Lower Blood Pressure Targets May Stave Off Cognitive Decline, SPRINT MIND Substudy Reveals

By Ronan Factora, MD

As geriatricians, we regularly see patients with memory problems and grapple with mysteries that continue to surround the development of Alzheimer’s disease and other forms of age-associated cognitive impairment. We are naturally excited to see large randomized controlled trials like the SPRINT study on optimizing blood pressure targets, where outcomes for multiple health dimensions are robust. In the SPRINT study (2009-2015) patients who met the inclusion criteria were medically managed to a systolic blood pressure target of <120 mmHg (vs. the standard <140 mmHg), and had significantly better outcomes in terms of cardiovascular and cognitive health as well as all-cause mortality.

A series of criticisms and concerns about study design, settings and methods of measuring blood pressure began to surface after publication. However, given the large numbers in the trial (n=9,361, ³50 years old), and the size of the deltas between treatment and control groups — including dramatic subanalysis findings on white matter lesions — it would be a mistake to throw the baby out with the bathwater.

SPRINT Mind results are a call to action

The SPRINT MIND subanalysis was conducted after publication of the core SPRINT study, and includes 673 patients, with 454 of these receiving brain MRIs upon entry into the study and again around four years later. The group that was managed to <120 mmHg had an increase in white matter lesion volume of 0.28 cm3 (cubed) compared with a 0.92 cm3 for the group managed to a <140 mmHg target, a factor of over three times less. Since larger amounts of white matter disease correlate to greater probability of cognitive impairment, this demonstration of brain tissue benefit provides a strong incentive to manage our hypertensive, but otherwise healthy, older patients toward the <120 blood pressure target.

At Cleveland Clinic, we are utilizing the Mini-Cog© instrument to identify early mild cognitive impairment (MCI). This test is now familiar to geriatricians and primary care doctors alike, with a clock to be drawn and three words to be recalled. It is particularly useful because patients who score poorly on the test may be functioning normally in their activities of daily living. Without the test, they might fall under the radar until after further deterioration occurs. Using this instrument, and knowing the SPRINT MIND trial results, we are in position to do more than prepare patients and their families for cognitive impairment – we may be able to help prevent or slow the decline in individuals who are at risk but have not yet developed MCI.

Significant caveats remain

The SPRINT findings are far from a one-size-fits-all prescription. Because some medications and diseases confound the impact of blood pressure management, the study excluded patients with existing diabetes, kidney disease, and a number of other conditions. Comorbidities such as neuropathy from diabetes, autonomic involvement in Parkinson’s disease and related conditions, and side effects of drugs like tamsulosin for prostate enlargement can complicate management of hypertension. Decisions on how to best manage these patients’ blood pressures must be made on a highly individualized basis.

For patients who do qualify for the more aggressive blood pressure control, physicians will want to watch for potential side effects of inducing hypotension. The more we push blood pressure down, the greater the risk of syncope and fall, particularly in those who have orthostatic blood pressure (a drop in blood pressure when changing from lying down to standing). If we achieve our targets but wind up with patients who have broken hips, instead of improving longevity, we have increased their one-year mortality odds manyfold.

We have to make sure the SPRINT guidelines are appropriate for each patient we see, taking into account that person’s medical conditions, medications, and ultimate goals of medical management. That said, if hypertension is the only significant medical problem they are dealing with, then I believe we have legitimate support from the SPRINT study to try to achieve the suggested blood pressure management goals.

The Mini-Cog as ongoing litmus test

As we collect the data from the Mini-Cog at Cleveland Clinic and other centers, and as these blood pressure targets are actually advanced, will we see less MCI? In a primary care setting where we screen with the Mini-Cog, managing blood pressure to the <120 mmHg target should result in fewer positive screenings. To the extent that we can get pre- and post-management MRI data, we will have even more useful data to answer this question.

My colleagues and I are working in that all-too-familiar territory where the evidence drives us from complacency with the status quo to action, even as we see the work yet to be done in stratifying the populations that will benefit and the finer points of the treatment. My team looks forward to being instrumental in that effort. While the concerns raised about the study should not be dismissed, what is clear is that the SPRINT Mind results are pointing us toward better prevention of MCI and dementia.