Sex differences in default mode network connectivity in healthy aging adults

Abstract Women show an increased lifetime risk of Alzheimer’s disease (AD) compared with men. Characteristic brain connectivity changes, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function throughout...

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Bibliographic Details
Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2023-05, Vol.33 (10), p.6139-6151
Main Authors: Ficek-Tani, Bronte, Horien, Corey, Ju, Suyeon, Xu, Wanwan, Li, Nancy, Lacadie, Cheryl, Shen, Xilin, Scheinost, Dustin, Constable, Todd, Fredericks, Carolyn
Format: Article
Language:English
Subjects:
Adult
Brain - diagnostic imaging
Connectome
Default Mode Network
Female
Healthy Aging
Humans
Magnetic Resonance Imaging - methods
Male
Nerve Net - diagnostic imaging
Neuropsychological Tests
Original
Sex Characteristics
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Summary:Abstract Women show an increased lifetime risk of Alzheimer’s disease (AD) compared with men. Characteristic brain connectivity changes, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function throughout aging is poorly understood. We investigated sex differences in DMN connectivity over the lifespan in 595 cognitively healthy participants from the Human Connectome Project-Aging cohort. We used the intrinsic connectivity distribution (a robust voxel-based metric of functional connectivity) and a seed connectivity approach to determine sex differences within the DMN and between the DMN and whole brain. Compared with men, women demonstrated higher connectivity with age in posterior DMN nodes and lower connectivity in the medial prefrontal cortex. Differences were most prominent in the decades surrounding menopause. Seed-based analysis revealed higher connectivity in women from the posterior cingulate to angular gyrus, which correlated with neuropsychological measures of declarative memory, and hippocampus. Taken together, we show significant sex differences in DMN subnetworks over the lifespan, including patterns in aging women that resemble changes previously seen in preclinical AD. These findings highlight the importance of considering sex in neuroimaging studies of aging and neurodegeneration.
ISSN:1047-3211
1460-2199
1460-2199
DOI:10.1093/cercor/bhac491