (SME) and several of Europe?s major brain research centres.