Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals

Deborah A Levine; Alden L Gross; Emily M Briceño; Nicholas Tilton; Mohammed U Kabeto; Stephanie M Hingtgen; Bruno J Giordani; Jeremy B Sussman; Rodney A Hayward; James F Burke; Mitchell S V Elkind; Jennifer J Manly; Andrew E Moran; Erin R Kulick; Rebecca F Gottesman; Keenan A Walker; Yuichiro Yano; Darrell J Gaskin; Stephen Sidney; Kristine Yaffe; Ralph L Sacco; Clinton B Wright; Veronique L Roger; Norrina Bai Allen; Andrzej T Galecki

doi:10.1001/jamaneurol.2020.0568

. 2020 Apr 13;77(7):1–10. doi: 10.1001/jamaneurol.2020.0568

Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals

Deborah A Levine ^1,^2,^3,^✉, Alden L Gross ⁴, Emily M Briceño ⁵, Nicholas Tilton ¹, Mohammed U Kabeto ¹, Stephanie M Hingtgen ¹, Bruno J Giordani ⁶, Jeremy B Sussman ^1,^3,⁷, Rodney A Hayward ^1,^3,⁷, James F Burke ^2,^3,⁷, Mitchell S V Elkind ^8,⁹, Jennifer J Manly ^8,¹⁰, Andrew E Moran ¹¹, Erin R Kulick ¹², Rebecca F Gottesman ¹³, Keenan A Walker ¹³, Yuichiro Yano ¹⁴, Darrell J Gaskin ¹⁵, Stephen Sidney ¹⁶, Kristine Yaffe ^17,^18,¹⁹, Ralph L Sacco ²⁰, Clinton B Wright ²¹, Veronique L Roger ²², Norrina Bai Allen ²³, Andrzej T Galecki ^1,²⁴

¹Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor

²Stroke Program, Department of Neurology, University of Michigan, Ann Arbor

³Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor

⁴Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, John Hopkins University, Baltimore, Maryland

⁵Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor

⁶Michigan Alzheimer’s Disease Center, Department of Psychiatry, University of Michigan, Ann Arbor

⁷VA Ann Arbor Healthcare System, Ann Arbor, Michigan

⁸Department of Neurology, Vagelos College of Physicians and Surgeons, New York, New York

⁹Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York

¹⁰Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York

¹¹Division of General Medicine, Department of Medicine, Columbia University, New York, New York

¹²Department of Epidemiology, Brown University, Providence, Rhode Island

¹³Department of Neurology, Johns Hopkins University, Baltimore, Maryland

¹⁴Department of Community & Family Medicine, Duke University, Durham, North Carolina

¹⁵Johns Hopkins Bloomberg School of Public Health, Department of Health Policy and Management, Johns Hopkins University, Baltimore, Maryland

¹⁶Kaiser Permanente Northern California Division of Research, Oakland

¹⁷Department of Psychiatry, University of California, San Francisco, San Francisco

¹⁸Department of Neurology, University of California, San Francisco, San Francisco

¹⁹Department of Epidemiology, University of California, San Francisco, San Francisco

²⁰Department of Neurology, University of Miami, Miami, Florida

²¹Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland

²²Department of Cardiology and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota

²³Department of Internal Medicine, Northwestern University, Chicago, Illinois

²⁴Department of Biostatistics, University of Michigan, Ann Arbor

^✉

Corresponding Author: Deborah A. Levine, MD, MPH, Department of Internal Medicine, University of Michigan, 2800 Plymouth Rd, NCRC 16-430W, Ann Arbor, MI 48109 (deblevin@umich.edu).

Accepted for Publication: February 1, 2020.

Published Online: April 13, 2020. doi:10.1001/jamaneurol.2020.0568

Author Contributions: Drs Levine and Tilton had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Levine, Tilton, Kabeto, Hayward, Burke, Moran, Roger, Galecki.

Acquisition, analysis, or interpretation of data: Levine, Gross, Briceno, Tilton, Kabeto, Hingtgen, Giordani, Sussman, Hayward, Burke, Elkind, Manly, Kulick, Gottesman, Walker, Yano, Gaskin, Sidney, Yaffe, Sacco, Wright, Roger, Allen, Galecki.

Drafting of the manuscript: Levine, Hingtgen, Giordani, Roger, Galecki.

Critical revision of the manuscript for important intellectual content: Levine, Gross, Briceno, Tilton, Kabeto, Giordani, Sussman, Hayward, Burke, Elkind, Manly, Moran, Kulick, Gottesman, Walker, Yano, Gaskin, Sidney, Yaffe, Sacco, Wright, Roger, Allen.

Statistical analysis: Levine, Gross, Tilton, Kabeto, Sussman, Hayward, Burke, Gaskin, Galecki.

Obtained funding: Levine, Elkind, Sidney, Yaffe, Sacco.

Administrative, technical, or material support: Levine, Briceno, Hingtgen, Giordani, Sussman, Kulick, Sacco.

Supervision: Levine, Giordani, Burke, Yano, Wright, Galecki.

Conflict of Interest Disclosures: Dr Levine reports grants from the National Institutes of Health (NIH) during the conduct of the study and outside the submitted work. Drs Tilton and Hingtgen report grants from the NIH/National Institute of Neurological Disorders and Stroke (NINDS) during the conduct of the study. Dr Sussman reports grants from US Department of Veterans Affairs during the conduct of the study. Dr Hayward reports grants from the NIH and US Department of Veterans Affairs during the conduct of the study. Dr Manly reports grants from NIH/National Institute on Aging during the conduct of the study. Dr Gottesman reports other support from the American Academy of Neurology outside the submitted work. Drs Gaskin and Galecki report grants from the NIH during the conduct of the study. Dr Sidney reports a contract from the National Heart, Lung, and Blood Institute outside the submitted work. Dr Yaffe reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Sacco reports grants from NINDS during the conduct of the study and grants from Boehringer Ingelheim, American Heart Association, and Florida Department of Health outside the submitted work. Dr Wright reports grants from NIH/NINDS during the conduct of the study and royalties from UpToDate for 2 chapters on vascular dementia. No other disclosures were reported.

