How the environment influences biological brain ageing

The biological age of the brain can be accelerated or slowed down by the cumulative environmental conditions in which people live, and the combined effect of these conditions is far more powerful than any single factor considered in isolation. This is the central finding of an international study led by Dr. Agustín Ibáñez, a collaborator of the BarcelonaBeta Brain Research Centre (BBRC). Published in Nature Medicine, the study analysed brain imaging and environmental data from 18,701 individuals across 34 countries, making it one of the most comprehensive global investigations into brain aging to date.

The study builds on the concept of the exposome, the totality of environmental exposures a person accumulates throughout life, from air pollution and climate variability to socioeconomic inequality and the strength of democratic institutions. Researchers quantified 73 country-level indicators spanning both the physical exposome (pollution, extreme temperatures, lack of green spaces) and the social exposome (poverty, inequality, limited civic participation), and examined how these jointly shape the pace at which the brain ages.

For Agustín Ibáñez, lead investigator and corresponding author, “we aimed to test whether the combined, syndemic effects of environmental exposures better explain variability in brain aging across populations than individual exposures or single clinical diagnoses”.

To measure brain aging, the researchers used brain clocks: computational models that estimate the biological age of the brain from neuroimaging data and compare it to a person's chronological age. The difference (known as the Brain Age Gap) reflects how fast or slowly an individual's brain is aging relative to what would be expected.

When modelled together, environmental exposures explained up to 15 times more variance in brain aging than any single factor alone, and their cumulative effect exceeded that of clinical diagnoses such as Alzheimer's disease or frontotemporal dementia. Physical exposures were primarily associated with structural brain changes in regions linked to memory and emotional regulation, while social exposures showed stronger links with functional alterations in networks involved in cognition and executive control.

BBRC’s contribution: data from the ALFA+ Study

The BBRC contributed to this global study through data from the ALFA+ study, a longitudinal cohort of cognitively unimpaired adults at elevated genetic risk for Alzheimer's disease, promoted by ”la Caixa” Foundation.

The data provided included high-resolution structural and anatomical MRI as well as resting-state functional MRI, which captures spontaneous brain activity at rest and allows the characterisation of large-scale functional brain networks. In addition, the ALFA+ dataset contributed contextual variables such as socioeconomic status, educational level, and APOE genotype key factors in understanding the intersection of biological risk and environmental exposure.

The findings challenge a prevention landscape that has focused largely on individual behaviours or clinical intervention, pointing instead to structural conditions: environmental regulation, social policy, urban design, and institutional quality, as meaningful levers for protecting brain health at the population level.

Reference Article: Legaz, A., Moguilner, S., Barttfeld, P. et al. The exposome of brain aging across 34 countries. Nat Med (2026). https://doi.org/10.1038/s41591-026-04302-z