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Brain change trajectories in healthy adults correlate with Alzheimer’s related genetic variation and memory decline across life

Author

Listed:
  • James M. Roe

    (University of Oslo)

  • Didac Vidal-Piñeiro

    (University of Oslo)

  • Øystein Sørensen

    (University of Oslo)

  • Håkon Grydeland

    (University of Oslo)

  • Esten H. Leonardsen

    (University of Oslo
    University of Oslo)

  • Olena Iakunchykova

    (University of Oslo)

  • Mengyu Pan

    (University of Oslo
    Lund University)

  • Athanasia Mowinckel

    (University of Oslo)

  • Marie Strømstad

    (University of Oslo)

  • Laura Nawijn

    (Department of Psychiatry and Amsterdam Neuroscience)

  • Yuri Milaneschi

    (Department of Psychiatry and Amsterdam Neuroscience)

  • Micael Andersson

    (Umeå University
    Umeå University)

  • Sara Pudas

    (Umeå University
    Umeå University)

  • Anne Cecilie Sjøli Bråthen

    (University of Oslo)

  • Jonas Kransberg

    (University of Oslo)

  • Emilie Sogn Falch

    (University of Oslo)

  • Knut Øverbye

    (University of Oslo)

  • Rogier A. Kievit

    (Radboud University Medical Center)

  • Klaus P. Ebmeier

    (Warneford Hospital)

  • Ulman Lindenberger

    (Max Planck Institute for Human Development
    Max Planck UCL Centre for Computational Psychiatry and Ageing Research)

  • Paolo Ghisletta

    (University of Geneva)

  • Naiara Demnitz

    (Copenhagen University Hospital – Amager and Hvidovre)

  • Carl-Johan Boraxbekk

    (University of Copenhagen
    Umeå University
    Copenhagen University Hospital Bispebjerg)

  • Christian A. Drevon

    (University of Oslo
    Oslo Science Park)

  • Brenda Penninx

    (Department of Psychiatry and Amsterdam Neuroscience)

  • Lars Bertram

    (University of Lübeck)

  • Lars Nyberg

    (University of Oslo
    Umeå University
    Umeå University
    Umeå University)

  • Kristine B. Walhovd

    (University of Oslo
    Oslo University Hospital)

  • Anders M. Fjell

    (University of Oslo
    Oslo University Hospital)

  • Yunpeng Wang

    (University of Oslo)

Abstract

Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer’s disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2–7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype. Next, we run machine learning on AD-control data from the Alzheimer’s Disease Neuroimaging Initiative using brain change trajectories conditioned on age, to identify AD-sensitive features and model their change in healthy adults. Genetic AD-risk linked with multivariate change across many AD-sensitive features, and we show most individuals over age ~50 are on an accelerated trajectory of brain loss in AD-sensitive regions. Finally, high genetic risk adults with elevated brain change showed more memory decline through adulthood, compared to high genetic risk adults with less brain change. Our findings suggest quantitative AD risk factors are detectable in healthy individuals, via a shared pattern of ageing- and AD-related neurodegeneration that occurs along a continuum and tracks memory decline through adulthood.

Suggested Citation

  • James M. Roe & Didac Vidal-Piñeiro & Øystein Sørensen & Håkon Grydeland & Esten H. Leonardsen & Olena Iakunchykova & Mengyu Pan & Athanasia Mowinckel & Marie Strømstad & Laura Nawijn & Yuri Milaneschi, 2024. "Brain change trajectories in healthy adults correlate with Alzheimer’s related genetic variation and memory decline across life," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53548-z
    DOI: 10.1038/s41467-024-53548-z
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    References listed on IDEAS

    as
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