Alzheimer’s disease (AD) is an irreversible, progressive brain disease that

slowly destroys memory and thinking skills and, eventually, the ability to
carry out the simplest tasks of daily living. In most people with AD,
symptoms first appear after age 60.

Alzheimer’s disease is a brain disorder named for German

physician Alois Alzheimer, who first described it in 1906.
Scientists have learned a great deal about Alzheimer’s disease in
the century since Dr. Alzheimer first drew attention to it. Today
we know that Alzheimer’s:

• Is a progressive and fatal brain disease. As many as 5.3

million Americans are living with Alzheimer’s
disease. Alzheimer's destroys brain cells, causing problems
with memory, thinking and behavior severe enough to
affect work, lifelong hobbies or social life. Alzheimer’s gets
worse over time, and it is fatal. Today it is the sixth-leading
cause of death in the United States. For more information,
see Warning Signs and Stages of Alzheimer’s Disease.

• Is the most common form of dementia, a general term

for the loss of memory and other intellectual abilities serious
enough to interfere with daily life. Vascular dementia,
another common type of dementia, is caused by reduced
blood flow to parts of the brain. In mixed dementia,
Alzheimer’s and vascular dementia occur together. For more
information about other causes of dementia, please see
Related Dementias.

• Has no current cure. But treatments for symptoms,

combined with the right services and support, can make life
better for the millions of Americans living with
Alzheimer’s. There is an accelerating worldwide effort under
way to find better ways to treat the disease, delay its onset,
or prevent it from developing. Learn more about recent
progress in Alzheimer science and research funded by the
Alzheimer’s Association in the Research section.

•
 • Alzheimer's and the brain
Just like the rest of our bodies, our brains change as we
age. Most of us notice some slowed thinking and occasional
problems remembering certain things. However, serious
memory loss, confusion and other major changes in the way
our minds work are not a normal part of aging. They may be
a sign that brain cells are failing.

The brain has 100 billion nerve cells (neurons). Each nerve
cell communicates with many others to form networks.

Nerve cell networks have special jobs. Some are involved in

thinking, learning and remembering. Others help us see,
hear and smell. Still others tell our muscles when to move.

To do their work, brain cells operate like tiny factories. They

take in supplies, generate energy, construct equipment and
get rid of waste. Cells also process and store information.
Keeping everything running requires coordination as well as
large amounts of fuel and oxygen.

In Alzheimer’s disease, parts of the cell’s factory stop

running well. Scientists are not sure exactly where the
trouble starts. But just like a real factory, backups and
breakdowns in one system cause problems in other areas.
As damage spreads, cells lose their ability to do their jobs
well. Eventually, they die.

• Early stage and younger onset

Early-stage is the early part of Alzheimer’s disease when
problems with memory, thinking and concentration may
begin to appear in a doctor’s interview or medical tests.
Individuals in the early-stage typically need minimal
assistance with simple daily routines. At the time of a
diagnosis, an individual is not necessarily in the early stage
of the disease; he or she may have progressed beyond the
early stage.

The term younger-onset refers to Alzheimer's that occurs in

a person under age 65. Younger-onset individuals may be
employed or have children still living at home. Issues facing
families include ensuring financial security, obtaining
benefits and helping children cope with the disease. People
who have younger-onset dementia may be in any stage of
dementia – early, middle or late. Experts estimate that
some 500,000 people in their 30s, 40s and 50s have
Alzheimer's disease or a related dementia.

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History
At a scientific meeting in November 1906, German physician
Alois Alzheimer presented the case of “Frau Auguste D.,” a
51-year-old woman brought to see him in 1901 by her
family. Auguste had developed problems with memory,
unfounded suspicions that her husband was unfaithful, and
difficulty speaking and understanding what was said to her.
Her symptoms rapidly grew worse, and within a few years
she was bedridden. She died in Spring 1906, of
overwhelming infections from bedsores and pneumonia.

Dr. Alzheimer had never before seen anyone like Auguste

D., and he gained the family’s permission to perform an
autopsy. In Auguste’s brain, he saw dramatic shrinkage,
especially of the cortex, the outer layer involved in memory,
thinking, judgment and speech. Under the microscope, he
also saw widespread fatty deposits in small blood vessels,
dead and dying brain cells, and abnormal deposits in and
around cells.

The condition entered the medical literature in 1907, when

Alzheimer published his observations about Auguste D. In
1910, Emil Kraepelin, a psychiatrist noted for his work in
naming and classifying brain disorders, proposed that the
disease be named after Alzheimer.
 Auguste D. Dr. Alois Alzheimer

• The role of plaques and tangles

Two abnormal structures called plaques and tangles are
prime suspects in damaging and killing nerve cells. Plaques
and tangles were among the abnormalities that Dr. Alois
Alzheimer saw in the brain of Auguste D., although he called
them different names.

o Plaques build up between nerve cells. They contain

deposits of a protein fragment called beta-amyloid
(BAY-tuh AM-uh-loyd). Tangles are twisted fibers of
another protein called tau (rhymes with “wow”).

o Tangles form inside dying cells. Though most people

develop some plaques and tangles as they age, those
with Alzheimer’s tend to develop far more. The plaques
and tangles tend to form in a predictable pattern,
beginning in areas important in learning and memory
and then spreading to other regions.

