Background: Women are more likely to develop age-related cognitive impairment compared with men of the same age. Pregnancy complications, such as preeclampsia (PE), and menopause may contribute to an elevated risk of cognitive decline with aging in women potentially through an adverse impact on vascular function. PE is associated with a heightened risk of hypertension and large elastic artery stiffness (i.e., aortic and carotid arteries) for several years postpartum. Persistent large artery stiffness may be further amplified in women with a history of PE during the menopause transition, which is marked by an accelerated rate of vascular aging. However, large artery stiffness has not been studied extensively in postmenopausal women with a history of PE. Age-related elevations in large artery stiffness are associated with cognitive decline in middle-aged and older adults however, this relation has not been investigated in young women with a history of PE. Moreover, the degree to which elevated large artery stiffness is amplified and associated with reduced cognitive function among postmenopausal women with a history of PE remains unknown. The purpose of this study was to examine the extent to which large elastic artery stiffness is associated with reductions in cognitive function in premenopausal and postmenopausal women with a history of PE. Methods: Large elastic artery stiffness and domains of cognitive function were assessed in young women one year postpartum (n=18, ages 24-41 yrs.) and postmenopausal women (n=19, ages 52-77 yrs.) thirty-five years postpartum. Aortic stiffness was measured via non-invasive applanation tonometry at the carotid and femoral pulse sites and expressed as carotid-femoral pulse wave velocity (cfPWV). Carotid artery stiffness was quantified as beta-stiffness index (β-stiffness) was measured via ultrasonography and carotid tonometry. Cognitive tests were administered to assess cognitive function in immediate and delayed recall, working memory, processing speed, and executive function. Results: Premenopausal women with a history of PE had higher systolic blood pressure (121 ± 4 vs. 101 ± 3 mmHg, p =0.01) one year postpartum but did not differ significantly from controls in cfPWV (6.2 ± 0.4 vs. 5.1 ± 0.2 m/s, p =0.08), β-stiffness (6.1 ± 0.5 vs. 6.1 ± 0.7 U, p =0.97), or cognitive domains of memory, executive function, or processing speed (all p>0.05). Higher systolic blood pressure was associated with lower executive function (r = -0.53, p = 0.05) in young women one year postpartum. Postmenopausal women with a history of PE did not differ from controls in blood pressure, large artery stiffness, or age-adjusted cognitive domains of memory, executive function, or processing speed (all p>0.05). Large artery stiffness was not associated with cognitive function in premenopausal or postmenopausal women. Conclusions: Young women with a history of PE had elevated systolic pressure one year postpartum, which was associated with reductions in executive function. Large artery stiffness was not elevated or related to cognitive function in postmenopausal women with a history of PE. These preliminary findings suggest that young women with a history of PE are susceptible to reductions in selective cognitive domains related to higher blood pressure, but this effect does not appear to extend into the postmenopausal period.

Despite advances, stroke remains the largest cause of disability and fourth leading cause of death in the United States. The relationship between changes in human vasculature (atherosclerosis and arteriosclerosis) prior to clinical incident, and other risk factors for stroke remains unclear. This dissertation represents work towards the identification of imaging biomarkers for vascular change, focusing on ultrasound to characterize persons at risk, including differences among race/ethnic groups. This research contained three distinct projects. The first goal was to determine if changes within ultrasonographic measures of carotid vasculature could be found across race/ethnic groups after adjustment for risk factors. The second was to determine if those same measures were related to changes in cerebral white matter known to be associated with ongoing cerebrovascular disease; we compared ultrasound to an MRI marker of subclinical vascular disease, white matter hyperintensity volume (WMHV). Finally, we sought to investigate a known and well-studied ultrasound marker for atherosclerosis, carotid intima-medial thickness, with those same MRI markers of subclinical vascular disease (WMHV). All studies were conducted within an on-going multiethnic cohort that has been followed since 1990, The Northern Manhattan Study. The population is comprised of persons who self-identify as Hispanic (52%), Black (24%), or White (21%), with less than 3% identified as “race/other.” We found race/ethnic differences in carotid arterial stiffness and diameter; carotid diameter increases with age among Hispanics, but not among blacks or whites. A significant correlation was also found between diastolic diameter and subclinical vascular disease, and this relationship was also increased among Hispanics; neither black race nor white race was associated with corresponding increases in both MRI white matter hyperintensity and diastolic diameter. Finally, using a surrogate marker for atherosclerosis, carotid intima-medial thickness (cIMT), we document for the first time, positive associations between cIMT and WMHV. There are important developments still to be made in the field of vascular risk. Use of inexpensive and non-invasive ultrasound technology to approximate ongoing cerebrovascular disease could lead to better understanding of the effect of known risk factors, and could help stroke risk assessment and treatment modification.