Drug Development

Sori Kim Lundin; Xinyue Hu; Jingna Feng; Karl Kristian Lundin; Lu Li; Yong Chen; Paul E Schulz; Cui Tao

doi:10.1002/alz.084745

Drug Development

Alzheimers Dement. 2024 Dec:20 Suppl 6:e084745. doi: 10.1002/alz.084745.

Authors

Sori Kim Lundin^{1

2}, Xinyue Hu^{1

3}, Jingna Feng^{1

3}, Karl Kristian Lundin⁴, Lu Li⁵, Yong Chen⁵, Paul E Schulz⁶, Cui Tao^{1

7}

Affiliations

¹ Center for Biomedical Semantics and Data Intelligence (CBSDI), University of Texas Health Science Center at Houston, Houston, TX, USA.
² School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
³ School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴ Baylor College of Medicine, Houston, TX, USA.
⁵ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ John P. and Kathrine G. McGovern Medical School at UTHealth, Houston, TX, USA.
⁷ McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.

PMID: 39782518
DOI: 10.1002/alz.084745

Abstract

Background: Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer's disease and related dementias (ADRD) and cognitive decline have been inconclusive.

Method: A total of 6,390,826 hypertensive individuals were included in this study from Optum's de-identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood-brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses.

Result: AHM non-users (N = 1,184,809) had a lower incidence of all comorbidities and consumption of metformin and statins compared to ARBs users (N = 1,839,176) and non-ARBs AHM users (N = 3,366,841) (all P<0.0001). The KM curve showed that ARB users had lower cumulative hazard than other AHM users or AHM non-users (P<0.0001). In Cox PH analysis, ARB users showed a 20% lower adjusted hazard of developing ADRD compared to angiotensin-converting enzyme inhibitor (ACEI) users and a 29% and 18% reduced risk when compared to non-ARB/ACEI AHM users and AHM non-users (all P<0.0001). Consumption of BBB-crossing ARBs was linked to a lower risk of ADRD development than non-BBB-crossing ARBs, undetermined ARBs, and non-consumption of AHMs by 11%, 25%, and 31% (all P<0.0001).

Conclusion: This study suggests that ARBs are superior to ACEIs, non-ARB/ACEI AHMs, or non-use of AHMs in reducing the risk of ADRD among hypertensive patients. Also, BBB-permeability in ARBs was associated with lower ADRD risk. There is no cure for AD, ADRD, or vascular dementia; hence, these findings are significant in preventing those disorders in an inexpensive, convenient, and safe way.