Alzheimer’s Disease Prevention
Preventing a Complex Disease Like AD Poses Big Challenges
Some diseases, like diabetes, heart disease, or arthritis, are very complex.
They develop when genetic, environmental, and lifestyle factors work together to
cause a disease process to start. The importance of these factors may differ for
each person. AD is another one of these complex diseases. It develops over many
years, and it appears to be affected by a number of factors that may increase or
decrease a person’s risk of developing the disease. We don’t have control over
some of the risk factors for AD; we can do something about other AD risk
factors, though.
What Can You Do?
Our knowledge is growing rapidly as scientists
expand their understanding of the many factors involved in the development of
AD. Right now, however, no treatments, drugs, or pills have been proven to delay
or prevent AD, and a person cannot do anything 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 actions include:
- lowering cholesterol and homocysteine levels
- lowering high blood pressure levels
- controlling diabetes
- exercising regularly
- engaging in intellectually stimulating activities
All of these strategies are good to do anyway because they lower risk for
other diseases and help maintain and improve overall health and well-being.
It is important to note that the Alzheimer’s disease process begins long
before symptoms appear. Therefore, to be really effective, prevention actions
should start early in life and continue through-out adulthood.
Another important action you can take is to join either the Genetics Study or
the Neuroimaging Initiative. People who participate in clinical studies say that
the biggest benefit is having regular contact with experts in AD who have lots
of practical experience and a broad perspective on the disease. They also feel
they are making a valuable contribution to knowledge that will help people in
the future who develop AD. Families interested in participating in the Genetics
study can contact the National Cell Repository for Alzheimer’s Disease (NCRAD)
at 1-800-526-2839. Information may also be requested through its website at:
http://ncrad.iu.edu. People who are interested
in joining the Neuroimaging Initiative should contact ADEAR at
www.alzheimers.org or call toll-free,
1-800-438-4380 for a referral to the nearest participating study site.
Learning About AD Risk Factors We Can’t Control
Age is the most important known risk factor for AD. The risk of developing
the disease doubles every 5 years over age 65. Several studies estimate that
around half the people over age 85 have AD. These facts are significant because
of the growing number of people 65 and older. More than 34 million Americans are
now 65 or older. Even more significant, the group with the highest risk of
AD—those older than 85—is the fastest growing older population group in the
country.
Genetics is the other known AD risk factor that a
person can’t control. Scientists have found genetic links to the two forms of
AD. Early-onset AD is a very rare form of the disease that can occur in people
between the ages of 30 and 60. In the 1980s, researchers found that mutations
(or changes) in certain genes on three chromosomes cause early-onset AD. A
person has a 50-50 chance of developing early-onset AD if one parent has any of
these genetic mutations.
Late-onset AD, the more common form, develops after age 65. In 1992,
researchers found that certain forms of the apolipoprotein E (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.
Researchers are now intensively searching for other genes that may be linked
to late-onset AD. Discovering these risk factor genes is essential for
understanding the causes of AD and pinpointing targets for drug development and
other prevention or treatment strategies.
In 2003, NIA announced a major expansion of AD genetics research efforts. The
AD Genetics Study is collecting genetic material and cell lines from individuals
in families with more than two living siblings who have late-onset AD. This
valuable resource will allow geneticists to speed up the discovery of additional
AD risk factor genes.
The Search for AD Prevention Strategies
Though we can’t do much about our age or genetic profile, recent research
suggests that maintaining good overall health habits may help lower the chances
of developing AD as well as reducing the chances of developing other serious
diseases. Scientists are studying a number of health, lifestyle, and
environmental factors that could make a difference.
Investigating heart disease risk.
In recent years, basic research in laboratories as well as population and animal
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 dementia and AD. Two recent population studies that examined
this question found reduced risk of dementia in people 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 other
action of the statins.
Other research has found that a high level of the amino acid homocysteine is
associated with an increased risk of developing AD. High levels of homocysteine
are known to increase heart disease risk, and 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.
Examining high blood pressure. There also may be
associations among AD, high blood pressure that begins in midlife, and other
risk factors of stroke. It is known that even in relatively healthy older
adults, high blood pressure and other stroke risk factors, such as age,
diabetes, and cardiovascular disease, can damage blood vessels in the brain and
reduce the brain’s oxygen supply. This damage may disrupt nerve cell circuits
that are thought to be important to decision-making, memory, and verbal skills.
