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Looking for the Causes of AD
One of the most important parts of unraveling the AD mystery is finding out
what causes the disease. What makes the disease process begin in the first
place? What makes it worse over time? Why does the number of people with the
disease increase with age? Why does one person develop AD while another remains
healthy?
Some diseases, such as measles or pneumonia, have clear-cut causes. They can
be prevented with vaccines or cured with antibiotics. Others, such as diabetes
or arthritis, develop when genetic, lifestyle, and environmental factors work
together to start a disease process. The role that any or all of these factors
play may be different for each individual.
AD fits into the second group of diseases. We do not yet fully understand
what causes AD, but we believe it develops because of a complex series of events
that take place in the brain over a long period of time. Many studies are
exploring the factors involved in the cause and development of AD.
 GENETIC
FACTORS AT WORK IN AD
Genetic studies of complex neurodegenerative diseases such as AD focus on two
main issues—whether a gene might influence a person’s overall risk of
developing a disease and whether a gene might influence some particular aspect
of a person’s risk, such as the age at which the disease begins. Slow and
careful detective work by scientists has paid off in discoveries of genetic
links to the two main types of AD.
One type is the rare, early-onset
Alzheimer’s disease. It usually affects people aged 30 to 60.
Some cases of early-onset disease are inherited and are called familial AD
(FAD). The other is late-onset
Alzheimer’s disease. It is by far the more common form and occurs
in those 60 and older. Gaining insight into the genetic factors associated with
both forms of AD is important because identifying genes that either cause the
disease or influence a person’s risk of developing it improves our ability to
understand how and why the disease starts and progresses.
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DNA, Chromosomes, and Genes: The
Body’s Amazing Control Center
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The nucleus of almost every human cell contains an encrypted
“blueprint,” along with the means to decipher it. This blueprint,
accumulated over eons of genetic trial and error, carries all the
instructions a cell needs to do its job. The blueprint is made up of DNA,
which exists as two long, intertwined, thread-like strands called chromosomes.
Each cell has 46 chromosomes in 23 pairs. The DNA in chromosomes is made
up of four chemicals, or bases, strung together in various sequence
patterns. The DNA in nearly all cells of an individual is identical.
Each chromosome contains many thousands of segments, called genes.
People inherit two copies of each gene from their parents, except for
genes on the X and Y chromosomes, which are chromosomes that, among
other functions, determine a person’s sex. Each person normally has
one pair of sex chromosomes (females are XX and males are XY). The
sequence of bases in a gene tells the cell how to make specific
proteins. Proteins in large part determine the different kinds of cells
that make up an organism and direct almost every aspect of the cell’s
construction, operation, and repair. Even though all genes are present
in most cells, the pattern in which they are activated varies from cell
to cell, and gives each cell type its distinctive character. Even slight
alterations in a gene can produce an abnormal protein, which, in turn,
may lead to cell malfunction and, eventually, to disease.
Any permanent change in the sequence of bases in a gene’s DNA that
causes a disease is called a mutation.
Mutations also can change the activation of a particular gene. Other
more common (or frequent) changes in a gene’s sequence of bases do not
automatically cause disease, but they can increase the chances that a
person will develop a particular disease. When this happens, the changed
gene is called a genetic
risk factor.
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Genes and
Early-Onset Alzheimer’s Disease
In the early days of AD genetics research, scientists realized that
some cases, particularly of the rare early-onset AD, ran in families. This led
them to examine DNA samples from these families to see whether they had some
genetic trait in common. Chromosomes 21, 14, and 1 became the focus of
attention. The scientists found that some families have a mutation in selected
genes on these chromosomes. On chromosome 21, the mutation causes an abnormal
amyloid precursor protein to be produced (see "From
APP to Beta-Amyloid Plaques" for more on APP). On chromosome 14, the
mutation causes an abnormal protein called presenilin 1 to be produced. On
chromosome 1, the mutation causes another abnormal protein to be produced. This
protein, called presenilin 2, is very similar to presenilin 1. Even if only one
of these genes that are inherited from a parent contains a mutation, the person
will almost inevitably develop early-onset AD. This means that in these
families, children have about a 50-50 chance of developing the disease if one of
their parents has it.
