Examining Cerebral Pulsatility as a Mechanism of Accelerated Cerebrovascular Aging across the Menopause Transition
Description: AHA recognizes the importance of the menopause transition for cardiovascular disease risk in women. Cardiovascular health in midlife and later-life brain health are strongly linked. Thus, the menopause transition may be a critical midlife period influencing later-life brain health in women, however this is underexplored. The importance of characterizing changes in cerebral mechanisms of brain health across the menopause transition is as self-evident as it is currently underappreciated. Our data suggest the menopause transition may accelerate increases in cerebral blood flow pulsatility (a measure of 'discontinuous' blood flow) which is associated with cerebrovascular disease risk and brain health. We will compare cerebral blood flow pulsatility and its vascular mechanisms between 210 middle-aged (40-64 yrs) pre-, peri-, and early postmenopausal women (n=70 per group), and examine longitudinal relationships between cerebral pulsatility, sex hormones, and brain health metrics (cognitive function, blood biomarkers) in 100 women at a 1-year follow-up. Menopausal stage will be categorized based on self-report according to STRAW+10 criteria. We will measure cerebral pulsatility at the middle cerebral artery via Doppler ultrasound. Vascular mechanisms of cerebral pulsatility will include large artery stiffness and characteristic impedance assessed via tonometry and Doppler/ultrasound. Sex hormones will include progesterone, estrogen, and follicle stimulating hormone, and brain health markers will include executive function and memory performance, and blood biomarkers of neurodegeneration (NfL) and Alzheimer’s disease pathology (pTau 217). We anticipate that cerebral pulsatility will be higher in early postmenopausal compared to pre- and perimenopausal women and remain after controlling for covariates (eg, age). Data from this study will 1) fill a critical gap in knowledge regarding changes in vascular mechanisms of brain health across the menopause transition, 2) identify vascular mechanisms of brain health (eg, pulsatility) that can be targeted to improve brain health via pharmaceutical (e.g., hormone replacement therapy, statins) or lifestyle (eg, aerobic exercise) strategies during menopause that can lower risk of cerebrovascular disease in women, and 3) provide key preliminary data for a cohort study to continue to track longitudinal changes in cerebral pulsatility during menopause.
Funder: American Heart Association
Amount: $300,000
Funding type: research
Funder scheme: Transformational Project Award
Start date: 2025-07-01
End date: 2028-06-30
Investigators: Wesley Lefferts, Wesley Lefferts
Institution: Iowa State University of Science and Technology
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 25TPA1473431
OpenAlex ID: G7703428076