Early menopause is associated with reduced global brain activity
Poster No:
899
Submission Type:
Abstract Submission
Authors:
Xufu Liu1, Yutong Mao1, Xiao Liu1
Institutions:
1Pennsylvania State University, State College, PA
First Author:
Co-Author(s):
Introduction:
Women who experienced early menopause face a higher risk of memory impairments and dementia (Ryan et al., 2014), particularly Alzheimer's disease (AD) (Costantino et al., 2022). Recent studies have identified a highly structured, infra-slow (<0.1 Hz) global brain activity and linked it to memory functions (Liu et al., 2021; Yang et al., 2024), neurodegenerative diseases(Han et al., 2023), and aging (Han et al., 2024). The global mean BOLD (gBOLD) signal, the fMRI measure of this global activity, has been shown to manifest as infra-slow waves propagating from the sensory/motor (SM) region to the default mode network (DMN) (Gu et al., 2021), coordinating sensory encoding and memory retrieval (Yang et al., 2024). Additionally, it is coupled to cerebrospinal fluid (CSF) flow (Fultz et al., 2019), and the strength of this coupling has been associated with AD pathologies, particularly the accumulation of amyloid-beta and tau (Han et al., 2023). However, it remains unclear whether early menopause affects this global brain activity and its coupling with CSF flow, and if so, how these changes may relate to memory functions. This study investigates the effects of early menopause on gBOLD activity, including its coupling with CSF flow, spatiotemporal patterns, and relationship to memory performance.
Methods:
We found 124 subjects with age at menopause information in the HCP-Aging project (Harms et al., 2018). To control for age differences (Fig. 1A), we excluded 34 individuals whose current age fell outside the range of 52.9 to 66.5 years. The remaining 90 subjects were then divided into three equally-sized groups-early, middle, and late menopausal groups, which show no differences in the current age (Fig. 1B-C). For each subject, we quantified the gBOLD amplitude, gBOLD-CSF coupling, gBOLD presence, and SM-DMN propagating waves (Gu et al., 2021; Han et al., 2023), and compared them across the three menopausal groups. We also examined the correlations between subjects' SM-DMN propagating waves and their performance on two memory tests: the Picture Sequence Memory Test (PSMT) and the Rey Auditory Verbal Learning Test (RAVLT).
Results:
Early menopausal women exhibit significantly weaker (i.e., less negative) gBOLD-CSF coupling compared to late menopausal women (p=0.017; Fig. 1D), likely driven by their reduced gBOLD amplitude (p=0.0005; Fig. 1E). The gBOLD presence maps showed significant differences between the early and late menopausal groups, primarily in higher-order brain regions (Fig. 1G) that largely overlap with the DMN and frontoparietal network (FPN) (Fig. 1F). Likewise, regional BOLD signals of similar higher-order brain regions are less strongly coupled with CSF flow in the early menopausal group (Fig. 1H). In early menopausal women, SM-to-DMN propagating waves exhibited weaker activations in higher-order brain regions compared to the age-matched late menopausal group (Fig. 2A-C). They also scored lower on episode memory, as measured by PSMT, than late menopausal women (p=0.008; Fig. 2D). Importantly, early menopausal women with higher PSMT scores had more frequent SM-to-DMN waves (Fig. 2E) and stronger activations in higher-order regions during these waves (Fig. 2F). Similar associations were observed between SM-DMN waves and RAVLT scores (Fig. 2F).
Conclusions:
Early menopausal women exhibited reduced gBOLD amplitude and weaker coupling with CSF flow, which has been linked to AD pathologies. The reduction in gBOLD activity results, at least in part, from its disengagement from higher-order brain regions as SM-to-DMN propagating waves. Notably, early menopausal women with weaker activations of higher-order regions during SM-to-DMN waves tended to perform worse on two memory tests, potentially explaining their increased risks for memory impairment and dementia.
Learning and Memory:
Long-Term Memory (Episodic and Semantic)
Lifespan Development:
Aging 1
Modeling and Analysis Methods:
Task-Independent and Resting-State Analysis 2
Keywords:
Aging
Cerebro Spinal Fluid (CSF)
FUNCTIONAL MRI
Memory
Other - Early Menopause
1|2Indicates the priority used for review
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