Early-onset AD is very rare, and mutations in these three genes do not play a
role in the more common late-onset AD. However, these findings were crucial
because they showed that genetics was indeed a factor in AD, and they helped to
identify some key cell pathways involved in the AD disease process. They showed
that mutations in APP can cause AD, highlighting the presumed key role of beta-amyloid
in the disease. Mutations in pre-senilin 1 and 2 also cause an increased amount
of the damaging beta-amyloid to be made in the brain.
A Different Genetic Story in Late-Onset Alzheimer’s Disease
While some scientists were studying the role of chromosomes 21, 14, and 1 in
early-onset AD, others were looking elsewhere to see if they could find genetic
clues for the late-onset form. By 1992, investigators had narrowed their search
to a region of chromosome 19. They found a gene on chromosome 19 that they were
able to link to late-onset AD.
This gene, called APOE, produces a protein called apolipoprotein
E. APOE comes in several forms, or alleles—ε2, ε3, and
ε4:
 | The APOE ε2 allele is relatively rare and may provide some protection
against the disease. If AD does occur in a person with this allele, it
develops later in life than in those with an APOE ε4 allele.
| APOE ε3 is the most common allele. Researchers think it plays a
neutral role in AD.
| APOE ε4 occurs in about 40 percent of all people who develop
late-onset AD and is present in about 25 to 30 percent of the population.
People with AD are more likely to have an APOE ε4 allele than people
who do not have AD. However, at least one-third of people with AD do not
have an APOE ε4 allele. Dozens of studies have confirmed that the APOE
ε4 allele increases the risk of developing AD, but how that happens is
not yet understood. These studies also have helped to explain some of the
variation in the age at which AD develops, as people who inherit one or two
APOE ε4 alleles tend to develop AD at an earlier age than those who do
not. However, inheriting an APOE ε4 allele does not mean that a person
will definitely develop AD. Some people with one or two APOE ε4 alleles
never get the disease, and others who do develop AD do not have any APOE
ε4 alleles. |
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The Hunt for New AD Genes
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|
 For
some time, scientists have suspected that, in addition to APOE ε4,
as many as half a dozen other risk-factor genes exist for late-onset AD,
but they have been unable to find them. In 2007, scientists unveiled
their discovery of one new AD risk-factor gene.
This AD risk-factor gene is called SORL1. It is involved in recycling
APP from the surface of cells, and its association with AD was
identified and confirmed in three separate studies. Researchers found
that when SORL1 is expressed at low levels or in a variant form, harmful
beta-amyloid levels increase, perhaps by deflecting APP away from its
normal pathways and forcing it into cellular compartments that generate
beta-amyloid.
As AD genetics research has intensified, it has become increasingly
clear that scientists need many different samples of genetic material if
they are to continue making progress in identifying new risk-factor
genes. Genetic material is also essential for identifying associated
environmental factors and understanding the interactions of genes and
the environment. These advances ultimately will allow investigators to
identify people at high risk of developing AD and help them focus on new
pathways for prevention or treatment.
In 2003, NIA launched the Alzheimer’s Disease Genetics
Study to identify at least 1,000 families with members who
have late-onset AD as well as members who do not have the disease. All
of these family members provide blood samples and other clinical data
for the initiative. The material collected allows investigators to
create and maintain “immortalized” cell lines—cells that are
continuously regenerated in the laboratory. These cell lines are crucial
for the exhaustive DNA analysis studies needed to identify risk-factor
genes, each of which may have relatively small effects on AD
development. More than 4,000 new cell lines are now available for
researchers to study risk-factor genes for late-onset AD.
