Intensive BP control reduces risk of mild cognitive impairment

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BloodIntensive control of blood pressure in older people significantly reduced the risk of developing mild cognitive impairment (MCI), a precursor of early dementia, in a clinical trial led by scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health. However, the National Institutes of Health-supported Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND) study did not prove that treating blood pressure to a goal of 120 mm Hg or less statistically reduced the risk of dementia. This result may have been due to too few new cases of dementia occurring in the study, the authors noted.

MCI is defined as a decline in memory and thinking skills that is greater than expected with normal ageing and is a risk factor for dementia. Dementia is defined as a group of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person’s ability to perform everyday activities.

“As doctors treating older patients, we are encouraged to finally have a proven intervention to lower someone’s risk for MCI,” said the study’s principal investigator, Dr Jeff Williamson, professor of gerontology and geriatric medicine at Wake Forest School of Medicine. “In the study, we found that just three years of lowering blood pressure not only dramatically helped the heart but also helped the brain.”

The objective of SPRINT MIND was to evaluate the effect of intensive blood pressure control on risk of dementia. Hypertension, which affects more than half of people over age 50 and more than 75% of those older than 65, has been identified as a potentially modifiable risk factor for MCI and dementia in previous observational studies.

The clinical trial, which enrolled 9,361 volunteers, was conducted at 102 sites in the US and Puerto Rico among adults 50 and older with hypertension but without diabetes or history of stroke. The participating group was 35.6% female, 30% black and 10.5% Hispanic and thus representative of the broader US population.

Participants were randomly assigned to a systolic blood pressure goal of either less than 120 mm HG (intensive treatment) or less than 140 mm HG (standard treatment). They were then classified after five years as having no cognitive impairment, MCI or probable dementia.

“Although the study showed a 15% reduction in dementia in the intensively controlled group, we were disappointed that the results did not achieve statistical significance for this outcome,” Williamson said. “Last week the Alzheimer’s Association agreed to fund additional follow-up of SPRINT MIND participants in the hope that sufficient dementia cases will accrue, allowing for a more definitive statement on these outcomes.”

SPRINT was stopped early due to the success of the trial in reducing cardiovascular disease. As a result, participants were on intensive blood pressure lowering treatment for a shorter period than originally planned. The authors concluded that the shorter time may have made it difficult to accurately determine the role of intensive blood pressure control on dementia cases.

Williamson said some caution should be exercised in interpreting the study result both because MCI was not the primary cognitive focus of the trial and because it is not clear what intensive blood pressure control may mean for the longer-term incidence of dementia. Although MCI considerably increases the risk of dementia, this progression is not inevitable and reversion to normal cognition is possible, he said.

Abstract
Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.
Objective: To evaluate the effect of intensive blood pressure control on risk of dementia.
Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018.
Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683).
Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia.
Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97).
Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point.

Authors
Jeff D Williamson, Nicholas M Pajewski, Alexander P Auchus, R Nick Bryan, Gordon Chelune, Alfred K Cheung, Maryjo L Cleveland, Laura H Coker, Michael G Crowe, William C Cushman, Jeffrey A Cutler, Christos Davatzikos, Lisa Desiderio, Guray Erus, Larry J Fine, Sarah A Gaussoin, Darrin Harris, Meng-Kang Hsieh, Karen C Johnson, Paul L Kimmel, Manjula Kurella Tamura, Lenore J Launer, Alan J Lerner, Cora E Lewis, Jennifer Martindale-Adams, Claudia S Moy, Ilya M Nasrallah, Linda O Nichols, Suzanne Oparil, Paula K Ogrocki, Mahboob Rahman, Stephen R Rapp, David M Reboussin, Michael V Rocco, Bonnie C Sachs, Kaycee M Sink, Carolyn H Still, Mark A Supiano, Joni K Snyder, Virginia G Wadley, Jennifer Walker, Daniel E Weiner, Paul K Whelton, Valerie M Wilson, Nancy Woolard, Jackson T Wright, Clinton B Wright

Wake Forest Baptist Medical Centre material
JAMA abstract


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