Sex differences in sleep and memory relationships in older adults at risk for Alzheimer’s disease
8 affiliations
- 1Department of Psychiatry and Human Behavior, University of California, Irvine
- 2Department of Cognitive Sciences, University of California, Irvine
- 3San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology
- 4Department of Psychiatry, University of Pittsburgh School of Medicine
- 5Department of Neurobiology and Behavior, University of California, Irvine
- 6Department of Psychiatry, Wisconsin Institute for Sleep and Consciousness, University of Wisconsin-Madison
- 7Department of Medicine, Division of Geriatrics and Gerontology, University of Wisconsin-Madison
- 8Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine
Abstract
Introduction: Biological sex is an important modifier of aging and Alzheimer’s disease risk, yet the sleep-related mechanisms through which sex and genetic risk interact to influence memory remain poorly understood. We examined whether associations among non-rapid eye movement sleep physiology, overnight memory retention, and apolipoprotein E ϵ4 ( APOE ϵ4) status, a genetic risk factor for Alzheimer’s disease, differed by sex in cognitively unimpaired older adults enriched for Alzheimer’s disease risk.
Methods: Eighty participants completed overnight polysomnography with high-density electroencephalography, and 65 also completed an evening encoding/immediate recall and morning delayed recall word-pair memory task.
Results: Overnight memory retention did not differ by sex. However, exploratory analyses of the proportional overnight retention measure suggested a sex × APOE ϵ4 interaction, such that female APOE ϵ4 carriers may exhibit reduced overnight forgetting relative to female non-carriers and male carriers. Although counterintuitive, this pattern may reflect compensatory or resilience-related sleep-memory mechanisms in cognitively unimpaired women at genetic risk for Alzheimer’s disease rather than a protective effect of APOE ϵ4 itself. Women spent more time in N3 sleep and had higher non-rapid eye movement delta and slow sigma power than men. Sleep-memory associations also differed by sex: greater N2 duration was more strongly associated with better overnight retention in men, whereas greater frontal slow sigma power and fronto-central fast sigma power were positively associated with retention in women. Exploratory APOE-stratified analyses suggested sex-specific differences in sleep stage-memory relationships, with more positive N2-memory associations in male than female APOE ϵ4 carriers and more positive N3-memory associations in female than male carriers; both differences remained significant after FDR correction. TFCE-corrected analyses further identified positive associations between NREM delta and sigma activity and overnight memory retention in female APOE ϵ4 carriers.
Discussion: These findings highlight sex-specific patterns in NREM sleep physiology and sleep-memory relationships in cognitively unimpaired older adults at risk for Alzheimer’s disease. More broadly, the results suggest that sex and APOE ϵ4 status may jointly shape the neurophysiological pathways linking sleep and memory, underscoring the importance of considering sex as a biological variable when studying sleep, cognitive aging, and Alzheimer’s disease vulnerability.
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BibTeX
@article{sattari2026differences,
title = {{Sex differences in sleep and memory relationships in older adults at risk for Alzheimer’s disease}},
author = {Negin Sattari and Abhishek Dave and Ivy Y. Chen and Kitty K. Lui and Miranda G. Chappel-Farley and Destiny E. Berisha and Kate E. Sprecher and Brady A. Riedner and Stephanie Jones and Barbara B. Bendlin and Bryce A. Mander and Ruth M. Benca},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1930177},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1930177/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sex differences in sleep and memory relationships in older adults at risk for Alzheimer’s disease
AU - Negin Sattari
AU - Abhishek Dave
AU - Ivy Y. Chen
AU - Kitty K. Lui
AU - Miranda G. Chappel-Farley
AU - Destiny E. Berisha
AU - Kate E. Sprecher
AU - Brady A. Riedner
AU - Stephanie Jones
AU - Barbara B. Bendlin
AU - Bryce A. Mander
AU - Ruth M. Benca
PY - 2026
DA - 2026/10/12
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1930177
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1930177/full
AB - Introduction: Biological sex is an important modifier of aging and Alzheimer’s disease risk, yet the sleep-related mechanisms through which sex and genetic risk interact to influence memory remain poorly understood. We examined whether associations among non-rapid eye movement sleep physiology, overnight memory retention, and apolipoprotein E ϵ4 ( APOE ϵ4) status, a genetic risk factor for Alzheimer’s disease, differed by sex in cognitively unimpaired older adults enriched for Alzheimer’s disease risk. Methods: Eighty participants completed overnight polysomnography with high-density electroencephalography, and 65 also completed an evening encoding/immediate recall and morning delayed recall word-pair memory task. Results: Overnight memory retention did not differ by sex. However, exploratory analyses of the proportional overnight retention measure suggested a sex × APOE ϵ4 interaction, such that female APOE ϵ4 carriers may exhibit reduced overnight forgetting relative to female non-carriers and male carriers. Although counterintuitive, this pattern may reflect compensatory or resilience-related sleep-memory mechanisms in cognitively unimpaired women at genetic risk for Alzheimer’s disease rather than a protective effect of APOE ϵ4 itself. Women spent more time in N3 sleep and had higher non-rapid eye movement delta and slow sigma power than men. Sleep-memory associations also differed by sex: greater N2 duration was more strongly associated with better overnight retention in men, whereas greater frontal slow sigma power and fronto-central fast sigma power were positively associated with retention in women. Exploratory APOE-stratified analyses suggested sex-specific differences in sleep stage-memory relationships, with more positive N2-memory associations in male than female APOE ϵ4 carriers and more positive N3-memory associations in female than male carriers; both differences remained significant after FDR correction. TFCE-corrected analyses further identified positive associations between NREM delta and sigma activity and overnight memory retention in female APOE ϵ4 carriers. Discussion: These findings highlight sex-specific patterns in NREM sleep physiology and sleep-memory relationships in cognitively unimpaired older adults at risk for Alzheimer’s disease. More broadly, the results suggest that sex and APOE ϵ4 status may jointly shape the neurophysiological pathways linking sleep and memory, underscoring the importance of considering sex as a biological variable when studying sleep, cognitive aging, and Alzheimer’s disease vulnerability.
SN - 1664-2392
ER -