Alzheimer's disease

Definition
Alzheimer's disease is the most common cause of dementia, which is the loss of
intellectual and social abilities severe enough to interfere with daily functioning.
Dementia occurs in people with Alzheimer's disease because healthy brain tissue
degenerates, causing a steady decline in memory and mental abilities.

About 4 million older Americans have Alzheimer's, a disease that usually develops in
people age 65 or older. This number is expected to triple by the year 2050 as the
population ages.

Although there's no cure for Alzheimer's disease, researchers have made progress.
Treatments are available that improve the quality of life for some people with
Alzheimer's. Also, more drugs are being studied, and scientists have discovered
several genes associated with Alzheimer's, which may lead to new treatments to block
progression of this complex disease.

In the meantime, caring for someone with Alzheimer's takes patience and a focus on
the things a person can still do and enjoy. Those with Alzheimer's — as well as those
who care for them — need support and affection from friends and family to cope.

Symptoms
Everyone has occasional lapses in memory. It's normal to forget the names of people
whom you rarely see. But it's not a normal part of aging to forget the names of
familiar people and objects.

Alzheimer's disease — a progressive, degenerative brain disease — causes more than

simple forgetfulness. It may start with slight memory loss and confusion, but it
eventually leads to irreversible mental impairment that destroys a person's ability to
remember, reason, learn and imagine.

Most people with Alzheimer's share certain signs and symptoms of the disease. These
may include:

 Increasing and persistent forgetfulness. At its onset, Alzheimer's disease is

marked by periods of forgetfulness, especially of recent events or simple
directions. But what begins as mild forgetfulness persists and worsens. People
with Alzheimer's may repeat things and forget conversations or appointments.
They routinely misplace things, often putting them in illogical locations. They
frequently forget names, and eventually, they may forget the names of family
members and everyday objects.
 Difficulties with abstract thinking. People with Alzheimer's may initially
have trouble balancing their checkbook, a problem that progresses to trouble
recognizing and dealing with numbers.
  Difficulty finding the right word. It may be a challenge for those with
Alzheimer's to find the right words to express thoughts or even follow
conversations. Eventually, reading and writing also are affected.
 Disorientation. People with Alzheimer's often lose their sense of time and
dates, and may find themselves lost in familiar surroundings.
 Loss of judgment. Solving everyday problems, such as knowing what to do if
food on the stove is burning, becomes increasingly difficult, eventually
impossible. Alzheimer's is characterized by greater difficulty in doing things
that require planning, decision making and judgment.
 Difficulty performing familiar tasks. Once-routine tasks that require
sequential steps, such as cooking, become a struggle as the disease progresses.
Eventually, people with advanced Alzheimer's may forget how to do even the
most basic things.
 Personality changes. People with Alzheimer's may exhibit mood swings.
They may express distrust in others, show increased stubbornness and
withdraw socially. Early on, this may be a response to the frustration they feel
as they notice uncontrollable changes in their memory. Depression often
coexists with Alzheimer's disease. Restlessness also is a common sign. As the
disease progresses, people with Alzheimer's may become anxious or
aggressive and behave inappropriately.

Because early Alzheimer's symptoms progress slowly, diagnosis is often delayed.

People developing the condition may be frighteningly aware of their problems — but
careful to keep them hidden, refusing to see a doctor. As a result, even their families
may fail to see what's going on. When the signs and symptoms are too obvious to
miss, those closest to the person often realize that similar — but less severe —
difficulties have been present for years.

The disease's course varies from person to person. Eight years is the average length of
time from diagnosis of Alzheimer's to death. Survival begins to decline three years
after diagnosis, but some people live more than a decade with the disease.

Causes
The causes of Alzheimer's are poorly understood, but its effect on brain tissue has
been demonstrated clearly. Alzheimer's damages and kills brain cells.

A healthy brain has billions of nerve cells called neurons. Neurons generate electrical
and chemical signals that are relayed from neuron to neuron to help you think,
remember and feel. Chemicals called neurotransmitters help these signals flow
seamlessly between neurons.

Initially in people with Alzheimer's, neurons in certain locations of the brain begin to
die. When they die, lower levels of neurotransmitters are produced, creating signaling
problems in the brain.

Plaques and tangles

Alzheimer's disease is named after Dr. Alois Alzheimer, a German neurologist. In
1906, he examined the brain of a woman who had died after years of progressive
dementia. Her brain tissue showed abnormal clumps and irregular knots of brain cells.
Today, these clumps (now called plaques) and knots (now called tangles) are
considered hallmarks of Alzheimer's disease.

