Blood Pressure and Vascular Cognitive Impairment

Abstract

High blood pressure (BP) is detrimental to brain health. High BP contributes to cognitive impairment and dementia through pathways independent of clinical stroke. Emerging evidence shows that the deleterious effect of high BP on cognition occurs across the life span, increasing the risk for early-onset and late-life dementia. The term vascular cognitive impairment (VCI) includes cognitive disorders associated with cerebrovascular disease, regardless of the pathogenesis. This focused report is a narrative review that aims to summarize the epidemiology of BP and VCI, including differences by sex, race, and ethnicity, as well as the management and reversibility of BP and VCI. It also discusses knowledge gaps and future directions.

Introduction

Understanding and reducing the deleterious effect of high blood pressure (BP) on cognitive health is a public health imperative. High BP is one of the top modifiable risk factors for all-cause dementia, especially vascular cognitive impairment (VCI).¹ More than 1.2 billion individuals worldwide have high BP—diagnosed and undiagnosed.² Racial and ethnic disparities in hypertension and dementia exist. For example, Black and Hispanic individuals are more likely to have worse BP control, dementia, and VCI than White individuals in the United States.^3–6 Although high BP levels in midlife are consistently associated with late-life dementia,⁷ evidence is growing that the detrimental effect of high BP on cognition could begin in childhood and young adulthood,^8–10 contributing to young-onset dementia,¹¹ and continue to exert effects in late life.¹² Despite improvements in detecting, treating, and controlling hypertension, particularly in middle-income and high-income countries, BP control remains inadequate,² putting individuals at risk for cognitive impairment.

This focused report aims to summarize the epidemiology, management, and reversibility of the effects of BP on VCI. We prioritized the inclusion of interventions tested in randomized controlled trials (RCTs). It also discusses the gaps and next steps. A separate paper in the series addresses pathophysiology.¹³

Definitions and Diagnostic Criteria

VCI refers to cognitive impairment and dementia associated with cerebrovascular disease regardless of pathogenesis: cardioembolic, atherosclerotic, ischemic, hemorrhagic, or genetic.¹⁴ Diagnostic criteria for VCI recognize its heterogeneous neurological features, vascular etiologies, brain imaging abnormalities, and cognitive deficits (Box 1).^15–17 VCI can involve global cognition and specific cognitive domains, including memory, visuospatial, and executive function.¹⁸

Box 1.

Diagnostic Criteria for VCI

Diagnostic Criteria for VCIa
• Objective cognitive impairment in 1 or more domains
• Cerebrovascular disease on brain imaging (e.g., infarct[s], intracerebral hemorrhage, cerebral microbleeds, or white matter hyperintensity lesions plus a lacune)
• Evidence of a vascular etiology

^aData are adapted from Sachdev P et al.¹⁶ and Skrobot OA et al.¹⁷

Determining that vascular disease is the dominant if not exclusive pathology that accounts for the cognitive deficits is a challenge of the current VCI criteria. Most cognitive impairment and dementia cases are mixed: multiple brain pathologies are present and cerebrovascular disease is common.^19–21 Pre-mortem diagnosis of dementia etiology is suboptimal.^{22, 23} As most cognitive impairment and dementia are mixed and diagnosing “pure” VCI is challenging, we include all-cause cognitive impairment and dementia along with VCI in this review.

Epidemiology of the Relationship between BP and VCI

Differences by Age

Evidence is consistent that mid-life (45–64) high BP is a risk factor for late-life cognitive decline,^{7, 12} cognitive impairment,²⁴ and dementia,²⁵regardless of initial cognitive ability in midlife. Adults with hypertension who use antihypertensives have slower cognitive decline than untreated individuals with hypertension.^{7, 12} Midlife hypertension is also associated with faster cognitive decline in midlife.²⁶ The detrimental effects of high BP on cognition may begin in childhood (10–18) and young adulthood (18 to 44).^8–10 For example, individuals with higher BP levels from young adulthood to midlife had worse cognitive performance in midlife.²⁷ High SBP in young adulthood is associated with young-onset dementia.¹¹ This combined research suggests that the harmful effect of BP on cognitive decline and dementia might operate over the life course.