A new initiative, the Alzheimer’s Disease Genetics
Consortium, was launched in 2007 to accelerate the
application of genetics technologies to late-onset AD through
collaborations among most of the leading researchers in AD genetics. The
ultimate goal of this effort is to obtain genetic material from 10,000
people with AD and 10,000 cognitively healthy people to comprehensively
scan the whole genome for the remaining AD risk-factor genes, as well as
those for age-related cognitive decline. Some of the genetic material
will be drawn from existing samples of blood and tissue; other genetic
material will be collected from new participants.
New AD genetics discoveries are possible largely because of close
collaboration among scientists, participation of volunteer families, new
genetics technologies, statistical and analytic advances, and rapid data
sharing. For example, the SORL1 studies involved 14 scientific
institutions in North America, Europe, and Asia and the participation of
more than 6,000 people who donated blood and tissue for genetic typing.
An important part of NIA’s efforts to promote and accelerate AD
genetics research is to make biological samples and data publicly
available to approved researchers.
|
OTHER FACTORS AT WORK IN AD
Genetics explains some of what might cause AD, but it does not explain
everything. So, researchers continue to investigate other possibilities that may
explain how the AD process starts and develops.
Beta-Amyloid
We now know a great deal about how beta-amyloid is formed and the steps by which
beta-amyloid fragments stick together in small aggregates (oligomers), and then
gradually form into plaques (see "From
APP to Beta-Amyloid Plaques" for more on this process). Armed
with this knowledge, investigators are intensely interested in the toxic effects
that beta-amyloid, oligomers, and plaques have on neurons. This research is
possible in part because scientists have been able to develop transgenic animal
models of AD. Transgenics are animals that have been specially bred to develop
AD-like features, such as beta-amyloid plaques.
Beta-amyloid studies have moved forward to the point that scientists are now
carrying out preliminary tests in humans of potential therapies aimed at
removing beta-amyloid, halting its formation, or breaking down early forms
before they can become harmful.
For example, one line of research by a pharmaceutical company started with
the observation that injecting beta-amyloid into AD transgenic mice caused them
to form antibodies to the beta-amyloid and reduced the number of amyloid plaques
in the brain. This exciting finding led to other studies and ultimately to
clinical trials in which human participants were immunized with beta-amyloid.
These studies had to be stopped because some of the participants developed
harmful side effects, but the investigators did not give up hope. Rather, they
went back to the drawing board to rethink their strategy. More refined antibody
approaches are now being tested in clinical trials, and additional research on
new ways of harnessing the antibody response continues in the lab.
Another important area of research is how beta-amyloid may disrupt cellular
communication well before plaques form. One recent study described how beta-amyloid
oligomers target specific synaptic connections between neurons, causing them to
deteriorate. Other scientists are studying other potentially toxic effects that
plaques have on neurons and in cellular communication. Understanding more about
these processes may allow scientists to develop specific therapies to block the
toxic effects.
Tau
Tau, the chief component of neurofibrillary tangles (see "Neurofibrillary
Tangles" for more on tau), is generating new excitement as an
area of study. The recent focus on tau has been spurred by the finding
that a mutant form of the protein is responsible for one form of frontotemporal
dementia, the third most common cause of late-life dementia, after AD and
vascular dementia. This form is known as frontotemporal dementia with
parkinsonism linked to chromosome 17 (FTDP-17). Finding this mutant protein was
important because it suggested that abnormalities in the tau protein
itself can cause dementia.
New transgenic mouse models of AD have helped tau research make
rapid progress. For example, a recent model, the “triple transgenic” mouse,
forms plaques and tangles over time in brain regions similar to those in human
AD. Another recent transgenic mouse model, which contains only human tau,
forms clumps of damaging tau filaments also in a region-specific
fashion similar to AD in humans.
These studies of tau also have suggested a mechanism for tau
damage that is different from that previously suspected. With these new
insights, scientists now speculate that one reason tau may damage and
kill neurons is because it upsets the normal activity of the cell, in addition
to forming neurofibrillary tangles.
