Is it Possible to Prevent Alzheimer's Disease?
The rapid pace of Alzheimer's disease research over the past 25 years has unlocked many secrets about this devastating disease. We now know a great deal about AD's major characteristics and how they affect memory, personality, behavior, and the ability to think and make decisions.
AD has no known cure, but findings from research supported by the National Institute on Aging (NIA) and others provide tantalizing clues about the origins and development of AD. These findings are leading investigators to wonder whether it might be possible to delay the onset of the disease, slow its progress, or someday, even prevent it altogether.
Many AD Risk Factors
Some diseases, like measles, malaria, or cholera, have clear-cut causes. Preventing them is pretty straightforward—get vaccinated, eliminate the cause (mosquitoes in the case of malaria), or make sure that drinking water is clean. Other diseases, such as diabetes, heart disease, or arthritis, are more complex. They develop when genetic, environmental, and lifestyle factors work together to cause the disease process to start. The importance of each risk factor may differ for each individual.
Everything we know about AD indicates that it falls into the second, more complex, group of diseases. This means that, right now, there is no "magic bullet" that can absolutely prevent the disease from happening. AD develops over many years and appears to be influenced by a number of risk factors. We can’t do anything about some of these risk factors. However, accumulating evidence from many studies suggests that we can do something about other factors that affect the likelihood that a person may develop AD.
AD Risk Factors We Can't Do Anything About
Age is the most important known risk factor of AD. The risk of developing the disease doubles every 5 years over the age of 65. Several studies calculate that around half of persons over the age of 85 have AD. These facts are significant because of the growing numbers of people older than 65. More than 34 million people in the United States are now 65 or older. Even more significant, those older than 85 – the group with the highest risk of AD – is the fastest growing population group in the country.
Genetic predisposition is the other known AD risk factor that a person has no control over. Scientists have found genetic links to the two forms of AD. Early-onset AD is a very rare form of the disease that occurs in people between the ages of 30 and 60. Late-onset AD is the much more common form that develops after the age of 60.
In the 1980s, researchers realized that early-onset AD ran in families. They began to examine DNA samples from the families, searching for a common genetic trait. They found that mutations in certain genes on three chromosomes cause early-onset AD. A person has a 50 percent risk of developing early-onset AD if one parent has any of these genetic mutations. One of these genes directs the production of a protein, part of which is involved in the formation of beta-amyloid plaques. The mutations in all 3 genes increase the production of the plaques. Beta-amyloid plaques are dense clumps of abnormal protein and other material found outside and around nerve cells in the brain. A large number of beta-amyloid plaques in brain tissue is one of the hallmarks of AD.
In 1992, investigators looking for genetic clues to late-onset AD found a gene, which they called APOE. The APOE protein helps carry cholesterol in the blood throughout the body. Since then, other studies have shown that slightly different forms of this APOE gene can influence AD risk:
- APOE e2, a rarely occurring form, may provide some protection;
- APOE e3, the most common form, appears to play a neutral role; and
- APOE e4, which is found in about 40 percent of people with AD, appears
to increase risk.
In 2003, investigators announced that they had located another gene that appears to influence the age at which symptoms begin to appear in people with AD. This finding came only days after other scientists reported that they had discovered that there are two chromosomes not previously linked to AD that contain genes also appearing to influence age-at-onset of AD. These findings are important because they may open up avenues to further research on late-onset genes and how they work. Knowledge gained could possibly lead to strategies for delaying the onset of AD. Delaying by even 5 years the time when AD symptoms begin could greatly reduce the numbers of people who have the disease.
In October 2003, the NIA announced a major expansion of AD and genetics research efforts. The AD Genetics Study will build a bank of genetic material and cell lines from individuals in families with more than two living siblings who have late-onset AD. The availability of this valuable resource will allow geneticists to speed up the discovery of additional AD risk factor genes. Discovering risk factor genes is essential for understanding the causes of late-onset AD and for developing effective treatments and prevention strategies in the future.
AD Risk Factors We Can Do Something About
Though we can’t do much about our age or genetic profile, recent research has suggested that a number of lifestyle and environmental factors also may play a role in AD. The good news is that these factors are related to other major health concerns as well. Maintaining healthy habits in these areas will help maintain a person’s overall health, and they may reduce the chances of developing AD.
