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Research

Below is a brief summary of some of the scientific studies on high blood pressure and dementia or cognitive impairment, with links to the study websites.

The Atherosclerosis Risk in Communities Study (ARIC)

The Atherosclerosis Risk in Communities Study (ARIC), sponsored by the National Heart, Lung, and Blood Institute (NHLBI) is a prospective epidemiologic study conducted in four U.S. communities. ARIC is designed to investigate the causes of atherosclerosis and its clinical outcomes, and variation in cardiovascular risk factors, medical care, and disease by race, gender, location, and date. To date, the ARIC project has published over 800 articles in peer-reviewed journals.

REasons for Geographic and Racial Differences in Stroke (REGARDS)

The REasons for Geographic and Racial Differences in Stroke (REGARDS) project, sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), is a national observational study focusing on learning more about the factors that increase a person's risk of having a stroke. The purpose of the REGARDS project is to understand why people in some parts of the country develop more strokes than people in other parts of the country, and why African Americans develop more strokes than other populations. The study aims to learn how to reduce the number of people having strokes.

NOrthern MAnhattan Study (NOMAS)

The Northern Manhattan Study (NOMAS) is a population-based study funded by the National Institute of Neurological Disorders and Stroke (NINDS) investigating predictors of stroke, cognitive impairment, and dementia in a tri-ethnic community. One goal of this study is to inform future intervention programs for prevention of stroke and cognitive decline in diverse populations.

Additional resources

The Centers for Disease Control and Prevention (CDC) has recently released recommendations in favor of self-measured blood pressure monitoring (SMBP). Additional resources for use in a clinical setting are included below.

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Overview of the evidence

Experts have long recognized the relationship between vascular brain pathology and syndromes of cognitive decline and dementia [Snowdon et al., 1997], but this notion has only recently gained significant momentum in the scientific community or in public health efforts. A wealth of observational data has accumulated supporting a link between midlife vascular risk factors and late-life cognitive outcomes. However, scientific and logistical challenges have precluded the “gold standard” randomized controlled trial (RCT) evidence needed to solidify clinical and public health recommendations. [Dufouil and Brayne, 2014; McGuinness et al., 2009; Gorelick and Nyenhuis, 2012]. One case in point is the landmark SPRINT trial which recently showed significantly greater protection from major cardiovascular events with blood pressure treatment to 120 mmHg compared to 140 mmHg [SPRINT Research Group, 2015]. The results from this study point to the significant public health benefits to be gained from better blood pressure control; however, the shorter term health benefits precludes completion of planned follow-up studies to test for positive benefits on cognition. Indeed, to measure the effects of midlife blood pressure control on late-life cognition over an extended follow-up period would be impractical, and randomization to a higher treatment target would be unethical due to the proven increased risk for major cardiovascular events.

Despite this lack of “gold standard” RCT data in the evidence base, a critical mass of experts in the cerebrovascular field are coalescing around the message that control of vascular risk factors in midlife, especially hypertension, reduces risk for cognitive decline and dementia in later life. This is based on research data from well-designed epidemiological studies demonstrating that individuals with high blood pressure in midlife are more likely to develop cognitive impairment or dementia in later life. Further, brain imaging and autopsy studies have demonstrated a link between vascular burden on brain MRI and poor cognitive function, and a significant overlap of Alzheimer’s and vascular pathology at autopsy examination in individuals with dementia [Attems and Jellinger, 2014; Schneider et al., 2007]. Research experts from multiple fields are working diligently to tease apart the underlying pathophysiology and specific disease mechanisms, so that we can begin to understand more precisely what leads to cognitive impairment and dementia and how vascular disease influences its development and progression. In the meantime, many experts and organizations are recognizing the potential to benefit from what we already know, and are creating public health messages to encourage use of proven stroke and heart disease prevention strategies to also reduce dementia risk.

Below are synopses of some of the major epidemiological studies that document an association between blood pressure and cognitive decline or dementia. In addition, we also provide summaries of some of the evidence linking subtle vascular damage in the brain (i.e. white matter abnormalities and silent infarcts, which are both linked to hypertension and stroke) to poorer cognition or dementia. A multitude of high-quality literature reviews and expert opinion statements provide an extensive overview of the scientific landscape and more in-depth analysis of the research data; we provide links and descriptions of some of these below.

