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.
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).
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).
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.
Telehealth enables the remote delivery of health care through telecommunication technologies and has substantially affected the evolving medical landscape. The COVID-19 pandemic accelerated the ...utilization of telehealth as health care professionals were forced to limit face-to-face in-person visits. It has been shown that information delivery, diagnosis, disease monitoring, and follow-up care can be conducted remotely, resulting in considerable changes specific to cardiovascular disease management. Despite increasing telehealth utilization, several factors such as technological infrastructure, reimbursement, and limited patient digital literacy can hinder the adoption of remote care. This scientific statement reviews definitions pertinent to telehealth discussions, summarizes the effect of telehealth utilization on cardiovascular and peripheral vascular disease care, and identifies obstacles to the adoption of telehealth that need to be addressed to improve health care accessibility and equity.
The effect of intensive blood pressure lowering on brain health remains uncertain.
To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain ...volumes.
A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016.
Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315).
The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome.
Among 670 recruited patients who had baseline MRI (mean age, 67.3 SD, 8.2 years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 95% CI, 0.69 to 1.14) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 95% CI, 1.21 to 1.70) in the standard treatment group (between-group difference in change, -0.54 cm3 95% CI, -0.87 to -0.20). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 95% CI, -32.3 to -28.8) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 95% CI, 24.8 to 28.8) in the standard treatment group (between-group difference in change, -3.7 cm3 95% CI, -6.3 to -1.1).
Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.
ClinicalTrials.gov Identifier: NCT01206062.
Although research has largely focused on the effects of physical activity (PA) on the brain, less is known about the influence of the brain on engagement in healthy-living behaviors, such as regular ...PA. In this secondary analysis of a study of brain activity and participation in healthy-living behaviors, we examined relationships between the activation of selected brain networks and PA in persons self-managing chronic conditions. Fifty-eight individuals with chronic conditions underwent functional magnetic resonance imaging while exposed to a protocol consisting of listening to emotion-focused and analytic-focused information and measures of activation of three neuromarkers were obtained: default mode network (DMN), task-positive network (TPN), and ventromedial prefrontal cortex (vmPFC). In an exploratory analysis, we assessed differences in neuromarker activation between two PA levels (representing higher and lower accelerometry-measured PA levels) of
) moderate-to-vigorous physical activity (MVPA) minutes,
) metabolic equivalents expended (METs), and
) daily steps. Results showed positive associations between MVPA and DMN (
= 0.31,
= 0.018), steps and DMN (
= 0.28,
= 0.035), and MVPA and vmPFC (
= 0.29,
= 0.026). No associations were found between the TPN and any of the PA measures. Individuals with high MVPA and METs had higher DMN values compared with those with low MVPA (
= -2.17,
= 0.035) and METs (
= -2.02,
= 0.048). No differences in TPN and vmPFC were found among PA levels. These results suggest that providing health information that activates the emotion-focused brain network may be more useful than analytic-focused information (centered on logic and reasoning) to assist people with chronic conditions to engage in more PA.
The influence of the brain on engagement in regular physical activity (PA) has not been well studied. We examined relationships between the activation of three neuromarkers and two PA levels in 58 persons self-managing chronic conditions. Findings suggest that individuals who optimally process health-information when the emotional tone is high (Empathic Network; DMN) may engage in more PA compared with individuals who respond to health information when the emotional tone is low (Analytic Network; TPN).
Abstract
BACKGROUND
The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease ...(CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups.
METHODS
We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death.
RESULTS
Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57–0.86), 0.71 (0.51–0.98), 0.62 (0.33–1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29–0.81), 0.77 (0.37–1.57), and 0.17 (0.01–1.08). All-cause mortality HRs were 0.61 (0.47–0.80), 0.92 (0.63–1.35), and 1.58 (0.73–3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons.
CONCLUSION
Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications.
CLINICAL TRIALS REGISTRATION
Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.
•Conventional ELISA techniques have limited analytical sensitivity.•This has hindered the use of circulating brain-specific proteins as stroke biomarkers.•Digital ELISA is a newly developed technique ...with improved analytical sensitivity.•We compared conventional and digital ELISA for detection of plasma NfL and tau in stroke.•The use of digital ELISA improves diagnostic performance.
