Exploring Diverging Paths: The Evolving Neuroimaging Biomarkers of Male and Female Brains
Poster No:
1681
Submission Type:
Abstract Submission
Authors:
Vasiliki Tassopoulou1, Sai Spandana Chintapalli1, Haochang Shou2, Christos Davatzikos1, Susan M. Resnick3
Institutions:
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA 2Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA 3Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA
First Author:
Co-Author(s):
Sai Spandana Chintapalli
Department of Bioengineering, University of Pennsylvania
Philadelphia, PA, USA
Department of Bioengineering, University of Pennsylvania
Philadelphia, PA, USA
Haochang Shou
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania
Philadelphia, PA, USA
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania
Philadelphia, PA, USA
Introduction:
Aging in the human brain exhibits sex-specific trajectories, with males and females showing divergent patterns of structural and functional decline. Prior studies have highlighted asymmetrical brain characteristics between males and females using cross-sectional imaging data. In this work we examine the sex differences in the progression of neuroimaging biomarkers. Leveraging longitudinal neuroimaging data from cognitively normal adults, this study investigates sex-specific differences in the longitudinal progression of volumetric regions of interest (ROIs), emphasizing the interplay of demographic, genetic, and racial factors in shaping these patterns.
Methods:
We analyzed longitudinal data from 1,335 cognitively normal individuals aged 50 years and older, using harmonized MRI scans from the iSTAGING consortium (Habes, 2021). Linear mixed-effects models assessed the associations between ROI volumes and predictors, including baseline age, sex, time, and intracranial volume, one-hot-encoded race effects and education years, while accounting for interaction effects such as Sex:Time and baseline age and time. Multiple comparison corrections were applied using the Benjamini-Hochberg method to ensure reliability. Also, we implement sensitivity analyses that stratified the data by APOE4 allele presence and racial groups (White and Black).
Results:
Significant Sex:Time interactions were observed, with males exhibiting steeper rates of volume decline across multiple regions. The most pronounced effects were found in the right angular gyrus, inferior temporal gyrus, parahippocampal gyrus, right central operculum, and precentral gyrus. These regions, integral to visuospatial, memory, and motor functions, showed faster structural aging in males. Sensitivity analyses confirmed these patterns across APOE4 subgroups and racial cohorts, with amplified sex differences in hippocampal and temporal regions among APOE4 homozygotes. Females demonstrated slower decline, consistent with greater resilience linked to hormonal and cognitive reserve mechanisms. Visualized in Figure 1, the stratification by APOE4 genotype and race highlights the consistency as well as the the differences within the racial and the genetic stratification. Figure 2 further illustrates the effect sizes and rates of change for ROIs that appeared to be significant across all the healthy control population stratified groups, demonstrating the steeper decline trajectories in males compared to females.
Conclusions:
Our findings highlight sex-specific trajectories of brain aging, with males showing accelerated atrophy in regions critical to cognitive and motor funtions. These structural differences align with prior evidence of steeper cognitive decline in males and cognitive resilience in females as reported in (McCarrey, 2016)
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
Univariate Modeling 1
Other Methods
Keywords:
Data analysis
Design and Analysis
STRUCTURAL MRI
1|2Indicates the priority used for review
Abstract Information
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Provide references using APA citation style.
McCarrey, A. C. (2016). Sex differences in cognitive trajectories in clinically normal older adults. Psychology and Aging, 31(2), 166–175. https://doi.org/10.1037/pag0000070