Important caveats to the data:

It is important to mention that the evidence base is strongest for midlife hypertension, and that the data is somewhat more complicated in older adults where results have been less consistent. One recent study suggested that the effects in older age may actually depend upon history of hypertension during midlife [Muller et al., 2014].

Another important caveat is that most of these studies have compared magnitude or rate of change in cognition over time, with very few specifying a clinical diagnosis. Further, while all use validated vascular and cognitive assessment tools, the specific methodologies vary between studies. However, despite these variations, most of the studies demonstrate the same nature of association and reach similar conclusions. While many studies measured the association between other cardiovascular risk factors (e.g. smoking status, cholesterol, weight, etc.) and cognitive change, these summaries focus only on the results related to hypertension.

Findings from major epidemiological studies

Several large-scale, longitudinal cohort studies link high blood pressure in midlife to poorer cognitive function or dementia later in life.

The Atherosclerosis Risk in Communities (ARIC) Study is a prospective study of almost 16,000 participants exploring the causes and consequences of atherosclerosis and other cardiovascular risk factors. The ARIC Neurocognitive Study is an additional component that is investigating the role of midlife vascular risk factors in dementia and cognitive impairment in a subset of participants. In this article, the ARIC investigators describe data from over 5,500 participants who had cognitive assessments and blood pressure measurements at three time points during follow-up, with the first measurement conducted in middle age (average age 57 years). They found that hypertension in midlife was associated with a steeper decline in scores of global cognition over the 20-year period, and the effect was most consistently observed in domains typically affected by vascular disease, i.e. executive function and processing speed. Systolic blood pressure was also nearly linearly associated with cognitive decline over the follow-up period. Further, the rate of decline was attenuated in individuals with hypertension who were taking anti-hypertension medication compared to those not taking antihypertensive medications. Importantly, hypertension in late-life (at the last examination point) was not associated with prior rates of decline suggesting, as other studies have, that the effects of blood pressure in older adults is more complicated. It is hoped that the final cognition results from the SPRINT-MIND study will divulge whether there is short term worsening of cognition due to aggressive blood pressure lowering in the elderly. Midlife Hypertension and 20-year Cognitive Change: the Atherosclerosis Risk in Communities Neurocognitive Study. JAMA Neurology. 2014; 71(10): 1218-1227.

The Honolulu-Asia Aging Study (HAAS) began in 1991 to assess diseases of old age, with an emphasis on brain aging and dementia, in the surviving participants from the Honolulu Heart Program cohort that originated in 1965. In this article, the HAAS investigators report results based on over 3,500 participants who underwent cognitive testing (Cognitive Abilities Screening Instrument, CASI) at an average age of 78, who had blood pressure measurements taken at three different time points starting in middle age (mean age of baseline measurement was 54 years). The investigators found that the risk for intermediate and poor CASI scores increased progressively with increasing levels of systolic blood pressure as measured in midlife, roughly 25 years prior. In addition, those with systolic blood pressure over 160 mmHg who had never used antihypertensive medications, had a high risk for poor cognitive scores, and every 10 mmHg of increased blood pressure resulted in parallel increased risk for intermediate and poor cognitive function. The Association Between Midlife Blood Pressure Levels and Late-Life Cognitive Function: The Honolulu-Asia Aging Study. JAMA. 1995; 274(23): 1846-1851.

Another analysis from the HAAS investigators attempted to address a critical public health question that has arisen in light of these epidemiological findings: “Will a shift in the population distribution of midlife BP to lower levels be associated with lower rates of dementia in the population?” After careful population-attributable risk (PAR) analyses based on the data collected over 25 years of the HAAS cohort, the authors conclude that 17% of late-life dementia cases may be attributable to midlife systolic blood pressure levels between 120 and 140 mmHg. Further, the number goes up to 27% of dementia cases for those with blood pressures greater than or equal to 120 mmHg who did not report taking antihypertensive medication in midlife. Their estimates accounted for other known or suspected dementia risk factors as well as the competing risk of mortality associated with high blood pressure. While these estimates reflect a specific cohort of men and may not generalize to all subgroups of the population at large, the data clearly suggest potential public health benefits of controlling midlife systolic blood pressure to reduce risk for developing dementia later in life. Lowering Midlife Levels of Systolic Blood Pressure as a Public Health Strategy to Reduce Late-Life Dementia: Perspective From the Honolulu Heart Program/Honolulu Asia Aging Study. Hypertension. 2010; 55: 1352-1359.