Scientists are not absolutely sure what role plaques and

tangles play in Alzheimer’s disease. Most experts believe
they somehow block communication among nerve cells and
disrupt activities that cells need to survive.

As many as 5.3 million people in the United States are living

with Alzheimer’s.

• Alzheimer's and dementia triple healthcare costs for

Americans age 65 and older.

• Every 70 seconds, someone develops Alzheimer’s.

• Alzheimer's is the sixth-leading cause of death.

• The direct and indirect costs of Alzheimer's and other

dementias to Medicare, Medicaid and businesses amount to more
than $148 billion each year.

New report says Alzheimer’s disease and dementia

triple healthcare costs for Americans age 65 and
older

Total healthcare costs are more than three times higher for
people with Alzheimer’s and other dementias than for other
people age 65 and older, according to the Alzheimer’s
Association’s 2009 Alzheimer’s Disease Facts and Figures,
released today.

New report
2009 Alzheimer's
Disease
Facts and Figures

Statistics that convey the

growing prevalence of
Alzheimer's and its
impact.

In the new report, total healthcare costs are calculated as per

person payments measured from all sources. Medicare payments
alone are almost three times higher for people with Alzheimer’s
and dementia than for others age 65 and over; Medicaid
payments alone are more than nine times higher.

“With the country facing unprecedented economic challenges and

a rapidly aging baby boomer population, now is the time to
address the burgeoning Alzheimer crisis that triples healthcare
costs for Americans age 65 and over,” said Harry Johns,
Alzheimer’s Association CEO.

“It is widely understood that addressing health care is key to the

country regaining its financial footing,” continued Johns. “And
there is no way this can be done without improving Medicare and
Medicaid which Alzheimer’s directly impacts. A strategy to
immediately confront Alzheimer’s has the potential to save
millions of lives and billions of dollars by reducing the burden on
Medicare and Medicaid.”

Average Per Person Payments by Source for Health and

Long-term Care Services. For Persons, Aged 65 Years and
Older, With and Without Alzheimer’s Disease and Other
Dementias, 2004

Beneficiaries with no Beneficiaries with

Average Per
Alzheimer's or Other Alzheimer's or Other
Person Payments
Dementias Dementias
Total payments* $10,603 $33,007
Medicare payments 5,272 15,145
Medicaid payments 718 6,605
Private insurance
1,466 1,847
payments
Other sources
211 519
payments
HMO payments 704 410
Out-of-pocket
1,916 2,464
payments
Uncompensated
201 261
care

* Payments by source do not exactly equal total payments due to the effect of population weighting.
Source: Alzheimer’s Association 2009 Alzheimer’s Disease Facts and Figures

People with Alzheimer’s are high consumers of hospital, nursing

home and other health and long-term care services, which
translates into high costs for Medicare, Medicaid and millions of
families. As families struggle to survive in a deepening recession
and as states grapple with budget shortfalls, Alzheimer’s disease
threatens to overwhelm them both. Most people with Alzheimer’s
also have one or more additional serious medical conditions, such
as diabetes or coronary heart disease. Their Alzheimer’s greatly
complicates the medical management for these other conditions
and drives up costs significantly.
 According to the Facts and Figures report, in 2006:

• Medicare beneficiaries with diabetes plus Alzheimer’s or

another dementia had 64 percent more hospital stays than
those with diabetes and no Alzheimer’s, and their average
per person Medicare costs were $20,655 compared to
$12,979 for beneficiaries with diabetes but no Alzheimer’s or
dementia.
• Medicare beneficiaries with coronary heart disease and
Alzheimer’s disease or another dementia had 42 percent
more hospital stays than those with coronary heart disease
and no Alzheimer’s or dementia, and their average per
person Medicare costs were $20,780 compared to $14,640
for beneficiaries with coronary heart disease but no
Alzheimer’s or dementia.

With family members providing care at home for about 70

percent of people with Alzheimer’s disease, the ripple effects of
the disease can be felt throughout the entire family. According to
Facts and Figures, in 2008, nearly 10 million Alzheimer caregivers
in the U.S. provided 8.5 billion hours of unpaid care valued at $94
billion. In addition to the unpaid care families contribute, the
report also reveals that Alzheimer’s creates high out-of-pocket
health and long-term care expenses for families.