Keeping your brain active. Studies have shown that engaging in intellectually stimulating activities is associated with reduced AD risk. For example, scientists funded by NIA have been studying a large group of older priests, nuns, and brothers since 1993. In one study of this group, more than 700 participants described the amount of time they spent in seven activities that involve significant information processing. These activities included listening to the radio, reading newspapers, playing puzzle games, and going to museums. After following the participants for 4 years, investigators found that the risk of developing AD was 47 percent lower, on average, in those who did the activities most frequently than in those who did them least frequently. Other research in this same group suggests that the more formal education a person has, the better his or her memory and learning ability, even in the presence of beta-amyloid plaques.
Another NIA-funded study of healthy older people and people with possible or probable AD also supported the value of lifelong learning and mentally stimulating activity. These scientists found that during their early and middle adulthood, the healthy older people engaged in more of those activities and spent more hours engaged in them than did those who ultimately developed AD.
The reasons for these findings aren't entirely clear, but it may be that mentally stimulating activities protect the brain in some way, perhaps by establishing a "cognitive reserve." Perhaps these activities help the brain become more adaptable and flexible in some areas of mental function so that it can compensate for declines in other areas. A third possibility is that a lower level of engagement in intellectual stimulation could reflect very early effects of the disease. Scientists are working hard to clarify the complicated role that education and intellectual stimulation may have on AD risk.
Reducing heart disease risk. Evidence is emerging that actions to reduce heart disease risk may have some broader benefits as well. In recent years, a number of test tube, animal, and population studies have suggested a connection between AD risk and high levels of cholesterol in the blood. These findings led scientists to wonder whether drugs that lower blood cholesterol might also lower the risk of developing symptoms associated with declining mental function (dementia) and AD. Two recent studies that examined this question found a significant reduction in dementia risk in individuals who took statins, the most commonly-prescribed cholesterol-lowering drug. The effects did not appear to be related to lowering cholesterol in and of itself, but rather to some action of the statins. NIA is now funding a clinical trial to determine whether a statin will slow the rate of decline in people with AD.
Other research has found that a high level of an amino acid called homocysteine is associated with an increased risk of developing AD. A high level of homocysteine is known to increase heart disease risk. NIA-funded studies in mice have shown that high levels of this amino acid can make neurons stop working and die. The relationship between AD risk and homocysteine levels is particularly interesting because blood levels of homocysteine can be reduced by increasing intakes of folic acid and vitamins B6 and B12. Currently NIA is funding a large and carefully controlled clinical trial to determine whether reducing homocysteine levels through high-dose supplements will slow the rate of decline in people with AD.
Some studies also suggest that high blood pressure in midlife, an important
heart disease risk factor, might also have a negative effect on cognitive
function in late life, particularly for those who carry the APOE e4
form of the APOE gene.
Being physically active. Evidence is also accumulating that being physically active may benefit more than just our hearts and waistlines. Research in animals has shown that both physical and mental function improve with aerobic fitness. So, scientists funded by NIA decided to see whether it might be true for humans as well. In a study of 124 older adults, they found that those who were assigned to walking for exercise became more physically fit than those who were assigned to a stretching and toning exercises group. As they became more physically fit, the walkers also showed greater improvements on "executive function" tests (planning, scheduling, decision-making) than did the other group.
Other Factors Under Study
Scientists are actively investigating several other areas that may be important to preventing AD someday. For example, they are looking at agents that may affect the AD disease process and investigating ways to assess very early changes in the brain associated with AD. Finally, research to develop an AD vaccine is underway.
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most important of these agents. Inflammation of tissues in the brain is a common feature of AD, but it is not clear whether it is a cause or effect of the disease. Some evidence from population studies suggests that NSAIDS, such as ibuprofen, naproxen, and indomethacin, are associated with a decreased AD risk. NIA is currently supporting a clinical trial to determine whether NSAIDs can prevent AD in people who are at risk, but who do not yet show symptoms of the disease.
