Risk factors of neurovascular ageing in women

Abstract

Biological sex and changes in sex hormones throughout life influence all aspects of health and disease. In women, changes in sex hormonal status reflect ovarian function, pregnancy and the use of exogenous hormonal treatments. Longitudinal data from defined cohorts of women will help to identify mechanisms by which the hormonal milieu contributes to cerebrovascular ageing, brain structure and ultimately cognition. This review summarises the phenotypes of three cohorts of women identified through the medical records‐linkage system of the Rochester Epidemiology Project and the Mayo Clinic Specialized Center of Research Excellence (SCORE) on Sex Differences: (i) menopausal women with histories of normotensive or hypertensive pregnancies; (ii) women who had bilateral oophorectomy ≤45 years of age; and (iii) women who experienced natural menopause and used menopausal hormone treatments for 4 years. Data from these cohorts will influence the design of follow‐up studies concerning how sex hormonal status affects neurovascular ageing in women.

Causal structure discovery identifies risk factors and early brain markers related to evolution of white matter hyperintensities

“…The possible explanations include genetic and hormonal factors, sexual dimorphism in WM microstructure, and their influence on CVD. A higher genetic heritability of WMH has been shown in women compared to men ( Miller et al, 2020 ). The major hormonal changes in women are associated with pregnancy and menopause.…”

Sex-dependent effects of CYP46A1 overexpression on cognitive function during aging

“…Moreover, early menopause before the age of 40-45, resulting from ovarian removal, premature ovarian insufficiency, chemotherapy and aromatase inhibitor treatment; represents a female-specific risk factor for higher cognitive decline and higher levels of AD neuropathology [67][68][69] . Abrupt loss of ovarian hormones, including E2, is therefore associated to age-related pathophysiological processes 70 . In light of these results, CYP46A1 activation could represent a pharmacological target for modulation of neurosteroidogenesis that could specifically enhance brain E2 signaling in women at risk of developing AD.…”

Sex Differences in Large Artery Stiffness: Implications for Cerebrovascular Dysfunction and Alzheimer’s Disease

“…The sex differences in the relation of arterial stiffness and cognitive decline are likely more complex than just differences in sex hormones. For example, history of pregnancy and childbirth may contribute as hemodynamic properties of the aorta are associated with cognitive function in post-menopausal females, but a history of preeclampsia influences this association for some cognitive abilities (Miller et al, 2020). Therefore, more research is needed to understand how sex may influence the effects of large artery stiffness on cognitive function.…”