# Hypertension, intracranial pulsatility and brain A-beta accumulation in older adults

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $672,027

## Abstract

Project Summary/Abstract
Recent studies in rodents demonstrate the existence of a brain-wide glymphatic system, which transports bulk
flow of cerebrospinal fluid (CSF) from the subarachnoid space into the brain parenchyma through the para-
arterial and para-venous spaces. This CSF flow flushes out interstitial soluble Aβ, tau and other toxic proteins,
ultimately influencing brain Aβ and tau protein homeostasis. The presence of intracranial pulsatility is
recognized as the driving force for the convection of CSF through these pathways. However, whether this
mechanism functions similarly in humans remains unknown. Hypertension accelerates brain aging and
increases the risk of Alzheimer's disease (AD). The underlying mechanism(s) are not well understood. Our
recent studies and others have demonstrated that elevated central pulsatility is associated with brain atrophy
and white matter lesions. How changes in central pulsatility are transmitted downstream into cerebral
microcirculation to generate intracranial pulsatility, and whether changes in intracranial pulsatility affect brain
Aβ and tau homeostasis also remain unknown. The overarching goal of this project is to test the
hypothesis that intensive antihypertensive treatment alters central and intracranial pulsatility which in
turn affect brain Aβ and tau protein homeostasis. Furthermore, we will determine whether changes in
intracranial pulsatility, Aβ and tau are associated with brain white matter integrity and neural network
functional connectivity. To achieve this goal, we will enroll 120 older adults age 60-79. Of those, 40 have
normal blood pressure (BP) (24-h BP<130/80 mmHg) and 80 have high systolic BP (24-h SBP ≥140). Patients
with hypertension will be randomized into a 12-month intensive treatment arm (24-h SBP≤125) and a control
arm of the standard care (24-h SBP≤140). Aim 1: Determine the effects of hypertension on intracranial
pulsatility, CSF Aβ and tau, brain white matter integrity, and neural network functional connectivity.
Hypotheses: Hypertension is associated with: 1) augmented central pulsatility, but reduced intracranial
pulsatility; 2) reductions in CSF soluble Aβ42, but increases in phosphorylated tau and total tau; 3) disruptions
in brain white matter integrity inferred by diffusion tensor imaging, and functional connectivity by resting-state
fMRI. We also will determine whether group differences in intracranial pulsatility, brain Aβ, and tau are
associated with white matter integrity and neural network functional connectivity; Aim 2: Determine the effects
of antihypertensive treatments on intracranial pulsatility, CSF Aβ and tau, brain white matter integrity and
neural network functional connectivity. Hypotheses: compared to standard care, intensive treatment confers
more benefits by: 1) reductions in central pulsatility, but increases in intracranial pulsatility; 2) increases in CSF
Aβ42, but reductions in phosphorylated tau and total tau; 3) improvement in brain white m...

## Key facts

- **NIH application ID:** 9975666
- **Project number:** 5R01AG057571-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** WANPEN VONGPATANASIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $672,027
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975666

## Citation

> US National Institutes of Health, RePORTER application 9975666, Hypertension, intracranial pulsatility and brain A-beta accumulation in older adults (5R01AG057571-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975666. Licensed CC0.

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