Blood pressure-lowering medicines reduce cases of mild cognitive impairment

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Older adults taking blood pressure-lowering medications known to cross the blood-brain barrier had better memory recall over time compared to those taking other types of medicines to treat high blood pressure, according to new research published today in the American Heart Association journal Hypertension.

High blood pressure, or hypertension, is a risk factor for cognitive decline and dementia in older adults. Nearly half of American adults have elevated blood pressure. Treating high blood pressure with blood pressure-lowering medicines reduced the cases of mild cognitive impairment by 19% in one large trial (SPRINT MIND).

ACE inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers and diuretics are different classes of blood pressure-lowering medicines. Each class acts in a different way to reduce blood pressure, and some cross the blood-brain barrier, thereby impacting cognitive function.

“Research has been mixed on which medicines have the most benefit to cognition,” said study author Daniel A. Nation, Ph.D., an associate professor of psychological science in the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine.

“Studies of angiotensin II receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors have suggested these medicines may confer the greatest benefit to long-term cognition, while other studies have shown the benefits of calcium channel blockers and diuretics on reducing dementia risk.”

This is the first meta-analysis to compare the potential impact over time of blood pressure lowering medicines that do vs. those that do not cross the blood-brain barrier. The medicines were evaluated for their effects on several cognitive domains, including attention, language, verbal memory, learning and recall.

“Hypertension occurs decades prior to the onset of dementia symptoms, affecting blood flow not only in the body but also to the brain,” Nation said . “Treating hypertension is likely to have long-term beneficial effects on brain health and cognitive function later.”

Researchers gathered information from 14 studies of nearly 12,900 adults ages 50 years and older. These included studies done in the United States, Australia, Canada, Germany, Ireland and Japan. The meta-analysis found:

  • Older adults taking blood pressure-lowering medicines that cross the blood-brain barrier had better memory recall for up to 3 years of follow-up compared to those taking medicines that do not cross the blood-brain barrier even though they had a higher level of vascular risk.
  • Adults taking hypertension medications that did not cross the blood-brain barrier had better attention for up to 3 years of follow-up.

“These findings represent the most powerful evidence to-date linking brain-penetrant ACE-inhibitors and angiotensin receptor blockers to better memory. It suggests that people who are being treated for hypertension may be protected from cognitive decline if they medications that cross the blood-brain barrier,” said study co-author Jean K. Ho, Ph.D., a postdoctoral fellow at the University of California, Irvine.

Blood pressure is considered elevated at 120/80 mm Hg and higher. The current American Heart Association/American College of Cardiology guidelines for treating high blood pressure suggest changes to diet and activity levels to lower blood pressure and adding blood pressure-lowering medication for people with levels of 130/80 mm Hg or higher depending on their risk status. If blood pressure reaches 140/90 mm Hg, blood pressure-lowering medication is recommended.

Limitations of this analysis are that the authors could not account for differences in racial/ethnic background based on the available studies, and there is a higher proportion of men vs. women in the group who took medications that cross the blood-brain barrier.

This is an important area of future research since previous studies have shown that people from various racial/ethnic backgrounds may respond differently to different blood pressure medications.


Hypertension guidelines have been a controversial topic in recent years [1]. The 2017 ACC/AHA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults (2017 ACC/AHA guidelines) defined hypertension as any systolic blood pressure (SBP) greater than 130 mmHg (≥130 mmHg), or diastolic blood pressure (DBP) greater than 80 mmHg (≥80 mmHg) [2].

These guidelines were changed to incorporate blood pressure (BP) in a spectrum as being normal (SBP <120 and DBP <80 mmHg), elevated (SBP 120-129 and DBP <80 mmHg), stage one high BP (SBP 130-139 mmHg or DBP 80-89 mmHg), and stage two high BP (SBP ≥140 or DBP ≥90 mmHg). The 2017 ACC/AHA guidelines suggested using a treatment goal of ≤130/80 mmHg for all ages, and all comorbidities, with few exceptions [2].