Another promising area of research relates to a longstanding theory of aging. This theory suggests that over time, damage from a kind of molecule called a free radical can build up in neurons. This damage, called oxidative damage, can result in a loss of function and contribute to AD. Some population and laboratory studies suggest that anti-oxidants from dietary supplements or food may provide some protection against oxidative damage. Several clinical trials are investigating whether two anti-oxidants—vitamins E and C—can slow cognitive decline and development of AD in normal aging individuals. The NIA and National Cancer Institute are currently funding a study to recruit volunteers for an anti-oxidant clinical trial that will examine whether taking vitamin E and/or selenium supplements over a period of 7 to 12 years can help to prevent memory loss and dementia. Other vitamins and food constituents are being actively studied.
Ginkgo biloba, a readily available natural product, has been the focus of recent media reports as a potential treatment for AD. Although a 1997 study in the U.S. suggested that a ginkgo extract may be of some help in treating the symptoms of AD and vascular dementia, there is no evidence that ginkgo biloba will cure or prevent AD. In addition, some recent studies imply that daily use of ginkgo biloba extracts may cause excessive bleeding, especially when combined with daily use of aspirin. Much more research is needed. At the NIH, the National Center for Complementary and Alternative Medicine is currently conducting a clinical trial to explore whether ginkgo has any effect on preventing or delaying cognitive decline in older adults.
Investigators are trying to discover biological markers that could indicate early AD changes in the brain. Understanding more about these markers, how they work, and what causes their levels to change, will help investigators answer questions about the cause and development of AD. These answers may lead one day to approaches for delaying or preventing AD. Investigators are also using neuroimaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), to measure brain structure and function. Another major NIA research program—the Neuroimaging and Biomarkers in Mild Cognitive Impairment (MCI) and AD Initiative—will fund a large study to determine whether MRI and PET scans, or other imaging or biological markers, can be used to identify early AD changes and progression. One day, these measurements may be able to identify those people who are at risk of AD before they develop symptoms and to more effectively assess efficacy of drug interventions.
Immunization is a common practice that protects people against disease. In the past few years, scientists have explored whether this approach also could be useful in preventing AD. Early studies in mice were so successful in reducing beta-amyloid deposits and improving performance on memory tests that investigators conducted preliminary trials in humans. These trials had to be stopped because of side effects that occurred in participants, but the study still provided a wealth of useful information that has been used in new NIA-funded studies in mice. Although scientists still have a long way to go, this exciting research is helping clarify the AD disease process, and it may still be one key to effective AD diagnosis, treatment, and prevention strategies in the future.
What's the Take-Home Message?
Though our knowledge is growing rapidly, we still don't know everything about what triggers the development of AD and how that process might be delayed or prevented. Scientists are working hard to understand the many factors involved in this complex disease.
Right now, no known treatments, drugs, or pills can delay or prevent AD. Furthermore, a person cannot do anything now about the major AD risk factors—age and genetics. On the other hand, people can take some actions that might reduce other possible AD risk factors. These include lowering cholesterol and homocysteine levels, lowering high blood pressure levels, being physically active, and engaging in intellectually stimulating activities. All of these risk-lowering strategies are good to do anyway because they lower risk for other diseases and can help to maintain and improve overall health and well-being.
It is important to note that the AD disease process begins long before symptoms appear. Therefore, to be really effective, a person should begin any prevention actions early in life and continue them throughout adulthood.
A Final Word of Caution
Because AD is such a devastating disease, caregivers and patients may be tempted by untried, unproven, and unscientific cures, supplements, or prevention strategies. Before trying pills or anything else that promises to prevent AD, families should use caution and check with their doctors first. These purchases might be unsafe or a waste of money. They might even interfere with other medical treatments that have been prescribed.
Becoming well-informed is another important step. Thousands of Internet websites provide health-related information, including information on Alzheimer's disease. Some of the information on these websites is reliable, but some is not. Health websites sponsored by the Federal government are good sources of information, as are websites of large professional organizations and well-known medical schools. Among the Federal resources available are:
- National Institute on Aging: www.nia.nih.gov.
Among the many topics offered by NIA are:
Each of these publications can be found at www.niapublications.org.
- Online Health Information: Can You Trust It?
- Life Extension: Science Fact or Science Fiction?
- Pills, Patches, and Shots: Can Hormones Prevent Aging?
- Alzheimer’s Disease Education and Referral (ADEAR) Center: www.alzheimers.org
- Other helpful Federal websites are: