High blood pressure, or what doctors refer to as hypertension, has long been known to increase the risk of developing Alzheimer's Disease and other forms of dementia. To some degree, this is due to the fact that high blood pressure increases the risk of developing heart disease, which is a major risk factor for dementia. However, high blood pressure itself is known to cause subtle damage to the fine network of blood vessels in the brain. Over time this results in inflammation, hardening of the arteries, poor blood flow, and secondary damage to the brain tissue that depends on these blood vessels for a steady supply of oxygen, fuel and nutrients. These insults to the brain increase the risk of Alzheimer's Disease.
Reducing blood pressure, by diet, exercise, and weight loss, is known to improve the chances of avoiding Alzheimer's Disease. A variety of antihypertensive medications that lower blood pressure have also been found to reduce the risk of dementia. Although treatment of high blood pressure itself reduces the risk of Alzheimer's Disease, recent evidence suggests that certain antihypertensive medications are more effective than others in helping prevent this disease. The mechanisms by which these blood pressure medications act in the brain may determine the degree to which they are able to help prevent dementia.
There are many different factors that affect blood pressure, and many systems in the body that work together to maintain normal pressure. Consequently, there are many different medications that act by quite different mechanisms to control blood pressure. One important system in the body involved in blood pressure is the renin-angiotensin system. The physiology of the renin-angiotensin system is fascinating. When the kidneys sense low blood pressure, special cells in that organ release renin. Renin, in turn, stimulates production of angiotensin type I in the blood stream, which is quickly converted into the active substance, angiotensin type II. Angiotensin II increases blood pressure in several different ways, including constricting blood vessels, increasing salt levels in the blood, making the kidneys retain more water, and stimulating thirst centers in the brain.
Activation of the renin-angiotensin system is one of the ways by which the body elevates low blood pressure. However, over activity of the system can cause high blood pressure. A class of drugs that prevents the enzymatic conversion of angiotensin I to active angiotensin II is useful in helping control high blood pressure. Since the enzyme that performs this conversion is Angiotensin Converting Enzyme, or ACE, these drugs are referred to as ACE inhibitors. Another class of drugs that acts on the rennin-angiotensin system to reduce high blood pressure are the angiotensin receptor blockers, or ARBs.
Angiotensin II performs its tasks by stimulating special angiotensin receptors on various cells of the body. For example, it causes us to feel thirsty by stimulating such receptors in the brain. Although the brain has long been known to possess angiotensin receptors that stimulate thirst, it has only recently been found that there are different kinds of angiotensin receptors in the brain. What has surprised neuroscientists is that some types of angiotensin receptors are involved in processes that have nothing to do with thirst or blood pressure. Of particular importance are recent findings that the various types of angiotensin receptors may be differentially involved in helping to maintain memory and cognitive function in the brain. It has been found that activation of one type of angiotensin receptor in the brain, known as AT1, blunts cognitive function, whereas activation of two other types of angiotensin receptors, AT2 and AT4, enhances cognitive function. ACE inhibitors prevent the production of angiotensin II that stimulates all of the angiotensin receptors. In contrast, the ARBs currently in use tend to block only the AT1 receptor, which when stimulated can cause both high blood pressure and decreases in cognitive function.
Another way in which the renin-angiotensin system impacts the brain and cognitive function is that the ACE enzyme plays a role in how the brain handles amyloid protein. Amyloid is an abnormal, sticky form of protein that builds up and forms plaque in brain tissue. This plaque is very damaging to brain tissue and function, and the build up of plaque is a major hallmark, if not the primary cause, of Alzheimer's Disease. ACE helps remove amyloid plaque from brain tissue, and thus helps free it of its amyloid burden. Thus, there is growing suspicion that increases in ACE activity in the brain may help prevent Alzheimer's Disease, whereas blocking the activity of the enzyme, such as occurs in people taking ACE inhibitors, may add extra risk of developing the illness. In fact, it has recently been shown that inheritance of genes that code for more active forms of ACE is associated with reduction in the risk of Alzheimer's Disease.
Together, the emerging data suggest that the ACE enzyme may help prevent amyloid build up in the brain, and activation of certain angiotensin receptors in the brain may help maintain normal cognitive function. Thus, simply blocking the activity of ACE may not be as helpful for preventing Alzheimer's Disease as blocking activation of specific subtypes of angiotensin receptors in the brain. For these reasons it appears that the use of angiotensin receptor blockers, or ARBs, may be more useful in the prevention of Alzheimer's Disease than the use of ACE inhibitors. Although both classes of drugs are useful to control high blood pressure and maintain normal heart function, the ARBs may be uniquely well suited to treat patients with high blood pressure, heart disease, and high risk of developing Alzheimer's Disease. Several recent studies have been consistent with this conclusion. Studies recently published in the British Medical Journal (Li, N-C., et al., 2010;340:b5465) and the American Journal of Geriatric Cardiology (Hanes DS, Weir MR. 2007 May-Jun;16(3):175-82.) suggest that ARBs offer benefits over ACE inhibitors in prevention of both Alzheimer's and vascular forms of dementia.
I feel obligated to note that because of their ability to lower blood pressure, and perhaps to block some bad effects of angiotensin II in the brain, ACE inhibitors, like many other blood pressure medications, do reduce some risk of developing dementia. Moreover, ACE inhibitors are prescribed for reasons other than merely to reduce blood pressure. You must not make any changes in your medications, including ACE inhibitors, without first discussing it with your doctor. Nonetheless, with the apparent advantages of ARBs over ACE inhibitors in reducing the risk of dementia, it might be worthwhile discussing this subject with him or her.
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