Significant reductions in the risk of mild cognitive impairment (MCI), and the combination of MCI and dementia, have been shown for the first time through aggressive lowering of systolic blood pressure in new research
The results are from the federally-funded SPRINT MIND Study reported at the Alzheimer’s Association International Conference (AAIC) 2018 in Chicago.
This is the first randomized clinical trial to demonstrate a reduction in new cases of MCI alone and the combined risk of MCI plus all-cause dementia.
The results of this large-scale, long-term clinical trial provide the strongest evidence to date about reducing risk of MCI and dementia through the treatment of high blood pressure.
Researchers pointed out that these results fit well with recent population data showing reductions in new cases of dementia in developed Western cultures.
These lower rates of dementia may be occurring as these societies have begun to improve control of cardiovascular disease risk factors through medication management, reducing smoking, and greater awareness of healthy lifestyle.
The Alzheimer’s Association U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a two-year clinical trial.
it aimed to evaluate whether lifestyle interventions can protect cognitive function in older adults at increased risk for cognitive decline.
The interventions include physical exercise, nutritional counseling and modification, cognitive and social stimulation, and improved self-management of health status.
At AAIC 2018, Williamson and colleagues reported preliminary results related to risk of dementia and cognitive decline from the Systolic Blood Pressure Intervention Trial (SPRINT).
SPRINT is a randomized clinical trial that compared two strategies for managing high blood pressure (hypertension) in older adults:
an intensive strategy with a systolic blood pressure goal of less than 120 mm Hg versus a standard care strategy targeting a systolic blood pressure goal of less than 140 mm Hg.
Previously, SPRINT demonstrated that more intensive blood pressure control reduced the risk for cardiovascular morbidity and mortality (NEJM, 11-26-15).
SPRINT helped inform the 2017 American Heart Association and American College of Cardiology high blood pressure clinical guidelines.
SPRINT Memory and Cognition IN Decreased Hypertension (SPRINT MIND) examined whether treating to the lower blood pressure target reduces the risk of developing dementia and/or MCI, and reduces the total volume of white matter lesions in the brain as shown by magnetic resonance imaging (MRI).
Study participants were 9,361 hypertensive older adults with increased cardiovascular risk (based on the Framingham risk score) but without diagnosed diabetes, dementia or prior stroke.
Participant mean age was 67.9 years (35.6% women) and 8,626 (92.1%) completed at least one follow-up cognitive assessment. In SPRINT MIND, the primary outcome was incident probable dementia.
Secondary outcomes included MCI and a composite outcome of MCI and/or probable dementia. Each outcome was adjudicated by an expert panel blinded to who was in each treatment group.
Recruitment for SPRINT began in October 2010. At one year, mean systolic blood pressure was 121.4 mmHg in the intensive-treatment group and 136.2 mmHg in the standard treatment group.
Treatment was stopped in August 2015 due to cardiovascular disease (CVD) benefit after a median follow up of 3.26 years, but cognitive assessment continued until June 2018.
Intervention—According to NEJM, 11-26-15, “All major classes of antihypertensive agents were included in the formulary and were provided at no cost to the participants.
SPRINT investigators could also prescribe other antihypertensive medications (not provided by the study).
The protocol encouraged, but did not mandate, the use of drug classes with the strongest evidence for reduction in cardiovascular outcomes, including thiazide-type diuretics (encouraged as the first-line agent), loop diuretics (for participants with advanced chronic kidney disease), and beta-adrenergic blockers (for those with coronary artery disease).
In SPRINT MIND, the researchers found a statistically significant 19% lower rate of new cases of MCI in the intensive blood pressure treatment group.
The combined outcome of MCI plus probable all-cause dementia was 15% lower in the intensive versus standard treatment group.
Serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure, but not injurious falls or bradycardia, occurred more frequently in the intensive-treatment group than in the standard-treatment group.
A total of 220 participants in the intensive-treatment group (4.7%) and 118 participants in the standard-treatment group (2.5%) had serious adverse events that were classified as possibly or definitely related to the intervention.
The magnitude and pattern of differences in adverse events according to treatment assignment among participants 75 years of age or older were similar to those in the overall cohort.
SPRINT MIND MRI Results
In a related abstract reported at AAIC 2018, researchers reported preliminary results from 673 participants in SPRINT MIND who were recruited for brain magnetic resonance imaging (MRI).
Primary outcomes included change in total white matter lesion (WML) volume and total brain volume (TBV).
Follow-up MRIs were obtained for 454 (67.4%) participants at a median of 3.98 years post-randomization.
In this sub-study, WML volume increased in both treatment groups, however the increase was significantly less in the intensive treatment group. There was no significant difference in total brain volume change.
In the intensive treatment group, WML volume increased by 0.28 cm3 compared to 0.92 cm3 in the standard treatment group.
TBV decreased by 27.3 cm3 in the intensive treatment group versus 24.8 cm3 in the standard treatment group.
White matter lesions are frequently indicative of small vessel disease and linked to higher risk of stroke, dementia and higher mortality.
While white matter lesions are thought to increase the risk of vascular dementia, they also may be a risk factor for Alzheimer’s disease.
People living with dementia may have Alzheimer’s disease and white matter lesions at the same time.
Research has demonstrated that when people have more than one type of disease-related brain changes, the cognitive consequences are greater.
Precision medicine emphasizes the customization and individualization of healthcare, with treatments and practices tailored to the specific patient’s situation and needs, often taking into account genes, environment, and lifestyle.
Sometimes called personalized medicine, it is a common approach in cancer and respiratory diseases.