The Framingham Heart Study is a community-based prospective cohort study that began in 1948 to explore risk factors for cardiovascular disease. In addition to the original cohort, their offspring and spouses of the offspring have been followed since 1971, and a third generation comprised of children from the largest offspring families have been followed since 2000. In this article, the study team describes data from over 1,000 Framingham Offspring Cohort participants who had vascular risk factor measurements at an average age of 54, followed by two cognitive and MRI assessments starting seven years later. The researchers found that hypertension and increasing systolic blood pressure in midlife were both associated with a more rapid increase in white matter abnormalities and steeper decline in performance on a measure of executive function. Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline. Neurology. 2011; 77(5): 461-468.

The Coronary Artery Risk Development in Young Adults (CARDIA) Study is an investigation of risk factors for and development of cardiovascular disease. The study cohort is comprised of over 5,000 young adults who were between 18 and 30 years of age at baseline in 1985-86. Examinations of vascular risk factors have been conducted every two to five years for 25 years. In this paper, the CARDIA study team describes data from nearly 3,500 CARDIA participants who completed the year 25 examination (which included cognitive assessments) and at least one prior risk factor measurement over the course of the study. The investigators examined the effects of early, cumulative exposure to vascular risk factors (systolic and diastolic blood pressures, fasting glucose levels, and total cholesterol levels) on cognitive function in midlife. The authors found that cumulative exposure to elevated systolic blood pressure was negatively associated with performance on all tests of cognitive function, and higher diastolic pressure was associated with worse performance on two of the three cognitive tests. Further, the effects of the elevated systolic blood pressure over time were evident in early adulthood (under age 35) as well as middle adulthood (over age 35). Finally, cumulative exposure to vascular risk factors at levels above what is recommended by American Heart Association guidelines led to higher risk of cognitive decline than at levels below the recommendations. This study is significant as it supports the notion that the risk of adverse outcomes due to high blood pressure and other cardiovascular risk factors begins at young ages, speaking even more to the need for risk factor prevention and control measures to begin early. Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function. Circulation. 2014; 129: 1560-1567.

The Maastricht Aging Study (MAAS) is a prospective cohort study that began in 1993 in the Netherlands to understand factors that influence age-related and pathological cognitive impairment. Comprehensive assessments of vascular risk factors and neurocognitive measures were conducted on this cohort of over 1,800 individuals aged 25-84 years, at three different time points over 12 years. In this paper, the MAAS investigators found that participants with hypertension at baseline demonstrated faster decline in cognitive tests of memory, executive function, and information processing speed. In addition, those who developed incident hypertension at follow-up also demonstrated faster decline in the tests measuring memory and processing speed, particularly in the latter half of the follow-up period. The effects were most prominent in midlife for both prevalent and incident hypertension, and for untreated or uncontrolled hypertension. These data suggest that incident hypertension in middle aged individuals, particularly if poorly controlled, may be a predictor for cognitive decline. Temporal evolution of cognitive changes in incident hypertension: prospective cohort study across the adult age span. Hypertension. 2014 Feb; 63(2): 245-51.

Observational studies link markers of cerebral small vessel disease to hypertension and cognitive decline

The Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study aims to explore modifiable lifestyle and cardiovascular risk and protective factors for dementia and structural brain changes in 1,500 Finnish participants over a 30-year follow-up period (participants were age 50 on average at the start of the study). The participants underwent neurological, cardiovascular and neuropsychological examinations and also completed self-report questionnaires on other health factors. A subset of participants underwent brain MRI evaluations after 21 years of follow-up. In this study, the investigators explored whether midlife blood pressure and other cardiovascular risk factors predicted presence of white matter lesions later in life. They found that an increased risk of late-life white matter lesions was associated with obesity and hypertension in midlife and late-life. These results indicate that early and sustained vascular risk factor control is associated with a lower likelihood of having more severe white matter lesions in late-life. Changes in Vascular Risk Factors from Midlife to Late Life and White Matter Lesions: A 20-Year Follow-Up Study. Dementia and Geriatric Cognitive Disorders. 2011; 31: 119–125.

