Repurposing antihypertensive drugs for the prevention of Alzheimer’s disease: a Mendelian Randomization study
Open accessPreprint — published as 10.1093/ije/dyz155 · Paper page
Abstract
Background: Evidence concerning the potential repurposing of antihypertensives for Alzheimer’s disease prevention is inconclusive. We used Mendelian randomization, which can be more robust to confounding by indication and patient characteristics, to investigate the effects of lowering systolic blood pressure (SBP), via different antihypertensive drug classes, on Alzheimer’s disease. Methods: We used summary statistics from genome wide association studies of SBP (from UK Biobank) and Alzheimer’s disease (from the International Genomics of Alzheimer’s Project) in a two-sample Mendelian randomization analysis. We identified single nucleotide polymorphisms (SNPs) that mimic the action of antihypertensive targets and estimated the effect of lowering SBP, via antihypertensive drug classes, on Alzheimer’s disease. We also report the effect of lowering SBP on Alzheimer’s disease by combining all drug targets and without consideration of the associated drugs. Results: There was limited evidence that lowering SBP, via antihypertensive drug classes, affected Alzheimer’s disease risk. For example, calcium channel blockers had an odds ratio (OR) per 10mmHg lower SBP of 1.53 (95% confidence interval (CI): 0.94 to 2.49; p=0.09; SNPs=17). We also found limited evidence for an effect of lowering SBP on Alzheimer’s disease when combining all drug targets (OR per 10mmHg lower SBP: 1.14; 95%CI: 0.83 to 1.56; p=0.41; SNPs=59) and without consideration of the associated drug targets (OR per 10mmHg lower SBP: 1.04; 95%CI: 0.95 to 1.13; p=0.45; SNPs=153). Conclusions: Lowering SBP itself is unlikely to affect risk of developing Alzheimer’s disease. Consequently, if specific antihypertensive drug classes do affect risk of Alzheimer’s disease, they are unlikely to do so via SBP. KEY MESSAGES: This is the first study to use Mendelian randomization to estimate the effects of the twelve most common antihypertensive drug classes on Alzheimer’s disease. Lowering systolic blood pressure itself is unlikely to affect risk of developing Alzheimer’s disease. If specific antihypertensive drug classes do affect Alzheimer’s disease risk, they are unlikely to do so via systolic blood pressure.
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- Authors
- Walker, V. M., Kehoe, P. G., Martin, R. M., & Davies, N. M.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Walker, Venexia M
- Venue
- International Journal of Epidemiology
- Publisher
- openRxiv
- Published
- 2018-12-13
- Volume
- 49
- Issue
- 4
- Pages
- 1132-1140
- ISSN
- 0300-5771 (ISSN-L)
- PMC
- PMC7751008
- OpenAlex
- W2951397190
- Cited by
- 96
- References
- 30
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 23 · 2023: 14 · 2022: 11 · 2021: 18 · 2020: 7 · 2019: 2
- FWCI
- 7.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- International Journal of Epidemiology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- Explore Bristol Research (submittedVersion, cc-by)
- Funders
- University of Bristol (MC_UU_00011/1, MC_UU_00,011/3)
- Medical Research Council (MC_UU_00011/3, MC_UU_00011/1, MC_UU_00011, MC_UU_00011/1, MC_UU_00011/3)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, antihypertensive drugs, drug repurposing, systolic blood pressure, blood pressure reduction, calcium channel blockers, protein targets, Alzheimer's disease prevention, Mendelian randomization
- MeSH terms
- Alzheimer Disease, Antihypertensive Agents, Blood Pressure, Humans, Hypertension, Genome-Wide Association Study, Mendelian Randomization Analysis, Drug Repositioning
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