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
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