Other studies of mutant tau in mice suggest that the accumulation of
tau in tangles may not even be the culprit in memory loss. Rather, as
with beta-amyloid, it may be that an earlier and more soluble abnormal form of
the protein causes the damage to neurons.
Protein Misfolding
Researchers have found that a number of devastating neurodegenerative diseases
(for example, AD, Parkinson’s disease, dementia with Lewy bodies,
frontotemporal lobar degeneration, Huntington’s disease, and prion diseases)
share a key characteristic—protein misfolding.
When a protein is formed, it “folds” into a unique three-dimensional
shape that helps it perform its specific function. This crucial process can go
wrong for various reasons, and more commonly does go wrong in aging cells. As a
result, the protein folds into an abnormal shape—it is misfolded. In AD, the
misfolded proteins are beta-amyloid (the cleaved product of APP; see "From
APP to Beta-Amyloid Plaques" for more on the formation of beta-amyloid)
and a cleaved product of tau.
Normally, cells repair or degrade misfolded proteins, but if many of them are
formed as part of age-related changes, the body’s repair and clearance process
can be overwhelmed. Misfolded proteins can begin to stick together with other
misfolded proteins to form insoluble aggregates. As a result, these aggregates
can build up, leading to disruption of cellular communication, and metabolism,
and even to cell death. These effects may predispose a person to AD or other
neurodegenerative diseases.
Scientists do not know exactly why or how these processes occur, but research
into the unique characteristics and actions of various misfolded proteins is
helping investigators learn more about the similarities and differences across
age-related neurodegenerative diseases. This knowledge may someday lead to
therapies.
| Researchers
Explore Neurodegenerative “Cousins” |
|
Neurodegenerative diseases like AD, Parkinson’s disease,
amyotrophic lateral sclerosis (ALS), and dementia with Lewy bodies share
more than the basic characteristic of misfolded proteins. They also
share clinical characteristics. For example, people with AD have trouble
moving, a characteristic of Parkinson’s disease. Sleep-wake disorders,
delusions, psychiatric disturbances, and memory loss occur in all of
these diseases. These diseases also result from a combination of
genetic, lifestyle, and environmental causes and they develop over many
years.
This graphic shows one way of thinking about how these diseases may
be linked as well as what makes them unique. By investigating the unique
characteristics of these diseases as well as the characteristics they
share, scientists hope to learn even more than they would if they
focused on each disease by itself.
(Click to Enlarge)
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The Aging Process
Another set of insights about the cause of AD comes from the most basic of all
risk factors—aging itself. Age-related changes, such as inflammation, may make
AD damage in the brain worse. Because cells and compounds that are known to be
involved in inflammation are found in AD plaques, some researchers think that
components of the inflammatory process may play a role in AD.
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Mitochondria and Free Radicals
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(Click to Enlarge)
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| Any given cell has hundreds of mitochondria.
This illustration shows two—a healthy mitochondrion and an
oxidatively stressed and damaged one. The arrows indicate the
movement of free radicals, which can spread easily from damaged
mitochondria to other parts of the cell. |
|
Other players in the aging
process that may be important in AD are free radicals, which are oxygen or
nitrogen molecules that combine easily with other molecules (scientists call
them “highly reactive”). Free radicals are generated in mitochondria, which
are structures found in all cells, including neurons.
Mitochondria are the cell’s power plant, providing the energy a cell needs
to maintain its structure, divide, and carry out its functions. Energy for the
cell is produced in an efficient metabolic process. In this process, free
radicals are produced. Free radicals can help cells in certain ways, such as
fighting infection. However, because they are very active and combine easily
with other molecules, free radicals also can damage the neuron’s cell membrane
or its DNA. The production of free radicals can set off a chain reaction,
releasing even more free radicals that can further damage neurons (see
illustration "Mitochondria and Free Radicals"). This kind of damage is
called oxidative
damage. The brain’s unique characteristics, including its high
rate of metabolism and its long-lived cells, may make it especially vulnerable
to oxidative damage over the lifespan. The discovery that beta-amyloid generates
free radicals in some AD plaques is a potentially significant finding in the
quest for better understanding of AD as well as for other neurodegenerative
disorders and unhealthy brain aging.
