A large-scale meta-analysis led by University of California, Irvine researchers provides the strongest evidence yet of which blood pressure medications help slow memory loss in older adults: those that can travel out of blood vessels and directly into the brain.
The findings, published in the American Heart Association journal Hypertension, will be of interest to the 91 million Americans whose blood pressure is high enough to warrant medication, as well as the doctors who treat them.
Previous studies have shown that some hypertension medications can help stave off dementia in individuals who are already hypertensive. However, which medications and how have been a mystery.
High blood pressure, or hypertension, is a risk factor for cognitive decline and dementia in older adults. Nearly half of American adults have elevated blood pressure.
Treating high blood pressure with blood pressure-lowering medicines reduced the cases of mild cognitive impairment by 19% in one large trial (SPRINT MIND).
ACE inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers and diuretics are different classes of blood pressure-lowering medicines. Each class acts in a different way to reduce blood pressure, and some cross the blood-brain barrier, thereby impacting cognitive function.
First study on blood pressure meds
“This wasn’t an examination of one specific drug or even one class of drugs; it was a property of the drug – whether it gets into the brain.
“If physicians were convinced that this property is valuable, it wouldn’t require a dramatic change to their prescribing practice. They could simply choose another drug within the same family that crosses the blood-brain barrier,” said corresponding author Daniel Nation, associate professor of psychological science at UCI.
This is the first meta-analysis to compare the potential impact over time of blood pressure lowering medicines that do vs. those that do not cross the blood-brain barrier. The medicines were evaluated for their effects on several cognitive domains, including attention, language, verbal memory, learning and recall.
“Hypertension occurs decades prior to the onset of dementia symptoms, affecting blood flow not only in the body but also to the brain,” Nation said. “Treating hypertension is likely to have long-term beneficial effects on brain health and cognitive function later.”
The meta-analysis by Nation and lead author Jean Ho was 10 times larger than any prior work isolating the blood-brain-barrier-crossing characteristic of hypertension drugs. It included more than 12,800 people age 50 and older in 14 studies carried out in the United States, Australia, Canada, Germany, Ireland and Japan.
Two classes of popular blood pressure medications were examined: angiotensin-converting enzyme inhibitors (“ACE inhibitors”) and angiotensin receptor blockers. But rather than sorting the drugs by type, the researchers categorized them by whether or not they cross the blood-brain barrier.
The researchers found that people who took hypertension medications that cross the blood-brain barrier experienced less cognitive decline over three years of follow-up than those who used blood pressure drugs that stay only in the bloodstream. Individuals had to take the medication for at least six months to be included in the study.
The meta-analysis covered a range of cognitive tests, but the aspect with statistically significant benefit was word list recall, which Nation said is a strong indicator of overall memory abilities.
“If a medication can have an effect on someone who has only mild memory changes in a relatively short period, like three years, that could change their trajectory over the long run,” said Ho, a postdoctoral scholar at the UCI Institute for Memory Impairments and Neurological Disorders.
What was not found
No measurable differences in effect were found between the two medication types when researchers looked at learning, language skills and executive function. However, there was one surprising result: The cohort that took drugs that do not cross the blood-brain barrier had better outcomes on attention.
Ho and Nation point out that while cardiovascular disease tends to negatively affect attention, such deficits are not a common sign of dementia. The two are pursuing new studies to better understand that finding.
Although there is no widespread agreement on which drugs cross the blood-brain barrier, the UCI researchers put the following in that category:
- Ramipril, and
- Telmisartan, and
When blood pressure is too high
Blood pressure is considered elevated at 120/80 mm Hg and higher. The current American Heart Association/American College of Cardiology guidelines for treating high blood pressure suggest changes to diet and activity levels to lower blood pressure.
The AHA/ACC also recommend adding blood pressure-lowering medication for people with levels of 130/80 mm Hg or higher depending on their risk status. If blood pressure reaches 140/90 mm Hg, blood pressure-lowering medication is recommended.
Limitations of this analysis are that the authors could not account for differences in racial/ethnic background based on the available studies, and there is a higher proportion of men vs. women in the group who took medications that cross the blood-brain barrier.
This is an important area of future research since previous studies have shown that people from various racial/ethnic backgrounds may respond differently to different blood pressure medications.