Out-of-pocket costs that are not covered by Medicare, Medicaid or

other sources of insurance are 28 percent higher for Medicare
beneficiaries with Alzheimer’s than those without. Individuals with
Alzheimer’s and other dementia living in nursing homes or
assisted living facilities incurred the highest out-of-pocket costs –
an average of $16,689 a year.

Growing prevalence of Alzheimer’s disease and dementia

According to the report, there are 5.3 million Americans living
with the disease and every 70 seconds someone in America
develops Alzheimer’s disease. By mid-century someone will
develop Alzheimer’s every 33 seconds. By 2010, there will be
nearly a half million new cases of Alzheimer’s each year; and by
2050, there will be nearly a million new cases per year.

Alzheimer’s is the sixth leading cause of death in the country,

surpassing diabetes; it is the fifth leading cause of death among
 individuals 65 and older. From 2000 to 2006, while deaths from
other major diseases dropped – heart disease (-11.5 percent),
breast cancer (-.6 percent), prostate cancer (-14.3 percent) and
stroke (-18.1 percent), deaths from Alzheimer’s disease rose 47.1
percent.

“Currently, there are no treatments that can prevent, delay or

reverse Alzheimer disease and research funding has been
stagnant for the past six years. With the first baby boomers
turning age 65 in just two short years – and entering the arena of
increasing risk for developing Alzheimer’s – an aggressive plan is
needed now to address the threat of this disease. There are too
many lives, too little time and too much at stake for anything
less,” Johns said.

Implications for states

Demographic trends indicate that the number of affected
individuals and families will grow significantly in the years to
come, not only having a profound effect on families and health
systems but on state budgets as well. In order for states to plan
for this rapidly growing population, they must first have reliable
information about the characteristics and needs of their residents
who are coping with Alzheimer’s or other dementia. An existing
survey process is the easiest way to obtain this important
information.

The Behavioral Risk Factors Surveillance System (BRFSS) is an

annual state public health survey done in conjunction with the
Centers for Disease Control and Prevention (CDC). Since 2003,
some states have added questions about caregiving for people
with Alzheimer’s and other dementias in their BRFSS surveys.

The new Facts and Figures report highlights the BRFSS survey
findings from the states of Washington and North Carolina. The
BRFSS survey allows residents to say for themselves what their
challenges are. For example in Washington, 48 percent of the
caregivers for individuals with memory loss or cognitive
impairment revealed that stress was the greatest difficulty they
faced. Beginning this year, an approved set of family caregiving
questions is available for all states to add to their BRFSS survey,
and another set of questions on cognitive impairment is being
 developed for 2010.

Mild Cognitive Impairment (MCI) – An emerging issue

Experts believe that early detection of Alzheimer’s disease and
early intervention with improved therapies provides the greatest
opportunity to delay or stop additional damage to the brain. To
that end, the new report highlights the emerging role of a
condition known as mild cognitive impairment (MCI). A person
with MCI has problems with memory, language or other essential
cognitive functions that are severe enough to be noticeable to the
individual and others, but not severe to interfere with daily life.

There is consensus within the scientific research community that

intervention with any disease-modifying treatment should occur
as early as possible, ideally even before symptoms appear.
Individuals with MCI have a higher risk for developing Alzheimer’s
disease, but more research is needed to determine why some
people with MCI go on to develop Alzheimer’s and why some do
not. By participating in scientific studies and clinical trials,
individuals with MCI will help to speed progress in finding ways to
prevent or cure Alzheimer’s by providing scientists with the
opportunity to test new Alzheimer treatments and learn faster
whether or not the treatments work.

“There is a rich, diverse variety of treatment possibilities for

Alzheimer’s that scientists are exploring, offering great hope that
drugs that may slow or even reverse disease progression could be
on the horizon – saving millions of dollars in public health
programs,” said Ronald Petersen, M.D., Ph.D, the Alzheimer’s
Association’s Medical Scientific Advisory Council Chair. “A national
strategy and a sustained commitment to Alzheimer research is
what is needed to today to make Alzheimer survivors tomorrow.”

Myth 1: Memory loss is a natural part of aging.

Reality: In the past people believed memory loss was a normal
part of aging, often regarding even Alzheimer’s as natural age-
related decline. Experts now recognize severe memory loss as a
symptom of serious illness.
 Whether memory naturally declines to some extent remains an
open question. Many people feel that their memory becomes less
sharp as they grow older, but determining whether there is any
scientific basis for this belief is a research challenge still being
addressed.

Myth 2: Alzheimer’s disease is not fatal.

Reality: Alzheimer's disease has no survivors. It destroys brain
cells and causes memory changes, erratic behaviors and loss of
body functions. It slowly and painfully takes away a
person's identity, ability to connect with others, think, eat, talk,
walk and find his or her way home.

