# Age-related Hypertension and Vascular Cognitive Impairment

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $793,084

## Abstract

ABSTRACT
Hypertension is a key risk factor for the development of cerebral small vessel disease, the foremost source of
vascular cognitive impairment which is the second most common cause of dementia after Alzheimer’s disease.
There is increasing evidence that blood brain barrier dysfunction and neuroinflammation play a pivotal role in
the pathophysiology of hypertension and contribute to the development of vascular cognitive impairment. While
Angiotensin II Type 1 receptor antagonists are first line therapy to treat hypertension they have recently been
demonstrated to improve neurocognitive function. Given the annual cost of dementia in the US is expected to
double by 2040, the prevalence of hypertension rises from 46% of U.S. adults aged 20-44 to >78% of U.S.
adults above the age of 65, and that hypertension incidence increases dramatically post-menopause there is a
critical public health need for a greater understanding of the mechanistic link(s) between sex, age-dependent
hypertension and vascular cognitive impairment. This application will test the global hypothesis that normal
aging evokes sex-dependent hypertension that drives central microvascular injury and neuroinflammation to
cause vascular cognitive impairment which can be ameliorated by Angiotensin II Type 1 receptor antagonism.
Our Aims will be conducted in male and female 3-, 8-, and 16-month-old Sprague-Dawley rats (model of
normal aging). The following Specific Aims will test this hypothesis: Specific Aim 1: Hypothalamic PVN blood
brain barrier dysfunction and neuroinflammation contribute to age-dependent hypertension via a reversible
sex-dependent Angiotensin II Type 1 receptor mechanism. Specific Aim 2: Age-dependent hypertension
evoked hippocampal microvascular injury and neural circuit dysfunction drives vascular cognitive impairment
via a reversible sex-dependent Angiotensin II Type 1 receptor mechanism. Our innovative approach is directly
aligned with NIA Stratetgic Goals that address Alzheimer's disease and its related dementias and is designed
to provide novel insights into the basic mechanisms contributing to sex- and age-dependent hypertension-
driven vascular cognitive impairment and fully meets the intent of PAR-19-070 and NOT-AG-20-038. Specific
Aim 1 will establish that hypothalamic PVN blood brain barrier dysfunction and neuroinflammation contribute to
the development of age-dependent hypertension, which drives vascular cognitive impairment, via a reversible
sex-dependent Angiotensin II Type 1 receptor mechanism. Specific Aim 2 will establish that age-dependent
hypertension evoked hippocampal microvascular injury and neural circuit dysfunction drives vascular cognitive
impairment via a reversible sex-dependent Angiotensin II Type 1 receptor mechanism. Our innovative
approach will directly investigate the sex dependent mechanistic sequelae of events and underlying neural
dysfunction in both the PVN and hippocampus that is associated with, and perhaps contributing to...

## Key facts

- **NIH application ID:** 10975734
- **Project number:** 7R01AG075963-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** David H Farb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $793,084
- **Award type:** 7
- **Project period:** 2022-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975734

## Citation

> US National Institutes of Health, RePORTER application 10975734, Age-related Hypertension and Vascular Cognitive Impairment (7R01AG075963-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10975734. Licensed CC0.

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