Summary: A new study reports controlling blood pressure has a measurable impact on mild cognitive impairment, a precursor of dementia.
Intensive lowering of blood pressure did not significantly reduce dementia risk but did have a measurable impact on mild cognitive impairment (MCI), according to the final, peer-reviewed results from the Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND). SPRINT MIND secondary results are the first to show an intervention that significantly reduces the occurrence of MCI, which is a well-established precursor of dementia. The results were reported Jan. 28, 2019 in the Journal of the American Medical Association. SPRINT MIND was an integral aspect of the initial design for SPRINT, a large, randomized clinical trial of intensive blood pressure lowering on cardiovascular and renal disease; both were funded by the National Institutes of Health.
“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” said Richard J. Hodes, M.D., director of the National Institute on Aging (NIA), part of NIH and the lead institute on Alzheimer’s research. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”
MCI is a condition in which people have more difficulty with cognition, thinking, remembering, and reasoning, than normal for people their age. Dementia is a more severe form of loss in cognitive functions that interferes with daily life. Alzheimer’s disease is the most common type of dementia. High blood pressure, or hypertension, is very common in persons over the age of 50 and a leading risk factor for heart disease, stroke, kidney failure, and a growing body of research suggests that it may increase risk for dementia later in life.
The participants in SPRINT were adults 50 years and older at high risk for cardiovascular disease. Results of the SPRINT trial, which ended early, showed that intensive blood pressure control, i.e., a systolic blood pressure target of less than 120 mmHg (<120 mmHg), compared to a standard target of less than 140 mmHg (<140 mmHg), reduced cardiovascular events and overall mortality. Between November 2010 and March 2013 more than 9,300 participants were randomized to the two target groups with nearly 4,700 in each group. In August 2015, the SPRINT trial was stopped after 3.3 years of treatment when the major beneficial effects of intensive blood pressure management on mortality and cardiovascular disease were discovered. Assessment for development of dementia and MCI continued for the full planned five years.
SPRINT MIND aimed to address whether intensive blood pressure control would also reduce the risk of developing dementia and cognitive impairment over the ensuing five years. Cognitive assessments were given to participants who had high blood pressure but no history of stroke or diabetes at the start of the trial, and over 91 percent had at least one follow up. Participants were classified into one of three categories: no cognitive impairment, MCI, or probable dementia.
The SPRINT MIND Research Group, including corresponding author Jeff D. Williamson, M.D., M.H.S., from Wake Forest School of Medicine, Winston-Salem, North Carolina, noted that the primary results of this analysis found no statistically significant difference between standard and intensive treatment in the proportion of participants that were diagnosed with dementia. The study, however, had fewer cases of dementia than expected. Nevertheless, the secondary results suggested that the intensive treatment reduced the risk of MCI and the combined risk of MCI and dementia. Due to the success of the SPRINT trial on the cardiovascular outcomes, the study intervention was stopped early; as a result, participants were treated for a shorter period than originally planned. The authors concluded that the shorter time and the unexpected fewer cases of dementia may have made it difficult to determine the role of intensive blood pressure control on dementia.
“The fact that there was still an MCI result when the study was cut short makes these results encouraging,” explained Laurie Ryan, Ph.D., chief of the Dementias of Aging Branch in the NIA Division of Neuroscience.
The authors emphasized that this is the first randomized clinical trial demonstrating that an intervention significantly reduces the occurrence of MCI, which is an established risk factor and often a precursor for dementia. An important conclusion from this research is that the intensive lowering of systolic blood pressure to <120 mmHg target - which reduces the risk of cardiovascular events and mortality - is safe for the brain.
“This is a landmark study in that it is the first trial of its size and scope to look at a modifiable risk factor for dementia and MCI,” said Lenore J. Launer, Ph.D., a senior investigator in the NIA Laboratory of Epidemiology and Population Sciences and co-author of the paper. “The study had a carefully designed hypothesis, used approved appropriate tools to assess dementia and MCI, was blinded for diagnosis, and got a good sample of older people.”
The authors noted that there currently are no proven interventions that prevent or delay the incidence of MCI or dementia. Therefore, people should consult with their healthcare providers to decide the best blood pressure goals for themselves and to determine how to reach those goals (for example, introducing lifestyle changes such as diet and exercise; or lifestyle changes with addition of blood pressure medications).
“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” added Ryan, who is also the program lead for SPRINT MIND. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”
These results also emphasize the connection between vascular health and the brain. In 2016, the NIH launched the Mind Your Risks campaign to make the public more aware of the link. For more on that visit the website, http://www.mindyourrisks.nih.gov.
Funding: SPRINT MIND was funded by NIH under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and interagency agreement A-HL-13-002-001. Clinical trial number: NCT01206062.
Source: Yasmin Anwar – NIH/NIA
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial” by The SPRINT MIND Investigators for the SPRINT Research Group in JAMA. Published January 28 2019.
Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Triale
There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT01206062