Hypertension Management

The lifestyle choices that you make to protect yourself from heart attack and stroke will likely protect the health of your brain as well. Some treatment options for hypertension may protect your brain in ways beyond blood pressure.

with   Strong  evidence
Very likely
with   Strong  evidence

Hypertension is a common condition of persistently high blood pressure, when blood in the arteries pushes against the blood vessel walls with high force. The heart must then work harder and the walls of the arteries likely harden over time contributing to atherosclerosis.

Although hypertension can sometimes be caused by kidney disease, tumors, thyroid disease, sleep apnea, supplements, certain medications, or birth control pills, most cases of hypertension have no known cause. However, the risk of hypertension is increased by high salt or alcohol intake, diabetes, lack of physical activity, smoking, obesity, childhood obesity, vitamin D deficiency, stress, aging, and a family history of hypertension.

Hypertension can be managed effectively with a wide variety of strategies. Here, we focus on how hypertension and the strategies used to manage hypertension might affect long-term brain health.

DID YOU KNOW:  The brain receives 15-20% of your total blood supply, even though it only makes up 2% of the average person's body's weight.

Your brain's health depends on proper blood flow. Blood flow to the brain is tightly coupled to brain activity, with local blood flow rising when a specific area of the brain is activated. This coupling suggests that hypertension may impair brain function when arteries stiffen and become less reactive [1] or go into spasm. Hypertension associates with more markers of age-related damage in the brain, as indicated by brain atrophy and white matter hyperintensities [2]. Hypertension also raises the risk of strokes and transient ischemic attacks or "ministrokes", both of which damage the brain and can lead to vascular dementia.

Some anti-hypertensive drugs may affect the brain in ways beyond blood pressure (info below).

Very Likely to protect against dementia, based on strong evidence. Managing your hypertension may protect against both Alzheimer's disease and the vascular dementia caused by strokes and microinfarcts. People who manage their hypertension with drugs had 9% less risk of developing dementia in a 2013 meta-analysis of clinical trials and observational research [3]. Hypertension in mid-life associates with greater risk of vascular dementia [4] and Alzheimer's disease [5]. However, this association with Alzheimer's disease is lost or even reversed later in life, although this change might be an artifact of the challenges in experimental design for research in elderly people with numerous health problems [5].

The research is somewhat inconsistent, ranging from no benefit to up to 70% protection from dementia with some types of anti-hypertensive drugs [3, 6]. In general, the protective association has been stronger in observational studies than in randomized clinical trials [3, 7]. Some scientists think that the observational data accurately reflects the benefit of longer community-based treatments; other scientists think that observational studies are unreliable because the people who successfully manage their hypertension likely have other characteristics that make them less prone to dementia.

Despite these discrepancies, managing hypertension is one of the most promising strategies to protect your aging brain [8], particularly in people with the APOE4 genetic risk factor for Alzheimer's disease [9, 10]. Some anti-hypertensive drugs like angiotensin-receptor blockers and calcium-channel blockers may be particularly protective (see below).

APOE4 carriers:  E4 carriers may be particularly likely to lower their risk of cognitive decline by effectively managing their hypertension in mid-life but this claim is based on a handful of observational studies and the relationship between cardiovascular health, APOE status, and cognition appears complex.  E4 carriers may be slightly more likely to develop hypertension to begin with, particularly if they have Asian background(11). 

Hypertension has been more strongly associated with future dementia or cognitive decline in E4 carriers compared to E4 non-carriers(9, 12-14).  Similarly, hypertension in E4 carriers specifically has been associated with increased beta-amyloid in the brain (a characteristic feature of Alzheimer’s disease)(10).  However, of the many studies looking at anti-hypertensive use and cognitive decline, only one has reported that the use of anti-hypertensive drugs is particularly strong in E4 carriers(15).  Moreover, in patients with Alzheimer’s disease, the relationship between cardiovascular risks, APOE status, and cognitive decline has sometimes contrasted with the idea that the brain health of E4 carriers is particularly vulnerable to cardiovascular problems (16).

Unknown, based on limited evidence.  Scientists don't yet know whether hypertension management can improve brain health in people with dementia or mild cognitive impairment. Small clinical trials suggest benefit from some anti-hypertensive drugs; larger studies are now testing those ideas.

For example, small clinical trials suggest that the dihydropyridine calcium-channel blocker nilvadipine safely protects against cognitive decline in Alzheimer's patients [17,18] and a larger clinical trial in Europe is currently testing the efficacy of nilvadipine in mild-to-moderate Alzheimer's disease (ISRCTN14485052). More info below.

Similarly, some small observational studies suggest that centrally-acting ACE-inhibitors may slow cognitive decline in Alzheimer's patients but only in the first 6 months of their use [19]. This idea is controversial and needs further study, as other research suggests that ACE-inhibitors could accelerate Alzheimer's disease pathology in contrast to angiotensin-receptor blockers [20]. More info below.

