High blood pressure is a known risk factor for dementia in older adults, but several studies have suggested that blood pressure medications may mitigate the harms of high blood pressure on cognition and memory. For example, in one large trial, treating high blood pressure with blood pressure-lowering drugs reduced cases of mild cognitive impairment (mild memory issues that may be a precursor for Alzheimer’s disease) by 19 percent. However, research has shown conflicting results when it comes to pinpointing which drugs may be most beneficial for cognition. A recent review set out to clarify matters by comparing the impact on memory over time associated with taking blood pressure drugs that cross the blood-brain barrier (a network of closely packed cells that block certain substances from entering the brain) versus those that do not.
Better Memory Recall
The review (Hypertension, September 2021) gathered information from 14 studies that included nearly 12,900 cognitively normal people ages 50 years and older. All of the participants were taking either angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Rather than sort the drugs by type, the researchers categorized them by whether they crossed the blood-brain barrier. Compared with participants who did not take blood pressure drugs that cross the blood-brain barrier, those who did take these drugs had better memory recall for up to three years of follow-up even though they had a higher level of vascular risk.
Angiotensin II In the Spotlight
It makes sense that blood-pressure lowering drugs might confer protection against memory decline. Your brain uses about 20 percent of your body’s oxygen, which is carried in the blood. If blood flow to your brain is reduced by high blood pressure it won’t get sufficient oxygen, and this will impact your brain function. But why should drugs that cross the blood-brain barrier confer most benefit? Mount Sinai neurologist Sam Gandy, MD, PhD, points to the effects of angiotensin II, a protein that contributes to high blood pressure by causing vasoconstriction (the narrowing of blood vessels). Dr. Gandy notes that in the brain, angiotensin II doesn’t just cause narrowed arteries and reduced blood flow. “It also is associated with chronic inflammation and the depletion of cholinergic neurons, brain cells that release acetylcholine, a chemical believed to be important for memory,” he explains. “ACE inhibitors and ARBs that cross the blood-brain barrier may attenuate these cognitive harms as well as lowering blood pressure.”
ARBs More Protective?
Delving deeper, Dr. Gandy posits that ARBs may be more protective of cognition than ACE inhibitors because of their mechanism of action. Angiotensin II achieves its constricting effect by activating specific receptors (essentially docking areas on the surface of cells). ACE inhibitors prevent the activation of these receptors by blocking the body’s production of angiotensin II. ARBs don’t interfere with angiotension II production—instead, they block one specific angiotensin II receptor. “They leave another type of angiotensin II receptor active,” Dr. Gandy notes. “Animal studies have associated the activation of this second receptor with brain cell repair and decreased inflammation in the brain.”
Some Caveats
Dr. Gandy points out that the participants in this study were cognitively normal—further research is needed to definitely show whether blood pressure drugs help people who already are cognitively impaired. He also notes that the participants’ memory recall was assessed by asking them to remember words from a list, and emphasizes that this type of test does not measure executive function. “Executive function is the ability to plan, organize and regulate thought processes, and it’s vital for independence as you age because it aids you with multitasking and decision-making,” Dr. Gandy says. “As an example, preparing a meal requires executive function—it enables you to cook two things on the stove at once and ensures you don’t forget that you also have something roasting in the oven. Most importantly, impairments in executive function are highly correlated with future dementia.”
Something to Go On
Overall, Dr. Gandy says we don’t yet know enough to repurpose blood pressure medications to prevent cognitive impairment. But he adds that these studies do provide us with something to go on. “If you are diagnosed with high blood pressure and medication is recommended, or you already take blood pressure meds, it may be worth checking with your doctor whether the medication crosses the blood-brain barrier,” he says. “If it doesn’t, you may be able to switch to one that does. But don’t rely just on medication—also follow lifestyle interventions that can help you maintain a normal blood pressure.” Self-help strategies include eating a healthful diet, getting plenty of physical activity, quitting smoking, and limiting your alcohol consumption.
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