Brain disorders are among the leading causes of reduced quality of life, both in Norway and globally. Several studies have shown a link between metabolic dysfunction, when the body’s metabolism does not work as it should, in midlife, and cognitive decline in later life.
“Both observational and genetic studies consistently connect midlife metabolic dysfunction to later-life cognitive decline,” says Professor Ole A. Andreassen at the Centre for Precision Psychiatry (SPP) at UiO and Oslo University Hospital (OUS).
“Yet we still know too little about the molecular mechanisms underlying this relationship. That makes it much harder to develop effective preventive strategies.”
Understanding these mechanisms is exactly what Andreassen and his colleagues at SPP now aim to do. They have received NOK 22 million from the Novo Nordisk Foundation for the project “MetaBrain: metabolic dysfunction underlying abnormal brain ageing – a Nordic health data AI collaboration”.
“We are deeply grateful to the Novo Nordisk Foundation for this support. This funding gives us a unique opportunity to uncover the molecular connections between midlife metabolic health and later brain ageing,” Andreassen says.
Our health in midlife shapes brain ageing
The MetaBrain project investigates how imbalances in metabolism between the ages of 40 and 60 may cause the brain to age faster and increase the risk of dementia later in life.
They will specifically look at how the body produces, uses, transports, and stores fats (lipid metabolism), how blood sugar is regulated (glucose homeostasis), how well the cells’ energy production works (mitochondrial function), and how chronic, low-grade inflammation in the body drives accelerated brain ageing and increases the risk of cognitive decline and dementia.
“By identifying the mechanisms that truly contribute to disease, we can translate this insight into robust predictive tools that can estimate an individual’s risk,” postdoctoral fellow Sara Stinson explains. “In the long term, this could help more people maintain good brain health and quality of life into older age.”
A personalised “Lifespan Avatar”
The MetaBrain project integrates metabolomics and proteomics data from blood samples collected in midlife with genetic data, longitudinal brain imaging, and health registry outcomes across the Nordic countries.
Using these combined data sets, the team will develop the “Lifespan Avatar”, a personalised predictive tool built with artificial intelligence. This avatar will model how a person’s midlife metabolic profile shapes the trajectory their long-term brain ageing trajectory.
“This project aims to shift the clinical paradigm from late-stage intervention after illness appears to early, personalized prevention,” Stinson says.
Building a Nordic research network
A key part of MetaBrain is the establishment of a Nordic research network spanning Norway, Sweden, Denmark, and Iceland.
“This funding enables us to build on our prior work with Nordic research infrastructure, where we combine large-scale longitudinal biobank data with advanced multi-omics profiling and AI-driven analytics,” Andreassen says.
The project brings together leading researchers from across the region. Collaborators include Professor Fang Fang at Karolinska Institute in Sweden, Professor Unnur Valdimarsdóttir at the Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, and Professor Thomas Werge at the Institute for Biological Psychiatry in Denmark.
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