Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions.

Importance: The effect of intensive blood pressure lowering on brain health remains uncertain. Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants: 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. Interventions: 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). Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results: 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]). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.

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. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Methods of a Study to Assess the Contribution of Cerebral Small Vessel Disease and Dementia Risk Alleles to Racial Disparities in Vascular Cognitive Impairment and Dementia.

Background Non-Hispanic Black adults have a higher proportion of vascular cognitive impairment and Alzheimer's disease and related dementias compared with non-Hispanic White adults that may be due to differences in the burden of cerebral small vessel disease and risk alleles for Alzheimer's disease and related dementias. We describe here the methods of an ancillary study to the REGARDS (Reason for Geographic and and Racial Difference in Stroke) study, which will examine the role of magnetic resonance imaging markers of cerebral small vessel disease and vascular as well as genetic risk factors for Alzheimer's disease and related dementias in racial disparity in the prevalence and trajectory of vascular cognitive impairment and dementia in non-Hispanic White and non-Hispanic Black participants. Methods In participants with no prior history of stroke who had an incident stroke or transient ischemic attack after enrollment in the study, magnetic resonance imaging scans will be evaluated using the Standards for Reporting Vascular Changes on Neuroimaging international consensus criteria and automated analysis pipelines for quantification of cerebral small vessel disease. Participants will be genotyped for APOE ε4 and TREM2 risk alleles for Alzheimer's disease and related dementias. The 6-item screener will define global cognitive function and be the primary cognitive outcome. Conclusions With at least 426 non-Hispanic Black and 463 non-Hispanic White participants who have at least 2 prior and 2 poststroke or transient ischemic attack cognitive assessments, we will have at least 80% power to detect a minimum effect size of 0.09 SD change in Z score, with correction for as many as 20 tests (ie, at P<0.0025, after adjusting for up to 20 covariates) for cognitive decline.

Correlates of subjective and objective everyday functioning in middle-aged and older adults with human immunodeficiency virus.

People with human immunodeficiency virus (HIV) (PWH) are at an increased risk for impaired everyday functioning and they may also experience poor awareness of their functional status. This study identified factors associated with (1) subjective and objective instrumental activities of daily living (IADLs) and (2) awareness of functional capacity in PWH. In this cross-sectional study, 236 PWH completed a neurobehavioral assessment, including self-report and performance-based measures of IADLs. Multiple regressions were performed to identify demographic, personality, and cognitive factors contributing to subjective and objective evaluation of everyday functioning, as well as discrepancy between self-report and performance-based measures of IADLs. Results indicated that increased depression was associated with worsened self-report of everyday functioning but not performance of IADLs. Cognitive function and age were associated with IADL performance. Most participants (58.1%) demonstrated a discrepancy between self-report and actual performance of IADLs. Worse processing speed was correlated with greater discrepancy. Inaccurate self-reporters had worse overall cognitive functioning and lower levels of personality traits, including openness, conscientiousness, and agreeableness. In conclusion, self-report and actual performance of IADLs in PWH is influenced by different factors. Self-report may be more affected by psychological variables, such as mood and personality, while actual performance is more sensitive to age and cognitive function.

Effect of intensive blood pressure control on subtypes of mild cognitive impairment and risk of progression from SPRINT study.

BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of <120 mm Hg (intensive treatment; n = 4678) or <140 mm Hg (Standard treatment; n = 4683). Outcomes included adjudicated MCI, MCI subtype (amnestic, non-amnestic, multi-domain, single domain), and probable dementia. Multistate survival models were used to examine transitions in cognitive status accounting for the competing risk of death. RESULTS: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 640 participants met the protocol definition for MCI, with intensive treatment reducing the risk of MCI overall (hazard ratio [HR], 0.81 [95% confidence interval {CI}, 0.69-0.94]), as previously reported. This effect was largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66-0.92]) and multi-domain subtypes (HR, 0.78 [95% CI, 0.65-0.93]). An adjudication of MCI, as compared with normal cognitive function, substantially increased the probability of progressing to probable dementia (5.9% [95% CI: 4.5%-7.7%] vs. 0.6% [95% CI: 0.3%-0.9%]) and to death (10.0% [95% CI: 8.3%-11.9%] vs. 2.3% [95% CI: 2.0%-2.7%]) within 2 years. CONCLUSIONS: Intensive treatment reduced the risk for amnestic and multi-domain subtypes of MCI. An adjudication of MCI was associated with increased risk of progression to dementia and death, highlighting the relevance of MCI as a primary outcome in clinical and research settings.

