Repurposing antihypertensive drugs for the prevention of Alzheimer’s disease: a Mendelian Randomization study

BackgroundEvidence concerning the potential repurposing of antihypertensives for Alzheimers 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 Alzheimers disease.\n\nMethodsWe used summary statistics from genome wide association studies of SBP (from UK Biobank) and Alzheimers disease (from the International Genomics of Alzheimers 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 Alzheimers disease. We also report the effect of lowering SBP on Alzheimers disease by combining all drug targets and without consideration of the associated drugs.\n\nResultsThere was limited evidence that lowering SBP, via antihypertensive drug classes, affected Alzheimers 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 Alzheimers 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).\n\nConclusionsLowering SBP itself is unlikely to affect risk of developing Alzheimers disease. Consequently, if specific antihypertensive drug classes do affect risk of Alzheimers disease, they are unlikely to do so via SBP.\n\nKEY MESSAGESO_LIThis is the first study to use Mendelian randomization to estimate the effects of the twelve most common antihypertensive drug classes on Alzheimers disease.\nC_LIO_LILowering systolic blood pressure itself is unlikely to affect risk of developing Alzheimers disease.\nC_LIO_LIIf specific antihypertensive drug classes do affect Alzheimers disease risk, they are unlikely to do so via systolic blood pressure.\nC_LI