Funding/Support: This research project is supported by the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and US Department of Health and Human Services (grant R01 NS102715). Additional funding was provided by National Institute of Aging (grant R01 AG051827, Dr Levine; grant K01 AG050699, Dr Gross), National Institute of Aging Claude Pepper Center (grant P30 AG024824; Drs Galecki and Kabeto), and National Institute of Aging Michigan Alzheimer’s Disease Core Center (grant P30 AG053760, Dr Giordani).

Role of the Funder/Sponsor: Representatives of the funding agency have been involved in the review of the manuscript but not directly involved in the collection, management, analysis or interpretation of the data.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health.

Additional Contributions: We thank the staff and participants of the Atherosclerosis Risk in Communities (ARIC) Study for their important contributions. The ARIC Study is carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute (NHLBI). Neurocognitive data were collected by grants supported by the National Institutes of Health (NIH) (NHLBI, National Institute of Neurological Disorders and Stroke [NINDS], National Institute on Aging [NIA], and National Institute on Deafness and Other Communication Disorders) and with previous brain magnetic resonance imaging examinations funded by the NHLBI. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham, Northwestern University, University of Minnesota, and Kaiser Foundation Research Institute. This manuscript has been reviewed by CARDIA for scientific content. The Cardiovascular Health Study (CHS) was supported by contracts and grants from the NHLBI, with additional contribution from the NINDS. Additional support was provided by grants from the NIA. A full list of principal CHS investigators and institutions can be found at https://chs-nhlbi.org/. The Framingham Heart Study is a project of the NHLBI of the NIH and Boston University School of Medicine. This project has been funded in whole or in part with federal funds from the NHLBI, NIH, and US Department of Health and Human Services. The Northern Manhattan Stroke study has been funded at least in part with federal funds from the NIH and NINDS.

^✉

Corresponding author.

PMCID: PMC7154952 PMID: 32282019

This cohort study assesses whether blood pressure levels are associated with racial differences in cognitive decline.

Key Points

Question

Do black individuals’ higher cumulative blood pressure levels contribute to their greater risk of cognitive impairment and dementia compared with white individuals?

Findings

In this pooled cohort analysis of 19 378 participants, black individuals, compared with white individuals, had significantly faster declines in global cognition. Differences between black and white individuals in global cognition decline were no longer statistically significant after adjusting for cumulative mean systolic blood pressure.

Meaning

Black individuals’ higher cumulative blood pressure levels may explain racial disparities in cognitive decline.

Abstract

Importance

Black individuals are more likely than white individuals to develop dementia. Whether higher blood pressure (BP) levels in black individuals explain differences between black and white individuals in dementia risk is uncertain.

Objective

To determine whether cumulative BP levels explain racial differences in cognitive decline.

Design, Setting, and Participants

Individual participant data from 5 cohorts (January 1971 to December 2017) were pooled from the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. The median (interquartile range) follow-up was 12.4 (5.9-21.0) years. Analysis began September 2018.

Main Outcomes and Measures

The primary outcome was change in global cognition, and secondary outcomes were change in memory and executive function.

Exposures

Race (black vs white).

Results

Among 34 349 participants, 19 378 individuals who were free of stroke and dementia and had longitudinal BP, cognitive, and covariate data were included in the analysis. The mean (SD) age at first cognitive assessment was 59.8 (10.4) years and ranged from 5 to 95 years. Of 19 378 individuals, 10 724 (55.3%) were female and 15 526 (80.1%) were white. Compared with white individuals, black individuals had significantly faster declines in global cognition (−0.03 points per year faster [95% CI, −0.05 to −0.01]; P = .004) and memory (−0.08 points per year faster [95% CI, −0.11 to −0.06]; P < .001) but significantly slower declines in executive function (0.09 points per year slower [95% CI, 0.08-0.10]; P < .001). Time-dependent cumulative mean systolic BP level was associated with significantly faster declines in global cognition (−0.018 points per year faster per each 10–mm Hg increase [95% CI, −0.023 to −0.014]; P < .001), memory (−0.028 points per year faster per each 10–mm Hg increase [95% CI, −0.035 to −0.021]; P < .001), and executive function (−0.01 points per year faster per each 10–mm Hg increase [95% CI, −0.014 to −0.007]; P < .001). After adjusting for cumulative mean systolic BP, differences between black and white individuals in cognitive slopes were attenuated for global cognition (−0.01 points per year [95% CI, −0.03 to 0.01]; P = .56) and memory (−0.06 points per year [95% CI, −0.08 to −0.03]; P < .001) but not executive function (0.10 points per year [95% CI, 0.09-0.11]; P < .001).

Conclusions and Relevance

These results suggest that black individuals’ higher cumulative BP levels may contribute to racial differences in later-life cognitive decline.

Introduction

Understanding and reducing black individuals’ higher rate of cognitive impairment and dementia (CID) is an urgent public health priority.^1,2 Older black individuals are 2 times more likely than older white individuals to have CID, including Alzheimer disease and related dementias.^3,4,5,6 Preventing or delaying CID can lead to better survival, less disability, less nursing home use and family burden, lower health care costs, and better quality of life, all of which are worse in black individuals than in white individuals in the US.⁵

High blood pressure (BP) level, particularly in midlife, is associated with increased risk for CID.^7,8 Black individuals have an earlier average age of onset and a greater severity of high BP levels than white individuals,⁹ making BP a potential leading contributor to racial disparities in health.^10,11 Black individuals are also more likely than white individuals to have detrimental brain effects associated with high BP levels,¹² including stroke¹³ and increased white matter hyperintensity volume.^14,15 Evidence is growing that the effect of high BP on cognition^16,17 and racial disparities in BP control¹⁰ might begin in young adulthood. The extent to which the cumulative effects of elevated BP levels explain the greater risk for CID in black individuals is uncertain.

