Based on “angiotensin hypothesis” that stimulation of AT2 receptors decreased risk for ischemia while stimulation of AT4 receptors help preserve memory, preDIVA trial was design to evaluate difference between angiotensin-II-stimulating (AT-II-S) and angiotensin-II inhibiting (AT-II-I) antihypertensive in lowering the risk for dementia. Non-demented community-dwelling individuals between 70-78 years old were follow up during 6-8 years. Antihypertensive were subcategorized on AT-II-S, AT-II-I and other. Cognitive status was evaluated using Mini-Mental State Examination and Visual Association Test and dementia was made according to DSM-IV criteria. Three models were designed to assess the influence of competing risk for death. Model 1 was unadjusted, model 2 was adjust for baseline systolic blood pressure (BP), diabetes mellitus, cardiovascular disease (CVD) and stroke, while model 3 was adjust for body mass index, hypolipemic drug use, glomerular filtration rate and trial intervention. Subgroup analyses stratified by history of diabetes, stroke, CVD, and systolic BP was also performed to exclude influence on the results. Dementia incidence was 5.6% in AT-II-S, 8.2% in AT-II-I, and 6.9% in both antihypertensive type users. AT-II-S group was associated with a 45% lower risk of incident dementia compared to AT-II-I group during the 6.7 years of follow-up, particularly evident in individuals without a history of CVD. Difference was not due to an increased risk of mortality and results were independent of systolic BP, cardiovascular risk factors, and history of stroke or diabetes. Among AT-II-S dihydropyridine calcium channels blockers were associated with highest and thiazides the lowest effect on dementia risk.
Jan Willem van Dalen, Zachary A Marcum, Shelly L Gray, Douglas Barthold, Eric P Moll van Charante, Willem A van Gool, Paul K Crane, Eric B Larson, Edo Richard. Association of Angiotensin II-Stimulating Antihypertensive Use and Dementia Risk: Post Hoc Analysis of the PreDIVA Trial. Neurology. 2021 Jan 5;96(1):e67-e80. doi: 10.1212/WNL.0000000000010996. https://pubmed.ncbi.nlm.nih.gov/33154085/