Hypertension and Cognitive Impairment: A Review of Mechanisms and Key Concepts

Abstract

Cognitive impairment, and dementia, are major contributors to global burden of death and disability, with projected increases in prevalence in all regions of the world, but most marked increases in low and middle-income countries. Hypertension is a risk factor for both Vascular Cognitive Impairment and Alzheimer's disease, the two most common causes of dementia, collectively accounting for 85% of cases. Key end-organ pathological mechanisms, for which hypertension is proposed to be causative, include acute and covert cerebral ischemia and hemorrhage, accelerated brain atrophy, cerebral microvascular rarefaction and endothelial dysfunction, disruption of blood-brain barrier and neuroinflammation that affects amyloid pathologies. In addition to the direct-effect of hypertension on brain structure and microvasculature, hypertension is a risk factor for other diseases associated with an increased risk of dementia, most notably chronic kidney disease and heart failure. Population-level targets to reduce the incidence of dementia are a public health priority. Meta-analyses of blood pressure lowering trials report a significant reduction in the risk of dementia, but the relative (7–11%) and absolute risk reductions (0.4% over 4 years) are modest. However, given the high lifetime prevalence of both conditions, such relative risk reduction would translate into important population-level reductions in dementia globally with effective screening and control of hypertension. Optimal blood pressure target, especially in older adults with orthostatic hypotension, and antihypertensive agent(s) are uncertain. In this review article, we will detail the observational and interventional evidence linking hypertension with cognitive impairment, summarizing the mechanisms through which hypertension causes cognitive decline.

Blood pressure control and risk of post-stroke dementia among the elderly: A population-based screening study

“…Therefore, PSD pathogenesis may be more complicated for elderly patients ( 35 ). Hypertension causes changes in macro- or micro-vasculature and pathological remodeling, damaging the integrity of vessels and blood brain barrier permeability ( 13 , 36 ), resulting in hypoxia, oxidative stress, abnormal mitochondrial function, neuroinflammation, and neurodegeneration, which lead to major alterations in the brain microenvironment. Therefore, the cognitive impairment of high blood pressure may be mediated by chronic vascular injury.…”

“…High blood pressure, which affects more than 75% of people over the age of 65 years, is the leading risk factor for stroke and many other vascular diseases ( 12 ). Thus, high blood pressure likely plays an important role in PSD development, although this association remains unclear ( 10 , 13 ). In several randomized clinical trials concerning the effects of blood pressure reductions on cognitive outcomes, results have generally been inconclusive ( 14 , 15 ).…”

Editorial: Highlights in Hypertension: 2021

“…Also, mild cognitive function is hard to assess using MoCA, and probably cognitive tests that are easier to administer like the questionnaire for mild cognitive impairment ( 1 ) could facilitate the diffusion of the assessment of cognitive function in the larger population of hypertensive patients. This will finally allow researchers to include the assessment of brain function in the evaluation of hypertension-related target organ damage ( 2 , 3 ).…”

Late-life hypertension as a risk factor for cognitive decline and dementia

“…Given that there are currently no available disease-modifying therapies, appropriate emphasis should be placed on efforts to address known modifiable risk factors [1]. Hypertension is a well-known risk factor for both vascular cognitive impairment and Alzheimer's disease, the two most common causes of dementia, which collectively account for 85% of cases [2].…”

“…Moreover, in a recent meta-analysis that included 12 trials with a total of 92,135 participants, blood pressure (BP) reduction with antihypertensive agents, compared with a control condition, was significantly associated with a reduced risk of incident dementia or cognitive impairment (7.0% vs. 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I 2 = 0.0%) [3]. In addition, although antihypertensive therapy is associated with only a modest reduction in the risk of dementia, even this slight decrease in the relative risk of dementia among individuals with hypertension would constitute a considerable reduction in the absolute frequency of dementia globally, given the high lifetime prevalence of both conditions [2].…”