in the United States every two minutes and takes a life every five minutes.
It's Alzheimer's disease, a progressive, irreversible disorder that kills
brain cells and eventually kills its victims. But researchers at the University
of North Texas Health Science Center at Fort Worth are working to determine
what causes Alzheimer's and how to treat and prevent the disease.
The symptoms of Alzheimer's disease, or AD, are well known: a gradual
loss of memory, confusion and impaired judgment, changes in personality
and behavior, dependence on others for the routine tasks of living. Four
million Americans, most of them elderly, have been diagnosed with AD;
without a cure or method of prevention, that number will rise to 14 million
by mid-century. Worldwide, many millions more will suffer from the disease
that some researchers are already calling the epidemic of the 21st century.
the exact cause of AD is still unknown, scientists' understanding of the
underlying mechanisms is growing. Researchers believe that processing
of certain proteins in the brain goes awry, resulting in the production
of toxic proteins that invade nerve cells (causing what are called neurofibrillary
tangles) and the spaces between nerve cells (leading to the accumulation
of insoluble deposits known as amyloid plaques).
researchers examine how and why the processing of these proteins is altered,
they continue to learn more about the risk factors associated with AD.
James Simpkins, Ph.D., chair of the Department of Pharmacology and
Neuroscience and director of the Institute for Aging and Alzheimer's Disease
Research at the Health Science Center, says there are several known risk
"Family history — a first-degree
relative (a parent or sibling) who has the disease —
puts you in a high-risk group," he says. "Being female is a risk factor.
Women are two to three times as likely to have AD as men. We believe that's
because of the estrogen reduction during menopause. Low educational attainment
is a risk factor, as is a history of head injuries that have resulted
in loss of consciousness. Having had a stroke is a risk factor. And an
obvious, major risk factor is age."
Without question, the likelihood of contracting AD
rises dramatically as a person ages. The increase in average life expectancy
over the past century from 48 to 76 years has brought with it a marked
rise in the number of cases of Alzheimer's, a disease that strikes most
frequently between the ages of 65 and 75.
is under way at the Health Science Center that uses protein biological
markers (biomarkers) in the blood to identify people who are at risk for
developing the disease. The goal of this research is to develop a test
that can provide a diagnosis for Alzheimer's before symptoms appear. An
accurate, early diagnosis gives affected individuals a greater chance
of benefiting from existing treatments.
"One such marker," says Robert W. Gracy, Ph.D., Alzheimer's
researcher and associate vice president for research and biotechnology
at the Health Science Center, "is damaged proteins that show up in blood
due to oxidative damage to cells in the brain."
As a consumer of a full fifth of the oxygen we take
in, the brain is exposed to potentially toxic oxygen free radicals, which
contribute to the production of the toxic proteins that can kill brain
cells, Gracy explains. Our body makes antioxidants to combat the oxygen
free radicals, and we obtain some in our diet. Research at the Health
Science Center is aimed at understanding why the body's defenses against
oxidative damage appear to diminish with age and which antioxidants are
the most effective and in what quantities. For example, vitamin E has
shown promise in slowing down the progression of AD, Gracy says.
"The goal of our research here is to treat what we
call preventable brain aging," says Simpkins. "We're looking at using
a number of therapies that we think are going to preserve brain health
and hopefully delay brain aging as well as delay or prevent AD. We believe
that if we can prevent nerve cell death, we can preserve cognitive function."
and mental exercise
addition to its research on amyloid plaques and neurofibrillary tangles
and its development of genetic and biological tests to detect the early
stages of AD, the Institute of Aging is researching ways to prevent brain
damage from stroke. And one of the most exciting areas of future research
at the institute is behavioral intervention —
the idea that simply using your brain may help keep it healthy.
"There is anecdotal evidence and hard data that what
I like to call 'mental exercise' is good for the aging brain and is probably
very good for the Alzheimer's brain, particularly if it's instituted prior
to the onset of the disease," Simpkins explains.
