# Chronic Lower Leg Heating for the Treatment of Hypertension in Older Women

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $354,353

## Abstract

Project Summary/Abstract
Almost two-thirds of Americans with Alzheimer’s disease and related dementias (AD/ADRD) are women. The
underlying mechanisms are unknown but may be associated with a higher prevalence of hypertension and lower
blood pressure (BP) control rate in older women than older men. Indeed, recent research implicates risk factors
such as hypertension and cerebrovascular dysfunction in the pathogenesis of AD. Cerebrovascular function and
cognition can be affected by BP dysregulation via the baroreflex, and baroreflex sensitivity is reduced in
hypertension and AD - an effect that is likely related to cerebrovascular dysfunction and arterial stiffening. Thus,
decreasing BP, increasing baroreflex sensitivity, and improving cerebrovascular health may be an important
preventive strategy for AD/ADRD in older women with hypertension. One non-drug approach that offers promise
is “heat therapy”. The objective of this administrative supplement is to leverage our existing clinical trial in order
to perform a proof-of-concept investigation to examine the effects of home-based lower leg heat therapy on
AD/ADRD risk, as reflected by changes in cerebrovascular function in older hypertensive women. To accomplish
this objective, we will enroll hypertensive women aged 65-79 and randomly assign them to either an intervention
group or a control group. Patients in the intervention group will perform 8 weeks of home-based lower leg heat
therapy via water immersion up to the knee in a circulated bath (water temperature 42°C, 4 times per week, 45
min per session), whereas patients in the control group will immerse their legs in a thermoneutral water bath
(33°C) at the same frequency and duration. All patients will also receive a fixed dose of chlorthalidone. Aim 1
will examine the effect of heat therapy on cerebral hemodynamics in older hypertensive women. We will use
transcranial Doppler to assess cerebral hemodynamics before and after heat therapy or control treatment.
Dynamic cerebral autoregulation will be evaluated by transfer function analysis. Aim 2 will examine the
mechanisms by which heat therapy impacts cerebral hemodynamics. We will measure ambulatory BP,
sympathetic and cardiovagal baroreflex sensitivities, and dynamic arterial compliance, β-stiffness index and wall
thickness of the carotid artery. The associations among cerebral hemodynamics, BP, baroreflex sensitivity, and
the carotid artery properties will be investigated. Aim 3 (exploratory) will examine the effects of heat therapy on
cognition and blood-based biomarkers of AD pathology and neurodegeneration in older hypertensive women.
We will use the NIH Toolbox Cognition Battery to assess cognitive function. Biomarkers of AD pathology and
neurodegeneration will be measured in plasma samples obtained before and after heat therapy or control.

## Key facts

- **NIH application ID:** 10121618
- **Project number:** 3R01AG059314-02S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** QI FU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,353
- **Award type:** 3
- **Project period:** 2019-03-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121618

## Citation

> US National Institutes of Health, RePORTER application 10121618, Chronic Lower Leg Heating for the Treatment of Hypertension in Older Women (3R01AG059314-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10121618. Licensed CC0.

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