Intensive BP Lowering Cuts MCI Risk: Results Published

Megan Brooks

Disclosures

January 28, 2019

Intensive blood pressure (BP) lowering cuts the risk for mild cognitive impairment (MCI), new research shows.

In results from the Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT MIND) published online in JAMA today, researchers found that targeting systolic blood pressure (SBP) to 120 mmHg lowered the risk for MCI by 19% compared with targeting to 140 mmHg.

The SPRINT MIND findings, which were featured prominently at the Alzheimer's Association International Conference (AAIC) 2018 and were reported by Medscape Medical News, were not definitive on reducing risk for dementia, however, perhaps because the trial wasn't long enough, the investigators note.

To further the investigation, the Alzheimer's Association has awarded more than $800,000 to fund a 2-year extension of the trial, named SPRINT MIND 2.0, to help clarify the impact of aggressive BP treatment on reducing the risk for dementia.

Overall, the SPRINT MIND results are "compelling and offer real hope," Maria C. Carrillo, PhD, chief science officer for the Alzheimer's Association, told Medscape Medical News.

"The mild cognitive impairment finding is tremendous. You have to go through mild cognitive impairment to get to dementia, and when you prevent new cases of mild cognitive impairment, you are preventing new cases of dementia. But we need clarity on the dementia component," Carrillo added.

"Important Public Health Message"

To recap, the parent SPRINT study enrolled nearly 9361 cognitively healthy adults (mean age, 68 years) with hypertension who were at increased risk for cardiovascular disease (CVD). The patients were randomly assigned to undergo intensive lowering of SBP (goal, <120 mmHg) or standard treatment (goal, <140 mmHg).

In 2015, the trial was stopped early because of findings indicating benefit on its primary outcome of CVD events and all-cause mortality.

The SPRINT MIND study was designed as part of SPRINT, with probable dementia as a primary outcome. Secondary outcomes were MCI and the composite of any cognitive impairment, probable dementia, or MCI. Analyses included 4278 individuals in the intensive treatment arm and 4285 in the standard treatment arm.

The median treatment period was 3.3 years, and total median follow-up was 5.11 years. During follow-up, patients in the intensive arm had statistically significant reductions in the risk for MCI (14.6 vs 18.3 cases per 1000 person-years; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 - 0.95) and the risk for combined cognitive impairment outcome (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74 - 0.97).

However, the reduction in all-cause probable dementia with intensive treatment failed to reach statistical significance (7.2 vs 8.6 cases per 1000 person-years; HR, 0.83; 95% CI, 0.67 - 1.04).

"The mild cognitive impairment finding, in and of itself, is an important public health message. Healthy blood pressure management does actually contribute to brain health and reduction of risk of mild cognitive impairment," Carrillo said.

But dementia takes longer to develop than MCI. "Consequently, the early termination of the study likely affected the number of dementia cases detected," SPRINT principal investigator Jeff Williamson, MD, chief of geriatric medicine and gerontology at Wake Forest School of Medicine, Winston-Salem, North Carolina, said in a news release.

With the funding from the Alzheimer's Association, more than 7000 of the participants will be followed for an additional 2 years in SPRINT MIND 2.0.

"Further cognitive assessment of the SPRINT MIND study participants might discover enough additional cases of probable dementia to support a more definitive conclusion," Williamson said.

Marathon Journey

Further assessment of potential side effects of intensive SBP lowering, as well as comparative data on the effects of different classes of antihypertensive agents on cognitive outcomes, are also needed, writes Kristine Yaffe, MD, San Francisco Veterans Affairs Medical Center and the Departments of Psychiatry, Neurology, and Epidemiology and Biostatistics at the University of California, San Francisco, in an accompanying editorial.

For older adults concerned about Alzheimer's disease (AD) and related dementia, "SPRINT MIND offers great hope," writes Yaffe.

"The study demonstrates that among those with hypertension, intensive SBP control can reduce the development of cognitive impairment. This approach should be studied with other vascular health interventions, such as physical activity and other promising approaches for prevention. Indeed, the timing is right to investigate multidomain risk reduction strategies personalized for older adults and their individual risk profiles," she adds.

Yaffe notes that, eventually, this "modifiable risk factor approach could be combined with disease-modifying drugs so that one day, it will be possible to identify persons at risk of AD and related dementia (either by biomarkers, genetics, or cognitive symptoms) and offer an effective strategy for prevention of cognitive impairment."

Although the approach investigated in the SPRINT MIND study may not be the final one for the prevention of AD or other cognitive impairment, the study represents a "major leap forward in what has emerged as a marathon journey," Yaffe concludes.

The SPRINT study is funded by the National Institutes of Health. Dr Williamson and Dr Carrillo have disclosed no relevant financial relationships. Dr Yaffe serves on the data safety and monitoring boards for National Institutes of Health–sponsored studies, Takeda, and Eli Lilly and is a member of the Beeson Scholars in Aging Scientific Advisory Board and a senate member of the German Center for Neurodegenerative Diseases.

JAMA. Published online January 28, 2019. Abstract, Editorial

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