Researchers also are studying age-related changes in the working ability of
synapses in certain areas of the brain. These changes may reduce the ability of
neurons to communicate with each other, leading to increased neuronal
vulnerability in regions of the brain important in AD. Age-related reductions in
levels of particular growth factors, such as nerve
growth factor and brain-derived
neurotrophic factor, also may cause important cell populations to
be compromised. Many studies are underway to tease out the possible effects of
the aging process on the development of AD.
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The Brain’s Vascular System
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(Click to Enlarge)
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| This image shows the complexity of the human
brain’s vascular system, particularly large and small arteries
that carry oxygen from the lungs to the brain. Although many
blood vessels are visible here, this image shows fewer than half
of the total number in the brain. |
|
Vascular Disease
For some time now, hints have been emerging that the body’s vast network of
small and large blood vessels—the vascular system—may make an important
contribution in the development of dementia and the clinical symptoms of AD.
Some scientists are focusing on what happens with the brain’s blood vessels in
aging and AD. Others are looking at the relationship between AD and vascular
problems in other parts of the body.
AD and Vascular Problems in the Brain
The brain requires a constant and dependable flow of oxygen and glucose to
survive and flourish. The brain’s blood vessels provide the highways to
deliver these vital elements to neurons and glial cells.
Aging brings changes in the brain’s blood vessels—arteries can narrow and
growth of new capillaries slows down. In AD, whole areas of nervous tissue,
including the capillaries that supply and drain it, also are lost. Blood flow to
and from various parts of the brain can be affected, and the brain may be less
able to compensate for damage that accumulates as the disease progresses.
For some time now, study of the brain’s blood vessel system in AD has been
a productive line of inquiry. One important finding has been that the brain’s
ability to rid itself of toxic beta-amyloid by sending it out into the body’s
blood circulation is lessened. Some scientists now think that poor clearance of
beta-amyloid from the brain, combined with a diminished ability to develop new
capillaries and abnormal aging of the brain’s blood vessel system, can lead to
chemical imbalances in the brain and damage neurons’ ability to function and
communicate with each other. These findings are exciting because they may help
to explain part of what happens in the brain during the development of AD. These
findings also suggest several new targets for potential AD therapies.
AD and Vascular Problems in Other Parts of the Body
Research also has begun to tease out some relationships between AD and other
vascular diseases, such as heart disease, stroke, and type 2 diabetes. It is
important to sort out the various effects on the brain of these diseases because
they are major causes of illness and death in the United States today.
Much of this evidence comes from epidemiologic studies, which compare the
lifestyles, behaviors, and characteristics of groups of people (see "Describing
Scientific Findings: The Type of Study Makes an Important Difference"
for more information about epidemiologic studies). These studies have found, for
example, that heart disease and stroke may contribute to the development of AD,
the severity of AD, or the development of other types of dementia. Studies also
show that high blood pressure that develops during middle age is correlated with
cognitive decline and dementia in later life.
Another focus of AD vascular research is the metabolic syndrome, a
constellation of factors that increases the risk of heart disease, stroke, and
type 2 diabetes. Metabolic syndrome includes obesity (especially around the
waist), high triglyceride levels, low HDL (“good cholesterol”) levels, high
blood pressure, and insulin resistance (a condition in which insulin does not
regulate blood sugar levels very well). Evidence from epidemiologic studies now
suggests that people with the metabolic syndrome have increased risk of
cognitive impairment and accelerated cognitive decline.
