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Although high blood pressure may put patients at risk for dementia, a class of antihypertensives appears to have a preventive effect.
Hypertension is a known risk factor for cognitive decline, Alzheimer disease, and vascular dementia, which has led to the exploration of the possible salutary effects of antihypertensives on cognitive function in aging adults. The findings from several studies have been equivocal, however.
Researchers from the University of Southern California in Los Angeles who are affiliated with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) have helped clarify the results of earlier studies. They found that angiotensin II receptor blockers (ARBs), particularly those that cross the blood-brain barrier, were associated with greater memory preservation and fewer white matter hyperintensities than other antihypertensives in a population of nondemented adults in the second half of life (age 55 to 91 years).1
Results of a meta-analysis
The ADNI researchers cited a systematic review that led to a closer examination of cognitive decline in patients receiving antihypertensive agents.2 That review consisted of 19 randomized trials (n = 18,â515) and 11 other studies (n =831,â674). It analyzed the effects of antihypertensive therapy on cognition and the incidence of dementia and found that although antihypertensive therapies appear to have beneficial effects, the effects may differ according to the drug class used. ARBs stood out as the most effective.
The ADNI study included 1626 participants who were divided into 3 groups: ARB users, users of other antihypertensive drugs, and normotensives. Participants were followed up for 3 years, and comparisons were made regarding cognition and magnetic resonance imaging measures of brain volume and white matter hyperintensities. Cognitive measures included elements of the Wechsler Memory Scale–Revised (WMS-R) Logical Memory II subtest, Rey Auditory Verbal Learning Test (RAVLT), Wechsler Adult Intelligence Scale–Revised Digit Span, Trail Making Tests, Animal Fluency and Vegetable Fluency tests, and the Boston Naming Test.
The researchers found that users of antihypertensives other than ARBs generally had poorer performance on cognitive tests than did normotensives at baseline, and the difference was statistically significant in regards to RAVLT Immediate Recall (P = .002), Delayed Recall (P < .001), and Recognition Memory (P = .001) and Trail Making tests A (P < .001) and B (P = .01). At 3 years’ follow-up, WMS-R Logical Memory Immediate and Delayed Recall scores were also poorer to a statistically significant degree (P = .02 and P = .007, respectively). As for ARB users, they demonstrated poorer performance on Trail A than normotensives at baseline.
Over the 3-year follow-up period, those in the ARB group who were taking agents that crossed the blood-brain barrier performed better on several parameters than those taking other agents: RAVLT Delayed Recall (P = .04), Logical Memory Immediate (P = .02), and Delayed Recall (P = 0.05). They also had fewer white matter hyperintensities than those taking other antihypertensive agents (P = .008) and those taking ARBs that do not cross the blood-brain barrier (P = .05). In fact, users of antihypertensive agents that crossed the blood-brain barrier performed better on RAVLT Delayed Recall over time than other study participants, including normotensives (P < .01).
The findings help clarify the beneficial role of antihypertensive therapy in reducing the risk of dementia in persons with cardiovascular disease. Although hypertensive patients may be at higher risk for cognitive decline than normotensive persons, use of ARBs that cross the blood-brain barrier appears to have a preventive effect.
1. Ho JK, Nation DA; Alzheimer’s Disease Neuroimaging Initiative. Memory is preserved in older adults taking AT1 receptor blockers. Alzheimers Res Ther. 2017;9:33.
2. Levi Marpillat N, Macquin-Mavier I, Tropeano AI, et al. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens. 2013;31:1073-1082.