Leveraging 5 population-based cohorts of individuals aged 5 to 95 years at cohort baseline with repeated objective measures of BP and cognition, we conducted a pooled cohort study to determine the extent to which differences between black and white individuals in cognitive decline are explained by black individuals’ higher cumulative BP levels. We hypothesized that differences between black and white individuals in cumulative BP levels contribute to racial disparities in cognitive decline.

Methods

Study Design, Participants, and Measurements

This pooled cohort analysis examined individual participant data from 5 well-characterized US prospective cohort studies with repeated measures of BP and cognition: Atherosclerosis Risk in Communities Study (ARIC),¹⁸ Coronary Artery Risk Development in Young Adults Study (CARDIA),¹⁹ Cardiovascular Health Study (CHS),²⁰ Framingham Offspring Study (FOS),²¹ and Northern Manhattan Study (NOMAS)²² for 1971 to 2017 (eMethods in the Supplement). The University of Michigan institutional review board approved this study. Participating institutions approved the cohort studies. Participants provided written informed consent, and minors provided assent. Data were collected from January 1971 to December 2017.

We required 2 or more measurements of cognition and 1 or more measurement of BP at or before the first cognition measurement. We excluded participants reporting a baseline history of stroke and those with incident stroke or cohort-defined incident dementia at or before the first cognitive measurement.

Cognitive Function Assessments

Trained cohort staff administered cognitive function tests longitudinally in person to participants using cognitive tests validated in black and white individuals^23,24 and consistent with the Vascular Cognitive Impairment Harmonization Standards.²⁵ In 3 cohorts (ARIC,¹⁸ CHS,²⁰ and NOMAS²²), trained staff administered global cognitive function tests (but not memory or executive function tests) by telephone for participants unable to attend some examination visits in person. Cognitive tests can be measured reliably and precisely over the telephone in adults with comparable results.²⁶

To make inferences about cognitive domains instead of individual cognitive test items and to resolve the challenge of different cognitive tests administered across the cohorts, we cocalibrated available cognitive test items into factors representing global cognition (global cognitive performance), memory (learning and delayed recall/recognition), and executive function (complex and/or speeded cognitive functions) using item response theory methods that leverage all available cognitive information in common across cohorts and test items unique to particular cohorts.²⁷ Cognitive outcomes were set to a t score metric (mean [SD], 50 [10]) at a participant’s first cognitive assessment; a 1-point difference represented a 0.1-SD difference in the distribution of cognition across the 5 cohorts. Higher cognitive scores indicate better performance (eMethods in the Supplement). The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function.

Measurement of Race

Participants self-reported race. We excluded participants who reported race other than black or white and those reporting Hispanic ethnicity from NOMAS.²²

Measurement of Blood Pressure

Each cohort study measured BP at in-person visits using standard protocols and equipment. We summarized systolic BP (SBP) as the time-dependent cumulative mean of all BPs before each cognitive measurement. Long-term cumulative mean SBP has improved prediction of clinical outcomes compared with single BP measurements²⁸ or mean BP over discrete intervals (eg, ≤1 year, 1-5 years) before outcome measurement.²⁹ We used SBP because it tends to be a stronger predictor of BP-related outcomes than diastolic BP.^8,29,30

Covariates

We used covariates measured closest to, but not after, the first cognitive assessment. Demographics included age, sex, years of school, and cohort study. Vascular risk factors included alcohol use, cigarette smoking, body mass index, waist circumference, physical activity, fasting glucose level, low-density lipoprotein cholesterol, and history of atrial fibrillation. Cohorts measured current hypertension medication use by evidence of medication bottles and self-report (eMethods in the Supplement).

Statistical Analysis

Following a prespecified analysis plan, we compared participant characteristics by race using a 2-sample t test with equal variance, Wilcoxon rank sum test, or χ² test as appropriate. Linear mixed-effects models measured changes in each continuous cognitive outcome over time by race. The models included covariates in Table 1, interaction terms for age at the time of first cognitive assessment × follow-up time, sex × follow-up time, and race × follow-up time, as well as participant-specific random effects for intercepts and slopes. All continuous variables were centered at the overall median, except cumulative mean SBP, which was centered at 120 mm Hg. Glucose, low-density lipoprotein cholesterol, and SBP values were divided by 10 so that the parameter estimates reflect a 10-unit change in the variables. Time was treated as a continuous measure defined as years since first measurement of each cognitive outcome.

Table 1. Characteristics of Participants at First Cognitive Assessment by Race: 1971 to 2017.

Variable	No. (%)
Variable	Black individuals (n = 3852)	White individuals (n = 15 526)
Age at first SBP measurement, y
Range	17-94	5-95
Median (IQR)	51.0 (29.0-63.0)	54.0 (45.0-64.0)
Age at first cognitive assessment, y
Range	41-95	25-96
Median (IQR)	54.8 (50.1-65.8)	59.0 (52.0-67.6)
Female	2433 (63.2)	8291 (53.4)
Cohort
ARIC¹⁸	1857 (48.2)	7313 (47.1)
CARDIA¹⁹	1051 (27.3)	1285 (8.3)
CHS²⁰	562 (14.6)	3599 (23.2)
FOS²¹	0 (0.0)	3016 (19.4)
NOMAS²²	382 (9.9)	316 (2.0)
Education
≤8th Grade	424 (11.0)	849 (5.5)
9th -11th Grade	605 (15.7)	1325 (8.5)
Completed high school	937 (24.3)	5003 (32.2)
Some college but no degree	736 (19.1)	2639 (17.0)
≥College graduate	1150 (29.9)	5710 (36.8)
Alcoholic drinks/wk
0	2596 (67.4)	7561 (48.7)
1-6	834 (21.7)	4909 (31.6)
7-13	231 (6.0)	1674 (10.8)
≥14	191 (5.0)	1382 (8.9)
Current cigarette smoking	816 (21.2)	2535 (16.3)
Any physical activity	2582 (67.0)	12907 (83.1)
BMI, median (IQR)	29.1 (25.8-33.4)	26.4 (23.7-29.5)
Waist circumference, median (IQR), cm	97.0 (88.0-107.0)	94.0 (85.0-103.0)
History of atrial fibrillation	50 (1.3)	264 (1.7)
Fasting glucose, median (IQR), mg/dL	97.5 (90.0-108.0)	98.0 (91.5-105.9)
LDL cholesterol, median (IQR), mg/dL	123.0 (101.0-148.8)	127.0 (105.6-150.8)
Antihypertensive medication use	1631 (42.3)	4087 (26.3)
Follow-up time from first cognitive assessment, median (IQR), y	6.0 (5.3-20.8)	14.9 (6.0-21.0)
SBP at first cognitive assessment, cumulative mean (SD), mm Hg	141.3 (18.3)	137.0 (18.8)
No. of SBP measurements, median (IQR)
Total	4.0 (3.0-7.0)	5.0 (4.0-8.0)
Before first cognitive assessment	1.0 (1.0-5.0)	1.0 (1.0-3.0)
Time from first SBP measurement to first cognitive assessment, median (IQR), y	2.9 (2.7-24.3)	2.9 (2.7-19.1)
Cognitive scores at first assessment, median (IQR)
General cognitive performance	47.6 (42.0-52.8)	53.3 (48.7-58.3)
Executive function	47.6 (41.6-52.9)	53.0 (47.9-58.0)
Memory	48.9 (45.7-52.4)	52.4 (48.9-55.9)
Cognitive scores at first assessment, mean (SD)
General cognitive performance	47.5 (8.0)	53.3 (7.0)
Executive function	47.4 (7.9)	53.0 (7.2)
Memory	49.1 (6.5)	52.1 (5.4)