Limited lower detection ranges associated with traditional immunoassay techniques have prevented the use of brain-specific proteins as blood biomarkers of stroke in the acute phase of care, as these proteins are often only present in circulation at low concentrations. Digital ELISA is a newly developed technique with allows for quantification of proteins in biofluids with up to 1000 times greater sensitivity than conventional ELISA techniques. The purpose of this study was to determine whether the extended lower limits of detection associated with digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage. Blood was sampled from ischemic stroke patients (n = 14) at emergency department admission, as well as from neurologically normal controls matched in terms of risk factors for cardiovascular disease (n = 33). Plasma levels of two brain-specific axonal proteins, neurofilament light chain (NfL) and tau, were measured via digital ELISA, and receiver-operating characteristic analysis was used to determine their ability to discriminate between groups. Plasma levels of NfL and tau were both significantly elevated in stroke patients versus controls, and could respectively discriminate between groups with 92.9% sensitivity / 84.9% specificity, and 85.7% sensitivity / 54.6% specificity. Furthermore, adjustment of measured NfL and Tau levels according to the lower-limits of detection associated with commercially-available conventional ELISA assays resulted in a dramatic and statistically significant decrease in diagnostic performance. Collectively, our results suggest that the increased analytical sensitivity of digital ELISA could enable the use of brain-specific proteins as blood biomarkers of ischemic stroke during triage.
Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but ...not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT.
SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure immediate recall, and Hopkins Verbal Learning Test-Revised delayed recall) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov, NCT01206062.
From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years SD 8·6, 1080 37% women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7–5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of −0·005 (95% CI −0·010 to 0·001) in the intensive treatment group and −0·001 (–0·006 to 0·005) in the standard treatment group (between-group difference −0·004, 95% CI −0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference −0·010, 95% CI −0·017 to −0·002; p=0·02), with an annual decline of −0·025 (–0·030 to −0·019) for the intensive treatment group and −0·015 (–0·021 to 0·009) for the standard treatment group.
Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains.
National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.
Uncontrolled blood pressure (BP) rates are persistently high among African Americans with hypertension. Although self-management is critical to controlling BP, little is known about the ...brain-behavior connections underlying the processing of health information and the performance of self-management activities.
In this pilot study, we explored the associations among neural processing of two types of health information and a set of self-management cognitive processes (self-efficacy, activation, decision-making, and hypertension knowledge) and behaviors (physical activity, dietary intake, and medication taking) and health status indicators (BP, health-related quality of life, anxiety, and depression).
Using a descriptive cross-sectional design, 16 African Americans with uncontrolled hypertension (mean age = 57.5 years, 68.8% women) underwent functional magnetic resonance imaging to assess activation of two neural networks, the task-positive network and the default mode network, and a region in the ventromedial prefrontal cortex associated with emotion-focused and analytic-focused health information. Participants completed self-reports and clinical assessments of self-management processes, behaviors, and health status indicators.
Our hypothesis that neural processing associated with different types of health information would correlate with self-management cognitive processes and behaviors and health status indicators was only partially supported. Home diastolic BP was positively associated with ventromedial prefrontal cortex activation ( r = .536, p = .09); no other associations were found among the neural markers and self-management or health status variables. Expected relationships were found among the self-management processes and behaviors and health status indicators.
To advance our understanding of the neural processes underlying health information processing and chronic illness self-management, future studies are needed that use larger samples with more heterogeneous populations and additional neuroimaging techniques.
Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially ...harmful cerebral hypoperfusion.
To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF).
This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure-lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021.
Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg.
The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF.
Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 95% CI, 0.08-2.83) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, -0.84 95% CI, -2.30 to 0.61 mL/100 g/min; between-group difference, 2.30 95% CI, 0.30-4.30; P = .02). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05).
Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease.
ClinicalTrials.gov Identifier: NCT01206062.
The SPRINT (Systolic Blood Pressure Intervention Trial) results have influenced clinical practice but have also generated discussion regarding the validity, generalizability, and importance of the ...findings. Following the SPRINT primary results manuscript in 2015, additional results and analyses of the data have addressed these concerns. The primary objective of this article is to respond to key questions that have been raised.
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