Myth 3: Only older people can get Alzheimer's

Reality: Alzheimer's can strike people in their 30s, 40s and even
50s. This is called younger-onset Alzheimer's. In 2009, it is
estimated that there are as many as 5.3 million people living with
Alzheimer’s disease in the United States. This includes 5.1 million
people age 65 and over and 200,000 people under age 65 with
younger-onset Alzheimer’s disease.

Myth 4: Drinking out of aluminum cans or cooking

in aluminum pots and pans can lead to Alzheimer’s
disease.
Reality: During the 1960s and 1970s, aluminum emerged as a
possible suspect in Alzheimer’s. This suspicion led to concern
about exposure to aluminum through everyday sources such as
pots and pans, beverage cans, antacids and antiperspirants.
Since then, studies have failed to confirm any role for aluminum
in causing Alzheimer’s. Experts today focus on other areas of
research, and few believe that everyday sources of aluminum
pose any threat.

Myth 5: Aspartame causes memory loss.

Reality: This artificial sweetener, marketed under such brand
names as Nutrasweet and Equal, was approved by the U.S. Food
and Drug Administration (FDA) for use in all foods and beverages
 in 1996. Since approval, concerns about aspartame's health
effects have been raised.

According to the FDA, as of May 2006, the agency had not been
presented with any scientific evidence that would lead to change
its conclusions on the safety of aspartame for most people. The
agency says its conclusions are based on more than 100
laboratory and clinical studies. Read the May 2006 FDA statement
about aspartame.

Myth 6: Flu shots increase risk of Alzheimer’s

disease
Reality: A theory linking flu shots to a greatly increased risk of
Alzheimer’s disease has been proposed by a U.S. doctor whose
license was suspended by the South Carolina Board of Medical
Examiners. Several mainstream studies link flu shots and other
vaccinations to a reduced risk of Alzheimer's disease and overall
better health.

• A Nov. 27, 2001, Canadian Medical Journal report suggests

older adults who were vaccinated against diphtheria or
tetanus, polio, and influenza seemed to have a lower risk of
developing Alzheimer’s disease than those not receiving
these vaccinations. The full text of this report is posted on
the journal’s Web site.

• A report in the Nov. 3, 2004, JAMA found that annual flu

shots for older adults were associated with a reduced risk of
death from all causes. The abstract of that report is posted
on PubMed.

Myth 7: Silver dental fillings increase risk of

Alzheimer's disease
Reality: According to the best available scientific evidence, there
is no relationship between silver dental fillings and Alzheimer's.
The concern that there could be a link arose because "silver"
fillings are made of an amalgam (mixture) that typically contains
 about 50 percent mercury, 35 percent silver and 15 percent tin.
Mercury is a heavy metal that, in certain forms, is know to be
toxic to the brain and other organs.

Many scientists consider the studies below compelling evidence

that dental amalgam is not a major risk factor for Alzheimer's.
Public health agencies, including the FDA, the U.S. Public Health
Service and the World Health Organization, endorse the
continued use of amalgam as safe, strong, inexpensive material
for dental restorations.

• March 1991, the Dental Devices Panel of the FDA concluded

there was no current evidence that amalgam poses any
danger.

• National Institutes of Health (NIH) in 1991 funded a study at

the University of Kentucky to investigate the relationship
between amalgam fillings and Alzheimer's. Analysis by
University statisticians revealed no significant association
between silver fillings and Alzheimer's. The abstract for this
study is posted on the Journal of the American Dental
Association Web site.

• October 30, 2003, a New England Journal of Medicine article

concluded that current evidence shows no connection
between mercury-containing dental fillings and Alzheimer's
or other neurological diseases. The abstract for this study is
posted on the New England Journal of Medicine Web site.

Myth 8: There are treatments available to stop the

progression of Alzheimer's disease

Reality: At this time, there is no treatment to cure, delay or stop

the progression of Alzheimer's disease. FDA-approved drugs
temporarily slow worsening of symptoms for about 6 to 12
months, on average, for about half of the individuals who take
them. Dementia
Dementia is a general term for loss of memory and other mental
abilities severe enough to interfere with daily life. It is caused
by changes in the brain.

Alzheimer’s disease is the most common form of dementia,

accounting for 50 to 70 percent of cases. Other types of dementia
include vascular dementia, mixed dementia, dementia with Lewy
bodies and frontotemporal dementia. For more information about
other causes of dementia, please see Related Dementias.

Doctors have identified other conditions that can cause dementia-

like symptoms. These dementia-like symptoms can be reversed if
they are caused by treatable conditions, such as depression, drug
interaction, thyroid problems, excess use of alcohol or certain
vitamin deficiencies.

Memory loss that disrupts everyday life is not a normal part of

aging. It may be a sign of Alzheimer's disease, a fatal brain
disease that gets worse over time and causes changes in
thinking, reasoning and behavior. Although the disease is more
common in people 65 and older, it can also strike those in their
30s, 40s and 50s.

