A Game-Changer to Prevent Cognitive Loss? Maybe Not

Kenneth W. Lin, MD, MPH


March 15, 2019

Editorial Collaboration

Medscape &

This transcript has been edited for clarity.

Hello, everyone. I'm Dr Kenny Lin, a family physician at Georgetown University Medical Center in Washington, DC, and I blog at Common Sense Family Doctor.

Family physicians know that lowering blood pressure (BP) with medication has risks and benefits for preventing heart attacks and strokes. But does it also reduce the risk of developing dementia? A 2009 Cochrane review[1] of four randomized controlled trials of BP treatment in 16,000 patients with an average age of 75 years found no differences in Mini-Mental State Examination changes or the incidence of dementia between treatment and placebo groups. Subsequently, two[2,3] analyses of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial found that, compared with a systolic BP target of 140 mm Hg, intensive treatment to a systolic of 120 in persons with type 2 diabetes did not affect cognitive function after nearly 7 years of follow-up.

Although observational studies[4] have shown associations between high blood pressure and dementia, it has been challenging to study the effect of lowering BP, for several reasons. First, it's a lot easier to measure a heart attack or stroke than subtle changes in cognition. And because studies generally focus on cardiovascular outcomes, they may not follow patients long enough to see significant changes in cognitive outcomes, if they exist. It also isn't clear whether mid-life hypertension is more of a risk factor for dementia than late-life hypertension, when cerebral small-vessel disease may already be established or irreversible.

The SPRINT Memory and Cognition in Decreased Hypertension (SPRINT MIND) study[5] was conducted as part of the NIH's Systolic Blood Pressure Intervention Trial (SPRINT), which I discussed in a previous Medscape commentary. Last July, the principal investigator announced that the group that had been randomized to a systolic BP target of 120 mm Hg had a significantly lower risk of developing mild cognitive impairment than the control group. Now that their complete findings have finally been published in JAMA, we can take stock of this study's implications for primary care.

In contrast to last summer's glowing headlines that heralded the study as a game-changer in preventing dementia, the actual results were mixed. Most important, SPRINT MIND did not demonstrate that intensive BP control prevents dementia, because the results for this outcome, the study's primary endpoint, were statistically nonsignificant.

For mild cognitive impairment, a secondary endpoint, the 19% reduction over a median follow-up of 5 years—which was significant—sounds impressive, but the absolute risk reduction was 1.34%. This means it was necessary to treat 75 persons to a lower BP goal—generally requiring one more antihypertensive medication—to prevent one case of mild cognitive impairment for the study duration. And many persons with mild cognitive impairment do not go on to develop dementia. So is this benefit alone worth the increased risks of syncope, severe hypotension, or acute kidney injury? I'm not sure that it is.

Even though I am not about to start BP medications in normotensive adults to lower their risk for cognitive impairment, the SPRINT MIND results may make the benefit-versus-harm assessment more favorable for patients already receiving treatment. In other words, if you and your hypertensive patient were already thinking about aiming for a lower systolic BP goal for cardiovascular prevention anyway, even the possibility of additional cognitive benefits might be good enough to sway your decision to treat.

There are some caveats, though. SPRINT did not include patients with a history of stroke or diabetes. As I noted, ACCORD found no cognitive or cardiovascular benefits from a lower systolic BP target. SPRINT participants were all 50 years or older and had an average Framingham risk score of 20%, so clinicians who apply the results to adults at low or intermediate cardiovascular risk do so at their patients' peril.

In summary, while not game-changing, these findings should be discussed with patients at high cardiovascular risk in decision-making about antihypertensive therapy, especially those who place greater value on preserving cognitive function relative to avoiding medication side effects.

This has been Dr Kenny Lin for Medscape Family Medicine. Thank you for listening.

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