However, the relationship between high BP and dementia risk in older adults (65+) is less consistent. Some longitudinal studies suggest that higher systolic BP (SBP) in older adults is associated with faster cognitive decline and higher dementia with potentially greater effects with increasing age.^{12, 28, 29} In contrast, other observational studies of individuals have found that late-life hypertension is associated with slower cognitive decline and lower dementia risk.³⁰ A United Kingdom study³¹ of BP and dementia/VCI found different results in two cohorts. In the Clinical Practice Research Datalink data, the association between higher SBP and higher vascular dementia risk decreased with age.³¹ Yet, higher SBP predicted 5-year all-cause dementia risk with no evidence of a negative association at older ages in the Oxford Vascular Study data.³¹ Other studies suggest a possible U-shaped association with high and low BP related to greater dementia risk in older adults; however, results vary widely by age, stroke history, follow-up time intervals, subgroup analyses, and individual studies.

Methodological issues such as the sensitivity of dementia measurement, selection bias, survivor bias, and reverse causality might explain studies suggesting a potential protective effect of high BP in late-life and dementia risk. It is plausible that older adults with dementia (undiagnosed and diagnosed) have low BP because BP can decrease years before a dementia diagnosis and as dementia progresses.³² The direction of the causality (i.e., whether the dementia pathology causes BP to decline or whether low BP increases dementia risk) remains uncertain. Since individuals’ BP can change with increasing age, studies using repeated BP measurements over time and life-course approaches provide insights. For example, adults with hypertension in midlife and hypotension (BP<90/60 mmHg) in late life had a higher risk of incident dementia than individuals who were normotensive throughout midlife and later life.³³ Pulse pressure (SBP-DBP) widens with age 50+ and might measure the combined effects of high SBP and low DBP on dementia risk. Higher pulse pressure is associated with faster global cognition declines independent of mean arterial pressure and age in older adults.¹²

In summary, evidence suggests that high BP in childhood, young adulthood, and midlife is associated with worse cognitive outcomes. Consistent with this research, some studies have shown that high SBP in late life is a risk factor for faster cognitive decline and higher dementia.^{12, 29} However, other studies have found that the negative effect of high BP on cognitive decline and dementia weakens with higher age or high BP has a protective effect on dementia risk. We need to understand better the methodological and biological reasons for these discrepant results between BP, cognitive decline, and dementia risk in older adults.

Differences by Sex

The relationship between BP, cognitive decline and incident dementia might vary by sex. Several studies have found that the association between hypertension in midlife and late-life and dementia risk is stronger in women than in men. In a population-based sample in the Canadian Study of Health and Aging, hypertension at baseline was associated with incident dementia over five years in women but not in men.³⁴ Among middle-aged adults in the Kaiser Permanente Northern California health care system, hypertension was associated with higher dementia incidence than normotension among women but not men,³⁵ consistent with a United Kingdom biobank study.³⁶

In contrast, some studies have found that the association between midlife and late-life hypertension and dementia risk is stronger in men than women. In the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, which is a national community sample with an over-representation of individuals residing in the southeast United States, elevated SBP was associated with faster declines in new list learning in middle-aged men compared to middle-aged women over a median follow-up time of 8 years.¹²

Although research is limited, the evidence suggests sex differences in the relationship between elevated BP and cognitive impairment or incident dementia. More research is needed to confirm these findings and identify the possible causes of these potential sex differences.

Differences by Race and Ethnicity

Racial differences in the association between BP and cognitive decline, cognitive impairment, and dementia are unclear. Some studies have found that the association between midlife and late-life hypertension and dementia risk is stronger in Black than White individuals. In a pooled cohort study, Black individuals (median age, 54.8 years) had faster declines in memory and global cognition than White individuals median age, 59 years) over a median follow-up time of 12.4 years; racial differences in cumulative mean SBP partially accounted for Black-White differences in cognitive decline.³⁷ In a community-based study of older adults (mean age of 73.7 years), the 10-year decline in global cognition was greater in those with higher SBP (≥150 mmHg) than in those with lower SBP (≤120 mmHg). The difference between high and low SBPs on the rate of cognitive decline was more significant in Black than White individuals, with Black individuals having a faster rate of decline in global cognition associated with higher SBP.³⁸

In contrast, some studies have found that the association between midlife and late-life hypertension and dementia risk is similar or weaker in Black individuals than White individuals. In a racially and ethnically diverse cohort in the Kaiser Permanente Northern California health care system, hypertension and other cardiovascular risk factors in midlife were associated with late-life cognitive decline independent of race and ethnicity.³⁹ Conversely, midlife hypertension was associated with later-life global cognitive decline in White individuals, not in Black individuals, in a different cohort possibly due to the greater attrition of Black individuals and a lack of power.⁷

Ethnic differences in the association between BP and cognitive function are unclear. An exploratory post hoc analysis of the SPRINT-MIND trial showed that high mean SBP was associated with a greater risk of incident dementia and mild cognitive impairment in Hispanic older individuals than non-Hispanic older individuals.⁴⁰ Hispanic older individuals with hypertension demonstrated worse performance on a measure of executive function than non-Hispanic White hypertensive older adults.⁴¹

Taken together, Black and Hispanic individuals may have a higher risk of hypertension-related cognitive decline and dementia than White individuals. More research is needed to evaluate whether improving BP control and eliminating racial/ethnic disparities in BP control could reduce racial/ethnic disparities in late-life cognitive decline and dementia.

Hypertension and Post-stroke Dementia and VCI

Whether high BP is associated with post-stroke dementia independent of recurrent stroke is uncertain. Most cohort studies have small stroke subsets, lack repeated cognitive measurements before and after stroke to estimate stroke-related changes in cognition, and have few Black individuals and adults older than 80. Another issue is the lack of agreement on the definition of post-stroke dementia versus vascular dementia in many of the current criteria.¹⁷ It is unclear whether and how much post-stroke BP levels contribute to post-stroke cognitive decline and dementia independent of pre-stroke BP levels. Optimal levels of post-stroke BP to prevent recurrent stroke and post-stroke dementia are unknown.⁴²

Management and Reversibility

Evidence summary

Pivotal studies

Given the strong evidence linking hypertension and cognitive function, many authors have suggested that lowering SBP may reduce the risk of cognitive impairment and dementia.¹ Many seminal RCTs from the 1990s to the present included stroke, major adverse cardiovascular events, and death as primary outcomes. One of the earliest intervention studies was the Medical Research Council’s trial of hypertension,⁴³ which found no difference in cognitive change between the active and placebo-treated groups but concluded that hypertension treatment caused no cognitive harms.⁴³ The Systolic Hypertension in the Elderly Program (SHEP) study,^{44, 45} the Hypertension in the Very Elderly Trial (HYVET, mean age, 83.5 years),⁴⁶ the Heart Outcomes Prevention Evaluation-3 (HOPE-3) study⁴⁷ and the Study on Cognition and Prognosis in the Elderly (SCOPE)⁴⁸ study excluded individuals with prior stroke or dementia. None found any significant difference in cognitive outcomes between active and control treatment groups. However, the Systolic Hypertension in Europe (Syst-Eur) follow-up study (mean age, 68 years) concluded that long-term anti-hypertensive treatment reduced dementia risk by 55%.⁴⁹