The Framingham Heart Study is a community-based prospective cohort study that began in 1948 to explore risk factors for cardiovascular disease. In addition to the original cohort, their offspring and spouses of the offspring have been followed since 1971, and a third generation comprised of children from the largest offspring families have been followed since 2000. In this study, investigators analyzed data from over 2,000 participants from the Framingham Offspring Cohort to determine the prevalence and risk factors for silent brain infarcts. They assessed whether Framingham Stroke Risk Profile score and individual measures of its components - age, systolic blood pressure, antihypertensive therapy, diabetes, smoking, cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy – were associated with prevalence of silent brain infarcts detected on MRI scans. The found that aggregate risk scores were correlated with the presence of silent infarcts, and that atrial fibrillation, hypertension, and systolic blood pressure were positively associated with risk of silent infarcts. Further analysis suggested the population-attributable risk of silent infarcts is 16.6% for hypertension. Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham Offspring Study. Stroke. 2008; 39: 2929–2935.

The Rotterdam Scan Study is a prospective, population-based cohort study that began in 1995-96 and was designed to explore the causes and consequences of brain changes in the elderly. Over 1,000 study participants underwent a structured interview, physical examination, blood sampling, neuropsychological tests and an MRI scan. Medical records were monitored for major clinical events and a second set of assessments was conducted on about 700 of the participants approximately 3.5 years after the initial examination. Criteria were used to determine status of dementia and cognitive impairment, and compound scores were developed for measuring the function of different cognitive domains. In this study, the researchers found that high blood pressure was independently associated with progression of white matter lesions. Importantly, progression of small vessel disease was associated with a parallel decline in cognitive function. Specifically, periventricular white matter lesion progression and incident lacunar infarcts were associated with a decline in general cognitive function as well as information processing speed; however, lesion progression was not associated with a change in memory function. Progression of Cerebral Small Vessel Disease in Relation to Risk Factors and Cognitive Consequences: Rotterdam Scan Study. Stroke. 2008; 39: 2712–2719.

In another analysis of the Rotterdam Scan Study cohort, the researchers found that presence of silent infarcts at baseline more than doubled risk of dementia, and greater severity of periventricular white matter lesions and cortical and subcortical atrophy was also associated with increased risk of dementia. They also found that development of silent infarcts, especially multiple infarcts, over the follow-up period was associated with greater global cognitive decline, regardless of whether they had infarcts at baseline. Silent Brain Infarcts and the Risk of Dementia and Cognitive Decline. New England Journal of Medicine. 2003; 348: 1215-1222.

Further reading

Expert perspectives and literature reviews

The synopses above represent highlights from selected articles in the literature. Numerous editorials and reviews have been published by leading experts in the field to bring attention to the link between blood pressure and cognitive impairment, and/or dementia, and to detail the underlying evidence. These provide more comprehensive summaries of the current state of the science and associated recommendations for research, practice, and policy.

Reviews and position statements from major organizations

Stroke and Potentially Preventable Dementias Proclamation. Stroke. 2015; 46: 3039-3040. Updated World Stroke Day Proclamation. In this World Stroke Organization editorial, Dr. Vladimir Hachinski discusses the public health burden and shared risk factors associated with dementia and stroke. He recommends several courses of action toward prevention of these devastating conditions, based on what is currently known about the contribution of modifiable risk factors.

Call to Preserve Cognitive Vitality. Stroke. 2015; 46: 3037-3038 World Stroke Day Proclamation 2015. In this related editorial, Dr. Philip Gorelick discusses the key tenets of the 2015 World Stroke Organization proclamation, which emphasize the potential to prevent both stroke and dementia by controlling shared risk factors, and suggests that more can be done to increase prevention with the knowledge that we currently have.

Blood Pressure and Treatment of Persons with Hypertension as it Relates to Cognitive Outcomes Including Executive Function. Journal of the American Society of Hypertension. 2012; 6(5): 309–315. In this American Society of Hypertension Position Statement, the authors explore the mechanistic and epidemiologic research on the relationship between blood pressure and cognition. Practical recommendations are provided regarding blood pressure treatment for reducing the risk of cognitive impairment and dementia.

Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke. 2011 Sep; 42(9): 2672-713. In this statement from the American Heart Association/American Stroke Association, an overview is provided on the evidence on vascular contributions to cognitive impairment and recommendations for practitioners. It points to midlife hypertension as a risk factor for cognitive decline and recommends antihypertensive treatment in individuals at risk for vascular cognitive impairment.

