Sex Differences in Age-Related Changes in Brain Network Segregation
Poster No:
1207
Submission Type:
Abstract Submission
Authors:
Abhijot Sidhu1, Kauê Duarte1, Louis Lauzon1, Cheryl McCreary1, Andrea Protzner1, Bradley Goodyear1, Richard Frayne1
Institutions:
1University of Calgary, Calgary, Alberta
First Author:
Co-Author(s):
Introduction:
The cortical regions of the human brain are organized into several functional networks that interact to facilitate higher-order cognition [1]. Resting-state functional magnetic resonance imaging (rs-fMRI) studies suggest that this interaction changes over the healthy adult lifespan, such that connectivity between networks strengthens as we age [2-3]. This redistribution is thought to be a compensatory response to age-related neurodegeneration to preserve cognitive function [2,4]. Sex differences in this aging process, however, have not been well characterized across the lifespan. Here we examine the influence of sex differences in a large cognitively healthy cohort.
Methods:
rs-fMRI and 3D T1-weighted magnetic resonance (MR) data from 377 cognitively healthy adults (age range: 18.2–91.8 y; 56.1% female; MoCA ≥ 24) of the Calgary Normative Study were used for this study [5]. Follow-up data from 77 participants (21.3–80.8 y, 64.9% F, interval 2.0–3.9 y) were also included. Connectivity within and between the somatomotor (SMN), ventral attention (VAN), dorsal attention (DAN), frontoparietal (FPN), default mode (DMN), and visual (VIS) networks were computed. For each network, the average within- and between- network z-transformed connectivity (zw and zb, respectively) were used to compute the segregation index: SI=(zw– zb )/zw. A linear-mixed effects model (LME) was used to investigate the relationship between SI and age, age2, sex, and age×sex, with subject as a random effect to account for longitudinal interindividual differences. Post-hoc LME tests were used to investigate which specific pairs of networks were associated with the observed network effects. Network and pairwise LME results were adjusted using Holm-Bonferroni multiple comparison correction.
Results:
Significant age effects were observed on SI for VIS (p < 0.001), SMN (p < 0.001), FPN (p = 0.049), VAN (p < 0.001), and DMN (p < 0.001), such that SI linearly decreased with increasing age for these networks. Significant sex effects were observed on SI for VAN (p < 0.001) and DMN (p < 0.001); females exhibited greater SI values regardless of age (Figure 1). Post-hoc pairwise analyses revealed significant age-associated increases in connectivity between FPN–VIS (p = 0.005), FPN–SMN (p = 0.039), and FPN–DAN (p = 0.006) network pairs. Post-hoc pairwise analyses also revealed significant sex differences in between-network connectivity for the SMN–DMN (p = 0.038), DAN–VAN (p < 0.001), DAN–FPN (p = 0.003), DAN–DMN (p = 0.026), and SVAN–FPN (p < 0.001) network pairs; females exhibited lower between-network connectivity for all network pairs regardless of age. No significant age2 and age×sex effects were observed.
Conclusions:
VIS, SMN, FPN, VAN, and DMN were all found to become less segregated across the healthy adult lifespan. Specifically, age-associated increases in between-network connectivity were restricted to pairs of sensory-associative and associative-associative networks. Females were observed to preserve VAN and DMN segregation relative to males, independent of age, and specifically, between associative networks. This suggests that female brains retain brain network segregation, which has been linked to healthy younger brains [1]. How sex differential brain aging patterns relate to cognitive function and how they are altered during pathological aging warrants further investigation.
Lifespan Development:
Aging 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
fMRI Connectivity and Network Modeling
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Normal Development
Keywords:
ADULTS
Aging
FUNCTIONAL MRI
NORMAL HUMAN
Sexual Dimorphism
Other - healthy brain aging; resting-state functional magnetic resonance imaging; segregation index; longitudinal analysis; sex differences
1|2Indicates the priority used for review
Provide references using author date format
2. Chan, C. (2014), ‘Decreased segregation of brain systems across the healthy adult lifespan’, Proceedings of the National Academy of Sciences, vol. 111, no.46, pp. E4997-E5006.
3. Malagurski, B. (2020), ‘Functional dedifferentiation of associative resting state networks in older adults – a longitudinal study’, Neuroimage, vol. 214, pp. 116680-116691.
4. Goh, JO. (2009), ‘Neuroplasticity and cognitive aging: The scaffolding theory of aging and cognition. Restorative Neurology and Neuroscience’, Restorative Neurology and Neuroscience, vol. 27, no. 5, pp. 391-403.
5. McCreary, C. (2020), ‘Calgary normative study: Design of a prospective longitudinal study to characterise potential quantitative MR biomarkers of neurodegeneration over the adult lifespan’, BMJ Open, vol. 10, no. 8.