The Perindopril Protection Against Recurrent Stroke Study (PROGRESS, mean age, 64 years) was one of the first trials to include individuals with prior stroke and transient ischemic attack (TIA).⁵⁰ Dementia and cognitive impairment were included a priori as secondary outcomes. They found a relative risk reduction of 12% for dementia and 19% for cognitive decline in the active group associated with recurrent stroke, with no clear effect on dementia or cognitive decline in the absence of recurrent stroke. Other studies to recruit stroke patients, such as the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET),⁵¹ found that patients with the lowest SBP had the highest preservation of cognitive function. However, meta-regression analyses did not show any benefits of BP lowering on cognition.⁵² The Prevention of Decline in Cognition after Stroke Trial (PODCAST) also included patients with recent stroke and normal cognition; however, intensive BP and lipid-lowering did not alter cognition over two years.⁵³ Additional trials of intensive BP lowering to prevent AD/ADRD in stroke survivors were negative.^54–57

In contrast, the impact of the SPRINT (Systolic Blood Pressure Intervention Trial) findings on clinical hypertension treatment is difficult to overstate.⁵⁸ Some researchers opined that the strongly positive primary outcome directly influenced changes to hypertension management guidelines.⁵⁹ The SPRINT-MIND study was a nested study with an a priori primary hypothesis that the incidence of all-cause probable dementia would be lower for participants who had high cardiovascular risk assigned to intensive treatment.⁶⁰ Among the 9361 randomized SPRINT participants (mean age, 67.9 years; 3332 women), 8563 completed one or more follow-up cognitive assessments, but the study was likely underpowered because of early study termination and fewer than expected cases of dementia. SPRINT combined with SPRINT-MIND gave definitive clinical trial evidence that aggressive BP control in individuals who have high cardiovascular risk reduced incident MCI and combined MCI and dementia, but not dementia specifically.⁶¹ SPRINT did not include individuals with a history of stroke.

Researchers questioned whether the effect of BP lowering on cognitive preservation in the SPRINT MIND trial resulted from reducing the accumulation of WMH of presumed vascular origin.⁶² Exploratory analysis of the SPRINT MRI data and the results from the Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People (INFINITY)⁶³ addressed this hypothesis. INFINITY (mean age 80.5 years) examined the effects of two levels of 24-hour average SBP on mobility, WMH progression, and cognitive function over three years. Although changes in gait speed and cognition were not different between treatment groups, the intensive SBP treatment group had less WMH accumulation than the standard SBP treatment.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Memory in Diabetes (MIND) trial assessed intensive BP lowering (with similar BP targets to SPRINT) and intensive glycemic control on cognitive function and brain volume in individuals with type 2 diabetes (mean age 62 years, 46.6% female, 30.3% non-white).^{64, 65} The investigators found no significant differences between the intensive and standard BP treatment groups in cognition and verbal memory, executive function, and processing speed. Surprisingly, they found a significantly greater decline in total brain volume in the intensive BP lowering group.⁶⁴ A subsequent SPRINT-MIND sub-study found no difference between intensive and standard BP treatment groups in most cognitive domains, although processing speed declined more in the intensive BP treatment group.⁶⁶

This decline in processing speed in the intensive BP treatment group of SPRINT seems contradictory given the decline in WMH accumulation. Some commentators⁶⁷ suggested that the sub-study did not select individuals with the most significant protective effect from intensive BP control: a potential volunteer bias. A SPRINT-MIND sub-study⁶⁰ also found that intensive BP treatment was significantly associated with a smaller increase in WMH volume and a greater decrease in total brain volume, although the differences were small.⁶⁸ Reassuringly, intensive BP lowering was not associated with progression of WMH in individuals with severe, symptomatic cerebral small vessel disease in a separate trial.⁶⁹ However, the reduction of brain atrophy in clinically diagnosed AD (RADAR) trial showed that 12 months of losartan treatment did not reduce the rate the rate of brain atrophy in individuals (55 or older) with clinically diagnosed mild-to-moderate AD.⁷⁰

