Gastric acid suppressants and cognitive decline in people with or without cognitive impairment
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Abstract Introduction Studies suggest associations between proton pump inhibitors (PPIs) and dementia risk; however, many neither considered histamine‐2 receptor antagonists (H2RAs) nor baseline cognitive status. Methods Participants (National Alzheimer's Coordinating Center Database; 2005–2021) using a PPI or H2RA were compared. Covariate‐adjusted Cox regression was used to estimate hazard ratios (HR) for progression from normal cognition to mild cognitive impairment (MCI), and from MCI to dementia over 5 years. In a propensity‐score–matched subsample of mild–moderate Alzheimer's disease (AD), mixed‐effects negative binomial regression was used to estimate decline in delayed recall memory. Results Compared to PPI, H2RA use was associated with earlier progression from MCI to dementia (HR = 1.40 [1.09–1.81]; n = 1701), and with faster memory decline in AD over time (rate ratio = 0.76 [0.64–0.92]; n = 628), but not with progression from normal cognition to MCI (HR = 0.94 [0.71–1.24]; n = 2784). Discussion Compared to PPIs, H2RAs were associated with cognitive decline, specifically among people with pre‐existing cognitive impairment.
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Gastric acid suppression by histamine-2 receptor antagonists has more reliably demonstrated associations between chronic use, dysbiosis, and cognitive decline.
“Intriguingly, gastric acid suppression by histamine-2 receptor antagonists has more reliably demonstrated associations between chronic use, dysbiosis, and cognitive decline (448).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [448]
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- Authors
- Wu, C., Xiong, L. Y., Ouk, M., Rabin, J. S., Herrmann, N., Lanctôt, K. L., Kapral, M. K., Law, M., Cogo‐Moreira, H., Edwards, J. D., & Swardfager, W.
- Affiliations
- University of Toronto (CA)
- Sunnybrook Research Institute (CA)
- Sunnybrook Health Science Centre (CA)
- University Health Network (CA)
- Østfold University of Applied Sciences (NO)
- University of Ottawa (CA)
- Corresponding author
- Swardfager, Walter
- ORCID
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- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2022-01
- Volume
- 8
- Issue
- 1
- Pages
- e12243-e12243
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC8829893
- OpenAlex
- W4211171955
- Cited by
- 13
- References
- 47
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- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 3
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- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 016976, P30AG053760, P30AG010129, P30AG010133, P30AG049638, P30AG028383, P30AG012300, P50AG005133, U01AG016976, P50AG005131, P50AG005138, AG019610, P30AG010124, P50AG016573, P50AG047366, P30AG008017, P30AG010161, P30AG008051, P50AG008702, P50AG033514, P30AG035982, AG013846, P50AG005681, P50AG005142, P50AG047270, P30AG019610, P50AG005146, P30AG013846, P50AG005136, P50AG005134, P30AG013854, P50AG025688, P50AG047266, P30AG072975, P50AG023501, P50AG016574)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- gastric acid suppressants, proton pump inhibitors, H2 receptor antagonists, cognitive decline, mild cognitive impairment, dementia, Alzheimer's disease, memory decline, delayed recall, drug safety
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