Nature Communications (Dec 2024)
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,
- Alzheimer’s Disease Neuroimaging Initiative,
- the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing,
- Brenda Penninx,
- Lars Bertram,
- Lars Nyberg,
- Kristine B. Walhovd,
- Anders M. Fjell,
- Yunpeng Wang
Affiliations
- James M. Roe
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Didac Vidal-Piñeiro
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Øystein Sørensen
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Håkon Grydeland
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Esten H. Leonardsen
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Olena Iakunchykova
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Mengyu Pan
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Athanasia Mowinckel
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Marie Strømstad
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Laura Nawijn
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry and Amsterdam Neuroscience
- Yuri Milaneschi
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry and Amsterdam Neuroscience
- Micael Andersson
- Department of Medical and Translational Biology, Umeå University
- Sara Pudas
- Department of Medical and Translational Biology, Umeå University
- Anne Cecilie Sjøli Bråthen
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Jonas Kransberg
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Emilie Sogn Falch
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Knut Øverbye
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Rogier A. Kievit
- Cognitive Neuroscience Department, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center
- Klaus P. Ebmeier
- Department of Psychiatry and Wellcome Centre for Integrative Neuroimaging, University of Oxford, Warneford Hospital
- Ulman Lindenberger
- Center for Lifespan Psychology, Max Planck Institute for Human Development
- Paolo Ghisletta
- Faculty of Psychology and Educational Sciences, University of Geneva
- Naiara Demnitz
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital – Amager and Hvidovre
- Carl-Johan Boraxbekk
- Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen
- Christian A. Drevon
- Department of Nutrition, Institute of Basic Medical Science, Faculty of Medicine, University of Oslo
- Alzheimer’s Disease Neuroimaging Initiative
- the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing
- Brenda Penninx
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry and Amsterdam Neuroscience
- Lars Bertram
- Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck
- Lars Nyberg
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Kristine B. Walhovd
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Anders M. Fjell
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- Yunpeng Wang
- Center for Lifespan Changes in Brain and Cognition (LCBC), Department of Psychology, University of Oslo
- DOI
- https://doi.org/10.1038/s41467-024-53548-z
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