Nearly one in five Americans older than age 60 has type 2 diabetes, and
epidemiologic studies suggest that people with this disease may be at increased
risk of cognitive problems, including MCI and AD, as they age. The higher risk
associated with diabetes may be the result of high levels of blood sugar, or it
may be due to other conditions associated with diabetes (obesity, high blood
pressure, abnormal blood cholesterol levels, progressive atherosclerosis, or too
much insulin in the blood). These findings about diabetes have spurred research
on a number of fronts—epidemiologic studies, test tube and animal studies, and
clinical trials. The objective of these studies is to learn more about the
relationship between diabetes and cognitive problems and to find out in clinical
trials whether treating the disease rigorously can positively affect cognitive
health and possibly slow or prevent the development of AD.
 Lifestyle
Factors
We know that physical activity and a nutritious diet can help people
stay healthy as they grow older. A healthy diet and exercise can reduce obesity,
lower blood cholesterol and high blood pressure, and improve insulin action. In
addition, association studies suggest that pursuing intellectually stimulating
activities and maintaining active contacts with friends and family may
contribute to healthy aging. A growing body of evidence now suggests that these
lifestyle factors may be related to cognitive decline and AD. Researchers who
are interested in discovering the causes of AD are intensively studying these
issues, too.
Physical Activity and Exercise
Exercise has many benefits. It strengthens muscles, improves heart and lung
function, helps prevent osteoporosis, and improves mood and overall well-being.
So it is not surprising that AD investigators began to think that if exercise
helps every part of the body from the neck down, then it might help the brain as
well.
Epidemiologic studies, animal studies, and human clinical trials are
assessing the influence of exercise on cognitive function. Here are a few things
these studies have found:
| Animal studies have shown that exercise increases the number of
capillaries that supply blood to the brain and improves learning and memory
in older animals.
| Epidemiologic studies show that higher levels
of physical activity or exercise in older people are associated with reduced
risk of cognitive decline and reduced risk of dementia. Even moderate
exercise, such as brisk walking, is associated with reduced risk.
| Clinical trials show some evidence of short-term positive effects of
exercise on cognitive function, especially executive function (cognitive
abilities involved in planning, organizing, and decision making). One trial
showed that older adults who participated in a 6-month program of brisk
walking showed increased activity of neurons in key parts of the brain. |
| |
More clinical trials are underway to expand our knowledge about the
relationship of exercise to healthy brain aging, reduced risk of cognitive
decline, and development of AD. (See "Participating
in a Clinical Trial" for more information).
|
If you want to know more about the benefits of
exercise and physical activity and learn ways to be active every day,
NIA has free information just for you! Call 1-800-222-2225 or visit www.nia.nih.gov/Exercise.
|
 Diet
Researchers have explored whether diet may help preserve cognitive function or
reduce AD risk, with some intriguing findings. For example, studies have
examined specific foods that are rich in antioxidants and anti-inflammatory
properties to find out whether those foods affect age-related changes in brain
tissue. One laboratory study found that curcumin, the main ingredient of
turmeric (a bright yellow spice used in curry), can bind to beta-amyloid and
prevent oligomer formation. Another study in mice found that diets high in DHA (docosahexaenoic
acid), a type of healthy omega-3 fatty acid found in fish, reduced beta-amyloid
and plaques in brain tissue.
Other studies have shown that old dogs perform better on learning tasks when
they eat diets rich in antioxidants, such as vitamin E and other healthful
compounds, while living in an “enriched” environment (one in which the dogs
have many opportunities to play and interact with people and other dogs).
Scientists also have examined the effects of diet on cognitive function in
people. A very large epidemiologic study of nurses found an association between
participants who ate the most vegetables (especially green leafy and cruciferous
vegetables) and a slower rate of cognitive decline compared with nurses who ate
the least amount of these foods. An epidemiologic study of older adults living
in Chicago found the same association. The researchers do not know the exact
reason behind this association, but speculate that the beneficial effects may
result from the high antioxidant and folate content of the vegetables.
Dietary studies, such as the curcumin study in mice or the vegetables study
in nurses, generally examine individual dietary components so that scientists
can pinpoint their specific effects on an issue of interest. This approach has
obvious limitations because people do not eat just single foods or nutrients.