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Abbreviations: ARIC, Atherosclerosis Risk in Communities Study; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); CARDIA, Coronary Artery Risk Development in Young Adults Study; CHS, Cardiovascular Health Study; FOS, Framingham Offspring Study; IQR, interquartile range; LDL, low-density lipoprotein; NOMAS, Northern Manhattan Study; SBP, systolic blood pressure.

SI conversion factors: To convert glucose to mmol/L, multiply by 0.0555; LDL cholesterol to mmol/L, multiply by 0.0259.

For each outcome, all available cognitive observations were used in the primary analysis except observations after the time of first cohort-adjudicated incident stroke during follow-up because incident stroke alters the cognitive trajectory.³¹ We evaluated model assumptions by inspecting residual plots. There was no evidence of nonlinear effects of SBP or other covariates on cognitive trajectories, or a significant interaction term for race × SBP × follow-up time in models (P > .05).

To estimate differences between black and white individuals in cognitive decline, model A included a black race × follow-up time interaction term. To examine whether time-dependent cumulative mean SBP explained the racial differences in cognitive decline, model B added SBP and an SBP × follow-up time interaction term to model A. To investigate whether hypertension treatment explained the racial differences in cognitive decline, model C added hypertension treatment and a hypertension treatment at first cognitive assessment × follow-up time interaction term to model B.

Given the large sample size, we put aside a 15% random subsample of participants within each cohort for model validation. We present results from the derivation cohort. We performed a complete case analysis excluding a small number of participants (n = 501) from the analytical data set owing to missing values in covariates. The Figure shows the derivation of the cohort. Statistical significance for all analyses was set as P < .05 (2-sided). All analyses were performed using SAS version 9.4 (SAS Institute). Analysis began September 2018.

Figure. — BP indicates blood pressure.

^aCategories for missing data on covariates are not mutually exclusive. Missing data for covariates included glucose (n = 240), alcohol use (n = 18), body mass index (n = 24), waist circumference (n = 77), smoking (n = 2), physical activity (n = 18), low-density lipoprotein cholesterol (n = 259), antihypertensive medication use (n = 14), and education (n = 128). No participants were missing history of atrial fibrillation.

Sensitivity Analyses

We repeated analyses including participants’ cognitive observations after the time of incident stroke and also after adding kidney function (glomerular filtration rate³²) and history of myocardial infarction because they may be on the causal pathway. We repeated analyses within cohorts to assess heterogeneity in the associations between race and BP with cognitive decline.

Results

The study sample included 19 378 participants (10 724 [55.3%] were female and 15 526 [80.1%] were white). Table 1 presents characteristics of participants by race. During a median (interquartile range) follow-up of 12.4 (5.9-21.0) years, the median (interquartile range) number of global cognition and memory assessments was 2 (2-4) for black individuals and 4 (2-7) for white individuals. The median (interquartile range) number of executive function assessments was 2 (2-3) for black individuals and 3 (2-3) for white individuals. eTable 1 in the Supplement shows characteristics of study participants by cohort. Because the secondary outcome measures were performed less frequently, the memory analysis included 13 145 participants, and the executive function analysis included 17 254 participants.

Change in Global Cognition

Black individuals, compared with white individuals, had significantly faster declines in global cognition (model A, Table 2). White men at a median age of 56 years experienced a decline in global cognition of −0.23 points per year (95% CI, −0.24 to −0.21; P < .001). Black men of similar age experienced a decline in global cognition of −0.26 points per year (95% CI, −0.29 to −0.22) (adjusted difference in slope between black individuals and white individuals: −0.03 points per year faster [95% CI, −0.05 to −0.01]; P = .004).

Table 2. Association of Global Cognition Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017^a.

