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Alzheimer's Disease: Unraveling
the Mystery
New Techniques Help in
Diagnosing AD
A healthy man in his early 60s begins to
notice that his memory isn't as good as it used to be. More and more
often, a word will be on the tip of his tongue but he just can't
remember it. He forgets appointments, makes mistakes when paying his
bills, and finds that he's often confused or anxious about the normal
hustle and bustle of life around him. One evening, he suddenly finds
himself walking in a neighborhood a couple of miles from his house. He
has no idea how he got there.
Not so long ago, this man's condition would
have been swept into a broad catch-all category called "senile dementia"
or "senility." Today, the picture is very different. We now know that
Alzheimer's and other illnesses with dementia are distinct diseases.
Armed with this knowledge, we have rapidly improved our ability to
accurately diagnose AD. We are still some distance from the ultimate
goal - a reliable, valid, inexpensive, and early diagnostic marker - but
experienced physicians now can diagnose AD with up to 90 percent
accuracy.
Early diagnosis has several advantages. For
example, many conditions cause symptoms that mimic those of Alzheimer's
disease. Finding out early that the problem isn't AD but is something
else can spur people into getting treatment for the real condition. For
the small percentage of dementias that are treatable or even reversible,
early diagnosis increases the chances of successful treatment.
Even when the cause of the dementia turns
out to be Alzheimer's disease, it's good to find out sooner rather than
later. One benefit is medical. The drugs now available to treat AD can
help some people maintain their mental abilities for months to years,
though they do not change the underlying course of the disease
Other benefits are practical. The sooner the
person with AD and family know, the more time they have to make future
living arrangements, handle financial matters, establish a durable power
of attorney, deal with other legal issues, create a support network, or
even make plans to join a research study. Being able to participate for
as long as possible in making decisions about the present and future is
important to many people with AD.
Finally, scientists also see advantages to
early diagnosis. Developing tests that can reveal what is happening in
the brain in the early stages of Alzheimer's disease will help them
understand more about the cause and development of the disease. It will
also help scientists learn when and how to start drugs and other
treatments so that they can be most effective.
Scientists are now exploring ways to help
physicians diagnose AD earlier and more accurately. For example, some
studies are focusing on changes in personality and mental functioning.
These changes can be measured through memory and recall tests. Tests
that measure a person's abilities in areas such as abstract thinking,
planning, and language can also help pinpoint changes in function.
Researchers are working hard to improve these standardized tests so that
they can better track the changes that might point to early AD or
predict which individuals are at higher risk of developing AD in the
future.
Other studies are examining the relationship
between early damage to brain tissue and outward clinical signs. Still
others are looking for changes in blood chemistry that might indicate
the progression of Alzheimer's disease.
One
of the most exciting areas of ongoing research in this area is
neuroimaging. Over the last decade, scientists have developed several
highly sophisticated imaging systems that have been used in many areas
of medicine, including Alzheimer's disease. Positron emission
tomography (PET), single photon emission computed tomography
(SPECT), and magnetic resonance imaging (MRI) are all
examples. These "windows" on the living brain can help scientists
measure the earliest changes in brain function or structure in order to
identify those people who are at the very first stages of the disease -
even before they develop signs and symptoms.
These types of scans are still primarily
research tools, but one day, neuroimaging might be used more commonly to
help physicians diagnose AD early. These tools may even be used someday
to monitor the progress of the disease and assess patient responses to
drug treatment.
The Human Side of AD Research
The Religious Orders Study
and the Nun Study: Lives of Service Continue Even After Death
One way that scientists have tried to
unravel the mystery of AD and other complex diseases, like heart
disease or cancer, is to compare the characteristics, lifestyles,
and disease rates of different groups of people. This approach has
often provided clues as to why some people get a disease and others
don't.
Another way is to study one group of
people over time. The notion here is that data gathered over a
period of years will reveal important clues about the origins of the
disease under investigation. The knowledge gained also may lay the
foundation for future treatment or prevention strategies. The
Framingham Heart Study is one famous example of this kind of study.
It has followed two generations of Massachusetts residents for 50
years, and its findings have revolutionized the way we think about,
treat, and prevent heart disease.
The National Institute on Aging is
funding two Alzheimer's disease studies that are using this approach
- but with a unique twist. These studies involve members of
religious communities.
Since 1990, scientists have been working
with more than 650 nuns of the School Sisters of Notre Dame, who are
located in various parts of the U.S. The Nun Study is an expansion
of a pilot project begun in 1986 with a School Sisters of Notre Dame
convent in Mankato, Minnesota.
Since 1993, scientists have also been
investigating the mental and physical capacities of older nuns,
priests, and brothers in the Religious Orders Study. More than 30
religious communities in a dozen States are participating in this
study.
All of the participants in both studies
agree to have detailed physical and mental function exams every
year. Volunteers may spend decades in the study, repeating the tests
each year. These exams help researchers better understand the
effects on the brain of aging, AD, and other disorders. Participants
also agree to donate their brains to the study when they die. This
allows the investigators to match many years' worth of clinical and
psychological information with the results of examinations of
after-death brain tissue. These volunteers consider participating in
these studies a wonderful chance to continue their lives of service
to others. As one participant in the Nun Study put it, "[They] can
have my brain. What good is it going to do me when I'm six
feet under?"
