Sex differences in the association between episodic memory residual reserve index and change in executive function

Cheyenne Chooi; Brandon E. Gavett; David Ames; Paul Maruff; Vincent Dore; Victor L. Villemagne; Pierrick Bourgeat; Ying Xia; Colin L. Masters; Ralph N. Martins; Kevin Taddei; Christopher C. Rowe; Michael Weinborn; Stephanie R. Rainey-Smith

doi:10.1016/j.nbas.2025.100146

Sex differences in the association between episodic memory residual reserve index and change in executive function

Cheyenne Chooi, Brandon E. Gavett, David Ames, Paul Maruff, Vincent Dore, Victor L. Villemagne, Pierrick Bourgeat, Ying Xia, Colin L. Masters, Ralph N. Martins, Kevin Taddei, Christopher C. Rowe, Michael Weinborn, Stephanie R. Rainey-Smith

Macquarie Medical School

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	100146
Pages (from-to)	1-13
Number of pages	13
Journal	Aging Brain
Volume	8
Early online date	Jul 2025
DOIs	https://doi.org/10.1016/j.nbas.2025.100146
Publication status	Published - 2025

Bibliographical note

Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Alzheimer's disease
Beta-amyloid
Cognitive reserve
Episodic memory
Residual reserve index
Sex differences

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10.1016/j.nbas.2025.100146Licence: CC BY

Publisher version (open access)Final published version, 1.55 MBLicence: CC BY

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Chooi, C., Gavett, B. E., Ames, D., Maruff, P., Dore, 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, 1-13. Article 100146. https://doi.org/10.1016/j.nbas.2025.100146

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title = "Sex differences in the association between episodic memory residual reserve index and change in executive function",

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.",

keywords = "Alzheimer's disease, Beta-amyloid, Cognitive reserve, Episodic memory, Residual reserve index, Sex differences",

author = "Cheyenne Chooi and Gavett, \{Brandon E.\} and David Ames and Paul Maruff and Vincent Dore and Villemagne, \{Victor L.\} and Pierrick Bourgeat and Ying Xia and Masters, \{Colin L.\} and Martins, \{Ralph N.\} and Kevin Taddei and Rowe, \{Christopher C.\} and Michael Weinborn and Rainey-Smith, \{Stephanie R.\}",

note = "Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2025",

doi = "10.1016/j.nbas.2025.100146",

language = "English",

volume = "8",

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journal = "Aging Brain",

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Chooi, C, Gavett, BE, Ames, D, Maruff, P, Dore, V, Villemagne, VL, Bourgeat, P, Xia, Y, Masters, CL, Martins, RN, Taddei, K, Rowe, CC, Weinborn, M & Rainey-Smith, SR 2025, 'Sex differences in the association between episodic memory residual reserve index and change in executive function', Aging Brain, vol. 8, 100146, pp. 1-13. https://doi.org/10.1016/j.nbas.2025.100146

TY - JOUR

T1 - Sex differences in the association between episodic memory residual reserve index and change in executive function

AU - Chooi, Cheyenne

AU - Gavett, Brandon E.

AU - Ames, David

AU - Maruff, Paul

AU - Dore, Vincent

AU - Villemagne, Victor L.

AU - Bourgeat, Pierrick

AU - Xia, Ying

AU - Masters, Colin L.

AU - Martins, Ralph N.

AU - Taddei, Kevin

AU - Rowe, Christopher C.

AU - Weinborn, Michael

AU - Rainey-Smith, Stephanie R.

N1 - Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Beta-amyloid

KW - Cognitive reserve

KW - Episodic memory

KW - Residual reserve index

KW - Sex differences

UR - https://purl.org/au-research/grants/nhmrc/1197315

UR - https://www.scopus.com/pages/publications/105012090887

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DO - 10.1016/j.nbas.2025.100146

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SN - 2589-9589

VL - 8

SP - 1

EP - 13

JO - Aging Brain

JF - Aging Brain

M1 - 100146

ER -

Sex differences in the association between episodic memory residual reserve index and change in executive function

Abstract

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