10 warning signs of Alzheimer's:

Memory loss.

Forgetting recently learned information is one of

the most common early signs of dementia. A
person begins to forget more often and is unable
to recall the information later.
What's normal? Forgetting names or appointments
occasionally.

Difficulty performing familiar tasks.

People with dementia often find it hard to plan or

complete everyday tasks. Individuals may lose
track of the steps to prepare a meal, place a
telephone call or play a game.
 What's normal? Occasionally forgetting why you came into a
room or what you planned to say.

Problems with language.

People with Alzheimer's disease often forget

simple words or substitute unusual words, making
their speech or writing hard to understand. They
may be unable to find their toothbrush, for
example, and instead ask for "that thing for my
mouth."

What's normal? Sometimes having trouble finding the right word.

Disorientation to time and place.

People with Alzheimer's disease can become lost in

their own neighborhoods, forget where they are
and how they got there, and not know how to get
back home.

What's normal? Forgetting the day of the week or where you

were going.

Poor or decreased judgment.

Those with Alzheimer's may dress inappropriately,

wearing several layers on a warm day or little
clothing in the cold. They may show poor
judgment about money, like giving away large
sums to telemarketers.

What's normal? Making a questionable or debatable decision

 from time to time.

Problems with abstract thinking.

Someone with Alzheimer's disease may have

unusual difficulty performing complex mental
tasks, like forgetting what numbers are and how
they should be used.

What's normal? Finding it challenging to balance a checkbook.

Misplacing things.

A person with Alzheimer's disease may put things

in unusual places: an iron in the freezer or a
wristwatch in the sugar bowl.

What's normal? Misplacing keys or a wallet

temporarily.

Changes in mood or behavior.

Someone with Alzheimer's disease may show rapid

mood swings – from calm to tears to anger – for
no apparent reason.

What's normal? Occasionally feeling sad or

moody.
 Changes in personality.

The personalities of people with dementia can

change dramatically. They may become extremely
confused, suspicious, fearful or dependent on a
family member.

What's normal? People’s personalities do change somewhat with

age.

Loss of initiative.

A person with Alzheimer's disease may become

very passive, sitting in front of the TV for hours,
sleeping more than usual or not wanting to do
usual activities.

What's normal? Sometimes feeling weary of work or social

obligations.

The difference between Alzheimer's and normal

age-related memory changes

Someone with Alzheimer's disease Someone with normal age-related

symptoms memory changes

Forgets entire experiences Forgets part of an experience

Rarely remembers later
Is gradually unable to follow
written/spoken directions
Is gradually unable to use notes as
reminders
Often remembers later
Is usually able to follow
written/spoken directions
Is usually able to use notes as
reminders
 Is gradually unable to care for self Is usually able to care for self

With early detection, you can:

Get the maximum benefit from available treatments – You
can explore treatments that may provide some relief of
symptoms and help you maintain a level of independence longer.
You may also increase your chances of participating in clinical
drug trials that help advance research.
Learn more about treatments.
Learn more about clinical studies.

Have more time to plan for the future – A diagnosis of

Alzheimer's allows you to take part in decisions about care,
transportation, living options, financial and legal matters. You can
also participate in building the right care team and social support
network.
Learn more about planning ahead.

Help for you and your loved ones – Care and support services
are available, making it easier for you and your family to live the
best life possible with Alzheimer’s or dementia.
Learn how the Alzheimer's Association helps families.

When you see your doctor

Your doctor will evaluate your overall health and identify any
conditions that could affect how well your mind is working. Your
doctor may refer you to a specialist such as a:

• Neurologist – specializes in diseases of the brain and

nervous system
• Psychiatrist – specializes in disorders that affect mood or
the way the mind works
• Psychologist – has special training in testing memory and
other mental functions
• Geriatrician – specializes in the care of older adults and
Alzheimer's disease

• What is the AEDA

• The Alzheimer's Association has formed the Alzheimer's Early
Detection Alliance (AEDA) to help educate everyone about the
 warning signs of Alzheimer's, the importance of early detection, and
the resources available to help them. The Alzheimer's Association is
inviting companies and organizations to be part of the AEDA and
help us spread the word as widely as possible.

Risk Factors

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• Introduction
• Risk factors

• Risk factors you may be able to influence

Introduction
While scientists know Alzheimer’s disease involves progressive
brain cell failure, they have not yet identified any single reason
why cells fail. However, they have identified certain risk factors
that increase the likelihood of developing Alzheimer’s.

Back to top

Risk factors
 Age
The greatest known risk factor for Alzheimer’s is increasing age.
Most individuals with the disease are 65 or older. The likelihood of
developing Alzheimer’s doubles about every five years after age
65. After age 85, the risk reaches nearly 50 percent.