Scientists are studying the connections between AD and high blood pressure in
hopes that knowledge gained will provide new insights into both conditions.
Learning about diabetes. Large-scale population studies show
that diabetes is associated with several types of dementia, including AD and
vascular dementia (a type of dementia associated with strokes). These studies
have found that AD and type 2 diabetes share several characteristics, such as
increasing prevalence with age, genetic predisposition, and deposits of damaging
amyloid protein (in the brain for AD and in the pancreas for type 2 diabetes).
Scientists are learning more about the possible relationships between these two
diseases. For example, researchers at the Honolulu-Asia Aging Study (a long-term
population study of stroke, neurodegenerative diseases, and aging) explored the
links between type 2 diabetes, APOE e4, AD, and vascular dementia. They found
that study participants with both type 2 diabetes and APOE e4 had a higher risk
of AD than did participants with neither. They also found that participants with
type 2 diabetes and APOE e4 had more plaques and tangles in their brains and had
a higher risk of amyloid deposits in the walls of arteries supplying the brain
than did participants with neither condition.
Since 1993, scientists funded by NIA have been working with a large group of
older priests, nuns, and brothers in an investigation called the Religious
Orders Study. This study has provided a wealth of information about many aspects
of AD, including the possible link between diabetes and cognitive decline. In
one analysis, researchers examined tests of five “cognitive systems” involved
with word and event memory, information processing speed, and the ability to
recognize spatial patterns in more than 800 participants. The researchers found
a 65 percent increase in the risk of developing AD among those with diabetes
compared with those who did not have diabetes. They also found that diabetes was
related to declines in some cognitive systems but not others. The findings from
these two studies and others have provided important insights into both AD and
diabetes and lay the groundwork for future research in this area.
Exploring intellectually stimulating activities. Studies
have shown that keeping the brain active is associated with reduced AD risk. In
the Religious Orders Study, for example, investigators periodically asked more
than 700 participants to describe 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 for those
who did the activities most frequently than for those who did them least
frequently. A growing body of research, including additional findings in this
group, suggests that the more formal education a person has, the better his or
her memory and learning ability, even in the presence of AD plaques.
Another NIA-funded study also supports the value of lifelong learning and
mentally stimulating activity. In this study of healthy older people and people
with possible or probable AD, 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 types of findings aren’t entirely clear.
- 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.
- Finally, perhaps people who engage in these activities have other
lifestyle features that may protect them against developing AD.
The only way to really evaluate these possibilities is by testing them in a
more controlled way in a clinical trial.
Several clinical trials have directly examined whether memory training and
similar types of mental skills training can actually improve the cognitive
abilities of healthy older adults and people with mild AD. In the Advanced
Cognitive Training for Independent and Vital Elderly (ACTIVE) trial, certified
trainers provided 10 sessions of memory training, or speed of processing
training to healthy adults 65 years old and older. The sessions improved
participants' mental skills in the area in which they were trained. Even better,
these improvements persisted for 2 years after the training was completed. In
another study, 25 participants with mild AD worked with researchers to learn how
to improve their ability to carry out various tasks, such as how to associate
names and faces, recall the names of objects, and pay bills correctly. Compared
to another group with mild AD who received more generic mental stimulation
activities, people in the "cognitive rehabilitation" group improved their
abilities more, and their abilities were still improved 3 months later.
Investigating physical activity. Accumulating evidence
suggests 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. In one study, scientists 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 a walking for exercise group became more
physically fit than those who were assigned to a stretching and toning exercise
group. As they became more physically fit, the walkers also showed greater
improvements on “executive function” tests (planning, scheduling, and
decision-making) than did the other group.
Examining nonsteroidal anti-inflammatory drugs (NSAIDs).
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 population studies
suggest an association between a reduced risk of AD and certain NSAIDs, such as
ibuprofen, naproxen, indomethacin, or certain cyclooxygenase-2, or COX-2
inhibitors, such as rofecoxib and celecoxib. Clinical trials thus far have not
demonstrated a benefit regarding AD from these drugs. One study of rofecoxib and
naproxen did not show any slowdown in the rate of cognitive decline among people
with mild to moderate AD with either intervention. Another trial, testing
whether naproxen or celecoxib could prevent AD in healthy older people at risk
of the disease, has been suspended as investigators examine data regarding
possible cardiovascular risk. However, scientific interest in addressing AD with
anti-inflammatory drugs remains, and researches will continue to look for ways
to test how anti-inflammatory drugs might affect the development or progression
of AD.