Coefficient	Model A: basic		Model B: cumulative mean SBP added as a time-varying covariate to model A		Model C: hypertension treatment added as a covariate to model B
Coefficient	Estimate (95% CI)	P value	Estimate (95% CI)	P value	Estimate (95% CI)	P value
Change in intercept per 10-y increase in age at first cognitive assessment	−2.22 (−2.35 to −2.09)	<.001	−2.01 (−2.15 to −1.88)	<.001	−2.01 (−2.14 to −1.88)	<.001
Difference in intercept between black and white individuals at first cognitive assessment	−5.74 (−5.98 to −5.51)	<.001	−5.68 (−5.92 to −5.44)	<.001	−5.68 (−5.92 to −5.44)	<.001
Change in slope per 10-y increase in age at first cognitive assessment per y	−0.123 (−0.131 to −0.115)	<.001	−0.125 (−0.133 to −0.116)	<.001	−0.13 (−0.14 to −0.12)	<.001
Slope in white men at median age per y	−0.23 (−0.24 to −0.21)	<.001	−0.20 (−0.21 to −0.19)	<.001	−0.20 (−0.22 to −0.19)	<.001
Difference in slope between black and white individuals per y	−0.03 (−0.05 to −0.01)	.004	−0.01 (−0.03 to 0.01)	.56	−0.01 (−0.03 to 0.01)	.41
Change in slope per 10–mm Hg in cumulative mean SBP per y	NA	NA	−0.018 (−0.023 to −0.014)	<.001	−0.020 (−0.024 to −0.015)	<.001
Change in slope associated with hypertension treatment per y	NA	NA	NA	NA	0.02 (0.002 to 0.04)	.03

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Abbreviations: NA, not applicable; SBP, systolic blood pressure.

^{^a}

N = 19 378. Global cognition measures global cognitive performance. All cognitive measures are set to a t score metric (mean [SD], 50 [10]) at a participant’s first cognitive assessment; a 1-point difference represents a 0.1-SD difference in the distribution of cognition across the 5 cohorts. Higher cognitive scores indicate better performance. Linear mixed-effects models included time since first cognitive assessment and baseline values (measured before or at time of first cognitive assessment) of race (black vs white), age, sex, cohort study, years of school, alcohol use, cigarette smoking, body mass index, waist circumference, physical activity, fasting glucose, low-density lipoprotein (LDL) cholesterol, history of atrial fibrillation, age × time, sex × time, and race × time. To take into account correlation between longitudinal cognitive measures, we included random intercept and slope effects associated with participants. All continuous variables were centered at the overall median, except cumulative mean SBP, which was centered at 120 mm Hg. Glucose, LDL cholesterol, and SBP values were divided by 10 so that the parameter estimates refer to a 10-unit change in the variables. Systolic blood pressure was the time-dependent mean of all SBPs before the measurement of cognition. To estimate differences between black and white individuals in cognitive decline, model A included a black race × follow-up time interaction term. To examine whether cumulative mean SBP, a time-varying covariate, explained the racial differences in cognitive decline, model B added SBP and an SBP × follow-up time interaction term to model A. To investigate whether hypertension treatment explained the racial differences in cognitive decline, model C added a hypertension treatment and hypertension treatment at first cognitive assessment × follow-up time interaction term to model B.

After adjusting for cumulative mean SBP, differences between black and white individuals in the decline in global cognition were no longer statistically significant (adjusted difference in slope between black and white individuals: −0.01 points [95% CI, −0.03 to 0.01]; P = .56) (model B, Table 2). Cumulative mean SBP was associated with faster declines in global cognition (−0.018 points per year faster per each 10–mm Hg increase [95% CI, −0.023 to −0.014]; P < .001). Further adjustment for antihypertensive medication use did not change the racial difference in decline in global cognition, although antihypertensive medication use was associated with slower declines in global cognition (0.02 points per year slower [95% CI, 0.002-0.04]; P = .03) (model C, Table 2).

Change in Memory

Black individuals, compared with white individuals, had significantly faster declines in memory (adjusted difference in slope between black and white individuals: −0.08 points per year faster [95% CI, −0.11 to −0.06]; P < .001) (model A, Table 3). After adjusting for cumulative mean SBP, differences between black and white individuals in memory decline were partially attenuated (adjusted difference in slope between black and white individuals: −0.06 points [95% CI, −0.08 to −0.03]; P < .001) (model B, Table 3). Cumulative mean SBP was associated with faster declines in memory (−0.028 points per year faster per each 10–mm Hg increase [95% CI, −0.035 to −0.021]; P < .001). Further adjustment for antihypertensive medication use did not change race differences in memory decline, and antihypertensive medication use was not associated with memory declines (change in slope associated with hypertension treatment, −0.003 points per year faster [95% CI, −0.03 to 0.02]; P = .84) (model C, Table 3).

Table 3. Association of Memory Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017^a.

Coefficient	Model A: basic		Model B: cumulative mean SBP added as a time-varying covariate to model A		Model C: hypertension treatment added as a covariate to model B
Coefficient	Estimate (95% CI)	P value	Estimate (95% CI)	P value	Estimate (95% CI)	P value
Change in intercept per 10-y increase in age at first cognitive assessment	−0.99 (−1.16 to −0.81)	<.001	−1.05 (−1.23 to −0.88)	<.001	−1.04 (−1.22 to −0.86)	<.001
Difference in intercept between black and white individuals at first cognitive assessment	−2.97 (−3.22 to −2.72)	<.001	−3.04 (−3.30 to −2.79)	<.001	−3.01 (−3.27 to −2.76)	<.001
Change in slope per 10-y increase in age at first cognitive assessment per y	−0.20 (−0.22 to −0.19)	<.001	−0.18 (−0.20 to −0.16)	<.001	−0.18 (−0.20 to −0.16)	<.001
Slope in white men at median age per y	−0.25 (−0.26 to −0.23)	<.001	−0.19 (−0.21 to −0.17)	<.001	−0.19 (−0.21 to −0.17)	<.001
Difference in slope between black and white individuals per y	−0.08 (−0.11 to −0.06)	<.001	−0.06 (−0.08 to −0.03)	<.001	−0.06 (−0.08 to −0.03)	<.001
Change in slope per 10–mm Hg in cumulative mean SBP per y	NA	NA	−0.028 (−0.035 to −0.021)	<.001	−0.028 (−0.035 to −0.020)	<.001
Change in slope associated with hypertension treatment per y	NA	NA	NA	NA	−0.003 (−0.03 to 0.02)	.84

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Abbreviations: NA, not applicable; SBP, systolic blood pressure.

