High Blood Pressure and Risk of Dementia: a Two-Sample Mendelian Randomization study in the UK Biobank

Abstract BACKGROUND Findings from randomized controlled trials have yielded conflicting results on the association between blood pressure (BP) and Dementia traits. We tested the hypothesis that a causal relationship exists between systolic (SBP) and/or diastolic (DBP) blood pressure and risk of Alzheimer’s Disease (AD). METHODS We performed a Generalized Summary Mendelian Randomization (GSMR) analysis using summary statistics of a Genome Wide Association Studies meta-analysis of 299,024 individuals of SBP or DBP as exposure variables against three different outcomes: ( 1 ) AD diagnosis (IGAP), ( 2 ) maternal (MFH-UKBB) and ( 3 ) paternal (PFH-UKBB) family history of AD. Finally, a combined meta-analysis of 368,440 individuals that included these three summary statistics was used as final outcome (MA-AD). RESULTS GSMR applied to IGAP revealed a significant effect of high SBP lowering the risk of AD (bGSMR = -0.19; p = .04). GSMR applied to MFH-UKBB (SBP, bGSMR = -0.12, p = .02; DBP, bGSMR = -0.10, p = .05) and to PFH-UKBB (SBP, bGSMR = -0.16; p = .02; DBP, bGSMR = -0.24, p = 7.4 x 10-4) showed the same effect. A subsequent meta-analysis (MA-AD) confirmed the overall significant effect for the other SBP analyses (bGSMR = -0.14, p = .03). The DBP analysis in the MA-AD also confirmed a DBP effect on AD (bGSMR = -0.14; p = .03). CONCLUSIONS A causal effect exists between high BP and a reduced late life risk of AD. The results were obtained through careful consideration of confounding factors and the application of complementary MR methods on independent cohorts.