Family history
Another risk factor is family history. Research has shown that
those who have a parent, brother or sister, or child with
Alzheimer’s are more likely to develop Alzheimer’s. The risk
increases if more than one family member has the illness. When
diseases tend to run in families, either heredity (genetics) or
environmental factors or both may play a role.

Genetics (heredity)
Scientists know genes are involved in Alzheimer’s. There are two
categories of genes that can play a role in determining whether a
person develops a disease. Alzheimer genes have been found in
both categories:

1) Risk genes increase the likelihood of developing a

disease, but do not guarantee it will happen. Scientists have
so far identified one Alzheimer risk gene called apolipoprotein E-
e4 (APOE-e4).

APOE-e4 is one of three common forms of the APOE gene; the

others are APOE-e2 and APOE-e3. APOE provides the blueprint for
one of the proteins that carries cholesterol in the bloodstream.

Everyone inherits a copy of some form of APOE from each parent.

Those who inherit one copy of APOE-e4 have an increased risk of
developing Alzheimer’s. Those who inherit two copies have an
even higher risk, but not a certainty. Scientists do not yet know
how APOE-e4 raises risk. In addition to raising risk, APOE-e4 may
tend to make symptoms appear at a younger age than usual.

Experts believe there may be as many as a dozen other

Alzheimer risk genes in addition to APOE-e4.

2) Deterministic genes directly cause a disease,

guaranteeing that anyone who inherits them will develop
the disorder. Scientists have found rare genes that directly
 cause Alzheimer’s in only a few hundred extended families
worldwide.

When Alzheimer’s disease is caused by deterministic genes, it is

called “familial Alzheimer’s disease,” and many family members
in multiple generations are affected. True familial Alzheimer’s
accounts for less than 5 percent of cases.

Genetic tests are available for both APOE-e4 and the rare genes
that directly cause Alzheimer’s. However, health professionals do
not currently recommend routine genetic testing for Alzheimer’s
disease. Testing for APOE-e4 is sometimes included as a part of
research studies.

Back to top

Risk factors you may be able to influence

Age, family history and heredity are all risk factors we can’t
change. Now, research is beginning to reveal clues about other
risk factors we may be able to influence.

Head injury: There appears to be a strong link between serious

head injury and future risk of Alzheimer’s. Protect your head by
buckling your seat belt, wearing your helmet when participating
in sports, and “fall-proofing” your home.

Heart-head connection: Some of the strongest evidence links

brain health to heart health. Your brain is nourished by one of
your body’s richest networks of blood vessels. Every heartbeat
pumps about 20 to 25 percent of your blood to your head, where
brain cells use at least 20 percent of the food and oxygen your
blood carries.

The risk of developing Alzheimer’s or vascular dementia appears

to be increased by many conditions that damage the heart or
blood vessels. These include high blood pressure, heart disease,
stroke, diabetes and high cholesterol. Work with your doctor to
monitor your heart health and treat any problems that arise.

General healthy aging: Other lines of evidence suggest that

strategies for overall healthy aging may help keep the brain
 healthy and may even offer some protection against developing
Alzheimer’s or related diseases. Try to keep your weight within
recommended guidelines, avoid tobacco and excess alcohol, stay
socially connected, and exercise both your body and mind.

For more information about keeping your brain healthy as you

age, please see our Brain Health section.
Steps to Diagnosis

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• Finding the right doctor

• Understanding the problem
• Reviewing medical history
• Mental status tests
• Physical exam and diagnostic tests
• Neurological exam

• Brain imaging

Finding the right doctor

The first step in following up on symptoms is finding a doctor you
feel comfortable with. Alzheimer’s Association clients report they
 are most likely to be satisfied seeing someone who is well
informed about Alzheimer’s disease. Your local Alzheimer’s
Association can help you find the right doctor.

There is no single type of doctor who specializes in diagnosing

and treating memory loss or Alzheimer’s disease. Many people
contact their regular primary care physician or internist about
their concerns. Primary care doctors often oversee the diagnostic
process and provide treatment themselves.

In some cases, the primary care doctor may refer a patient to

one of the following specialists:

• A neurologist, who specializes in diseases of the brain and

nervous system
• A psychiatrist, who specializes in disorders that affect
mood or the way the mind works
• A psychologist with advanced training in testing memory,
concentration, problem solving, language and other mental
functions

Back to top

Understanding the problem

There is no single test that proves a person has Alzheimer’s. The
medical workup is designed to evaluate overall health and identify
any conditions that could affect how well the mind works.

Experts estimate a skilled physician can diagnose Alzheimer’s

with more than 90 percent accuracy. Doctors can almost always
determine that a person has dementia, but it may sometimes be
difficult to pin down the exact cause.

