Hypertension and Dementia: A Mendelian Randomisation Study Assessing Potential Causal Relationships with All-Cause Dementia, Alzheimer’s Disease and Vascular Dementia in the UK Biobank

Hypertension is a key modifiable risk factor for longevity. However, evidence linking hypertension to dementia remains inconsistent, potentially due to subtype-specific effects. We aimed to examine relationships between systolic blood pressure (SBP) and risk of Alzheimer’s disease (AD) and vascular dementia (VaD) using individual-level Mendelian randomization (MR) analyses. Logistic and Cox regressions assessed the association of blood pressure traits with all-cause dementia, AD and VaD in the UK Biobank cohort. Observational analyses indicated SBP was associated with increased risk of all dementia outcomes. MR analyses indicated genetically proxied SBP was associated with increased risk of all-cause dementia (OR=1.26, [95% CI:1.15;1.38]; HR=1.28, [95% CI:1.17;1.40]). When stratified by subtype, higher SBP was associated with increased risk of VaD (OR=1.56, [95% CI:1.25;1.93]; HR=1.58, [95% CI:1.28;1.97]), but not AD (OR=1.10, [95% CI:0.95;1.26]; HR=1.11, [95% CI:0.97;1.28]). Post-hoc analyses supported a differential effect. Hypertension appears to be a greater risk factor for VaD than AD.