# Guiding next steps for SPRINT-MIND implementation: Identifying high-benefit subgroups and comparative effects of ARB- vs. ACEI-based regimens

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $671,692

## Abstract

PROJECT SUMMARY
Alzheimer’s disease and related dementias (ADRD) are the leading cause of dependence and disability in the
elderly population worldwide, costing the US healthcare system over $200 billion annually. Because ADRD
represents a continuous irreversible physical and cognitive decline, identifying effective approaches for its
prevention is imperative. Hypertension, particularly in midlife, is associated with an increased risk of cognitive
decline and ADRD. Recent data from the randomized Systolic Blood Pressure (SBP) Intervention Trial
(SPRINT) Memory and cognition IN Decreased hypertension (SPRINT MIND) demonstrated that intensive
SBP control (<120 mmHg) reduced the combined incidence of adjudicated mild cognitive impairment (MCI)
and probable dementia, as well as abnormal white matter lesion (WML) volume compared to standard BP
control (<140 mmHg) over five years follow up. To maximize public health impact, it is critical to identify which
patients derive the greatest cognitive and net (overall) benefit from intensive SBP treatment and if cognitive
benefits were due to direct effects of specific antihypertensive medications on cognition independent of, or in
addition to, their BP-lowering effect. Prior animal and human studies, as well as our preliminary data, suggest
that angiotensin II receptor blockers (ARB) have greater effects on cognition than angiotensin-converting-
enzyme inhibitors (ACEI). If verified, this finding would be significant since ARBs and ACEIs are currently
among the medications most commonly prescribed to older adults and are thought to be equivalent in benefit
and safety. Our objective is to answer remaining questions of how to safely implement SPRINT in older
patients most likely to derive cognitive benefits from intensive SBP treatment. With its large sample size, 5
years follow-up, and high-quality repeated measures of rigorously adjudicated cognitive outcomes, brain
imaging, and antihypertensive medication use, SPRINT MIND provides a unique, cost-efficient, and ideal
setting to answer these questions. We aim to: (1) develop and validate a prediction tool that quantifies
patients’ expected cognitive benefits and net (overall) benefit incorporating cognitive and
cardiovascular benefit and risk of SAEs under intensive SBP treatment, and (2) determine comparative
effects, including dose-response, of ARB- vs. ACEI-based antihypertensive medication regimens on
cognitive and brain structure outcomes independent of SBP-lowering effects. Though SPRINT MIND is
among the first randomized trials to demonstrate a beneficial preventive effect on cognition, it is uncertain how
SPRINT-MIND should be implemented and in which patients. Successful completion of this project will
guide next steps for implementation by determining: (1) which patients derive the greatest cognitive and
net (overall) benefit from intensive SBP treatment and (2) if ARBs have greater beneficial effects on cognitive
outcomes and WML volume than ACEIs,...

## Key facts

- **NIH application ID:** 10225636
- **Project number:** 5R01AG065805-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adam P Bress
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $671,692
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225636

## Citation

> US National Institutes of Health, RePORTER application 10225636, Guiding next steps for SPRINT-MIND implementation: Identifying high-benefit subgroups and comparative effects of ARB- vs. ACEI-based regimens (5R01AG065805-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225636. Licensed CC0.

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