This treatment goal differs from the earlier 2014 Eighth Joint National Committee (JNC-VIII) guidelines for hypertension. Their findings suggested that in ages 60 or greater, a treatment goal of ≤150/90 mmHg should be pursued with pharmacologic treatment. For ages 30 to 59, they suggested a treatment goal of ≤140/90 mmHg, with pharmacologic therapy [3].

Apart from referring to age, the JNC-VIII guidelines also established chronic kidney disease (CKD) and diabetes as important comorbidities and separated this patient population from the rest of the general patient population. They specifically mentioned patients with cardiovascular diseases such as stroke as high-risk populations, and the panel members could not reach unanimity for SBP treatment goals in these high-risk groups [3].

In terms of treatment, the 2014 JNC-VIII guidelines suggested diabetes, CKD, and race as a specific patient population group with specific antihypertensive medication guidelines [3]. As such, the treatment algorithm from JNC-VIII guidelines suggested the use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) for hypertensive patients with CKD for all races, thiazides or calcium channel blockers (CCB) for black, non-CKD hypertensive patients, and ACE/ARB, thiazides, or CCB for non-black, non-CKD hypertensive patients (Figure ​(Figure1)1) [3].

An external file that holds a picture, illustration, etc.
Object name is cureus-0012-00000012035-i01.jpg
Classification of antihypertensive medications and their mechanism
NaCl: sodium chloride, ACE: angiotensin-converting enzyme

The 2017 ACC/AHA guidelines suggested that relative risk reduction for cardiovascular diseases (specifically noted as chronic heart disease, heart failure, and stroke) by using antihypertensive medications (AHM) was fairly similar across the general patient population in terms of age, sex, body mass, CKD, diabetes mellitus (DM), and atrial fibrillation (AF) [2].

They recommended starting pharmacologic treatment for anyone with stage two high BP and anyone with stage one high BP plus a clinical atherosclerotic cardiovascular disease (ASCVD) risk of ≥10%. For treatment strategy, the study indicated leniency to chose any antihypertensive, except in certain cases such as race or clinical comorbidity. For example, in cases where a far greater benefit was observed, i.e., beta-blockers (BB) after myocardial infarction, diuretics in heart failure patients (Figure ​(Figure11).

These guidelines also highlighted the impact of cardiovascular diseases, such as chronic heart disease, myocardial infarction, stroke [2], and suggested treating BP to prevent the development of cognitive decline (CD) and dementia [2,4-9]. Chronic high blood pressure is also a risk factor for cerebrovascular disease, leading to vascular dementia complications. The prevalence of hypertension seemed to increase with age and was greatest in those more than 75 years of age, with >79% of this population being hypertensive [2]. The elderly patient population also reported the greatest cognitive dysfunction, including the spectrum from mild cognitive impairment (MCI) to dementia [10,11]

Hypertension might be a contributing risk factor for MCI and dementia and can be targeted for therapy [12-14]. The healthcare burden of taking care of elderly patients with dementia is not a small number, and Hurd et al. even placed the cost to be among the highest healthcare expenditure, including heart disease and cancer [15]. Findings from observational studies suggested that treating hypertension in midlife and long-term might prevent CD in the elderly patient population [2,14,16].

However, treating hypertension in the elderly population and its contributing effect on cognition is not very clear. The question is, how and why does hypertension affect cognition, and can AHM play a role in preventing cognitive dysfunction?

Cognitive dysfunction covers a spectrum from MCI to dementia [12,17]. The pathophysiology surrounding cognitive dysfunction is varied. Some etiologies of dementia, such as Alzheimer’s disease (AD), have novel treatments; however, there is no specific treatment for vascular dementia [12]. Over time, as the United States population ages, it is becoming imperative that we have a greater understanding of treating hypertension in elderly populations.

The topic is worth investigating and few studies have also developed study protocols and feasibility trials for studying vascular dementia [18,19]. In keeping with these views, the purpose of this review was to investigate studies that dealt with hypertension and AHM and to assess their association with cognitive dysfunction.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797448/


More information: Hypertension (2021). DOI: 10.1161/HYPERTENSIONAHA.121.17049

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