ABSTRACT: BACKGROUND:The objective was a large-scale analysis of the relation between hypertension, memory problems, and brain function. METHODS:The study design was to measure the association between a history of hypertension, and the functional connectivity between 94 brain regions, and prospective and numeric memory, in 19,507 participants from the UK Biobank, with cross-validation in 1,002 participants in the Human Connectome Project, and 13,441 individuals in the second release of the UK Biobank. A history of hypertension was measured by whether individuals were admitted to hospital for the treatment of hypertension, with the control group admissions for other reasons. FINDINGS:A history of hypertension was associated with reduced functional connectivity of the hippocampus, and with reduced prospective memory score (FDR correction p<0.01). The reduced functional connectivity mediated the association between the hypertension history and the prospective memory score. A graded linear relation between both the hippocampal functional connectivity and memory impairment, was found across a wide range of blood pressure (r=-0.04). In 502,537 participants from the UK Biobank, a history of hypertension was associated with impaired prospective memory (p = 9.1 × 10-41, Cohen's d=-0.08) and numeric memory (p = 4.7 × 10-24, Cohen's d=-0.10). The association between hypertension, functional connectivity, and impaired memory was cross-validated with 1,002 participants from the Human Connectome Project; and for functional connectivity in 13,441 individuals in the second release of the UK Biobank imaging dataset. INTERPRETATION:The reduced functional connectivity of the hippocampus, and the memory impairments, both related to hypertension across a wide range of blood pressure, are important for clinical practice.