Observational studies suggest protective effects of antihypertensive medications on risk of
dementia1–6 independently or in addition to their ability to control blood pressure, and that
these effects may be specific to the class of drugs to which they belong. A postmortem study of
subjects with Alzheimer disease (AD) dementia showed that treated hypertensive subjects had
less AD dementia neuropathology than untreated hypertensive and normotensive subjects,7
while imaging studies showed preserved hippocampus in normotensive and treated hypertensive
subjects.8,9 However, clinical trials evaluating antihypertensive medications for dementia prevention
found no risk reduction,10–12 which could be explained by dementia being a secondary
outcome and therefore insufficiently powered. Additionally, the majority of these studies were
confounded by combined antihypertensive medication use11,13–16 to achieve acceptable blood
pressure. There are few studies with equivocal evidence regarding the role of hypertension
(HTN) and no randomized clinical trials evaluating the effects of antihypertensive medications
on progression of mild cognitive impairment (MCI) to dementia.17–19