Disease (AD) is a form of dementia,
which is a medical condition that disrupts the way the brain
works, causing progressive decline in intellectual functioning
severe enough to interfere with a person's daily life activities
and social relationships. AD is named after the German neurologist,
Alois Alzheimer [1864-1915], who first studied the disease.
It is also sometimes called senile dementia of the Alzheimer
AD is defined by the presence of specific
anatomic abnormalities in the brain, called amyloid
plaques and neurofibrillary
tangles. These can only be detected by direct examination
of brain tissue, which means that Alzheimer's disease is only
diagnosed after death, via autopsy. In a living patient, doctors
diagnose "probable AD" if a patient shows all the behavioral
symptoms of AD, and if all other possible causes of dementia
are ruled out.
AD accounts for more than 50% of all cases
of dementia. The most common form of Alzheimer's occurs in
people older than 65 years, but there is also a form called
early-onset Alzheimer's disease or presenile dementia which
can begin as early as age 40. A recent study estimated that
about 4% of Americans between the ages of 65-74 have AD, and
the rate grows steadily with age until about 50% of Americans
over age 85 may have the disease.
Symptoms of Alzheimer's Disease
Alzheimer's disease is progressive, meaning
that symptoms get worse as the disease progresses. The earliest
recognized symptoms of Alzheimer's disease are often mild
memory loss; a sufferer may begin to forget recent conversations
or what year it is. There may be disorientation (e.g. getting
lost in familiar surroundings), problems with routine tasks
(like using a microwave), and changes in personality and judgment.
As the disease progresses, patients begin
to have difficulty with the activities of daily living, and
may require help feeding and bathing. There may be anxiety
(suspiciousness and agitation), sleep disturbance, wandering
and pacing, difficulty recognizing family and friends.
In the most advanced stages of the disease,
patients suffer loss of the ability to speak, weight loss,
lack of appetite, and loss of bowel and bladder control. By
this point, patients require round-the-clock caregiving.
While AD itself is not directly fatal, it
may leave patients vulnerable to infections and other diseases
such as pneumonia, which may become the ultimate cause of
death. Often, patients with the disease suffer increasing
debilitation over a period of about 4-8 years, but an otherwise
healthy individual can survive for decades.
Anatomical Changes in the Brain
Alzheimer's disease is characterized by
anatomical changes, including the development of amyloid
plaques and neurofibrillary
plaques are sticky buildup which accumulates outside the
nerve cells in the brain. Amyloid is a protein which is normally
found throughout the body. In AD this protein begins to divide
improperly, creating a substance called beta amyloid which
is toxic to brain cells. As the beta amyloid builds up, the
brain cells begin to die.
tangles are the second anatomical hallmark of AD. Normally,
every brain cell contains long fibers made of protein which
act as scaffolds, holding the brain cell in its proper shape
and also helping transport of nutrients within the cell. In
AD, these fibers begin to twist and tangle. The brain cell
loses its shape and also becomes unable to transport nutrients
properly; it eventually dies.
As enough plaques and tangles accumulate
in the brain, widespread cell death occurs throughout the
brain. At this point, it is unclear exactly why plaques and
tangles begin to form in the brain of a person with AD. Many
researchers are studying this question and trying to develop
ways to halt or reverse the degeneration.
The plaques and tangles characteristic of
Alzheimer's can be observed only through biopsy, which is
usually done during an autopsy. This means that a doctor can
only diagnose "probable" Alzheimer's in a living patient based
on the pattern of behavioral symptoms, and by ruling out other
possible causes. The firm diagnosis of Alzheimer's is made
or ruled out after death.
A recent report announced the discovery
of a vaccine that may hold promise for preventing or treating
AD. The study considered mice who had been specifically bred
to develop AD-like plaques in their brains. Young mice given
the vaccine showed little or no development of plaques as
they aged. When older mice, who had already developed plaques,
were given the vaccine, the plaques appeared to dissolve.