BP variability (BPV) might be more critical. Increased systolic BPV is associated with stroke, cardiovascular disease, dementia, and mild cognitive impairment.⁷¹ A post hoc analysis of the SPRINT-MIND trial found the rate of dementia increased by ascending BPV tertile: i.e., higher BPV was associated with the development of probable dementia despite excellent BP control.⁷² The authors of a meta-analysis of studies reporting mean BP, BPV, and dementia or cognitive impairment found that mean BP effect sizes were less strong than BPV effect sizes: that is, evidence of the relative contribution of BPV exceeded that of the mean BP.⁷¹ Differential associations between BPV, dementia subtypes and cognitive domains are inconsistent. The authors noted high methodological and statistical heterogeneity and concluded that BPV might be a future target for prevention studies, but more studies are needed.”

Guidelines and recommendations

The Canadian consensus guidelines⁷³ recommended intensive hypertension management to reduce stroke risk but stated intensive BP lowering in middle-aged individuals with vascular risk factors was only weakly recommended. European guidelines for managing covert small vessel disease⁷⁴ strongly recommended BP treatment in individuals with hypertension and established cerebral small vessel disease to prevent disease progression even though the evidence strength was low. Clinical guidelines endorsed BP lowering to prevent cognitive decline and dementia in adults with hypertension (moderate strength of recommendation (IIa), moderate quality evidence).⁵⁹

Meta-analyses

Hughes’ and co-authors’ meta-analysis concluded that BP lowering with anti-hypertensive medication was significantly associated with a lower risk of incident dementia or cognitive impairment.⁷⁵ Ou and co-authors found moderate evidence that anti-hypertensive use was associated with a 21% lower risk of dementia and a high level of evidence for a strong protective effect of anti-hypertensive medication use over five years on the risk of all-cause dementia.⁷⁶

Gaps and Challenges

These trials were strongly positive for their primary outcomes. Overall, while there is evidence that BP reductions are associated with reductions in dementia risk in individuals without cerebrovascular disease, the level of evidence remains low. The commonest criticisms from hypertension researchers were the inconsistent definitions of BP exposure, inconsistent measurement of BP, and varying population characteristics. All studies had statistical power for cardiovascular endpoints but not cognitive outcomes, and only SPRINT-MIND included expert adjudication of dementia or cognitive decline as the primary outcome measure. The two potentially most relevant studies for cerebral small vessel disease, SPRINT-MIND and ACCORD-MIND, excluded patients with prior stroke. Only ACCORD-MIND specifically included people with type 2 diabetes mellitus. Methodological issues include using the Mini-Mental State Exam (MMSE) to detect a cognitive change, accounting for BP falls around the time of dementia diagnosis, and adjudicating the cognitive decline/dementia diagnoses.⁷⁷ Still, some have argued that cumulative evidence has shown that BP control is associated with improved cognitive outcomes and compelling observational data support anti-hypertensive medication use for dementia prevention.⁷⁸ A 2021 Cochrane review concluded: “High certainty randomised controlled trial evidence regarding hypertension treatment on dementia and cognitive decline does not yet exist.”⁷⁹

The obvious omission is that none of these pivotal trials included VCI or vascular dementia as their primary outcome. Only a handful included vascular dementia in their syndromic allocations. Dementia researchers have criticized the choice of cognitive tests, adjudication of dementia/cognitive impairment diagnoses, and timing of interventions. Most studies measured cognitive change using changes in the MMSE or Montreal Cognitive Assessment (MoCA) score, although neither test is suitable for repeated measures and the MMSE is insensitive to executive function and processing speed declines. Standardized, validated cognitive tests that measure clinically meaningful change and VCI are lacking. Ideally, we want measures that capture cognitive function’s effect on daily activities, but this area is underdeveloped.

Some have raised concerns regarding the inclusion of socioeconomically, racially and ethnically diverse individuals.⁷⁸ Despite high overall visit adherence in the SPRINT-MIND study, individuals who did not complete a cognitive assessment during follow-up were more likely to be women, Black, frail, and depressed, with lower cognitive scores at baseline. Individuals with low baseline education were often excluded from trial participation, prompting some authors to call for more studies on optimal timing of BP lowering, specific BP targets, and the inclusion of more diverse populations.⁷⁸

INFINITY is the only trial that specifically examined WMH as a potential risk factor or co-pathology of VCI, including both mobility and change in WMH as their primary outcomes.⁶³ Post hoc analyses of SPRINT-MIND have revealed that intensive BP lowering may modify brain changes associated with neurodegeneration, hippocampal atrophy, and WMH accumulation. However, neither INFINITY nor SPRINT-MIND demonstrated a substantial benefit on WMH progression. This finding is surprising given the clear reduction in BP and suggests that the cerebral impacts of hypertension may be more pervasive than those imaged on routine MRI scans.⁸⁰

Another significant omission has been the exclusion of individuals with pre-existing cognitive complaints or impairment. The exclusion of individuals with cognitive impairment at baseline is understandable because most studies required high levels of engagement and participation over time. Individuals with a diagnosis of VCI likely have compromised microvascular perfusion and cerebral hemodynamics, raising the question whether it is safe to aggressively lower BP. Some researchers have pointed out that optimal targets for BP in individuals with dementia and mild cognitive impairment are not known.⁶⁷ However, the benefits to brain health from a reduction in stroke recurrence could indicate that reducing overall cardiovascular burden may translate to improving vascular cognitive impairments. Participants in these studies were overall relatively elderly, raising the question of the optimal time for BP interventions to prevent vascular brain injury. While midlife may be the optimal time to intervene on BP to prevent late-life dementia, it is also plausible that identifying and treating high BP in young adulthood could prevent young-onset dementia.^{8, 11, 81}

Next Steps

Major questions are unanswered: when to commence anti-hypertensive medication to prevent VCI, how to select populations most at risk for VCI, whether a cognitive test score alone is an appropriate outcome measure or whether to combine a cognitive test(s) with blood or imaging biomarkers, and critically, whether a “prodromal” population should be targeted based on brain imaging changes coupled with sensitive tests of executive function. Neurodegenerative and cerebrovascular diseases do not fully explain adults’ late-life cognitive decline.⁸² We need to understand better the pathophysiological mechanisms that drive late-life cognitive decline to identify modifiable targets and develop effective treatments that prevent or reduce dementia including VCI.

Optimize outcome measures

The association of WMH and functional impairment and decline has been well-established. WMH is a cardinal feature of VCI. Overall, a reduction in WMH progression correlates with better BP control.⁸³ WMH volume does not necessarily increase over time: studies have shown WMH regression after stroke in individuals with larger BP reductions.⁸⁴ This finding suggests that WMH volume change could be a surrogate endpoint. Several problems are associated with using WMH volume change as an outcome measure: 1) the lack of consensus on its reliable and reproducible measurement, 2) the requirement for MRI scans would exclude some vascular populations, and 3) the large sample sizes required to demonstrate potential benefit, especially with the use of visual rating scales.⁸⁵ Brain atrophy rates could serve as an objective quantitative biomarker independent of educational status or language.^{86, 87}

The disadvantage of both imaging-based measures is repeated MRI, which is not accessible to all populations and may limit participant inclusion. However, large RCTs could use these endpoints for Phase IIb studies before translating to functional and cognitive outcomes. There are now several validated cognitive screens for VCI populations, including the MoCA, and cognitive tests sensitive to executive, visuospatial and attention impairments, such as Trail Making Test B and clock drawing task, can be used and are less dependent on first language and education. A composite outcome measure may be preferable, to ensure that imaging and cognitive measure changes are associated with functional benefits.

It would be important to include both people with and without evidence of cognitive impairment on traditional measures of executive and visuospatial function and processing speed (the best tests to detect VCI) for two reasons: to examine the safety of intensive BP control in a broader cohort of high-risk individuals and to better understand the timing of the intervention. We should consider the inclusion of less canonical markers of VCI, such as measures of depression and behavioral scores, as mood and behavior are often impacted by WMH burden causing dysfunction to fronto-insular networks and the widely distributed networks of human attention. Late-life depression might be a marker of vascular risk (vascular depression),⁸⁸ and apathy might indicate VCI. ^{89, 90}

Optimize participant inclusion and timing of intervention

Hypertension causes neurovascular dysfunction and might promote Aβ accumulation and tau phosphorylation.⁹¹ White matter lesions or WMH are core features of AD,^{92, 93} and vascular co-pathologies are common in post-mortem pathological series of people with MCI and AD.⁹⁴ Cerebral microbleeds and hypertension-related intracerebral hemorrhage are imaging features of VCI. The presence of microbleeds was not an exclusion criterion for the studies discussed. However, both high burden of WMH and multiple cerebral microbleeds have been exclusion criteria for most of the MCI and AD trials to date. As a result, these trials excluded a large percentage of the individuals most at risk for cognitive decline.

Another limitation of prior studies is the exclusion of individuals with a history of stroke. For most studies, stroke was an endpoint, not an inclusion criterion.⁹⁵ The arbitrary separation of “vascular” versus “post-stroke” cognitive impairment has meant that interventions designed to prevent vascular dementia or slow cognitive decline have required a false division of vascular populations into two groups, those with clinical stroke and those without clinical stroke. It is implausible that individuals with subclinical or silent brain infarcts have VCI, but those who present with a clinical stroke have a different entity.

Future trials will need to include all vascular participants, whether they are identified incidentally on a clinical scan or present to the stroke service with an acute event. More controversially, we should consider recruiting individuals who would not normally fall under the umbrella of neurologists, such as individuals with late-life depression and high WMH burden on MRI, individuals on the cardiac ward with recent myocardial infarction or acute coronary syndromes, or individuals with hypertension or diabetes. These are the populations most at risk of VCI and future dementia.

Conclusions

More than 55 million individuals have dementia worldwide and disease modifying treatments for dementia are lacking.⁹⁶ VCI needs an integrated multidisciplinary approach to identify effective, sustainable treatments.⁹⁷ High BP is a modifiable risk factor for dementia and VCI, but control rates are suboptimal. It is critical that individuals, especially Black individuals, have high BP detected early after onset and controlled to optimal levels with standard, low-cost treatments to reduce their risk of VCI and preserve their brain health.

Non-standard Abbreviations and Acronyms

AD

Alzheimer’s disease

ADRD

Alzheimer’s disease and related dementias

BP

blood pressure

BPV

blood pressure variability

DBP

diastolic blood pressure

HYVET

Hypertension in the Very Elderly Trial

HOPE-3

Heart Outcomes Prevention Evaluation-3

INFINITY

Intensive Versus Standard Blood Pressure Lowering to Prevent Functional Decline in Older People

MCI

mild cognitive impairment

MMSE

Mini-Mental State Exam

MoCA

Montreal Cognitive Assessment

ONTARGET

Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial

PODCAST

Prevention of Decline in Cognition after Stroke Trial

PROGRESS

Perindopril Protection Against Recurrent Stroke Study

RCTs

randomized controlled trials

SBP

systolic blood pressure

SCOPE

Study on Cognition and Prognosis in the Elderly

SHEP

Systolic Hypertension in the Elderly Program study

SPRINT

Systolic Blood Pressure Intervention Trial

Syst-Eur

Systolic Hypertension in Europe

TIA

transient ischemic attack

VCI

vascular cognitive impairment

WMH

white matter hyperintensity