"We don't know the kind of mental exercise that's best,
nor the amount that's best. We don't know if it's a short bout daily or
long bouts less frequently that are more effective. We will be able to
design studies that get at those issues. Hopefully we'll be able to come
up with prescribed behavioral modifications for people who are showing
evidence of dementia."
The Health Science Center is also developing new drugs
for the treatment of Alzheimer's and plans a facility in which to conduct
clinical trials to establish their effectiveness, Simpkins says.
"We have coming out of our lab 50 different compounds,
some of which we hope to start in clinical development," he says.
Such optimism characterizes Simpkins' view of the future
of Alzheimer's research and treatment at the Health Science Center.
"The issues we're looking at are not being addressed
today anywhere else," he says. "They're very important subjects."
The estrogen connection
appear to be two to three times more likely than men to develop
Alzheimer's, says James Simpkins, Ph.D., chair of the Department
of Pharmacology and Neuroscience and director of the Institute
for Aging and Alzheimer's Disease Research at the UNT Health Science
The fact that women tend to outlive men makes
women more likely to reach the age at which the risk of getting
AD increases dramatically. But Simpkins believes another factor
is at play: estrogen reduction during menopause.
"Being post-menopausal and not on estrogen replacement
is a risk factor," he says.
A study being conducted at the Health Science
Center is examining the estrogen-Alzheimer's link. A team led
by Janice Knebl, D.O., chief of geriatrics and director of the
Gerontology Assessment and Planning Program, is evaluating the
effectiveness of hormone replacement therapy coupled with the
drug donepezil hydrochloride, which helps conserve the brain's
neurotransmission chemical, acetylcholine.
It's an area that has engaged Simpkins for more
than 15 years. In tests, he says, estrogens have reduced the deposition
in the brain of beta amyloid, a cause of senile plaques commonly
found in Alzheimer's patients. Estrogens also appear to stabilize
microtubules, which Simpkins describes as small canals that run
up and down the nerve cells and transport materials to the cells.
The canals become twisted and tangled in Alzheimer's patients,
and estrogens appear to maintain the function of these canals.
"If you take estrogens away from a woman or
animal," Simpkins says, "the brain doesn't seem to do as well.
Therefore, loss of estrogens at menopause is having some fundamental
effect on the ability of the brain to age well."
"The clinical evidence is that if you're on
estrogen replacement therapy, you have about a 50 percent lower
incidence of AD," Simpkins says. "That's been seen again and again
in epidemiological studies that look back and ask who got the
disease and what is interesting about their life related to getting
or not getting the disease."
The goal, he says, is to design therapies that
take advantage of estrogen's apparent positive effects on Alzheimer's
while minimizing potential negative effects. He says compounds
are being produced containing estrogen that may protect nerve
cells without the risk of cancer associated with the use of estrogen.
In ongoing prevention trials at the Health Science
Center, women who appear to be cognitively normal but have risk
factors for developing Alzheimer's are being studied.
"If you put part of the group on estrogens,"
Simpkins says, "is there a difference in the incidence of AD after
four or five years? We're trying to determine if a compound or
behavior can prevent a disease from happening."
What can we do?
progress in Alzheimer's disease research has been dramatic, but
there is still much to learn before a cure can be discovered.
In the meantime, according to the latest research, there are several
ways to reduce the risk of developing the disease.
"We're approaching the time when we can say,
'Here are the things you ought to be doing by the age of 55 or
60,'" says Simpkins.
"Certainly, keeping mentally engaged is one.
With people who are cognitively active, the prediction is and
the data support that they're less likely to show up with cognitive
Keeping physically active also appears to be
beneficial, Simpkins says. Exercising, as well as keeping one's
blood pressure in check and quitting smoking, can help reduce
the risk of stroke, which is strongly associated with Alzheimer's
The incidence of head trauma, another risk factor,
can be reduced through the use of sports helmets and seat belts.
It appears likely that antioxidant supplements such as vitamin
E have a positive effect. "But to get the effect, you probably
need a much higher dose than that found in typical multivitamins,"
In addition, some studies have shown anti-inflammatories,
such as ibuprofen, to be beneficial in treating or slowing the
progression of the disease.