Neuroendocrine-vascular interaction is associated with thalamocortical disorganization and cognitive decline in perimenopausal hypertension

Background: Hypertension (HTN) during perimenopause significantly increases the risk of cognitive decline. However, how hemodynamic stress and hormonal fluctuations (e.g., estradiol depletion) interact to reshape the brain's macroscale organization remains poorly understood. This study aimed to map the "hormone-thalamus-cortex" axis to explore these mechanisms. Methods: Thirty perimenopausal women with HTN and 30 healthy controls (HC) underwent 3-T MRI, blood pressure monitoring, and serum hormone analysis. We constructed individual cortical morphometric similarity (MS) gradients and segmented the thalamus into 52 subregions to analyze the interplay between hormones, brain structure, and cognition. Results: We found that the principal MS gradient exhibited a distinct "stretching" pattern in the HTN group compared with HC, characterized by a significant positive spatial correlation with the HC gradient. The HTN group exhibited significantly elevated gradient values in the Visual and Somatomotor networks (VIS and SMN), as well as in specific regions within the frontoparietal network (FPN, left parietal subregion-4) and ventral attention network (VAN, right medial subregion-5). Thalamic analysis revealed a bidirectional remodeling pattern: atrophy in sensory/executive nuclei (e.g., VPL, LGN, MDm) and hypertrophy in intralaminar nuclei (e.g., CL, AV). Critically, estradiol (E2) depletion and FSH elevation were linked to specific thalamic atrophy (e.g., Right Pc), which in turn predicted lower MMSE scores and VAN disruptions. Conclusion: Perimenopausal HTN is associated with a neuroendocrine-modulated reorganization of the brain's hierarchy. The findings suggest that hormonal shifts exacerbate thalamic vulnerability, potentially contributing to cortical instability and cognitive impairment. This identifies perimenopause as a critical window for integrated vascular and hormonal interventions to preserve cognitive health.