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

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, Micael Andersson, Sara Pudas, Anne Cecilie Sjøli Bråthen, Jonas Kransberg, Emilie Sogn Falch, Knut Øverbye, Rogier A. Kievit, Klaus P. Ebmeier, Ulman Lindenberger, Paolo Ghisletta, Naiara Demnitz, Carl-Johan Boraxbekk, Christian A. Drevon, Brenda Penninx, Lars Bertram, Lars Nyberg, Kristine B. Walhovd, Anders M. Fjell and Yunpeng Wang
Additional contact information
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
Olena Iakunchykova: University of Oslo
Mengyu Pan: University of Oslo
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
Sara Pudas: 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
Paolo Ghisletta: University of Geneva
Naiara Demnitz: Copenhagen University Hospital – Amager and Hvidovre
Carl-Johan Boraxbekk: University of Copenhagen
Christian A. Drevon: University of Oslo
Brenda Penninx: Department of Psychiatry and Amsterdam Neuroscience
Lars Bertram: University of Lübeck
Lars Nyberg: University of Oslo
Kristine B. Walhovd: University of Oslo
Anders M. Fjell: University of Oslo
Yunpeng Wang: University of Oslo

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53548-z

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