Learning about antioxidants. Another promising area of
research focuses on highly-active molecules called free radicals. Damage from
these free radicals can build up in nerve cells and result in a loss of cell
function, which can contribute to AD. Some population and laboratory studies
suggest that antioxidants from dietary supplements or food may provide some
protection against oxidative damage, but other studies show no effect. Clinical
trials may provide some answers. Several studies are investigating whether two
antioxidants—vitamins E and C—can slow cognitive decline and development of AD
in healthy older individuals. The NIA is currently funding an antioxidant
clinical trial that will examine whether taking vitamin E and/or selenium
supplements over a period of 7 to 12 years can help prevent memory loss and
dementia.
Expanding knowledge about estrogen. This hormone is produced
by a woman’s ovaries during her childbearing years. After this time, estrogen
production declines dramatically. Over the past 25 years, some laboratory and
animal research, as well as studies in women, have suggested that estrogen used
by women to treat the symptoms of menopause also protects the brain, and experts
have wondered whether using estrogen could reduce the risk of AD or slow the
disease.
However, clinical trials testing this approach on postmenopausal women have
found that using estrogen to prevent AD may not be effective. One study showed
that estrogen does not slow the progression of already diagnosed AD. Other
research found that women older than 65 who use estrogen alone or estrogen with
a progestin may be at greater risk of dementia, including AD.
Further research may clarify the role that estrogen may play in preventing
AD. For example, scientists now are trying to find out whether estrogen can
prevent the development of AD in women with a family history of the disease or
in younger women. Important questions also focus on the timing of estrogen
therapy, with scientists looking at whether starting therapy around the time of
menopause, rather than at age 65 or older, could protect memory or prevent AD.
Investigating ginkgo biloba. This 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 fact, some recent
studies imply that daily use of ginkgo biloba extracts may cause excessive
bleeding, especially when combined with daily use of aspirin. At the NIH, the
National Center for Complementary and Alternative Medicine and NIA are currently
supporting a clinical trial to explore whether ginkgo has any effect on
preventing or delaying cognitive decline in older adults.
Exploring immunization. Will a vaccine someday prevent AD?
Scientists are studying whether immunizing against beta-amyloid (the major
component of the plaques that develop in the brains of people with AD) might
prevent AD. Early vaccine studies in mice were so successful in reducing
beta-amyloid deposits and improving brain performance on memory tests that
investigators conducted preliminary clinical trials in humans. These studies had
to be stopped because of side effects that occurred in some participants, but
research on this strategy is continuing on a number of fronts. This research is
helping clarify the AD disease process and scientists continue to explore this
approach as a possible AD prevention strategy.
Understanding social engagement. Evidence from studies of
animals, nursing home residents, and community-dwelling older people has
suggested a link between social engagement and cognitive performance. Older
adults who have a rich social network and participate in may social activities
tend to have reduced cognitive decline and decreased risk of dementia. In the
NIA-funded Chicago Health and Aging Project, a high level of social engagement
was associated with a significant reduction in cognitive decline. More research
is needed to understand why social ties may have a protective effect. For
example, is it simply because lifestyles that involve much social interaction
and diverse social activities are cognitively challenging? Or, do these
lifestyles contribute in some other way to brain reserve?
The Search for Other Clues that May Contribute to Prevention Strategies
Investigators also are trying to discover whether
changes in blood, urine, or cerebrospinal fluid could indicate early AD changes
in the brain. Understanding more about these biological markers, how they work,
and what causes their levels to change, is important to help scientists answer
questions about the cause and development of AD. Learning more about these very
early stages in the AD process may lead to new prevention strategies in the
future.
One major effort involves the use of imaging
techniques, such as magnetic resonance imaging (MRI) and positron emission
tomography (PET), to measure brain structure and function. An NIA public-private
partnership—the AD Neuroimaging Initiative—is a large study that will 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
as well as help physicians assess the response to treatment of people who
already have AD. To learn more about the Neuroimaging Initiative, visit NIA’s
Alzheimer’s Disease Education and Referral Center (ADEAR) at
www.alzheimers.org or call toll-free at
1-800-438-4380.
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