Possibly, based on moderate evidence. Reducing hypertension can protect against stroke and cardiovascular causes of death, thus extending healthy lifespan for many individuals [21]. However, in elderly patients, the safety of hypertension treatments and their potential interactions with other medications must be carefully monitored [22].

Managing hypertension is critical for long-term health, based on strong evidence. Work carefully with your doctor to avoid safety risks.

Managing hypertension with behavior, diet, and/or drugs can reduce the risk of cardiovascular disease and death in many people. However, doctors debate the degree to which blood pressure should be lowered, especially in very old people [23]. Some treatment strategies may be safer than others depending on your specific health risks.

Some anti-hypertensive medications interact with other drugs, sometimes in dangerous ways. Elderly patients must be particularly careful when managing their hypertension as they often take multiple medications and their bodies may handle anti-hypertensive drugs differently than younger patients [22]. Work openly with your doctor to safely manage your hypertension.

Any physician-guided treatment to reduce hypertension is probably good for long-term brain health. Many treatment options exist, with varying cost, safety, and sometimes beneficial effects on the brain beyond blood pressure. Elderly patients should be careful when beginning anti-hypertensive treatments, particularly if they are taking multiple medications and if the blood pressure treatment is aggressive.

Behavior Changes: Behavior can go a long way to managing hypertension [24]. The Mayo Clinic website has more information about non-drug strategies to manage hypertension. These strategies can also affect the brain.

  • Reduce weight if your body mass index is over 30. Although a few extra pounds probably will not hurt your long-term health, obesity in mid-life raises the risk of many health problems including Alzheimer's disease. On the other hand, elderly people who are underweight may also have a higher risk of Alzheimer's disease. More info.
  • Alcohol consumption in moderation. Over-indulging in alcohol can raise blood pressure and reduce the effectiveness of some anti-hypertensive drugs. On the other hand, in moderation, alcohol can slightly lower blood pressure. Similarly, over-indulgence in alcohol can lead to dementia while moderate alcohol use associates with slightly less risk of Alzheimer's disease. More info on the relationship between alcohol and the brain can be found here.
  • Physical exercise. Exercise can help to manage hypertension. It may also reduce the risk of dementia. In a meta-analysis of 16 observational studies that tracked over 160,000 people over several years, physical activity associated with 45% less risk of Alzheimer's disease and 28% less risk of dementia in general [25].
  • Stop Smoking: Amongst the many dangers of tobacco, nicotine raises your blood pressure. Scientists have also observed that smokers have a greater risk of developing dementia compared to non-smokers [8].

Diet choices: The food that we eat can prevent or lower high blood pressure and probably protects the brain. The DASH diet and Mediterranean diets are two diets with strong evidence for long-term health benefits, including the brain. More info here.

Drugs: Many different drugs can treat hypertension. The choice depends on the patient. Drugs vary in side-effects, costs, interaction with other medications, and benefits for other medical conditions.

Some drugs may affect the brain in ways beyond reduced blood pressure. For example, in one study, hypertensive people who used anti-hypertensive drugs had less signs of Alzheimer's disease in their brains upon death than people who never had hypertension in the first place [26].

  • Angiotensin receptor blockers (ARBs or Sartans) are a class of anti-hypertensive drugs that may be more likely to protect the brain than other anti-hypertensive drugs [27] but the data for this claim are currently weak. Theoretically, sartans protect the brain both by reducing hypertension and by inhibiting the AT1 receptor of Angiotensin II while leaving the rest of the angiotensin system intact [20]. However, sartans are relatively new drugs with less evidence for their long-term effects on health and dementia risk. More info here.
  • ACE Inhibitors (Angiotensin Converting Enzyme Inhibitors) are a class of widely-used anti-hypertensive drugs. Some evidence suggests that ACE inhibitors reduce the risk and progression of dementia [28], particularly if they can penetrate into the brain [19] (many ACE inhibitors cannot cross the blood-brain barrier). However, other research suggests that ACE inhibitors could accelerate Alzheimer's disease when compared to other anti-hypertensive drugs [20]. More info here.
  • Dihydropyridine calcium channel blockers may protect the brain but the evidence is surprisingly inconsistent. In a clinical trial, a long-acting calcium-channel blocker called nitrendipine reduced the risk of Alzheimer's disease, vascular dementia, and fatal stroke by 40-50% in elderly people with hypertension. However, some scientists have questioned the reliability of those analyses [7]. In observational studies, people who use calcium-channel blockers have sometimes but not always had less risk of dementia or cognitive impairment [28]. More info here.
  • Discuss your options and choices with your health care providers. The right drug or treatment option will depend heavily on other aspects of your health, like your history of cerebrovascular disease, atrial fibrillation, your use of other medications, and your tolerance of side effects.
  • Disclose all the drugs and supplements that you take to your health-care provider. Some hypertension medications can dangerously interact with other drugs or supplements.
  • Ask your doctor about monitoring your blood pressure levels at regular intervals rather than only in a medical office. This "ambulatory" blood pressure monitoring can better detect blood pressure variability and may give a more accurate estimate, particularly for people who get nervous in doctor's offices.
  • Consider buying a home sphygmomanometer for far less than $100 and track your pressure as it varies by activity, rest, time of day, etc.

