
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.08.28.24312754
preprint
1
Article
Antihypertensive medications and dementia in older adults with hypertension
Orchard Suzanne G. http://orcid.org/0000-0003-0211-3183

Zhou Zhen http://orcid.org/0000-0002-0835-8686

Fravel Michelle
Ryan Joanne http://orcid.org/0000-0002-7039-6325

Woods Robyn L. http://orcid.org/0000-0003-1249-6149

Wolfe Rory http://orcid.org/0000-0002-2126-1045

Shah Raj C.
Murray Anne http://orcid.org/0000-0002-2787-8433

Sood Ajay
Reid Christopher M. http://orcid.org/0000-0001-9173-3944

Nelson Mark R. http://orcid.org/0000-0001-9941-7161

Bellin Lawrie http://orcid.org/0000-0003-4853-7360

Polkinghorne Kevan R
Stocks Nigel
Ernst Michael E. http://orcid.org/0000-0003-0267-4888

29 8 2024
2024.08.28.24312754https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.08.28.24312754
nihpp-2024.08.28.24312754.pdf
ABSTRACT

Background

Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults.

Methods

A post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use.

Results

Most hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, ‘any’ AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and β-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk.

Conclusions

Overall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and β-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults.
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pmc