Be prepared for the doctor to ask:

• What kind of symptoms have you noticed?

• When did they begin?
• How often do they happen?
• Have they gotten worse?
 Dementia screening tests

An increasing number of test developers, health care facilities and

others are marketing dementia screening tests directly to
consumers. The Alzheimer's Association believes that home
screening tests can not and should not be used as a substitute for
a thorough examination by a skilled doctor. There is an
established diagnostic criteria that physicians adhere to when
evaluating someone for Alzheimer's disease.

Although dementia screening tests don't claim to offer a definitive

diagnosis, any test that plants the idea of a serious illness has the
potential to cause great psychological distress to the test taker.
The whole process of assessment and diagnosis should be carried
out within the context of an ongoing relationship with responsible
health care professionals.

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Reviewing medical history

The doctor will interview the person being examined or family
members to gather information about current and past illnesses.
The doctor will also obtain a history of medical conditions
affecting other family members, especially whether they may
have had Alzheimer’s disease or a related disorder.

It is helpful to bring a list of all the medications the person is

taking. The doctor will obtain a history of key medical conditions
affecting other family members, especially whether they may
have had Alzheimer's disease or related disorders.

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Mental status tests

Mental status testing gives the doctor a general idea of whether a
person:

• Is aware of having symptoms or feels nothing is wrong

• Knows the date, time and where he or she is
• Can remember a short list of words, follow instructions and
 do simple calculations

Mini-mental state exam (MMSE)

The mini-mental state examination (MMSE) is one of the tests

most commonly used to assess mental function. In the MMSE, a
health professional asks a patient a series of questions designed
to test a range of everyday mental skills.

Examples of questions include:

• Remember and repeat a few minutes later the names of

three common objects (for instance, horse, flower, penny)
• State the year, season, day of the week and date
• Count backward from 100 by 7s or spell “world” backwards
• Name two familiar objects present in the office as the
examiner points to them
• Identify the location of the examiner’s office (state, city,
street address, floor)
• Repeat a common phrase or saying after the examiner
• Copy a picture of two interlocking shapes
• Follow a three-part instruction, such as: take a piece of
paper in your right hand, fold it in half, and place it on the
floor

The maximum MMSE score is 30 points. A score of 20 - 24

suggests mild dementia, 13 - 20 suggests moderate dementia,
and less than 12 indicates severe dementia. On average, the
MMSE score of a person with Alzheimer’s declines about 2 - 4
points each year.

About the mini-cog

Another popular mental status test is the “mini-cog,” which

involves two tasks: (1) remembering and a few minutes later
repeating the names of three common objects, and (2) drawing a
face of a clock showing all 12 numbers in the right places and a
time specified by the examiner.

In addition to assessing mental status, the doctor will evaluate a

person’s sense of well-being to detect depression or other mood
disorders that can cause memory problems, loss of interest in
 life, and other symptoms that can overlap with dementia.

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Physical exam and diagnostic tests

The physician will

•Ask about diet, nutrition and use of alcohol.

• Review all medications. It is helpful to bring a list or the
containers of all medicines currently being taken, including
over-the-counter drugs and supplements.
• Check blood pressure, temperature and pulse.
• Listen to the heart and lungs.
• Collect samples of blood and urine.

Information from these tests can help identify other disorders

that may cause memory loss, confused thinking, trouble focusing
attention, or other symptoms similar to dementia. Such disorders
include:

• Anemia, malnutrition or certain vitamin deficiencies

• Excess use of alcohol
• Medication side effects
• Certain infections
• Diabetes
• Kidney or liver disease
• Thyroid abnormalities
• Problems with the heart, lung or blood vessels

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Neurological exam
The neurological examination is an important part of the physical.
Its goal is to assess the function of the brain and nervous system
to identify symptoms of brain disorders other than Alzheimer’s.

During the neurological exam, the physician may test:

• Reflexes
• Coordination and balance
 • Muscle tone and strength
• Eye movement
• Speech
• Sensation

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Brain imaging
New imaging technologies have revolutionized our understanding
of the structure and function of the living brain.

• Structural imaging provides information about the shape,

position or volume of brain tissue. Structural techniques
include magnetic resonance imaging (MRI) and computed
tomography (CT).
• Functional imaging reveals how well cells in various brain
regions are working by showing how actively the cells use
sugar or oxygen. Functional techniques include positron
emission tomography (PET) and functional MRI (fMRI).

Currently, a standard medical workup for Alzheimer’s disease

often includes structural imaging with MRI or, less frequently, CT.
These images are used primarily to detect tumors, evidence of
small or large strokes, damage from severe head trauma or a
buildup of fluid.

Promising areas for brain imaging research

Researchers are studying whether the use of MRI and other

imaging methods may be expanded to play a more direct role in
diagnosing Alzheimer’s. Many studies have shown that the brains
of people with Alzheimer’s shrink significantly as the disease
progresses.

