Sex differences in healthy brain aging are unlikely to explain higher Alzheimer’s disease prevalence in women

A Anne Ravndal (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) A Anders M. Fjell (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) D 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) E Emilie S. Falch (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) J Julia Kropiunig (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) P Pablo F. Garrido (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) J James M. Roe (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) J José-Luis Alatorre-Warren (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) M Markus H. Sneve (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) D David Bartrés-Faz (Department of Medicine, Faculty of Medicine and Health Sciences and Neurosciences Institute, University of Barcelona) A Alvaro Pascual-Leone (Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife) A Andreas M. Brandmaier (Center for Lifespan Psychology, Max Planck Institute for Human Development) S Sandra Düzel (Center for Lifespan Psychology, Max Planck Institute for Human Development) S Simone Kühn (Center for Lifespan Psychology, Max Planck Institute for Human Development) U Ulman Lindenberger (Center for Lifespan Psychology, Max Planck Institute for Human Development) L Lars Nyberg (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) L Leiv Otto Watne (Oslo Delirium Research Group, Institute of Clinical Medicine, Campus Ahus, University of Oslo) R Richard N. Henson (Medical Research Council Cognition and Brain Sciences Unit, Department of Psychiatry, University of Cambridge) K Kristine B. Walhovd (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo) H Håkon Grydeland (Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo)

Abstract

As Alzheimer’s disease (AD) is diagnosed more frequently in women, understanding the role of sex has become a key priority in AD research. However, despite aging being the primary risk factor for AD, it remains unclear whether men and women differ in the extent of brain decline with age. Using 12,638 longitudinal brain MRIs from 4,726 participants aged 17 to 95 y across 14 cohorts, we examined sex differences in structural brain changes over time, controlling for differences in head size. Men showed greater cortical thickness (CT) decline in the cuneus, lingual, parahippocampal, and pericalcarine regions; surface area decline in the fusiform and postcentral regions; and in older adults, greater subcortical decline in the caudate, nucleus accumbens, putamen, and pallidum. In contrast, women only showed greater surface area decline in the banks of the superior temporal sulcus and greater ventricular expansion in older adults. These results suggest that sex differences in age-related brain decline are unlikely to contribute to the higher AD diagnosis prevalence in women, necessitating research into alternative explanations.

Article Details

Volume / Issue Vol. 122, Issue 42
Published October 21, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (21)

A

Anne Ravndal

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

A

Anders M. Fjell

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

D

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

E

Emilie S. Falch

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

J

Julia Kropiunig

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

P

Pablo F. Garrido

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

J

James M. Roe

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

J

José-Luis Alatorre-Warren

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

M

Markus H. Sneve

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

D

David Bartrés-Faz

Department of Medicine, Faculty of Medicine and Health Sciences and Neurosciences Institute, University of Barcelona

A

Alvaro Pascual-Leone

Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife

A

Andreas M. Brandmaier

Center for Lifespan Psychology, Max Planck Institute for Human Development

S

Sandra Düzel

Center for Lifespan Psychology, Max Planck Institute for Human Development

S

Simone Kühn

Center for Lifespan Psychology, Max Planck Institute for Human Development

U

Ulman Lindenberger

Center for Lifespan Psychology, Max Planck Institute for Human Development

L

Lars Nyberg

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

L

Leiv Otto Watne

Oslo Delirium Research Group, Institute of Clinical Medicine, Campus Ahus, University of Oslo

R

Richard N. Henson

Medical Research Council Cognition and Brain Sciences Unit, Department of Psychiatry, University of Cambridge

K

Kristine B. Walhovd

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo

H

Håkon Grydeland

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo