American Heart Association Statement on Hypertension and Cognitive Function

Dementia is a major, growing public health problem, and cardiovascular risk factors and conditions are also highly prevalent. The American Heart Association (AHA) had previously addressed the role of vascular risk factors in cognitive impairment, but has now critically reviewed current evidence regarding the association of cognitive function with hypertension.

The goal of the present AHA statement is to examine the contribution of chronic arterial hypertension to age-related cognitive dysfunction. It aims to inform healthcare professionals regarding recent advances, as well as to highlight remaining questions and guide future research.

Study synopsis and perspective

High blood pressure is a major risk factor for vascular cognitive impairment and is emerging as a potential risk factor for Alzheimer's disease, concludes a new statement from the AHA.

"We know treating blood pressure is important for reducing cardiovascular events," chair of the writing committee Costantino Iadecola, MD, from the Brain and Mind Research Institute at Weill Cornell Medicine, New York City, commented to Medscape Medical News. "The relationship to dementia is not fully established, but putting all the data together on the issue, it does appear that increased blood pressure in midlife is bad for the brain."

He added, "Epidemiological studies suggest that treating blood pressure in midlife should have a positive effect on cognitive impairment later in life. But this has not yet been proven definitively."

Dr Iadecola emphasized the need for prospective randomized trials to determine the exact relationship between blood pressure and dementia, and whether lowering blood pressure can protect against later dementia. One such trial, SPRINT MIND, is expected to report next year. "Until then, we should treat blood pressure judiciously on a patient-by-patient basis," he concluded.

The statement was published online October 10 in Hypertension.

As background, Dr Iadecola explained that as both hypertension and dementia were very common disorders, and it is known that chronic arterial hypertension is linked to vascular cognitive impairment, "we thought it was timely to conduct a comprehensive review of the literature on the issue of hypertension and dementia, including Alzheimer's. The present statement therefore seeks to provide an appraisal of the contribution of hypertension to age-related cognitive dysfunction."

"The evidence suggests a very strong link between hypertension during midlife (age 50 - 60) and dementia later in life (age 80 plus). And this is for Alzheimer's as well as vascular dementia."

He noted that although this has been suggested before in individual reports, this is the first time all the evidence has been reviewed so comprehensively. In addition, trials have not looked at each individual age groups, and most studies have been retrospective.

"Many of the individual studies are difficult to interpret because they have not used cognition as a primary endpoint; it has generally been a secondary endpoint, and different definitions have been used," he said.

Dr Iadecola was not in favor of recommending a single value for the optimal blood pressure for the whole of life.

"This probably changes with age," he said. "In the elderly, we think a slightly higher blood pressure may be beneficial, as when carotid stenosis starts to develop, then you need a higher pressure to push blood through the brain. A pressure of 120/80 may be too low for someone with severe cerebrovascular disease. So I think the ideal blood pressure needs to be personalized."

He said he finds it "bizarre" that "in the age of precision medicine, when we are sequencing genes to personalize medical care, something as simple as blood pressure is still viewed as a 1-size-fits-all."

In the statement, the authors note that hypertension disrupts the structure of cerebral blood vessels, promotes atherosclerosis, and impairs vital cerebrovascular regulatory mechanisms. These vascular changes increase the susceptibility of the brain to ischemic injury, especially in vulnerable white matter regions critical for cognitive function, and may promote Alzheimer's pathology.

The evidence to date points strongly to a deleterious influence of midlife hypertension on cognitive function in midlife and late life. Executive function and processing speed seem to be the cognitive domains most affected, but memory can also be impaired, they report.

On the subject of aging, they say: "Although the data are not conclusive, there is evidence of an association between higher late-life [blood pressure] and better cognition, highlighting the complexities of recommending uniform levels of [blood pressure] across the life course."

In addition to aging, other factors that may affect the relationship of hypertension in cognitive decline are given as menopausal status, APOE ε4 genotype, insulin resistance, and systemic inflammation.

The statement says that the effects of hypertension treatment on cognitive function is less clear. "[E]vidence from randomized, double-blind, clinical trials that treatment of high [blood pressure] at any stage over the life course improves cognition is far from conclusive."

On Alzheimer's disease, it states: "An intriguing relationship has emerged between hypertension and [Alzheimer's], raising the prospect that a chronic elevation in [blood pressure] aggravates [Alzheimer's] pathology, contributing to dementia. These findings are critically important because they raise the possibility that treatment of hypertension may also contribute to reduce the development or progression of [Alzheimer's]. Because no evidence-based recommendations can be made at this time, treatment of high [blood pressure] in midlife and judicious use of antihypertensives in late life, taking into account cerebrovascular status and comorbidities, seem justified," the authors conclude.

Study highlights

• Vascular dementia is a form of age-related dementia caused by cerebrovascular factors.
• Chronic arterial hypertension is a known risk factor for vascular dementia, as well as for Alzheimer's disease, but mechanisms underlying the associations are still unclear.
• A multidisciplinary team of experts reviewed pertinent literature and summarized available data.
• Hypertension disrupts cerebral vasculature structure and function, causing ischemic damage to white matter regions underlying cognitive function.
• Related mechanisms include development of atherosclerosis and impairment of cerebrovascular regulation.
• Hypertension-induced amyloid production and deposition may also promote Alzheimer's pathology, and whole brain and hippocampal atrophy over time are also likely to reduce brain processing power.
• Underlying cellular and molecular mechanisms are incompletely understood, although oxidative stress may be involved.
• Evidence is strong for a harmful effect of midlife (age 50-60 years) hypertension on late-life (age ≥80 years) cognitive function and risk for Alzheimer's/vascular dementia, but weaker for the cognitive effect of late-life hypertension.
• Affected cognitive domains include executive function and processing speed, and sometimes memory.
• Hypertension appears to have a cumulative effect on cerebrovascular damage, according to observational studies.
• The effect of antihypertensive treatment on cognition is inconclusive, according to evidence from randomized, double-blind, clinical trials, because of difficulties in conducting decades-long longitudinal studies, lack of appropriate and uniform cognitive outcomes across trials, and the complex associations of hypertension with ethnicity, age, sex, and cerebrovascular risk factors.
• Findings of the SPRINT-MIND trial are forthcoming and may help answer questions regarding the potential role of antihypertensive treatment on preventing cognitive impairment.
• On the basis of their findings, the AHA group concluded that data were insufficient for evidence-based recommendations.
• They note that careful, patient-specific hypertension treatment, considering care goals, age, menopause, APOE ε4 genotype, metabolic traits, insulin resistance, systemic inflammation, and comorbidities, is warranted to protect vascular health, and therefore brain health.
• Optimal blood pressure most likely changes with age, and may need to be slightly higher when carotid stenosis begins to develop.
• Despite the relative safety and availability of antihypertensive drugs, it is still unclear how best to use them over the life course, based on patient-specific characteristics.
• It is also still unknown whether specific drug classes offer cognitive benefits beyond BP reduction.
• Better understanding of the cellular and molecular pathology of the cerebrovascular tree and associated cells, and development and use of new imaging tools, biomarkers, and genomic-proteomic approaches in clinical trials, should help resolve these uncertainties and develop new treatments.

Clinical implications

• Evidence is strong for a harmful effect of midlife hypertension on late-life cognitive function and dementia risk, but weaker for the cognitive effect of late-life hypertension, according to an AHA statement.
• Data regarding the effects of blood pressure treatment on dementia risk were insufficient for the AHA group to make evidence-based recommendations.
• Implications for the Healthcare Team: Careful, patient-specific hypertension treatment is warranted to protect vascular health, and therefore brain health.

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References(s): 
1). AHA: Relationship Between Hypertension, Cognitive Function. Medscape. Released: 11/22/2016. Accessed and downloaded on 12/12/2016. Available here: http://www.medscape.org/viewarticle/870678