This vaccine is causing tremendous excitement
among those who study AD, since it suggests it might be possible
to develop a way to immunize people against AD or reduce AD
in those who already suffer the disease. However, it is important
to remember that the rats in this study did not have AD: they
were bred to develop plaques, but they did not develop neurofibrillary
tangles. Some researchers suspect that the tangles, rather
than the plaques, are the culprits that cause most of the
damage in AD. Worse, not every person who dies of AD has plaques
in his brain. Thus, a vaccine that fights plaques may not
be enough to prevent or cure AD. It will take years of further
study in animals to answer some of these questions, and years
more before a human treatment becomes available. Nonetheless,
this study is an example of the progress that is being made
in understanding the various components of AD.
Possible Causes of Alzheimer's Disease
Several possible causes have been implicated
in the development of AD. About 10% of patients with AD have
the early-onset form of the disease, in which symptoms can
appear as early as the 30s and 40s. Scientists have discovered
that many people with this form of the disease have a specific
genetic abnormality: mutation in genes located on chromosomes
1, 14, and 21. However, the correlation isn't perfect; people
with these genetic abnormalities account for only 50% of all
known cases of early-onset AD.
The more common form of AD is late-onset
AD, in which symptoms begin to appear only late in life. This
form of AD is also linked to a genetic abnormality. Chromosome
19 contains a gene called apoE which helps carry cholesterol
in the blood and also helps nerves to recover after injury.
Each of us has two copies of apoE - one inherited from each
parent - and each copy can come in one of several forms: apoE2,
apoE3, and apoE4. ApoE3 is the most common in the general
population. But people who inherit one apoE4 gene have an
increased risk of developing AD, and people who inherit two
copies of apoE4 are about eight times as likely to develop
AD as people with two copies of the "normal" apoE3 variant.
Interestingly, the rarest apoE2 form of the gene may lower
an individual's risk of AD.
A simple blood test is available to determine
which forms of apoE a person has. However, this test cannot
tell you whether or not you will develop AD, or when. Over
half of the people who develop late-onset AD do not have the
apoE4 gene, and not everyone with apoE4 does develop the disease.
Right now, the blood test is most useful as a research tool,
helping scientists study AD risk factors in large groups of
people. Most scientists and health professionals do not recommend
routine apoE4 tests for predicting AD risk in individuals,
although it may be useful as part of a medical evaluation
of a patient who already shows AD symptoms.
In addition to genetic factors, many biological
factors have been implicated in AD. One of the best-studied
is overproduction of free
radicals, substances formed when the body metabolizes
oxygen. Normally, free
radicals serve important functions, such as helping the
immune system fight off disease. However, too many free radicals
can start to cause problems. Brain cells producing the mutated
form of amyloid protein - the beta amyloid that forms the
plaques in AD - seem to produce more free radicals. At this
point, it's unclear whether free radicals boost beta amyloid
production or vice versa.
There are also several environmental factors
which have been suspected of contributing to AD risk. One
of the earliest suspects was aluminum, which is a common contaminant
in drinking water. Both the plaques and tangles in AD contain
illuminum, and early studies linked AD with aluminum ingested
through drinking water or even by using aluminum cooking utensils.
However, most researchers are currently not convinced that
there is a strong link between aluminum and AD.
Other environmental suspects which have
been suggested to promote AD include zinc (normally found
in shellfish, beans and dark turkey meat), smoking, high exposure
to paint solvents, and exposure to electromagnetic fields
(EMFs), the high-electricity areas around power lines and
electrical machinery. People who have experienced head injuries
or strokes may also
be more prone to develop AD. Viral infections, such as HIV
(the virus that causes AIDS), may also leave the brain vulnerable
Neither toxin ingestion, nor brain injury,
nor viral infection alone is enough to cause AD. However,
in people genetically predisposed to AD, these environmental
factors may help trigger the disease or cause symptoms to
appear earlier. Currently, much more research is needed to
identify other triggering factors, to determine just how much
they increase risk, and to learn what can be done to offset
Drugs to Treat Alzheimer's Disease
The search for a treatment or cure for Alzheimer's
disease is one of the hottest fields in medical research.
Several pharmaceutical companies are in the final stages of
developing new drugs which may be ready for widespread trials
soon. Before a drug can be sold in this country, it must undergo
trials with thousands of people to determine whether the drug
produces the effects its makers claim without unacceptable
side effects. The average drug can take $300,000,000 and 12-25
years to develop and test before it can reach the market,
and only a fraction of drugs make it this far.
At present, the only Alzheimer's drugs with
FDA approval in this
country are cholinergic
drugs such as tacrine
(brand name Cognex), donepezil
(brand name Aricept), rivastigmine
(brand name Exelon) and galantamine
(brand name Reminyl). In AD, neuron death is worse in some
areas of the brain than others. The learning and memory centers
in the medial temporal lobes are particularly susceptible
to damage, as are a small group of cells known as the basal
forebrain, which produce a chemical called acetylcholine
that is important for learning. When these cells die, brain
levels of acetylcholine fall. The cholinergic drugs help to
keep brain acetylcholine levels from falling too far. So far,
these drugs have had only limited success in halting the progress
of AD. Tacrine also causes severe side effects, so it is seldom
Cholinergic drugs are not the only class
of drug under study. Other researchers are investigating other
avenues: developing drugs which affect other brain chemicals,
or which interfere with the formation of plaques and tangles
in AD, or which bolster the brain's ability to grow new neurons
to replace the ones killed off by the disease. These approaches
hold some promise, and at this point several new drugs are
in clinical trials to determine whether they produce reliable
long-term effects. As with any kind of medicine, the advertising
claims often outstrip the scientific proof. People who try
new drugs and supplements which have not yet received FDA
approval, or who participate in clinical trials, may be among
the first to receive the benefits of a miraculous new medicine.
But they should also be aware that some of these substances
may have harmful long-term effects which have not yet been
There is also some limited evidence that
dietary supplements can help fight or prevent AD. Some of
the damage in AD is attributed to free
radicals; compounds called anti-oxidants
which fight free radical damage are found in vitamin
C and vitamin
E and in beta carotene (associated with vitamin
A). There is some evidence that vitamin C or vitamin E
supplements can slow down the course of AD over several years.
Other anti-oxidants, such as gingko
biloba and phosphatidylserine (abbreviated PS) are also
marketed as AD treatments, though there is less evidence as
yet to support this claim. Supplements containing high doses
of anti-oxidants can cause severe side effects including internal
bleeding - and can even be toxic in individuals taking anticoagulant
medication. No one should take these or any supplements without
consulting a doctor first.
A much safer way to consume anti-oxidants
is as part of a healthy diet. Anti-oxidants are plentiful
in fruits and vegetables (especially blueberries and yellow
fruits and vegetables), in brown rice and whole grains, and
in meats, eggs and dairy products. Caffeine is also an anti-oxidant.
drugs, such as aspirin and NSAID painkillers (ibuprofen, naproxen
sodium, etc.) reduce inflammation in the brain. There is some
limited evidence that people who regularly take NSAIDs over
an extended period (e.g for arthritis) have a lower incidence
of AD and, if they do develop AD, show a slower rate of mental
decline. There is less evidence that aspirin is effective
against AD. NSAIDs have potentially serious side effects;
some 100,000 Americans are hospitalized annually for NSAID-induced
ulcers, and over 16,000 die. So, currently, doctors don't
prescribe NSAIDs for AD protection alone. Researchers are
working to develop a new kind of NSAID which protects the
brain without causing such severe side effects.
Article : "7-MINUTE
Article : "CROSSING
Article : "ESTROGEN
Article : "PUTTING
GINGKO TO THE TEST"
Article : "NEW
ALZHEIMER'S DRUG HELPS CAREGIVERS, TOO"
Article : "UNMASKING
Article : "THE
COLOR OF RISK"
Article : "CARING
Article : "MINORITY
NEURONS: EXERCISE TO MAINTAIN A HEALTHY BRIAN
by Catherine E. Myers. Copyright © 2006 Memory Loss and the Brain