About

BRain Imaging, cognition, Dementia and next generation GEnomics: a Transdisciplinary approach to search for risk and protective factors of neurodegenerative disease

Facts and Figures

Acronym: BRIDGET
Start date: May, 2016 
Duration:  66 months
End date:  March 31, 2021
Project coordinator:  Prof. Stephanie Debette, University of Bordeaux
Consortium: 7 partners and 7 external collaborators- major universities and research institutes - from 9 countries
Total funding: € 2 518 874
Australian contribution: € 727 646

Context

With expanding longevity, the number of dementia cases is expected to triple over the next 40 years, resulting in a major burden at the individual and socio-economic level .
Pathological processes leading to Alzheimer disease (AD) begin many years before clinical diagnosis, hence efficient prevention should be initiated very early. This requires identifying individuals in the general population who are at high risk of developing dementia and exploring the molecular pathways underlying the structural brain alterations that precede the occurrence of dementia, an essential step for identifying novel relevant drug targets.
Establishing efficient prevention strategies for dementia and AD is a major health priority for the coming years.

Objectives

Our main objective is to enrich our understanding of the biological mechanisms underlying early structural brain alterations that portend an increased dementia risk, and thus contribute to the discovery of novel therapeutic targets.
More specifically, we aim to:

  • Identify rare (and common) genetic variants associated with structural markers of brain aging in older community persons
  • Explore lifetime determinants of brain aging, with longitudinal profiling of genomic, epigenomic, and environmental markers
  • Assess the impact of genetic determinants for structural brain aging on cognitive performance and dementia and perform extensive functional exploration of these genetic variants

We propose to explore the genetic and epigenetic determinants of quantitative MRI-markers of brain aging that are powerful predictors of dementia/AD risk, and to examine the clinical significance of the markers in a population-based setting.
We aim to translate this findings into the basis for the development of novel preventive strategies for dementia and AD.

Outputs/Deliverables

TF1: Sequencing, joint calling
TF2: Image processing - harmonization
WP1: Rare variants and MRI-markers of brain aging (older cohorts); Common & rare variants and novel MRI-markers; Spatial and temporal mapping
WP2: Association with early structural brain changes in the young; Epigenetic (methylome) associations with structural brain changes; Interaction with vascular comorbidities & psychosocial factors
WP3:Association with cognitive performance / decline & dementia; Functional exploration of susceptibility loci

Data & Power

We will utilize extensive phenotypic and genomic data gathered from the largest European population-based samples with high resolution brain imaging combined with extensive cognitive testing, incident dementia surveillance, and extensive and repeated assessment of clinical comorbidities and socio-economic factors. 
All the cohort-studies comprise about 36.700 participants and cover a broad age range from very young to late-middle-aged to   older   participants.
For extension of our findings we will explore results obtained in the discovery in a large (N~1,000) Japanese genomic study on brain imaging. In addition, a lifetime approach using brain imaging studies in young participants will capture the impact of genetic / epigenetic determinants on early structural brain alterations.

Impact

Enriching our understanding of the biological mechanisms underlying early structural brain alterations that portend an increased dementia risk, we can contribute to the discovery of novel therapeutic targets.
Findings from this project may also:

  • contribute to identifying populations at higher risk of accelerated brain aging, more likely to benefit from early interventions aiming at preventing dementia;
  • help define quantitative intermediate endpoints for future clinical trials;
  • provide useful information on the optimal timing for preventative interventions.

Taken together, this project has an important potential of facilitating the development of novel preventive strategies for dementia and AD.

Updated on 17/11/2022