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Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts

Periodic Reporting for period 2 - Lifebrain (Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts)

Reporting period: 2018-07-01 to 2019-12-31

A healthy brain is essential to enjoy a healthy and productive human life. A complex interplay of biological, environmental, social, occupational, and lifestyle factors continuously influence brain health across the lifespan. The Lifebrain project aims at identifying risk and protective factors, and to understand how these influence the brain, cognition and mental health at different stages of life. Such knowledge will greatly improve our ability to prevent mental diseases and neurodegenerative disorders.

Lifebrain integrates data from approximately 5300 European research participants collected in 11 European brain-imaging studies in 7 countries spanning ages 4 - 90. Lifebrain will collect additional cognitive, behavioural and lifestyle data online and biological samples from approximately 4.700 participants.
Lifebrain involves the public to influence the research process by actively engaging patient organizations, policy makers, and clinical and research centres.

The project will provide evidence-based knowledge for prevention and intervention, aiming to improve clinical practice and public policies for brain health.
Lifebrain has made great progress in the first two project periods and delivered on all project milestones.

An extensive system has been developed for the data sharing between the scientific partners. The infrastructure for secure data storage and management has been developed and established on a dedicated Lifebrain project area on the secure services for sensitive data system of UiO.

Data categorization as part of the data harmonization task has been fulfilled for all Lifebrain studies and time points at the 7 data collection sites. Variables of interest have been identified, site-specific codebooks established, guidelines and templates have been designed for establishing data tables shaping the basis for the core Lifebrain database.

To harmonize the analyses of the available Lifebrain brain imaging data , a standardized imaging analysis stream has been developed based on a Brain Imaging Data Structure (BIDS). Partner sites are in the process of transferring imaging data in BIDS format to the central processing site. While awaiting this task to be completed, existing structural imaging measures are used in ongoing Lifebrain specific analyses and studies. Sites have reprocessed and analysed structural magnetic resonance imaging (MRI) images using the same image software versions.

Online data enrichment is in progress in order to maximize data comparability across the Lifebrain sites. The translations of questionnaires, tasks and instructions were finalized at the enrichment sites.

Part of the data enrichment process includes Dried Blood Spots (DBS) home kits. These have been developed by Vitas AS and delivered to the partners to measure specific biomarkers. Approximately 1400 Lifebrain DBS samples have been sent to Vitas for analysis from 4 different centres, and 500 new samples are expected in 2020. For many of the submitted samples, analyses are finalised.

UzL has distributed buccal swabs for self-sampling of cells from the inside of the cheek for genetic analyses. UzL has reached out to all relevant Lifebrain collaborators with respect to the existence, availability and accessibility of Genome-Wide Association Study (GWAS) data. Approximately 5350 samples have been collected for the GWAS analyses in Lifebrain. Of these, approximately 3800 have been subject to DNA methylation profiling for the purpose of Epigenome Wide Association Study (EWAS). Most of the GWAS-relevant data and all of the EWAS-relevant data have been newly generated from Lifebrain funding.

Most of the data collection took place in 2019 and is nearly finished. Ethical clearance is available for all sites regarding the existing data and the data enrichment.

Novel longitudinal statistical tools have been developed to exploit the potential of the large Lifebrain cohorts. Among these, a statistical framework accustomed to estimate reliability and to identify sources of measurement error in order to improve the precision of measurement in future study designs. Two open-access manuscripts describing this framework have been published. One published open-access methods paper concerns reducing the dimensionality of complex data, while accommodating for known structure. A pre-print manuscript on meta-analyses on longitudinal neuroimaging data has been submitted for publication along with an open source statistical tool.

Lifebrain organises stakeholder engagement activities, including workshops, public lectures and conferences. We have also published a qualitative in-depth interview study that collected information on the views and perceptions of healthy adults participating in brain research studies, at 4 sites, on brain health and personalized brain health prevention. Based on the findings of this study we developed an international questionnaire and initiated a global brain health survey. The survey is currently available in 14 languages. More than 12000 respondents have already answered the survey, which will be open until August 2020.

Lifebrain continuously disseminates information about current research results, publications, events and deliverables via the Lifebrain website, Facebook page, Twitter account, as well as a monthly e-newsletter. The two stakeholder workshops in which clinicians, policymakers and patient organisations participated, provided the basis for channeling the upcoming Lifebrain results into clinical practice and health policy. Lifebrain has hosted three public lectures and co-organized one conference. These events attracted the general public, were well attended and disseminated the latest research results in the brain health field. A policy review has been conducted and reported on European policies. The review explores how Lifebrain results could be relevant and may be used to promote personalized health policies.
Integration, harmonization and enrichment of major European neuroimaging studies of age differences and lifespan changes, allow us to establish an unparalleled database of fine-grained measures of brain, cognition and mental health issues of more than 5300 individuals. Elucidating the interrelationships between biological, demographic, behavioural, cognitive, and brain imaging data across the lifespan will enable us to identify key risk and protective factors of brain health, throughout the lifespan. Additional insights will be gained by linking Lifebrain to other databases and biobanks. The novel insights that Lifebrain will provide will strongly contribute to strategies that promote general brain health and prevent brain diseases.

The established data harmonization and data storage and management strategies provide major conceptual, methodological and analytical contributions towards integrating existing study cohorts and their efficient exploitation.
Lifebrain has already produced and validated novel DBS methods for biomarker analyses that can be applied in future academic projects and exploited in several business models. Areas of application include personalized nutrition and medicine.
Lifebrain has successfully contributed to the development of novel longitudinal statistical methods that optimize the exploitation of longitudinal cohorts and multi-site studies.
Lifebrain will influence public health policies for brain health and improve clinical practice through stakeholder engagement activities.