Several recent epidemiologic studies have taken a different approach and looked
at an entire dietary pattern.
In one of these studies, researchers worked with older adults living in New
York who ate the “Mediterranean diet”—a diet with lots of fruits,
vegetables, and bread; low to moderate amounts of dairy foods, fish, and
poultry; small amounts of red meat; low to moderate amounts of wine; and
frequent use of olive oil. The researchers found that sticking to this type of
diet was associated with a reduced risk of AD and that the association seemed to
be driven by the whole approach, rather than by its individual dietary
components. A follow-up study found that this pattern also was associated with
longer survival in people with AD.
All of these results are exciting and suggestive, but they are not
definitive. To confirm the results, scientists are conducting clinical trials to
examine the relationship of various specific dietary components and their effect
on cognitive decline and AD.
Intellectually Stimulating Activities and Social Engagement
Many older people love to read, do puzzles, play games, and spend time with
family and friends. All these activities are fun and help people feel alert and
engaged in life. Researchers are beginning to find other possible benefits as
well, for some studies have shown that keeping the brain active is associated
with reduced AD risk. For example, over a 4-year period, one group of
researchers tracked how often a large group of older people did activities that
involved significant information processing, such as listening to the radio,
reading newspapers, playing puzzle games, and going to museums. The researchers
then looked at how many of the participants developed AD. The researchers found
that the risk of developing AD was 47 percent lower in the people who did them
the most frequently compared with the people who did the activities least
frequently. Another study supported the value of lifelong learning and mentally
stimulating activity by finding that, compared with older study participants who
may have had AD or who had AD, healthy older participants had engaged in more
mentally stimulating activities and spent more time at them during their early
and middle adulthood.
Studies of animals, nursing home residents, and people living in the
community also have suggested a link between social engagement and cognitive
performance. Older adults who have a full social network and participate in many
social activities tend to have less cognitive decline and a decreased risk of
dementia than those who are not socially engaged.
The reasons for these findings are not entirely clear, but a number of
explanations are possible. Among them:
| Intellectually stimulating activities and social engagement may protect
the brain in some way, perhaps by establishing a cognitive reserve.
| These activities may help the brain become more adaptable and flexible in
some areas of mental function so that it can compensate for declines in
other areas.
| Less engagement with other people or in intellectually stimulating
activities could be
the result of very early effects of the disease rather than its cause.
| People who engage in stimulating activities may have other lifestyle
qualities that may protect them against developing AD. |
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Describing Scientific Findings: The
Type of Study Makes an Important Difference
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These days, the media are full of stories about scientific studies.
It can be hard to know what to conclude about their findings. Knowing
how the study was conducted can help put the results into the right
perspective.
One main type of research is the epidemiologic study. These studies
are observational—they gather information about people who are going
about their daily lives. Study participants follow many behaviors and
practices. It is difficult, therefore, to determine the exact benefits
or risks of one particular behavior from among all the healthy or
harmful behaviors followed by the participants. That is why, in
epidemiologic studies of AD, scientists only say that a finding is
“associated with” AD, or not. The epidemiologic evidence linking a
behavior and AD is, at best, suggestive, but we do not know that the
behavior by itself actually helps to cause or prevent AD.
Other types of research—test tube studies and studies in
animals—add to the findings from epidemiologic studies. Scientists use
them to examine the same issue but in ways in which the various factors
that might influence a result are controlled to a greater degree. This
element of control allows scientists to be more certain about why they
get the results they do. It also allows them to be more definitive in
the words they use to describe their results. Of course, showing a
cause-and-effect relationship in tissue samples or even in animal
studies still does not mean that the relationship will be the same in
humans. Clinical trials in humans are the gold standard for deciding
whether a behavior or a specific therapeutic agent actually prevents or
delays AD (see "Participating
in a Clinical Trial" for more on this kind of research).
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