Hypertension Can Lead to Cognitive Decline

Approximately 49.9% of Americans over 20 years old have hypertension, according to the CDC.¹ Additionally, the World Health Organization reports that worldwide, an estimat- ed 1.28 billion individuals aged 30 to 79 years have hypertension, with approximately 46% unaware they have the condition.²

Blood pressure (BP) is the force of blood against the artery wall. The measurement has 2 numbers: the first is the force of pressure during contraction of the heart, and the second is the force of pressure between beats. BP fluctuates throughout the day. Hypertension is defined as a BP consistently greater than normal, and should be diagnosed when a patient consistently has BP readings of 130/80 mm Hg or above, according to 2017 guidelines.¹

Hypertension is often referred to as “the silent killer,” because individuals may show no signs or symptoms. Therefore, it is important to check BP on a regular basis. This is often done at a physician’s office during a medical visit but can also be done at home. Those with diagnosed hypertension should check their pressure regularly at home and document the readings.

Sequelae of Hypertension

Early detection of hypertension is vital, as it may cause damage to end organs if it remains untreated. Hypertension can cause the following conditions³:

• Angina. Damage to blood vessels leading to the heart may cause microvascular disease, resulting in severe chest pain.
• Cognitive decline. Hypertension results in anatomic and functional changes to the brain’s vascular system.
• Heart attack. Damage to the arter- ies of the heart from hypertension may cause the arteries to become blocked and prevent blood flow to the heart muscle.
• Heart failure. The increased work- load of the heart may cause the heart to enlarge, making it unable to supply blood to the body.
• Stroke. Hypertension can cause the arteries to the brain to become blocked or even rupture.
• Kidney disease or failure. Damage to the arteries surround- ing the kidneys may reduce their ability to effectively filter blood.
• Peripheral artery disease. Atherosclerosis is a common con- sequence of hypertension. This narrowing of the arteries to the arms, head, legs, and stomach can cause fatigue and pain.
• Sexual dysfunction. Hypertension may reduce blood flow to sexual organs, causing decreased libido in women and erectile dysfunction in men.
• Vision loss. Hypertension can damage or strain blood vessels in the eyes, resulting in vision loss.

The mechanisms underlying cognitive decline are complex. Age-related functional and structural changes in cerebrovascular large and small blood vessels play a role in cognitive decline. These changes adversely affect brain circulation, which is exacerbated by arterial hypertension. Therefore, hypertension-related cognitive dysfunction develops due to the imbalance of autoregulation of cerebral blood flow and cerebral vascular alterations.⁴

The prefrontal region is the most developed region of the brain and processes the most complex intellectual tasks, such as cognition, concentration, perceptions, and volition, as well as emotions.

Damage to this region brings about “executive dysfunction,” characterized by apathy, attention deficit, difficulty planning and/or starting an activity, impaired mental performance, loss of inhibition, psychomotor retardation, and spatial and visual alterations. This impairment involves loss of voluntary attention control, resulting in immediate (short-term) and time-dependent (long-term) memory loss and potentially in emotional instability.⁴

In addition to these slow-developing dysfunctions, hypertension is a major cause of stroke. Approximately 10% to 30% of patients who have had a stroke develop dementia within 3 months.³

Preventing and Slowing Cognitive Decline

The results of several controlled, randomized, well-designed trials have shown a positive effect of antihypertensive therapy in preventing and slowing cognitive decline associated with hypertension. These studies primarily focused on calcium channel blockers and renin-angiotensin-aldosterone system (RAAS) antagonists.³

Calcium Channel Blockers

Intracellular calcium homeostasis is heavily involved in cognitive function. Aging impairs the ability of the brain’s intracellular degradation system, leading to a cellular buildup of calcium. This induces cellular damage. Neuroprotective effects of calcium channel blockers have been shown independent of BP status.³

Renin-Angiotensin-Aldosterone System

One treatment option is aldosterone antagonists. Increased plasma aldosterone levels have been associated with decreased cerebrovascular function in hypertensive patients. These findings need to be confirmed with large, randomized, controlled trials.³

Further, angiotensin-converting enzyme (ACE) inhibitors reduce the accumulation of amyloid β peptides through substance P that may degrade brain amyloid β peptide and increase acetylcholine. ACE inhibitors may also decrease neuronal injury through an antioxidative pathway. Those that cross the blood-brain barrier have been found to be more efficacious in slowing cognitive decline than non–brain penetrating ACE inhibitors or calcium channel blockers.³

Finally, angiotensin II receptor blockers (ARBs) may have neuroprotective effects because they cross the blood-brain barrier and increase brain blood flow. However, findings from studies have shown mixed results.³

β-Adrenergic Blockers

The beneficial effects of β-blockers on cognitive function have not yet been established. One major limitation is the fact that β-blockers are not commonly used as monotherapy. They are usually prescribed in combination with ACE inhibitors, ARBs, calcium channel blockers, and/or diuretics.³

Available evidence suggests that a reduction in cognitive decline appears to be achieved with all antihypertensive drug classes, including β-blockers. However, the neuroprotective effects of β-blockers appear to be inferior to other classes.³

Conclusion

The contribution of hypertension to cognitive decline is well recognized. In view of an aging population, the global burden of hypertension, and the low quality of life associated with cognitive decline, not to mention all the other comorbidities of uncontrolled hypertension, there is a great rationale for improving BP control.

Special attention should be paid to reducing hypertension in midlife, as it reduces the risk of developing cognitive decline later in life.

Evidence supports the use of any antihypertensive drug class. However, greater efficacy has been demonstrated with ACE inhibitors, ARBs, and calcium channel blockers in preventing and slowing cognitive decline. Combination antihypertensive therapy is preferable to monotherapy, as it provides additive and possible synergistic effects in BP control, prevention of stroke, and cognitive impairment.³

Cautious management of hypertension is imperative with older individuals, as there is a potential for an increased incidence of dementia and mortality in patients with low BP. Cognitive tests should be implemented into practice before starting therapy, especially in older patients who are hypertensive.

Kathleen Kenny, PharmD, RPh, has more than 25 years of experience as a community pharmacist. She is a freelance clinical medical writer based in Colorado Springs, Colorado.

References

1. Hypertension. CDC. Updated January 6, 2022. Accessed February 8, 2022. https://www.cdc.gov/nchs/fastats/hypertension.htm

2. Hypertension. World Health Organization. August 25, 2021. Accessed February 8, 2022. https://www.who.int/news-room/fact-sheets/detail/ hypertension

3. Health threats from high blood pressure. American Heart Association. Updated October 31, 2016. Accessed February 11, 2022. https://www.heart. org/en/health-topics/high-blood-pressure/health-threats-from-high- blood-pressure

4. Tadic M, Cuspidi C, Hering D. Hypertension and cognitive dysfunction in elderly: blood pressure management for this global burden. BMC Cardiovasc Disord. 2016;16(1):208. doi:10.1186/s12872-016-0386-0