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NIH grant 1K23AG103833-01: Vascular Aging and Adverse Brain Health in Older Adults
Institute: {'code': 'AG', 'abbreviation': 'NIA', 'name': 'National Institute on Aging', 'admin_org_id': '12500002', 'admin_funding_url': ''}. PI: Amalia Peterson. Award: $176904.
Start: 2026-09-11T00:00:00.
ABSTRACT. Two-thirds of all prevalent cases of Alzheimer’s disease affect females, with sex differences in
neuropathological burden that remain poorly understood. Sex-specific effects of arterial aging may be one
contributor to these sex differences. Age-related arterial changes have well-established connections to adverse
brain aging and striking differences between males and females. However, it remains unknown whether sex
modifies the relationship between altered arterial hemodynamics in aging (i.e., stiffness, pulsatile load) and
adverse brain aging. This critical gap must be addressed to inform precision medicine approaches to
prevention and treatment strategies for Alzheimer’s disease and related dementias. With aging, increased
central arterial stiffness limits the aorta’s ability to dampen pulsatile blood flow transmitted from the heart,
increasing pulsatile blood pressure and flow. In addition, pulsatile load, a measure of hemodynamic stress on
the arteries, increases. These modified arterial hemodynamics relate to reduced cerebral blood flow and are
linked to the accumulation of Alzheimer’s disease pathology, temporal lobe white matter hyperintensities, and
declines in temporal lobe-mediated memory performance. Estrogen is vascular protective and promotes
arterial compliance. Females have a greater increase in stiffness than males beginning at menopause, when
estrogen levels decline. Further, the association between pulsatile load and mortality is stronger in females
compared to males, suggesting that the downstream effects of altered arterial hemodynamics are greater in
females. I have compelling preliminary data that increased aortic stiffness relates to white matter changes in
females but not males. My central hypothesis is that altered arterial hemodynamics relate to adverse brain
aging more strongly in females compared to males. In this K23 proposal, I will leverage data from the
Vanderbilt Memory and Aging Project to test this hypothesis. I will use complementary markers of arterial
hemodynamics, including a gold-standard measure of central arterial stiffness captured on magnetic
resonance imaging (aortic pulse wave velocity) and an accessible peripheral measure of pulsatile load (pulse
pressure), allowing for a more comprehensive assessment of arterial aging. The proposal aims to determine
the sex-specific effects of arterial hemodynamics on 1) cognition and 2) white matter microstructure, as well as
3) whether reproductive factors modify these relationships in females. I will gain advanced training in 1)
vascular contributions to Alzheimer’s disease and related dementias; 2) neuroimaging measurement, analysis,
and interpretation; 3) vascular sex differences in Alzheimer’s disease and related dementias; and 4) leadership
and professional development skills. This research will add new and important insights into vascular
contributions to Alzheimer’s disease and related dementias and position me for an independent research
career focused on vascular contributions to sex differences in Alzheimer’s disease and related dementias.document fetched 2026-09-20 02:42