^{^a}

n = 13 145. Memory measures learning and delayed recall/recognition. All cognitive measures are set to a t score metric (mean [SD], 50 [10]) at a participant’s first cognitive assessment; a 1-point difference represents a 0.1-SD difference in the distribution of cognition across the 5 cohorts. Higher cognitive scores indicate better performance. Linear mixed-effects models included time since first cognitive assessment and baseline values (measured before or at time of first cognitive assessment) of race (black vs white), age, sex, cohort study, years of school, alcohol use, cigarette smoking, body mass index, waist circumference, physical activity, fasting glucose, low-density lipoprotein (LDL) cholesterol, history of atrial fibrillation, age × time, sex × time, and race × time. To take into account correlation between longitudinal cognitive measures, we included random intercept and slope effects associated with participants. All continuous variables were centered at the overall median, except cumulative mean SBP, which was centered at 120 mm Hg. Glucose, LDL cholesterol, and SBP values were divided by 10 so that the parameter estimates refer to a 10-unit change in the variables. Systolic blood pressure was the time-dependent mean of all SBPs before the measurement of cognition. To estimate differences between black and white individuals in cognitive decline, model A included a black race × follow-up time interaction term. To examine whether cumulative mean SBP, a time-varying covariate, explained the racial differences in cognitive decline, model B added SBP and an SBP × follow-up time interaction term to model A. To investigate whether hypertension treatment explained the racial differences in cognitive decline, model C added a hypertension treatment and hypertension treatment at first cognitive assessment × follow-up time interaction term to model B.

Change in Executive Function

Black individuals, compared with white individuals, had significantly slower executive function declines (adjusted difference in slope between black and white individuals: 0.09 points per year slower [95% CI, 0.08-0.10]; P < .001) (model A, Table 4). After adjusting for cumulative mean SBP, differences between black and white individuals in executive function decline slightly increased (adjusted difference in slope between black and white individuals: 0.10 points [95% CI, 0.09-0.11]; P < .001) (model B, Table 4). Cumulative mean SBP was associated with faster declines in executive function (−0.01 points per year faster per each 10–mm Hg increase [95% CI, −0.014 to −0.007]; P < .001). Further adjustment for antihypertensive medication use did not change the racial differences in executive function decline, and antihypertensive medication use was not associated with declines in executive function (change in slope associated with hypertension treatment, 0.01 points per year slower [95% CI, −0.01 to 0.02]; P = .25) (model C, Table 4).

Table 4. Association of Executive Function Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017^a.

Coefficient	Model A: basic		Model B: cumulative mean SBP added as a time-varying covariate to model A		Model C: hypertension treatment added as a covariate to model B
Coefficient	Estimate (95% CI)	P value	Estimate (95% CI)	P value	Estimate (95% CI)	P value
Change in intercept per 10-y increase in age at first cognitive assessment	−2.72 (−2.86 to −2.58)	<.001	−2.49 (−2.63 to −2.34)	<.001	−2.48 (−2.62 to −2.33)	<.001
Difference in intercept between black and white individuals at first cognitive assessment	−6.28 (−6.51 to −6.04)	<.001	−6.22 (−6.45 to −5.98)	<.001	−6.19 (−6.43 to −5.95)	<.001
Change in slope per 10-y increase in age at first cognitive assessment per y	−0.011 (−0.018 to −0.005)	<.001	−0.017 (−0.023 to −0.010)	<.001	−0.017 (−0.024 to −0.011)	<.001
Slope in white men at median age per y	−0.35 (−0.36 to −0.34)	<.001	−0.33 (−0.34 to −0.32)	<.001	−0.33 (−0.34 to −0.32)	<.001
Difference in slope between black and white individuals per y	0.09 (0.08 to 0.10)	<.001	0.10 (0.09 to 0.11)	<.001	0.10 (0.09 to 0.11)	<.001
Change in slope per 10–mm Hg in cumulative mean SBP per y	NA	NA	−0.01 (−0.014 to −0.007)	<.001	−0.01 (−0.015 to −0.008)	<.001
Change in slope associated with hypertension treatment per y	NA	NA	NA	NA	0.01 (−0.01 to 0.02)	.25

Open in a new tab

Abbreviations: NA, not applicable; SBP, systolic blood pressure.

^{^a}

n = 17 254. Executive function measures complex and/or speeded cognitive functions. All cognitive measures are set to a t score metric (mean [SD], 50 [10]) at a participant’s first cognitive assessment; a 1-point difference represents a 0.1-SD difference in the distribution of cognition across the 5 cohorts. Higher cognitive scores indicate better performance. Linear mixed-effects models included time since first cognitive assessment and baseline values (measured before or at time of first cognitive assessment) of race (black vs white), age, sex, cohort study, years of school, alcohol use, cigarette smoking, body mass index, waist circumference, physical activity, fasting glucose, low-density lipoprotein (LDL) cholesterol, history of atrial fibrillation, age × time, sex × time, and race × time. To take into account correlation between longitudinal cognitive measures, we included random intercept and slope effects associated with participants. All continuous variables were centered at the overall median, except cumulative mean SBP, which was centered at 120 mm Hg. Glucose, LDL cholesterol, and SBP values were divided by 10 so that the parameter estimates refer to a 10-unit change in the variables. Systolic blood pressure was the time-dependent mean of all SBPs before the measurement of cognition. To estimate differences between black and white individuals in cognitive decline, model A included a black race × follow-up time interaction term. To examine whether cumulative mean SBP, a time-varying covariate, explained the racial differences in cognitive decline, model B added SBP and an SBP × follow-up time interaction term to model A. To investigate whether hypertension treatment explained the racial differences in cognitive decline, model C added a hypertension treatment and hypertension treatment at first cognitive assessment × follow-up time interaction term to model B.

Sensitivity Analyses

Results were similar in analyses including participants’ cognitive observations after the time of incident stroke and adding glomerular filtration rate and history of myocardial infarction as covariates (eTables 2 and 3 in the Supplement). There was heterogeneity in the associations between race and BP with cognitive decline across cohorts (eTable 4 in the Supplement).

