Abstract
Background: Despite various hypotheses, including differences in longevity, hormones, genetics, and neuroanatomy, the reasons for the higher prevalence of Alzheimer's disease in older women compared to men remain unclear. Emerging evidence suggests that the precuneus, a key region of the default mode network, is linked to internally focused processes like memory retrieval. We examined the relationship between precuneus volumes and task performance (accuracy and reaction time) during working memory retrievals in cognitively normal older adults. Method: A cohort of older participants (N = 45; 25 women; Mage = 77) from the University of Kentucky Alzheimer's Disease Research Center (UK-ADRC) performed the modified delayed match-to-sample working memory task while undergoing functional magnetic resonance imaging in a 3T Siemens scanner. Result: We found the accuracy of working memory retrieval correlates more frequently with the left precuneus in women (r = 0.54; p < 0.05) than in men. Similarly, volumes in the left precuneus displayed a significant negative correlation with reaction time in response to memory target (r = −0.426; p = 0.038) and memory distractor (r = −0.549; p < 0.01) in women. There is a sex difference in the accuracy and speed trade-off. While men were faster in reaction time, women were better at the accuracy of the memory task. We found no sex differences in the percentage of fMRI signal change across reaction time in response to the memory target for men (R2 linear = 0.011) and women (R2 linear = 0.003). Particularly noteworthy was the consistent association in women, where neurocognitive measures (trail A, r = −0.50; p = 0.010; trail B, r = −0.06; p = 0.002) reliably correlated with volumes in the left precuneus—a relationship not observed in men. Discussion: Our findings suggest that the left precuneus volume is associated with processing speed and accuracy of working memory performance, especially in women. Given that the left precuneus plays a key role in supporting various aspects of cognition, including memory retrieval, our findings point to the potential of reaction time serving as a surrogate marker for functional MRI in predicting cognitive decline, particularly in older women.
| Original language | English |
|---|---|
| Article number | e70912 |
| Journal | Brain and Behavior |
| Volume | 15 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2025 |
Bibliographical note
Publisher Copyright:© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.
Funding
DE was supported by the National Institute on Aging (R00AG078286) and Alzheimer's Association Research Fellowship to Promote Diversity, AARF-D (23AARFD-1029261). The project was partially supported by NIH / NIA P30AG028383; UL1TR000117; P30AG072946; K99AG078286.We thank A. Anderson and E Wallis for volume analysis, the human participants from the University of Kentucky Alzheimer's Disease Research (UK-ADRC) Cohort, and members of the Aging Brain and Cognition (ABC) laboratory. : DE was supported by the National Institute on Aging (R00AG078286) and Alzheimer's Association Research Fellowship to Promote Diversity, AARF‐D (23AARFD‐1029261). The project was partially supported by NIH / NIA P30AG028383; UL1TR000117; P30AG072946; K99AG078286. Funding
| Funders | Funder number |
|---|---|
| University of Kentucky | |
| National Institutes of Health (NIH) | |
| Aging Brain and Cognition | |
| U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) | P30AG028383, UL1TR000117, R00AG078286, P30AG072946 |
| Alzheimer's Association | 23AARFD‐1029261 |
Keywords
- cognitive decline
- precuneus volumes
- sex differences
- working memory retrieval
ASJC Scopus subject areas
- Behavioral Neuroscience
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