Cerebral Pulsatility as a Mechanism of Accelerated Cerebrovascular Aging across the Menopause Transition - Project Summary The menopause transition has emerged as a key period for cardiovascular disease risk, but its implications for cerebrovascular and brain health, and potential role in accelerating the disproportionate risk of Alzheimer’s disease and related dementias among aging women are underappreciated. Cerebral pulsatility describes the discontinuous nature of blood flow in the brain that increases with age and damages cerebral vessels and structures. Our recent data suggest cerebral pulsatility and its vascular contributors (large artery stiffness and characteristic impedance) may increase more drastically among women during midlife, and thus may be candidate mechanisms through which the menopause transition contributes to brain aging. Currently, changes in cerebrovascular mechanisms of brain health such as cerebral pulsatility are poorly characterized across the stages of the menopause transition in women and represents a critical gap in understanding that limits mechanism-driven preventive strategies to improve brain health among aging women and attenuate disproportionate Alzheimer’s disease and related dementias burden among women. We have assembled a transdisciplinary research team to address the novel hypothesis that menopause status increases cerebral pulsatility, thereby potentially contributing to accelerated brain aging and disproportionate cerebrovascular and Alzheimer’s disease and related dementias risk among women over time. The specific aims of this study are to determine differences in 1) cerebral pulsatility (primary) and cerebral blood flow (secondary), and 2) vascular contributors to cerebral pulsatility (large artery characteristic impedance and stiffness) between pre-, peri-, and post-menopausal women, and 3) assess whether cerebral pulsatility and its vascular contributors are associated with sex hormones across groups. 159 Pre-, peri-, and post-menopausal women (n=53 per group) aged 40-64 years will undergo assessment of cerebral pulsatility, large artery stiffness and characteristic impedance, serum sex hormones, and secondary outcomes (e.g., aerobic fitness, physical activity, cognitive function, menopause symptoms). This project incorporates an innovative and underappreciated vascular mechanism of brain health in during midlife, the time of the menopause transition and a critical window of vascular aging that is highly predictive of later-life brain health. Understanding how menopause status alters vascular targets of brain health such as cerebral pulsatility is critical in the struggle to attenuate the disproportionate burden of Alzheimer’s disease and related dementias among aging women. This study will serve as the first step in the long-term goal of identifying therapeutic, vascular targets of brain health in women to create and optimize mechanism-driven preventive strategies to prevent accelerated cerebrovascular aging during menopause, ultimately advancing our ability to attenuate disproportionate risk of Alzheimer’s disease and related dementias among aging women.