Discussion

Among 19 378 individuals pooled from 5 prospective cohort studies, black individuals’ higher BP levels were associated with faster decline, compared with white individuals, in global cognition and memory but not executive function. Antihypertensive medication use did not change the differences between black and white individuals in cognitive decline independent from their association with BP reduction. Systolic BP had a linear effect on cognitive decline, so lower SBP levels are associated with slower cognitive decline. We found no evidence that the magnitude of the association of SBP with cognitive decline differed between white and black individuals.

Our results, when combined with previous research,⁸ provide evidence suggesting that black individuals’ higher cumulative BP levels contribute to differences between black and white individuals in cognitive decline. A previous study³³ suggested that black individuals’ lower socioeconomic status (eg, education and literacy) largely explain their higher rates of CID. We found that black individuals’ faster declines in global cognition and memory than white individuals persisted after adjusting for years of school and vascular risk factors and were partially attenuated after adjusting for cumulative mean BP. Our results might differ because we included young and middle-aged adults, included repeated BP measurements, measured cognitive trajectories (not incident dementia³³) and controlled for age and sex differences in cognitive decline.

If causal, the differences between black and white individuals in the declines in global cognition and memory due to long-term BP levels we observed, equivalent to 2.5 to 4 years of cognitive aging, would undoubtedly be clinically significant. The faster declines in mean cognitive scores associated with black race can be associated with approximate equivalent changes in years of brain or cognitive aging by calculating the ratio of slope coefficients for black race and age on cognition. Declines in global cognition and memory substantially increase the risk of death, dementia, and functional disability.^34,35,36 The combination of black individuals’ lower initial cognitive scores and faster declines in global cognition and memory mean they would reach a threshold of clinical dementia earlier in adulthood than white individuals.

Black individuals might be more likely than white individuals to experience deleterious brain effects from elevated BP levels owing to earlier age of onset, longer duration, greater severity, and worse BP control over the life course. Black individuals’ disproportionate burden of elevated BP levels across the life span might lead to greater severity of arterial stiffness, vascular brain injury, small vessel disease, and atherosclerosis^12,13,14,15 that in turn cause cognitive decline through mechanisms of inflammation, oxidative stress, and damage to white matter integrity^37,38,39 as well as neurodegeneration.^40,41 There is a compelling need to study the mechanisms by which age of onset, duration, and severity of BP levels over the life course contribute to racial differences in the risk of cognitive decline.

The associations of race and BP with cognitive decline are modest, and pooling individual participant data from multiple cohorts enhanced the detection of these associations. We found a significant average difference in cognitive decline by race for 2 of 3 outcomes (global cognition and memory) and a significant average difference in cognitive decline by SBP for all cognitive outcomes. We were surprised that black individuals had slower declines in executive function than white individuals because executive function has been associated with vascular disease.⁸ Causes of persistent racial differences in decline in memory and executive function are uncertain and might include socioeconomic factors not captured by adjustment for years of education (eg, literacy,³³ quality of education,⁴² childhood socioeconomic status, wealth) as well as dietary or lifestyle factors and early-life exposures. It is also possible that the memory and executive function measures are more sensitive than the global cognition measure to detect racial differences in cognitive decline.

Our findings of heterogeneity of white race, black race, and BP-related differences in cognitive decline across cognitive domains and cohorts are consistent with prior evidence.^7,8,43 Some studies,^43,44 but not all,⁷ have shown differences between black and white individuals in cognitive decline similar to those we observed in the CARDIA¹⁹ and NOMAS²² cohorts. Race categories can be a proxy for differences in social determinants of health that vary across populations. The potential reasons for the heterogeneity of the associations of race and BP with cognitive trajectories are unclear and include unmeasured socioeconomic, geographic, environmental, and early-life factors as well as cohort differences in sampling strategies, eligibility criteria, and cognitive tests. It is plausible that the racial differences in cognitive decline in the present study are driven by observations in younger adults where differences between black and white individuals’ BP levels and incident hypertension are largest.^9,10,45 Indeed, in the youngest cohort, CARDIA,¹⁹ racial differences in cognitive decline were present and attenuated after adjustment for cumulative mean SBP for global cognition, memory, and executive function. High and increasing BP from early adulthood into midlife is associated with increased white matter hyperintensity volume and smaller brain volumes later in life.⁴⁶

Strengths and Limitations

Our study has several strengths. We had longitudinal BP and cognitive assessments in a large number of young, middle-aged, and older adults to estimate the effects of cumulative BP levels on cognitive decline in black and white individuals. The cohort studies systematically measured cognitive domains commonly affected by vascular factors such as hypertension, global cognition, memory, and executive function.²⁵ We had repeated cognitive measures during up to 21 years of follow-up.

Our study has potential limitations. We adjusted for educational years but not for other socioeconomic factors^33,42 or depressive symptoms because they were unavailable for all cohorts at or before the first cognitive assessment. Studies suggest that socioeconomic factors tend to influence baseline cognition (intercept) rather than the change in cognition over time (slopes).^47,48 Selective attrition of participants with cognitive impairments could underestimate the rate of cognitive decline⁴⁹ or not.⁵⁰ Estimating the potential clinical effect of racial differences in cognitive decline by correlating with decline owing to aging is a common approach, but it does not directly measure clinical impact, and a clinically meaningful change might vary by an individual’s age, educational quality, sex, and baseline cognition.⁵¹ Black individuals were more likely to be excluded than white individuals because of stroke or dementia before first cognitive assessment; however, this would reduce racial differences in cognitive decline. We did not study incident dementia because some cohort studies lacked these data. By study design, we did not adjust for baseline cognition.⁵² We did not study any particular age interval or BP level associated with greatest risk of BP-related cognitive decline. Race was self-reported. Heterogeneity of the effect between cohorts might affect the statistical validity of the summary estimate of the effect in the pooled cohort. Smaller sample size and fewer cognitive assessments might reduce precision of estimates of cognitive decline in black individuals.

