Blood Pressure Medications that Cross Blood-Brain Barrier Could Help Preserve Memory Recall in Older Adults


A meta-analysis of 14 studies suggests use of antihypertensive agents known to cross the blood-brain barrier was associated with improved memory recall over time compared to nonpenetrant agents in older adults with hypertension.

Daniel Nation, PhD, University of California, Irvine

Daniel Nation, PhD

Data from a large meta-analysis suggests some blood pressure medications were linked to better memory recall in aging adults than others.

Results of the meta-analysis, which included data from more than a dozen studies, indicates use of blood pressure medications known to cross the blood-brain barrier were associated with better memory recall over up to 3 years of follow-up compared to those taking nonpenetrant medications, despite being at a higher vascular risk burden.

“Research has been mixed on which medicines have the most benefit to cognition,” said study investigator Daniel Nation, PhD, an associate professor of psychological science in the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine, in a statement from the American Heart Association. “Studies of angiotensin II receptor blockers and angiotensin-converting-enzyme (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.”

In what investigators are calling the first of its kind, the National Institute on Aging of the National Institutes of Health-funded study was designed as a meta-analysis aimed at comparing the impact of blood pressure medications that do cross the blood-brain barrier to those that do not on cognitive health of aging adults with hypertension. Searching the ALOIS, Web of Science, and multiple ProQuest databases, Nation and a team of colleagues identified 14 studies for inclusion in their meta-analysis.

The main inclusion criterion for the meta-analysis required studies to involve adult humans aged 50 years and older with hypertension, assess the effects of ACEs or ARBs, assess at least 1 neuropsychological outcome, and provide sufficient data to calculate for effect sizes. Investigators noted only 3 types of study were included in the meta-analysis: randomized, double-blind trials, prospective cohort studies, and retrospective cohort studies. Additionally, randomized clinical trials were required to have an intervention period of at least 6 months as previous research indicates this is the minimum amount of treatment time required for benefits to be achieved.

Of the 14 studies identified for inclusion, 10 were prospective cohort studies, 3 were retrospective cohort studies, and 1 was a randomized trial. From these studies, investigators identified a cohort of 12,849 patients without evidence of dementia at baseline for analysis.

Results of the investigators’ analyses indicated effect sizes for change in cognitive domains varied among the 7 domains included in the analysis. The maximum effect size was observed for verbal memory (0.07; 95% CI, 0.01-0.12), which investigators pointed out suggests those using drugs crossing the blood-brain barrier exhibited better memory recall over the 3-year follow-up.

Investigators also pointed out the minimum effect size was observed for attention (-0.17; 95% CI, -0.23 to -0.10; P=.02), which indicates those using nonpenetrant displayed better on attention measures over time than those using drugs with the potential to cross the blood-brain barrier. However, investigators suggested could be attributable to a lower baseline vascular risk seen among these patients.

Investigators also highlighted there were no significant differences over time based on type of medication in regard to mental status or other cognitive domains, including executive function (-0.03; 95% CI, -1.10 to 1.04], P=.80), language (-0.01; 95% CI, -0.06 to 0.04; P=.41), or verbal memory (learning) (g=0.05; 95% CI, -0.05 to 0.15; P=.19).

Investigators noted multiple limitations within their analysis for consideration. These included the inability to account for differences based on racial/ethnic background from available studies and the apparent disparity in rates of men versus women who receiving medications that cross the blood-brain barrier.

“These findings represent the most powerful evidence to-date 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 medications that cross the blood-brain barrier,” said study co-investigator Jean K. Ho, PhD, a postdoctoral fellow at the University of California, Irvine, in the aforementioned statement.

This study, “Blood-Brain Barrier Crossing Renin-Angiotensin Drugs and Cognition in the Elderly,” was published in Hypertension.

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