Improving Population Blood Pressure Control for Brain and Heart Health. Public Health Reports. 2015 Jul-Aug; 130(4): 302-6. In this Executive Perspective from the CDC’s Division for Heart Disease and Stroke Prevention, the authors discuss opportunities for improving brain health and preventing cognitive decline by preventing and controlling hypertension and other cardiovascular risk factors throughout the life course.

Summary of the Evidence on Modifiable Risk Factors for Cognitive Decline and Dementia: A Population-Based Perspective. Alzheimer’s & Dementia. 2015 Jun; 11(6): 718-26. This paper summarizes an assessment conducted by the Alzheimer’s Association on the state of the science supporting modifiable risk factors for cognitive decline and dementia.

Literature and systematic review articles

Brain Health and Shared Risk Factors for Dementia and Stroke. Nature Reviews Neurology. 2015; 11, 651–657. In this review article, the authors posit that many vascular risk factors are shared predictors for poor brain health, and that subclinical markers of vascular damage seen on brain MRI can be used for early identification of risk and intervention for stroke and dementia prevention. The authors call for a shift in focus from vascular risk factors to determinants of brain health, global campaigns to reduce cardiovascular disease to improve brain health, and more research on the distinct and overlapping etiologies of brain health conditions as well as associated biomarkers.

Antihypertensive Treatment can Prevent Stroke and Cognitive Decline. Nature Reviews Neurology. 2013 Mar; 9(3): 174-8. In this review article, the authors discuss the evidence for hypertension as a highly prevalent and modifiable risk factor for stroke, dementia, and small vessel disease, and argue for greater efforts to improve hypertension control as a way to prevent the most common brain diseases.

Target Risk Factors for Dementia Prevention: A Systematic Review and Delphi Consensus Study on the Evidence from Observational Studies. International Journal of Geriatric Psychiatry. 2015; 30(3): 234–24. In this paper, a detailed systematic literature review was conducted, followed by a Delphi consensus study whereby international experts ranked and weighed identified dementia risk factors in terms of their importance for prevention. Midlife hypertension was identified as an important preventable risk factor for dementia. The paper is part of a European project called In-MINDD (Innovative Midlife Intervention for Dementia Deterrence), which has the goal of decreasing dementia risk or delaying onset through lifestyle interventions in midlife.

Hypertension and Dementia. American Journal of Hypertension. 2010 Feb; 23(2): 116-24. The authors of this paper discuss the role of hypertension as a risk factor for cognitive impairment and dementia, and the potential benefit of antihypertensive therapy for dementia prevention.

Hypertension and Cognitive Function. Clinics in Geriatric Medicine. 2009 May; 25(2): 259-88. This article reviews the current evidence base that shapes our understanding of the relationship between hypertension and cognitive health, and discusses potential mechanisms by which hypertension influences cognition.

Hypertension: A Harbinger of Stroke and Dementia. Hypertension. 2013; 62: 810-817. This review discusses how hypertension alters the structure and function of the brain vasculature, the pathophysiological basis for the effects of hypertension on stroke and cognition, and potential strategies to prevent and attenuate the adverse effects of hypertension on the brain.

Vascular Aspects of Cognitive Impairment and Dementia. Journal of Cerebral Blood Flow & Metabolism. 2013; 33, 1696–1706. This article reviews research data on the relationship between hypertension, stroke, and dementia and the potential impact of preventive treatments targeting risk factors for cognitive impairment and dementia.

The Epidemiology of Silent Brain Infarction: A Systematic Review of Population-Based Cohorts. BMC Medicine. 2014 Jul 9; 12: 119. In this systematic review, the authors present the evidence base on the prevalence and incidence of silent brain infarcts and the link with known risk factors.

The Clinical Importance of White Matter Hyperintensities on Brain Magnetic Resonance Imaging: Systematic Review and Meta-Analysis. BMJ. 2010. This meta-analysis and systematic review explores the evidence linking white matter lesions with stroke, cognitive decline, dementia and death.

2001-2011: A Decade of the LADIS (Leukoaraiosis And DISability) Study: What Have we Learned About White Matter Changes and Small-Vessel Disease? Cerebrovascular Diseases. 2011; 32(6): 577-88. This paper provides an overview of findings from the LADIS study, which has investigated the role of white matter changes in predicting disability, and also suggests future areas of research in this field.

Cerebral Microinfarcts: the Invisible Lesions. Lancet Neurology. 2012; 11(3): 272–282. This paper reviews evidence linking microinfarcts (which are only detectable in brain tissue slices) with cognitive dysfunction.