Certain antihypertensive drugs yield less memory decline in older adults
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Older adults who received antihypertensive drugs that crossed the blood-brain barrier demonstrated improved memory recall compared with those who received other types of antihypertensive drugs, according to new results.
In a press release, Daniel A. Nation, PhD, associate professor of psychological science at University of California, Irvine, said available research has been mixed on which medicines confer the most benefits regarding cognition.
“Studies of angiotensin II receptor blockers and ACE inhibitors have suggested these medicines may confer the greatest benefit to long-term cognition, while other studies have shown the benefits of calcium channel blockers and diuretics on reducing dementia risk,” Nation said.
He added that hypertension occurs decades before the onset of dementia symptoms, affecting blood flow to both the body and the brain. “Treating hypertension is likely to have long-term beneficial effects on brain health and cognitive function later,” he said in the release.
Nation, Jean K. Ho, PhD, postdoctoral scholar at the University of California, Irvine, and colleagues conducted a large, longitudinal meta-analysis that included 12,849 hypertensive patients (aged 50 years) from Australia, Canada, Germany, Ireland, Japan and the United States. Researchers determined blood-brain barrier-crossing potential of antihypertensive drugs used by cognitively normal individuals and assessed the following cognitive domains: attention, executive function, language, verbal memory learning, recall, mental status and processing speed.
According to the researchers, at 3 years, the blood-brain barrier crossing potential of angiotensin II receptor blockers and ACE inhibitors yielded better verbal memory compared with nonpenetrant drugs, despite increasing vascular risk burden. Conversely, older adults receiving nonblood-brain barrier-crossing drugs exhibited better attention over follow-up vs. the blood-brain barrier-crossing group. This latter observation was unexpected, Ho and colleagues wrote, and may be explained by factors unrelated to neuropathological processes, such as test engagement, stress and depression.
Study limitations included the researchers being unable to account for differences in racial/ethnic background and the higher proportion of men vs. women who took blood-brain barrier-crossing drugs.
Ho said the findings represent the most powerful evidence linking brain-penetrant ACE inhibitors and angiotensin receptor blockers to better memory. “It suggests that people who are being treated for hypertension may be protected from cognitive decline if they [receive] medications that cross the blood-brain barrier,” she said in the release.
Perspective
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Suzanne Oparil, MD
This study is a very important contribution because it tested whether the ability to cross the blood-brain barrier determines whether renin-angiotensin system (RAS)-blocking drugs, including ACE inhibitors and angiotensin receptor blockers, are effective in preserving cognitive function and preventing dementia in older adults with hypertension.
The data summarized in the article come from a variety of sources, including randomized, double-blind trials of antihypertensive treatments, prospective cohort studies and retrospective observational studies and provide more or less strong evidence that the ability to cross the blood-brain barrier of ACE inhibitors and angiotensin receptor blockers is associated with a reduction in cognitive dysfunction (memory and recall) in adults aged at least 50 years with hypertension. However, there was a dissonance in that the apparent cognitive benefit did not seem to correlate with the ability to pay attention. In fact, ACE inhibitors and angiotensin receptor blockers that did not penetrate the blood-brain barrier appeared to have a more beneficial effect on measures of attention, and there was no evidence of an effect of brain barrier crossing potential on a variety of cognitive domains, eg, executive function, language and verbal memory (learning). So, the issue is complicated. Further, much of the background literature cited refers to studies done in rodents, and it is not clear whether rat and mouse studies correlate well findings in humans. Importantly, it is not clear whether the evidence is so strong that patients should quit taking some of the very popular RAS-blocking agents that apparently do not cross the blood-brain barrier, yet have been shown to reduce BP and CVD events in randomized controlled clinical trials. This is an important issue for health care providers as well as patients, and more research is clearly needed.
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