# Informing optimal first-line antihypertensive therapy: A rigorous comparative effectiveness analysis of ARBs vs. ACEIs on long-term risk of dementia, cancer, heart disease, and quality of life

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $83,579

## Abstract

PROJECT
Chronic
individuals
dementias
kidney
CKD.
risk
SUMMARY
kidney disease (CKD) is a highly morbid disease t hat disproportionately affects older
and is associated with a significantly increased risk of Alzheimer's and related
(ADRD). However, many older adults have “benign” kidney senescence, in which
function declines due to natural aging, and do not experience the extrarenal sequelae of
Research is needed to target therapies towards older patients with CKD who are at high
for ADRD.
Renin-angiotensin
treatment.
effects
to
dysregulation
pathologic
mitigation
enormous
The
kidney
system (RAS) inhibition with ARBs or ACEIs is the backbone of CKD
 Preliminary evidence suggests that ARBs may have greater beneficial cognitive
than ACEIs in the general population. Older individuals with pathologic CKD, as opposed
kidney senescence, may particularly benefit cognitively from ARBs vs. ACEIs due amplified
of the RAS in CKD. It is still unknown, however, how to distinguish patients with
 CKD versus benign senescence. D etermining if ARBs vs. ACEIs have greater
of the long-term ADRD risk in older patients with pathologic CKD could have an
public health impact in this vulnerable population.
 
proposed study aims to evaluate the benefit of ARBs vs ACEIs in older adults with reduced
function. Utilizing theelectronic health record data from the Veterans Health
Administration linked with Medicare, we will estimate the effects of ARB- vs. ACEI-based
medication regimens on the incidence of dementia using advanced causal inference methods.
Subsequently, we will perform a cluster analysis to identify phenotypic subgroups of older adults
with CKD based on clinical, demographic and laboratory data and will test whether any of these
groups show differential cognitive outcomes with ARBs vs ACEIs.
In
Diversity Supplement will
machine
will
treatment
conjunction with her prepared areer development plan, the proposed project for the
provide Dr. Shulman with training in dvanced causal inference and
learning techniques and will generate four first-author manuscripts These experiences
inform her planned submission of a career development award focused on advancing the
and prevention of adverse cognitive outcomes in older patients with CKD.
c NIA
a
.

## Key facts

- **NIH application ID:** 11046297
- **Project number:** 3R01AG074989-03S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Adam P Bress
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $83,579
- **Award type:** 3
- **Project period:** 2022-03-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11046297

## Citation

> US National Institutes of Health, RePORTER application 11046297, Informing optimal first-line antihypertensive therapy: A rigorous comparative effectiveness analysis of ARBs vs. ACEIs on long-term risk of dementia, cancer, heart disease, and quality of life (3R01AG074989-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11046297. Licensed CC0.

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