Depressive Symptoms and Risk of Stroke in a National Cohort of Black and White Participants From REGARDS.

OBJECTIVE: The purpose of this study was to examine depressive symptoms as a risk factor for incident stroke and determine whether depressive symptomatology was differentially predictive of stroke among Black and White participants. METHODS: The study comprised 9,529 Black and 14,516 White stroke-free participants, aged 45 and older, enrolled in the REasons for Geographic and Racial Differences in Stroke (2003-2007). Incident stroke was the first occurrence of stroke. Association between baseline depressive symptoms (assessed via the 4-item Center for Epidemiologic Studies Depression Scale [CES-D-4]: 0, 1-3, or ≥4) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographics, stroke risk factors, and social factors. RESULTS: There were 1,262 strokes over an average follow-up of 9.21 (SD 4.0) years. Compared to participants with no depressive symptoms, after demographic adjustment, participants with CES-D-4 scores of 1-3 had 39% increased stroke risk (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.23-1.57), with slight attenuation after full adjustment (HR = 1.27, 95% CI = 1.11-1.43). Participants with CES-D-4 scores of ≥4 experienced 54% higher risk of stroke after demographic adjustment (HR = 1.54, 95% CI = 1.27-1.85), with risk attenuated in the full model similar to risk with 1-3 symptoms (HR = 1.25, 95% CI = 1.03-1.51). There was no evidence of a differential effect by race (p = 0.53). CONCLUSIONS: The association of depressive symptoms with increased stroke risk was similar among a national sample of Black and White participants. These findings suggest that assessment of depressive symptoms should be considered in primary stroke prevention for both Black and White participants.

Cognitive and Everyday Functioning in Older and Younger Adults with and without HIV.

The purpose of this study was to: (1) examine cognitive performance differences in older and younger adults with and without HIV, and (2) determine if such differences were related to a laboratory measure of instrumental activities of daily living (IADLs). Ninety-eight HIV-positive (69 younger, 29 older) and 103 HIV-negative (84 younger, 19 older) adults were evaluated on a number of cognitive measures. Controlling for a number of confounders, age by HIV status interactions were found on two cognitive measures, indicating poorer cognitive performance for those aging with HIV. Poorer performance on these cognitive measures corresponded with poorer performance on the Timed Instrumental Activities of Daily Living (TIADL) test. These findings suggest that as adults age with HIV, they may be at risk for cognitive declines that would impair their ability to engage in activities important for maintaining independent living.

THE RELATIONSHIP OF MEMORY, REASONING, AND SPEED OF PROCESSING ON FALLING AMONG OLDER ADULTS.

Older adults are at higher risk of falling and of suffering greater devastating effects from such falls. The objective of this study was to longitudinally examine predictors for risk of falling such as cognitive composites (reasoning, memory, speed of processing) along with traditional predictors. Data on falls, cognition, objective functional tests, visual acuity, and demographics were collected on older adults at baseline (N = 698) and at a two-year annual follow-up (n = 550). By using hierarchical multiple regression, we found that older age, being an older Caucasian woman, poorer performance on Turn 360 at baseline, and having a better memory at baseline predicted higher reports of falling in the past two months at the two-year annual follow-up. These results confirm prior findings except for memory; however, better memory as a predictor of falls may indicate that there is a recall bias dependent on memory function.