Scientists are mining existing clinical trial data to better understand which hypertension therapies have the best long-term outcomes [29]. Several studies are exploring if the choice of anti-hypertensive medication can affect the risk or progression of dementia and brain aging.

  • Could the choice of a sartan versus an ACE inhibitor to manage hypertension affect brain health? A clinical trial funded by Alzheimer's Drug Discovery Foundation Canada will be comparing telmisartan versus perindopril over 1 year in hypertensive Alzheimer's patients. Another clinical trial will compare candesartan versus Lisinopril for executive function in older hypertensive patients without dementia (NCT01984164).
  • In mildly-hypertensive people at risk of Alzheimer's disease, does treatment with the beta-blocker Ramipril prevent Alzheimer's disease? A 4-month Phase IV clinical trial has tested this idea but results are not yet available  (NCT00980785).
  • Is the anti-hypertensive drug nilvadipine a useful treatment for mild to moderate Alzheimer's patients? A Phase III clinical trial is testing this treatment idea (NCT02017340), with an add-on study of the drug's effect on cerebral autoregulation funded by the Alzheimer's Drug Discovery Foundation.
  • Will intensive versus standard blood pressure lowering prevent functional decline in older people with hypertension? The University of Connecticut Health Center is currently recruiting participants for a clinical trial. NCT01650402.
  • The Mayo Clinic has free online information about managing hypertension for cardiovascular health.
  • The Cleveland Clinic Center for Continuing Education has detailed information about hypertension, its diagnosis and its treatment options.
  • The neurovascular underpinnings of Alzheimer's disease: a free webinar from AlzForum.org.
  • ScienceDaily article on a research study reporting that hypertension management may protect against dementia particularly in people who carry the APOE4 genetic risk factor for Alzheimer's disease.

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2. Firbank, M.J., et al., Brain atrophy and white matter hyperintensity change in older adults and relationship to blood pressure.  J Neurol, 2007. 254(6): p. 713-21.
3. Levi Marpillat, N., et al., Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis.  J Hypertens, 2013. 31(6): p. 1073-82.
4. Sharp, S.I., et al., Hypertension is a potential risk factor for vascular dementia: systematic review.  Int J Geriatr Psychiatry, 2011. 26(7): p. 661-9.
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6. Yasar, S., et al., Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study.  Neurology, 2013. 81(10): p. 896-903.
7. McGuinness, B., et al., Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev, 2009(4): p. CD004034.
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9. Bangen, K.J., et al., APOE Genotype Modifies the Relationship between Midlife Vascular Risk Factors and Later Cognitive Decline.  J Stroke Cerebrovasc Dis, 2013. 22(8): p. 1361-9.
10. Rodrigue, K.M., et al., Risk factors for beta-amyloid deposition in healthy aging: vascular and genetic effects.  JAMA Neurol, 2013. 70(5): p. 600-6.
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12. de Frias, C.M., K.W. Schaie, and S.L. Willis, Hypertension moderates the effect of APOE on 21-year cognitive trajectories.  Psychol Aging, 2014. 29(2): p. 431-9.
13. Yasuno, F., et al., Effect of plasma lipids, hypertension and APOE genotype on cognitive decline. Neurobiol Aging, 2012. 33(11): p. 2633-40.
14. Qiu, C., et al., Combined effects of APOE genotype, blood pressure, and antihypertensive drug use on incident AD.  Neurology, 2003. 61(5): p. 655-60.
15. Guo, Z., et al., Apolipoprotein E genotypes and the incidence of Alzheimer's disease among persons aged 75 years and older: variation by use of antihypertensive medication? Am J Epidemiol, 2001. 153(3): p. 225-31.
16. Mielke, M.M., et al., Interaction between vascular factors and the APOE epsilon4 allele in predicting rate of progression in Alzheimer's disease.  J Alzheimers Dis, 2011. 26(1): p. 127-34.
17. Kennelly, S., et al., Apolipoprotein E genotype-specific short-term cognitive benefits of treatment with the antihypertensive nilvadipine in Alzheimer's patients--an open-label trial. Int J Geriatr Psychiatry, 2012. 27(4): p. 415-22.
18. Kennelly, S.P., et al., Demonstration of safety in Alzheimer's patients for intervention with an anti-hypertensive drug Nilvadipine: results from a 6-week open label study.  Int J Geriatr Psychiatry, 2011. 26(10): p. 1038-45.
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29. Hutton, B., et al., Comparative effectiveness of monotherapies and combination therapies for patients with hypertension: protocol for a systematic review with network meta-analyses.  Syst Rev, 2013. 2: p. 44.


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