Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change
Abstract
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 leverages 13 longitudinal datasets, including 3737 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 assess whether memory decline aligns with a global pattern of atrophy or stems from distinct regional contributions. Our mega-analysis reveals a nonlinear relationship between memory decline and brain atrophy, primarily affecting individuals with above-average brain structural decline. The associations are stronger in the hippocampus but also spread across diverse cortical and subcortical regions. The associations strengthen with age, reaching moderate associations in participants in their eighties. While APOE ε4 carriers exhibit steeper brain and memory loss, genetic risk has 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.
Article Details
Authors (74)
Didac Vidal-Piñeiro
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Øystein Sørensen
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Marie Strømstad
Inge K. Amlien
William Baaré
David Bartrés-Faz
Department of Medicine, Faculty of Medicine and Health Sciences and Neurosciences Institute, University of Barcelona
Andreas M. Brandmaier
Center for Lifespan Psychology, Max Planck Institute for Human Development
Gabriele Cattaneo
Sandra Düzel
Center for Lifespan Psychology, Max Planck Institute for Human Development
Paolo Ghisletta
Richard N. Henson
Medical Research Council Cognition and Brain Sciences Unit, Department of Psychiatry, University of Cambridge
Simone Kühn
Center for Lifespan Psychology, Max Planck Institute for Human Development
Ulman Lindenberger
Center for Lifespan Psychology, Max Planck Institute for Human Development
Athanasia M. Mowinckel
Lars Nyberg
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Alvaro Pascual-Leone
Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife
James M. Roe
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Javier Solana-Sánchez
Cristina Solé-Padullés
Leiv Otto Watne
Oslo Delirium Research Group, Institute of Clinical Medicine, Campus Ahus, University of Oslo
Thomas Wolfers
Carol E. Franz
William S. Kremen
Michael J. Lyons
Anders M. Dale
Jeremy A. Elman
Christine Fennema-Notestine
Matthew S. Panizzon
Chandra A. Reynolds
Institute for Behavioral Genetics, University of Colorado Boulder
Katherine Bangen
Tyler R. Bell
Corwin Boake
Divya S. Bolar
Randy Buckner
Alice Cronin-Golomb
Stephen M. Dorros
Lindon Eaves
Seth Eisen
Lisa T. Eyler
Nathan A. Gillespie
Eric Granholm
Daniel E. Gustavson
Institute for Behavioral Genetics, University of Colorado Boulder
Donald J. Hagler
Richard L. Hauger
Diane Jacobs
Kristen Jacobson
Amy Jak
Gig Levine
Thomas Liu
Mark Logue
Linda K. McEvoy
Ruth E. McKenzie
Sally Mendoza
Michael C. Neale
Robert A. Rissman
Nicholas Smith
Rongxiang Tang
Rosemary Toomey
Ming Tsuang
Xin M. Tu
Art Wingfield
Hong Xian
Dirk Hellhammer
Warner Schaie
Sonia Lupien
Bruce Fischl
Larry Seidman
Brinda Rana
Terry Jernigan
Claire Murphy
Wesley Thompson
Nicholas Schork
Kristine B. Walhovd
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo
Anders M. Fjell
Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo