Author Identifier (ORCID)

Ralph N. Martins: https://orcid.org/0000-0002-4828-9363

Kevin Taddei: https://orcid.org/0000-0002-8106-7957

Stephanie R. Rainey-Smith: https://orcid.org/0000-0001-7328-9624

Abstract

Sex differences in cognitive reserve might contribute to females being disproportionately affected by Alzheimer's disease (AD). We investigated sex differences in the protective effects of cognitive reserve, and whether brain beta-amyloid accounts for differences. Older adults (n = 997 from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing) diagnosed as Cognitively Normal, Mild Cognitive Impairment, or AD at baseline were assessed every 18 months for up to a maximum of seven visits. Cognitive reserve was calculated from the variance in episodic memory not explained by demographic or brain measures. Executive functioning (EF) intercept and slope were regressed onto the main and interaction effects of cognitive reserve x brain integrity x sex, plus covariates (age, number of APOE ε4 alleles). A three-way interaction was observed between cognitive reserve, brain integrity, and sex on the EF slope. Females benefitted more than males from the protective effects of cognitive reserve at low levels of brain integrity. Sex differences in the protective effect of cognitive reserve were not moderated by brain beta-amyloid burden.

Document Type

Journal Article

Date of Publication

1-1-2025

Volume

8

Publication Title

Aging Brain

Publisher

Elsevier

School

School of Medical and Health Sciences

Funders

Alzheimer’s Association (US) / Alzheimer’s Drug Discovery Foundation / Anonymous Foundation / Science and Industry Endowment Fund / Dementia Collaborative Research Centres / Victorian Government’s Operational Infrastructure Support Program / Australian Alzheimer’s Research Foundation / National Health and Medical Research Council / The Yulgilbar Foundation

Grant Number

NHMRC Number : GNT1197315

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Comments

Chooi, C., Gavett, B. E., Ames, D., Maruff, P., Doré, V., Villemagne, V. L., Bourgeat, P., Xia, Y., Masters, C. L., Martins, R. N., Taddei, K., Rowe, C. C., Weinborn, M., & Rainey-Smith, S. R. (2025). Sex differences in the association between episodic memory residual reserve index and change in executive function. Aging Brain, 8, 100146. https://doi.org/10.1016/j.nbas.2025.100146

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Link to publisher version (DOI)

10.1016/j.nbas.2025.100146