It is becoming increasingly clear that what’s good for the cardiovascular system is good for the brain—and that a crucial factor is blood pressure control. The strongest evidence yet for this comes from the SPRINT MIND study, which appeared in the Journal of the American Medical Association in January 2019.
What does the acronym SPRINT MIND stand for? Don’t even try to guess.
A study to remember
The new study is a follow-up to the landmark NIH-funded SPRINT trial, published in 2015. SPRINT involved more than 9,300 people (ages 50 and over, average age 68) with hypertension and at least one other cardiovascular risk factor (but not diabetes, dementia, or history of stroke), who received carefully supervised hypertension treatment at 102 medical centers across the U.S. Half were randomly assigned intensive treatment—that is, they took medication to reduce their systolic blood pressure (the top number) to a goal of less than 120, considered normal. The other half aimed for the standard systolic target of 140 or lower.
SPRINT was halted early, in 2015, after three years, when it was found that cardiovascular events and mortality rate were reduced by one-quarter in the intensive-treatment group compared to standard treatment. These findings were largely responsible for the still-debated lowering of blood pressure goals—from 140/80 to 130/80—by the American College of Cardiology and the American Heart Association in 2017.
After SPRINT ended and the supervised interventions stopped, the MIND phase began, with researchers continuing to follow 8,560 of the participants for two more years to see if the two groups differed in terms of cognitive health and dementia incidence. During this follow-up period, differences in systolic blood pressure between the groups narrowed. Cognitive testing found no statistically significant difference in the incidence of “probable dementia” over the total five-year period, which was the primary endpoint.
Normally, that would be the end of the story. But what garnered the attention of researchers and the general public were the secondary endpoints. There was a 19 percent lower rate of new cases of mild cognitive impairment (MCI) in the intensive treatment group. (MCI is a gray area between normal cognition and early dementia, involving cognitive problems more severe than those seen with normal aging but less severe than dementia.) In absolute numbers, 287 of 4,280 intensive-treatment participants and 353 of 4,280 in the standard-treatment group developed MCI over the total five-year period. That means that 65 people would need to be treated intensively to prevent one case of MCI. Results were similar for another secondary endpoint, a composite of MCI plus probable dementia—402 versus 469 cases, a 15 percent reduction.
Secondary endpoints are tricky—less reliable and harder to interpret than primary endpoints, for a number of methodological reasons. As the authors noted about the MCI finding, “some caution should be exercised in interpreting this result, both because MCI was not the primary cognitive outcome of the trial and because it is not clear what this effect may mean for the longer-term incidence of dementia.” While MCI is often a precursor to dementia, such progression is not inevitable; indeed, many people with MCI remain stable for years, and some even improve and revert to normal cognition.
The bigger picture
Many smaller clinical trials have looked at whether treating hypertension can reduce the risk of cognitive impairment and dementia, including Alzheimer’s disease, and the results have been mixed. It makes sense that high blood pressure is bad for the brain. After all, it can harm small blood vessels that nourish brain cells, resulting in damage that increases the risk of dementia as well as stroke; and vascular factors may affect amyloid and other neurodegenerative protein deposits in the brain.
What’s more, large, long-term observational studies have found that people with midlife hypertension, especially when it is untreated or poorly controlled, are more likely to develop serious cognitive decline and dementia later in life. But that doesn’t necessarily mean that lowering blood pressure with medication, especially if started at older ages, will reduce those risks.
If hypertension is linked to dementia risk, why is it hard to prove that lowering blood pressure reduces that risk? For one thing, there are different kinds of blood pressure medications, and they may not be equally effective at reducing dementia risk. (SPRINT MIND did not differentiate among different drugs in terms of effect on blood pressure or cognition; most people in the intensive treatment group took more than one drug.) Age is another variable. The brain benefits of lowering blood pressure may be most pronounced in people who develop hypertension and start treatment in midlife.
In addition, it may take even larger, longer studies than SPRINT to prove benefits against dementia. Had the intensive SPRINT hypertension treatment continued as planned and not been halted early because of the striking cardiovascular findings, the reduction in dementia incidence might have achieved statistical significance, the researchers suggested. In fact, cognitive benefits may still be accruing, which is why the Alzheimer’s Association is funding a two-year continuation of SPRINT MIND that will also examine whether any particular hypertension drugs have had a stronger cognitive benefit.
Still, it may be tricky to generalize from SPRINT, since participants received top-notch and frequent medical supervision (including highly accurate blood pressure readings, monitoring of adverse effects, and adjustment of medications when needed), which many people don’t get in the real world. And since SPRINT excluded people with diabetes or a history of strokes, it’s not known if the findings would apply to them—or to younger people.
SPRINT MIND “offers great hope,” according to the accompanying editorial, that lowering elevated blood pressure may help protect against cognitive impairment. Nevertheless, even with intensive blood pressure treatment, many participants still developed MCI and dementia. And there are risks in aiming for more aggressive blood pressure targets. The original SPRINT study found that people in the intensive-treatment group were somewhat more likely to have complications, notably hypotension (low blood pressure), fainting, electrolyte abnormalities, and acute kidney injury or failure, despite adjustment of medication when needed and frequent monitoring for adverse effects. Critics of intensive treatment worry that those potential adverse effects will occur more often in real-world settings, especially for older people, and will make the lower goals unachievable or unsustainable.
Bottom line: lower is better
If the latest findings are confirmed by other ongoing trials, that will be another reason to lower elevated blood pressure to as close to normal as possible—to reduce the risk of cognitive decline, MCI, and dementia. But setting appropriate targets for blood pressure will always require balancing risks and benefits for each individual. So if you are being treated for hypertension, discuss your progress with your doctor, as well as the potential benefits and risks of lower treatment goals.
Achieving normal blood pressure (less than 120/80)—or the latest ACC/AHA goal (130/80)—is very difficult for many people with hypertension. Even the longtime standard goal of 140/90 can be hard to achieve. Furthermore, the debate about blood pressure goals is largely academic for the millions of Americans with hypertension who are taking inadequate steps to control it or have little or no access to medical care, and whose numbers thus remain far above any of the goals.
Of course, the best option is to lower blood pressure via lifestyle changes such as losing excess weight, improving diet, exercising, limiting sodium intake, and not smoking. Such steps may make drugs unnecessary or, if medication is needed, allow you to take a lower dose or fewer drugs.