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.

Keywords: aortic blood pressure; brain volume; cognition; menopause; oestradiol; pregnancy; white matter hyperintensities.

Figure 1

Flow chart characterising the cohorts to examine the long‐term effects of pregnancy on cardiovascular risk factors and cognition in middle‐aged women

Figure 2

Voxel‐based analysis from magnetic resonance imaging of brains of women with a history of pre‐eclampsia. The red areas are voxels that showed a lower cortical volume in women with a history of pre‐eclampsia and current hypertension compared to women with a history of pre‐eclampsia and no current hypertension (P < 0.001). Modified with permission from Raman et al12

Figure 3

Cumulative incidence of cognitive impairment or dementia in women with bilateral oophorectomy at age ≤48 years or at age >48 years, as well as in referent women. HR, hazard ratio. Modified with permission from Rocca et al12

Figure 4

Longitudinal change in ventricular volumes and white matter hyperintensities (WMH) in women who had been randomised to placebo, oral conjugated equine oestrogen (o‐CEE) or transdermal 17β‐oestradiol (t‐E₂) for 4 years. Data are shown as the mean ± SD prior to randomisation (0 months), at the conclusion of treatment (48 months), and 3 years after cessation of treatment (84 months). Modified with permission from Kantarci et al12