Conclusions

Our study has policy implications. Although prominent organizations⁵³ recommend improved BP treatment and control in black individuals to reduce cardiovascular disease risk and disparities between black and white individuals in cardiovascular outcomes, our results suggest that improved BP control may also reduce black individuals’ risk of accelerated cognitive decline and racial disparities in cognitive outcomes. Between 2014 and 2060, the number of black individuals in the United States is expected to increase from 42 million to 60 million.⁵⁴ Along with early life interventions to improve racial differences in baseline cognitive performance,^55,56,57 our results suggest that effective interventions⁵⁸ to improve BP control in black individuals may also be strategies to reduce racial disparities in cognitive decline.⁵⁹ The critical need is that adults, especially black individuals, receive standard and low-cost treatments to control high BP levels. Our results also suggest that cognitive decline and CID are potential outcomes for health care systems and payers to evaluate the effectiveness and costs of BP-lowering interventions. These results suggest that black individuals’ higher cumulative BP levels and worse control contribute to differences between black and white individuals in later-life cognitive decline.

Supplement.

eMethods.

eTable 1. Characteristics of Participants at First Cognitive Assessment by Race in Pooled Cohort Sample by Cohort, 1971 to 2017

eTable 2. Sensitivity Analysis of Association of Global Cognition Decline with Race and Systolic Blood Pressure over Time Including Cognitive Observations after Incident Stroke, 1971 to 2017

eTable 3. Sensitivity Analysis of Association of Global Cognition Decline with Race and Systolic Blood Pressure over Time Including Kidney Function and History of Myocardial Infarction as Covariates, 1971 to 2017

eTable 4. Association of Cognitive Decline with Race and Systolic Blood Pressure over Time by Cohort, 1971 to 2017

eReferences.

Click here for additional data file.^{(235.9KB, pdf)}

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53.Whelton PK, Einhorn PT, Muntner P, et al. ; National Heart, Lung, and Blood Institute Working Group on Research Needs to Improve Hypertension Treatment and Control in African Americans . Research needs to improve hypertension treatment and control in African Americans. Hypertension. 2016;68(5):1066-1072. doi: 10.1161/HYPERTENSIONAHA.116.07905 [DOI] [PMC free article] [PubMed] [Google Scholar]
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55.Snowdon DA, Kemper SJ, Mortimer JA, Greiner LH, Wekstein DR, Markesbery WR. Linguistic ability in early life and cognitive function and Alzheimer’s disease in late life. Findings from the Nun Study. JAMA. 1996;275(7):528-532. doi: 10.1001/jama.1996.03530310034029 [DOI] [PubMed] [Google Scholar]
56.Hair NL, Hanson JL, Wolfe BL, Pollak SD. Association of child poverty, brain development, and academic achievement. JAMA Pediatr. 2015;169(9):822-829. doi: 10.1001/jamapediatrics.2015.1475 [DOI] [PMC free article] [PubMed] [Google Scholar]
57.Luby J, Belden A, Botteron K, et al. The effects of poverty on childhood brain development: the mediating effect of caregiving and stressful life events. JAMA Pediatr. 2013;167(12):1135-1142. doi: 10.1001/jamapediatrics.2013.3139 [DOI] [PMC free article] [PubMed] [Google Scholar]
58.Victor RG, Lynch K, Li N, et al. A cluster-randomized trial of blood-pressure reduction in black barbershops. N Engl J Med. 2018;378(14):1291-1301. doi: 10.1056/NEJMoa1717250 [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Williamson JD, Pajewski NM, Auchus AP, et al. ; SPRINT MIND Investigators for the SPRINT Research Group . Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321(6):553-561. doi: 10.1001/jama.2018.21442 [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplement.

eMethods.

eTable 1. Characteristics of Participants at First Cognitive Assessment by Race in Pooled Cohort Sample by Cohort, 1971 to 2017

eTable 2. Sensitivity Analysis of Association of Global Cognition Decline with Race and Systolic Blood Pressure over Time Including Cognitive Observations after Incident Stroke, 1971 to 2017

eTable 4. Association of Cognitive Decline with Race and Systolic Blood Pressure over Time by Cohort, 1971 to 2017

eReferences.

Click here for additional data file.^{(235.9KB, pdf)}

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PERMALINK

Association Between Blood Pressure and Later-Life Cognition Among Black and White Individuals

Deborah A Levine, MD, MPH

Alden L Gross, PhD

Emily M Briceño, PhD

Nicholas Tilton, PhD

Mohammed U Kabeto, MS

Stephanie M Hingtgen, MPP

Bruno J Giordani, PhD

Jeremy B Sussman, MD, MS

Rodney A Hayward, MD

James F Burke, MD, MS

Mitchell S V Elkind, MD, MS

Jennifer J Manly, PhD

Andrew E Moran, MD, MPH

Erin R Kulick, PhD

Rebecca F Gottesman, MD, PhD

Keenan A Walker, PhD

Yuichiro Yano, MD, PhD

Darrell J Gaskin, PhD

Stephen Sidney, MD, MPH

Kristine Yaffe, MD

Ralph L Sacco, MD, MS

Clinton B Wright, MD, MS

Veronique L Roger, MD, MPH

Norrina Bai Allen, PhD

Andrzej T Galecki, MD, PhD

Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Main Outcomes and Measures

Exposures

Results

Conclusions and Relevance

Introduction

Methods

Study Design, Participants, and Measurements

Cognitive Function Assessments

Measurement of Race

Measurement of Blood Pressure

Covariates

Statistical Analysis

Table 1. Characteristics of Participants at First Cognitive Assessment by Race: 1971 to 2017.

Figure. Participant Cohort.

Sensitivity Analyses

Results

Change in Global Cognition

Table 2. Association of Global Cognition Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017a.

Change in Memory

Table 3. Association of Memory Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017a.

Change in Executive Function

Table 4. Association of Executive Function Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017a.

Sensitivity Analyses

Discussion

Strengths and Limitations

Conclusions

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases

Table 2. Association of Global Cognition Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017^a.

Table 3. Association of Memory Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017^a.

Table 4. Association of Executive Function Decline With Race and Systolic Blood Pressure Over Time, 1971 to 2017^a.