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Cited by 8Dementia and Cognitive Impairment ResearchRenin-Angiotensin System StudiesMedication Adherence and Compliance

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Effect of Initiation and Continuous Adherence to ARBs Versus ACEIs on Risk of Adjudicated Mild Cognitive Impairment or Dementia

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Derington, Catherine G, Berchie, Ransmond O, Scharfstein, Daniel O, Andrews, Ryan M, Greene, Tom H, Xu, Yizhe, King, Jordan B, Supiano, Mark A, Sonnen, Joshua A, Williamson, Jeff, Pajewski, Nicholas M, Pruzin, Jeremy J, Cohen, Jordana B, Bress, Adam P·2025·The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
DOI 10.1093/gerona/glaf028PMC PMC12287627
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Abstract

Background: Whether the differing mechanistic effects between angiotensin-2 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on the renin-angiotensin system translate to differential effects on clinical cognitive outcomes is unclear. Methods: We employed an active comparator, new-user cohort study to emulate a target trial evaluating the per-protocol effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated amnestic mild cognitive impairment (MCI) and probable dementia (PD) in the Systolic Blood Pressure Intervention Trial (SPRINT). Inverse probability of treatment and censoring weighted cumulative incidence functions accounted for confounding, the competing risk of death, adherence, and loss to follow-up. Results: Of 9,361 SPRINT participants (mean age 67.1 ± 9.5 years, 36.7% female, 58.7% non-Hispanic White), 710 and 1,289 were new users of an ARB or ACEI. Overall, 291 (41.0%) ARB initiators and 854 (66.3%) ACEI initiators were nonadherent during follow-up. The IP-weighted 4-year probabilities of full adherence and being alive among ARB was 56.0% (95% CI: 52.2%–59.9%) and 30.5% (95% CI: 28.0%–33.1%) for ACEI. The 4-year weighted risk ratios (RR) for amnestic MCI/PD and for amnestic MCI/PD/death with initiation and full adherence to ARB versus ACEI were 0.94 (95% CI: 0.66–1.29) and 0.79 (95% CI: 0.58–1.06). The weighted 4-year weighted RR for all-cause death with ARB versus ACEI initiation and adherence was 0.36 (95% CI: 0.14-0.76). Conclusions: In this target trial emulation of older adults at high risk for cardiovascular disease, there was insufficient evidence to conclude a beneficial effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated clinical cognitive outcomes.

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Metadata

Authors
Derington, C. G., Berchie, R. O., Scharfstein, D. O., Andrews, R. M., Greene, T. H., Xu, Y., King, J. B., Supiano, M. A., Sonnen, J. A., Williamson, J., Pajewski, N. M., Pruzin, J. J., Cohen, J. B., & Bress, A. P.
Affiliations
  • Intermountain Healthcare (US)
  • Boston University (US)
  • University of Utah (US)
  • McGill University (CA)
  • Wake Forest University Health Sciences (US)
  • Banner Alzheimer’s Institute (US)
  • University of Pennsylvania (US)
Corresponding author
Derington, Catherine G
ORCID
Venue
The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
Publisher
Oxford University Press (OUP)
Published
2025-02-13
Volume
80
Issue
7
ISSN
  • 1079-5006 (ISSN-L)
  • 1758-535X
DOI
10.1093/gerona/glaf028
PMC
PMC12287627
OpenAlex
W4407548924
Cited by
8
References
4
Citations by year
2026: 6 · 2025: 2
FWCI
5.38
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journals of Gerontology Series A (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (R01G065805, R01AG74989, K24AG080168, R01AG065805, R01HL139837, R01AG055606)
  • National Heart, Lung, and Blood Institute (R01-HL153646, R01-HL157108, U01-HL160277, U01TR003734)
  • National Center for Advancing Translational Sciences (R01DK123104, U24DK060990)
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • American Heart Association Bugher (R01AG067497, R01AG065359)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
Keywords
ACE inhibitors, antihypertensive medication adherence, amnestic mild cognitive impairment, dementia, renin-angiotensin system, SPRINT trial, target trial emulation, all-cause mortality, older adults, cardiovascular disease
MeSH terms
Aged, Angiotensin-Converting Enzyme Inhibitors, Dementia, Female, Humans, Hypertension, Male, Middle Aged, Angiotensin Receptor Antagonists, Cognitive Dysfunction

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