The
large numbers enrolled in the study ensure that some volunteers will
still have normal brain function at the time of death. Others will
have developed the clinical signs of AD. Still others will have
other neurological disorders, such as Parkinson's disease. The
yearly examinations enable researchers to detect signs of AD among
participants and to track, year by year, the progress and treatment
of the disease among those who develop it.
But why work with religious orders?
What's special about them? One reason why members of religious
orders are good study participants is that they often live together
and have similar lifestyles, educational levels, daily routines, and
activities. This cuts down on the variations among participants that
make it difficult for scientists to interpret research results. It
also makes it easy for study staff to keep track of volunteers over
time and to maintain complete information on them.
Working with these participants has
allowed the research teams to explore several exciting ideas. For
example, the Religious Orders Study team recently worked with their
participants to examine a "use-it-or-lose-it" brainpower hypothesis.
At an initial evaluation, the researchers asked more than 700
priests and nuns about the amount of time they spent in seven common
activities that involve significant information processing -
watching television; listening to the radio; reading newspapers or
magazines; reading books; playing cards, checkers, and puzzle games;
and going to museums. After tracking the participants for 4 1/2
years, the researchers found that, on average, the risk of
developing AD was 47 percent lower in those who did these activities
most frequently than in those who did them least frequently. The
reasons for this finding aren't entirely clear yet, but it may be
that mentally stimulating activities protect the brain in some way.
Or, perhaps some other mechanism may be at work that strengthens
information processing skills to compensate for age-related declines
in other cognitive areas.
The Nun Study has one particularly rich
treasure trove to work with - the autobiographies written by the
nuns when they entered the order. These personal records provide
basic information on the nuns' early lives and families and are an
objective measure of each woman's ability to think, remember, and
present ideas in writing. Study investigators have found a
fascinating link between their early writing skills and later
cognitive abilities. The researchers performed an analysis of the
autobiographies to determine the grammatical complexity and the
"density" of ideas in each. They then examined brain tissue from
nuns who had died. The investigators found that most of the nuns
whose brain tissue showed significant signs of AD had written
autobiographies with low grammatical complexity and idea density.
Though the reasons for this link aren't fully understood, a higher
linguistic ability early in life may provide some protection against
the influences that lead to AD.
Causes of
Dementia
Dementia is the loss of cognitive functioning
- thinking, remembering, and reasoning - to such an extent that it
interferes with a person's daily life and activities. It is not a
disease itself, but a group of symptoms that often accompanies a disease
or condition. Some dementias are treatable or curable; others are less
responsive to treatment.
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Treatable Causes of
Dementia
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medication side effects
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depression
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vitamin B12 deficiency
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chronic alcoholism
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certain tumors or infections of
the brain
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blood clots pressing on the
brain
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metabolic imbalances, including
thyroid, kidney, or liver disorders
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Other Causes of Dementia
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Current Tools For Diagnosing AD
A definitive diagnosis of Alzheimer's
disease is still only possible after death, during an autopsy, when the
plaques and tangles can actually be seen. But with the tools now
available, experienced physicians can be pretty confident about making
an accurate diagnosis in a living person. Here's how they do it.
They take a detailed patient
history, including:
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A description of how and when symptoms
developed
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A description of the patient's and his
or her family's overall medical condition and history
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An assessment of the patient's emotional
state and living environment
They get information from family members
or close friends:
They conduct physical and neurological
examinations and laboratory tests:
They do a computerized tomography (CT) scan or a magnetic resonance
imaging (MRI) test:
They conduct neuropsychological testing:
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Q&A tests or other tasks that measure
memory, language skills, ability to do arithmetic, and other
abilities related to brain functioning help indicate what kind of
cognitive changes are occurring.
Criteria for "Probable" Alzheimer's Disease
Because
no simple and reliable biological test for AD is available, the National
Institute of Neurological and Communicative Disorders and Stroke and the
Alzheimer's Association together established criteria to help physicians
diagnose AD. These criteria also help physicians distinguish between AD
and other forms of dementia. "Probable" Alzheimer's disease is
determined when a person has:
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Dementia confirmed by clinical and
neuropsychological examination
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Progressive worsening of memory and
other mental functioning
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No disturbances of consciousness (no
"blacking out")
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Symptoms beginning between ages 40 and
90
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No other disorders that might account
for the dementia
As they get older, some people develop a
memory deficit greater than that expected for their age. However, other
aspects of cognition are not affected, so these people do not meet all
the accepted criteria for AD. Thus, they are said to have "mild
cognitive impairment" (MCI). About 40 percent of these individuals will
develop AD within 3 years. Others, however, do not seem to progress to
AD, at least in the time frame studied thus far (up to approximately 6
years). Understanding more about the characteristics and development of
MCI is essential in helping clinicians diagnose early stages of AD. |