Studies of plaques and tangles from the brains of people who have died of
Alzheimer's suggest several possible roles these structures might play in the disease.
Some of the theories:

 Possible role of plaques. Plaques are made up of a normally harmless protein

called beta-amyloid. Although the ultimate cause of neuron death in
Alzheimer's isn't known, mounting evidence suggests that a form of beta-
amyloid protein may be the culprit. Three genetic mutations — in amyloid
precursor protein and presenilin 1 (PS1) and presenilin 2 (PS2) proteins — are
known to cause a small number of early-onset forms of Alzheimer's disease.
These mutations result in the production of amyloid plaques. Together, these
three genetic mutations account for less than 10 percent of all Alzheimer's
cases.
 Possible role of tangles. The internal support structure for brain neurons
depends on the normal functioning of a protein called tau. In people with
Alzheimer's, threads of tau protein undergo alterations that cause them to
become twisted. Many researchers believe this may seriously damage neurons,
causing them to die.

Inflammatory response as the common path. Researchers have observed

inflammation in the brains of some people with Alzheimer's disease. Inflammation is
your body's response to injury or infection and a natural part of the healing process.
Even as beta-amyloid plaques develop in the spaces between neurons, immune cells
are at work getting rid of dead cells and other waste products in the brain. Although
researchers believe the inflammation occurs before plaques have fully formed, they
aren't sure how this development relates to the disease process. There's also debate
about whether inflammation has a damaging effect on neurons or whether it is
beneficial in clearing away plaques.

Risk factors
Alzheimer's is a complex disease likely caused by a combination of factors — such as
infection or reduced circulation — and genetic susceptibility. Although all the
contributing factors may never be known, scientists have identified several common
threads. They include:

 Age. Alzheimer's usually affects people older than 65, but can, rarely, affect
those younger than 40. Less than 5 percent of people between 65 and 74 have
Alzheimer's. For people 85 and older, that number jumps to nearly 50
percent.
 Heredity. Your risk of developing Alzheimer's appears to be slightly higher if
a first-degree relative — parent, sister or brother — has the disease. Although
the genetic mechanisms of Alzheimer's among families remain largely
unexplained, researchers have identified a few genetic mutations that greatly
increase risk in some families. Three genetic mutations are known to cause
 early-onset Alzheimer's. In addition, one form of the apolipoprotein E (APOE)
gene increases your chance of developing late-onset Alzheimer's.
 Sex. Women are more likely than men are to develop the disease, in part
because they live longer.
 Lifestyle. The same factors that put you at risk of heart disease, such as high
blood pressure and high cholesterol, may also increase the likelihood that
you'll develop Alzheimer's disease. Poorly controlled diabetes is another risk
factor. And keeping your body fit isn't your only concern — you've got to
exercise your mind as well. Some studies have suggested that remaining
mentally active throughout your life, especially in your later years, reduces the
risk of Alzheimer's disease.
 Education levels. Studies have found an association between less education
and the risk of Alzheimer's. Some researchers theorize that the more you use
your brain, the more synapses you create, which provides a greater reserve as
you age. It remains unclear, however, whether less education and less mental
activity create a risk of Alzheimer's or if it's simply harder to detect
Alzheimer's in people who exercise their minds frequently or who have more
education.
 Toxicity. One long-standing theory is that overexposure to certain trace metals
or chemicals may cause Alzheimer's. For a time, aluminum seemed a likely
candidate, because some people with Alzheimer's have deposits of aluminum
in their brains. After many years of studies, however, no one has been able to
link aluminum exposure directly to Alzheimer's. At this point, there's no
evidence that any particular substance increases a person's risk of Alzheimer's.
 Head injury. The observation that some ex-boxers eventually develop
dementia suggests that serious traumatic injury to the head (for example, a
concussion with a prolonged loss of consciousness) may be a risk factor for
Alzheimer's. Several studies indicate a definite link between the two, but
others show no link.
 Hormone replacement therapy. The exact role hormone replacement therapy
may play in the development of dementia isn't yet clear. Throughout the 1980s
and '90s, evidence seemed to show that estrogen supplements given after
menopause could reduce the risk of dementia. But results from the large-scale
Women's Health Initiative Memory Study indicated an increased risk of
dementia for women taking estrogen after age 65. The verdict is not yet in on
whether estrogen affects the risk of dementia if given at an earlier age.

Tests and diagnosis

There's no one test to diagnose Alzheimer's disease. Typically, doctors start the
diagnostic process by ruling out other diseases and conditions that also can cause
memory loss.

Small, undetected strokes, for example, can cause dementia by temporarily

interrupting blood flow to the brain. People with Parkinson's disease, a degenerative
nerve disorder, also can develop dementia. Depression, too, can cause lapses in
memory. In addition, many older adults are on multiple medications that may impair
their ability to think clearly.
To help distinguish Alzheimer's disease from other causes of memory loss, doctors
typically rely on the following:

 Medical history. Doctors may ask about a person's general health and past medical
problems. They'll want to know about any problems a person may have in carrying out daily
activities. If possible, doctors will also want to speak with a person's family or friends to get
more information.
 Basic medical tests. Blood tests may be done to help doctors rule out other potential causes
of the dementia, such as thyroid disorders or vitamin deficiencies.
 Mental status evaluation. These tests screen memory, problem-solving abilities, attention
spans, counting skills and language. They help doctors pinpoint specific problems a person
may have with cognition. For instance, doctors might test recent and long-term memory by
asking: What day is it today? Or: When was World War II? Recall tests are another
example. Doctors may list familiar objects, and then ask a person to repeat them
immediately, and again five minutes later.
 Neuropsychological testing. Sometimes doctors undertake a more extensive assessment of
memory, problem-solving abilities, attention spans, counting skills and language. This is
especially helpful in trying to detect Alzheimer's and other dementias at an early stage.
Doctors use formal psychological tests to determine if a person's mental abilities are as
expected for his or her age and education. The patterns of any mental deficits observed
during neuropsychological testing can help doctors sort out possible causes of dementia.
 Brain scans. Doctors may want to take a picture of the brain using a brain scan. Several
types of brain scans are available — including a computerized tomography (CT) scan, a
magnetic resonance imaging (MRI) scan and a positron emission tomography (PET) scan.
By looking at images of the brain, doctors may be able to pinpoint any visible abnormalities.
Researchers are studying whether brain scans can eventually be used to detect an increased
risk of Alzheimer's in healthy people before symptoms begin.

Using the methods above, doctors can accurately diagnose 90 percent of Alzheimer's
cases. Alzheimer's can be diagnosed with complete accuracy only after death, using a
microscopic examination of brain tissue, which checks for plaques and tangles.

Genetic testing for Alzheimer's is in its beginning stages. Blood tests are available
that can tell whether a person carries the genetic mutations believed to be associated
with Alzheimer's, but the tests can't tell who will or will not get the disease.
Complications
In advanced Alzheimer's disease, people may lose all ability to care for themselves.
This can make them more prone to additional health problems such as:

 Pneumonia. Difficulty swallowing food and liquids may cause people with
Alzheimer's to inhale (aspirate) some of what they eat and drink into their
airways and lungs, which can lead to pneumonia.
 Infections. Urinary incontinence may require the placement of a urinary
catheter, which increases the risk of urinary tract infections. Untreated urinary
tract infections can lead to more serious, life-threatening infections.
 Falls and their complications. People with Alzheimer's may become
disoriented, increasing their risk of falls. Falls can lead to fractures. In
addition, falls are a common cause of serious head injuries, such as bleeding in
the brain. Surgery to repair injury from a fall carries risks as well. For
instance, prolonged immobilization — which may be necessary to recover
from injuries related to a fall — increases the risk of a blood clot in the lungs
(pulmonary embolism), which can be life-threatening.

Treatments and drugs

Currently, there's no cure for Alzheimer's disease. Doctors sometimes prescribe drugs
to improve symptoms that often accompany Alzheimer's, including sleeplessness,
wandering, anxiety, agitation and depression. But only two varieties of medications
have been proved to slow the cognitive decline associated with Alzheimer's.

Cholinesterase inhibitors
This group of medications — which includes donepezil (Aricept), rivastigmine
(Exelon) and galantamine (Reminyl) — works by improving the levels of
neurotransmitters in the brain. Donepezil has been approved by the Food and Drug
Administration for the treatment of mild, moderate and severe Alzheimer's disease.

Donepezil also appears to delay the onset of Alzheimer's for about a year in people
who have mild cognitive impairment (MCI). People who have MCI have more
memory problems than other people their age, but they are not demented.

Cholinesterase inhibitors don't work for everyone. As many as half the people who
take these drugs show no improvement. Other people may choose to stop taking the
drugs because of the side effects, which include diarrhea, nausea and vomiting.

Memantine (Namenda)
The first drug approved to treat moderate to severe stages of Alzheimer's, memantine
(Namenda), protects brain cells from damage caused by the chemical messenger
glutamate. It sometimes is used in combination with a cholinesterase inhibitor.
Memantine's most common side effect is dizziness, although it also appears to
increase agitation and delusional behavior in some people.

Prevention
Right now, there's no proven way to prevent the onset of Alzheimer's disease.
Researchers had developed what looked to be a promising vaccine against
Alzheimer's that worked by stopping deposits of beta-amyloid in the brain. Animal
studies were so encouraging that human trials began in 2001. Unfortunately, they
soon had to be stopped because some people experienced serious inflammation of the
brain. While these results were disappointing, scientists learned from these
experiments and many researchers continue to look for ways to reduce the risk of this
disease. Several leads are hopeful, but still preliminary. They include:

 Healthy aging. Some of the most recent research indicates that taking steps to
improve your cardiovascular health, such as losing weight, exercising and
controlling high blood pressure and cholesterol, may also help prevent
Alzheimer's disease.
 Nonsteroidal anti-inflammatory drugs (NSAIDs). Several studies have
shown that the NSAIDs ibuprofen (Advil, Motrin, others), naproxen sodium
(Aleve) and indomethacin (Indocin) may reduce the risk of developing
Alzheimer's. This may be because inflammation appears to play a role in
Alzheimer's. What isn't known, however, is whether inflammation is a cause
of Alzheimer's or simply an effect of the disease. Because NSAIDs can cause
serious gastrointestinal bleeding, clinical trials need to be completed before it's
clear whether people should take NSAIDs solely to prevent Alzheimer's.
 Statins. These drugs — a class that includes atorvastatin (Lipitor),
rosuvastatin (Crestor) and simvastatin (Zocor) — are normally used to lower
 cholesterol levels, but recent studies have shown that they may also reduce the
risk of Alzheimer's disease. More studies are being done to determine exactly
what role, if any, statins may have in Alzheimer's prevention.
 Selective estrogen receptor molecules (SERMs). A SERM called raloxifene
(Evista) is used to protect against the bone loss associated with osteoporosis. It
also appears to lower the risk of developing mild cognitive impairment, a
memory disorder that often precedes Alzheimer's.
 Vitamin E and ginkgo. Both these substances have been linked to
improvements in cognitive abilities, and their potential effects on Alzheimer's
are being studied. One large study, however, showed that vitamin E has no
effect on the development of Alzheimer's in people who have mild cognitive
impairment.
 Mental fitness. Maintaining mental fitness may delay onset of dementia.
Some researchers believe that lifelong mental exercise and learning may
promote the growth of additional synapses, the connections between neurons,
and delay the onset of dementia. Other researchers argue that advanced
education gives a person more experience with the types of memory and
thinking tests used to measure dementia. This advanced level of education
simply may help some people "cover up" their condition until later.

Delaying the onset of Alzheimer's is an important step in fighting the disease. If the
onset of Alzheimer's could be postponed by just five years, it would dramatically
reduce the number of people who have the disease.

Coping and support

People with Alzheimer's disease often experience a mixture of emotions — confusion,
frustration, anger, fear, uncertainty, grief and depression. You can help a person cope
with the disease by being there to listen, reassuring the person that life can still be
enjoyed, providing unconditional love, and doing your best to help the person retain
dignity and self-respect.

A calm and stable home environment reduces behavior problems. New situations,
noise, large groups of people, being rushed or pressed to remember, or being asked to
do complicated tasks can cause anxiety. As a person with Alzheimer's becomes upset,
the ability to think clearly declines even more.

Providing care for a person with Alzheimer's disease is physically and emotionally
demanding. Feelings of anger and guilt, frustration and discouragement, worry and
grief, and social isolation are common. If you're a caregiver for someone with
Alzheimer's disease, you can help yourself by:

 Asking friends or other family members for help when you need it
 Taking care of your health
 Learning as much about the disease as you can
 Asking questions of doctors, social workers and others involved in the care of
your loved one
 Joining a support group
Many people with Alzheimer's and their families benefit from counseling or local
support groups. Contact your local Alzheimer's Association affiliate to get connected
with support groups, doctors, resources and referrals, home care agencies, supervised
living facilities, a telephone help line, and educational seminars.