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Publications

Journal Article Preprint Epublish 3 citations

PubMed: 40196574 DOI: 10.1101/2025.03.27.642988

Vulnerability to memory decline in aging - a mega-analysis of structural brain change.

bioRxiv

Authors: Didac Vidal-Piñeiro, Øystein Sørensen, Marie Strømstrad, Inge K Amlien, William Baaré, David Bartrés-Faz, Andreas M Brandmaier, Gabriele Cattaneo, Sandra Düzel, Paolo Ghisletta, Richard N Henson, Simone Kühn, Ulman Lindenberger, Athanasia M Mowinckel, Lars Nyberg, Alvaro Pascual-Leone, James M Roe, Javier Solana-Sánchez, Cristina Solé-Padullés, Leiv Otto Watne, Thomas Wolfers, Kristine B Walhovd, Anders M Fjell

Affiliations

  • Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
  • Danish Research Centre for Magnetic Resonance, Department of Radiology and Nuclear Medicine, Copenhagen University Hospital-Amager and Hvidovre, Copenhagen, Denmark.
  • Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
  • Institut Guttmann, Institut Universitari de Neurorehabilitació adscrit a la UAB, Badalona, Barcelona, Spain.
  • Institut de Recerca Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
  • Department of Psychology, MSB Medical School Berlin, Berlin, Germany.
  • Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berling, Germany, and London, UK.
  • Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Barcelona, Spain.
  • Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland.
  • MRC Cognition and Brain Sciences Unit, University of Cambridge, United Kingdom.
  • Department of Psychiatry and Psychotherapy, Department of Psychiatry, University Medical Center Hamburg-Eppendorf, Germany.
  • Center for Environmental Neuroscience, Max Planck Institute for Human Development, Germany.
  • Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
  • Department of Medical and Translational Biology, Umeå University, Sweden.
  • Department of Diagnostics and Intervention, Umeå University, Sweden.
  • Hinda and Arthur Marcus Institute for Aging Research, Deanna and Sidney Wolk Center for Memory Health, Harvard Medical School, Hebrew SeniorLife, Boston, MA, United States.
  • Department of Neurology, Harvard Medical School, Boston, MA, United States.
  • Oslo Delirium Research Group, Institute of Clinical Medicine, Campus Ahus, University of Oslo, Norway.
  • Department of Geriatric Medicine, Akershus University Hospital, Norway.
  • Department of Psychiatry and Psychotherapy, German Center for Mental Health, University Clinic Tübingen, Tübingen, Germany.
  • Computational Radiology and Artificial Intelligence, Department of Radiology and Nuclear Medicine, Oslo University Hospital, Norway.

Abstract

Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leveraged 13 longitudinal datasets, including 3,737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimer's Disease. Both factors are associated with accelerated brain decline, yet it remains unclear whether memory loss is exacerbated beyond what atrophy alone would predict. Additionally, we assessed whether memory decline aligns with a global pattern of atrophy or stems from distinct regional contributions. Our mega-analysis revealed a nonlinear relationship between memory decline and brain atrophy, primarily affecting individuals with above-average brain structural decline. The associations were stronger in the hippocampus but also spread across diverse cortical and subcortical regions. The associations strengthened with age, reaching moderate associations in participants in their eighties. While APOE ε4 carriers exhibited steeper brain and memory loss, genetic risk had no effect on the change-change associations. These findings support the presence of common biological macrostructural substrates underlying memory function in older age which are vulnerable to multiple age-related factors, even in the absence of overt pathological changes.

MeSH

Atrophy, Aging, Brain, Memory