Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change

Didac Vidal-Pineiro*, Yunpeng Wang, Stine K. Krogsrud, Inge K. Amlien, William F.C. Baaré, David Bartres-Faz, Lars Bertram, Andreas M. Brandmaier, Christian A. Drevon, Sandra Düzel, Klaus Ebmeier, Richard N. Henson, Carme Junqué, Rogier Andrew Kievit, Simone Kühn, Esten Leonardsen, Ulman Lindenberger, Kathrine S. Madsen, Fredrik Magnussen, Athanasia Monika MowinckelLars Nyberg, James M. Roe, Barbara Segura, Stephen M. Smith, Øystein Sørensen, Sana Suri, Rene Westerhausen, Andrew Zalesky, Enikő Zsoldos, Kristine Beate Walhovd, Anders Fjell

*Corresponding author for this work
    32 Citations (Scopus)


    Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two indepen-dent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

    Original languageEnglish
    Article numbere69995
    Publication statusPublished - 11.2021


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