Research has also shown that shrinkage in specific brain regions

may be an early sign of Alzheimer’s. However, scientists have not
yet agreed upon standardized values that would establish the
significance of a specific amount of shrinkage for any individual
person at a single point in time.

Research with PET and other functional imaging methods also

suggests that those with Alzheimer’s typically have reduced brain
 cell activity in certain regions. However, as with the shrinkage
detected by structural imaging, there is not yet enough
information to translate these general patterns of reduced activity
into diagnostic information about individuals.

At this time, PET is used primarily in research studies in hopes of

gaining further knowledge about its potential for wider use in
diagnosing Alzheimer’s and monitoring progression and response
to treatment.

Today, Medicare will cover a PET scan for Alzheimer’s only to help
distinguish the disease from frontotemporal dementia, a rare
related disorder that may cause dramatic loss of function in the
front and side regions of the brain.

Another promising area of functional imaging research focuses on

developing tracer compounds that will attach to key abnormal
brain deposits implicated in Alzheimer’s. For example, preliminary
data suggests that one such tracer, called Pittsburgh compound
B, may attach to beta-amyloid and “light up” in a PET scan.
Once testing is complete, the doctor will review results and share
conclusions.

A diagnosis of Alzheimer’s disease reflects a doctor’s best

judgment about the cause of a person’s symptoms. You may
want to ask the doctor to explain:

• Why the diagnosis is Alzheimer’s

• Where you or your loved one may be in the course of the
disease
• What to expect in the future

Find out if the doctor will manage care going forward and, if not,
who will be the primary doctor. The diagnosing doctor can then
schedule the next appointment or provide a referral.

A diagnosis of Alzheimer’s disease is life-changing for both

diagnosed individuals and those close to them. While there is
currently no cure, treatments are available that may help relieve
some symptoms. Research has shown that taking full advantage
of available treatment, care and support can make life better.
 Finding support
We are here to help you live with Alzheimer’s disease.

• Our 24/7 Helpline at 1.800.272.3900 provides information,

referrals and care consultation.
• Join our online community and share your experiences with
others who know what you are going through.
• See Living with Alzheimer's for tips to cope with the changes
you may be experiencing
• Your local Alzheimer’s Association offers programs and
services tailored to your needs.

Planning ahead
Planning for the future plays an important part in making life
better for those living with Alzheimer’s. Advance planning enables
individuals with Alzheimer’s to make their wishes about medical
care and living arrangements known. Knowing what to expect can
help foster ease of mind for all concerned.

You can plan for the right care by using the Alzheimer’s
Association CareFinder™. This Web guide helps individuals and
families make informed decisions when selecting a care provider
for home-based or residential care.

After you enter information about your situation, the guide gives
you a confidential, customized report with care recommendations
and questions to ask providers. The CareFinder guide will also
help you learn how to recognize good care, plan for care,
communicate with care providers and find local support.

Treatments

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Currently, there is no cure for Alzheimer's. But drug and non-

drug treatments may help with both cognitive and behavioral
symptoms.

Researchers are looking for new treatments to alter the course of

the disease and improve the quality of life for people with
dementia.

In this section:

• Standard Treatments
• Vitamin E
• Treatments for Sleep Changes
• Alternative Treatments

Standard Treatments

• Introduction
• Treatments for cognitive symptoms
• Treatments for behavioral symptoms
 • Talking with the doctor

• More information

Introduction
Health professionals often divide the symptoms of Alzheimer's
disease into "cognitive" and "behavioral and psychiatric"
categories.

• Cognitive symptoms affect memory, language, judgment,

planning, ability to pay attention and other thought
processes.
• Behavioral and psychiatric symptoms affect the way we feel
and act.

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Treatments for cognitive symptoms

The U.S. Food and Drug Administration (FDA) has approved two
types of medications to treat cognitive symptoms of Alzheimer's
disease. These drugs affect the activity of two different chemicals
involved in carrying messages between the brain's nerve cells.

1. Cholinesterase (KOH-luh-NES-ter-ays) inhibitors prevent

the breakdown of acetylcholine (a-SEA-til-KOH-lean), a chemical
messenger important for learning and memory.

These drugs:

• Support communication among nerve cells by keeping

acetylcholine levels high.
• On average, delay worsening of symptoms for 6 to 12
months for about half the people who take them. Some
experts believe a small percentage of people may benefit
more dramatically.

Three cholinesterase inhibitors are commonly prescribed:

Donepezil (Aricept), approved to treat all stages of

•
Alzheimer's disease.
• Rivastigmine (Exelon), approved to treat mild to moderate
 Alzheimer's.
• Galantamine (Razadyne), approved to treat mild to
moderate Alzheimer's.

2. Memantine (Namenda) works by regulating the activity of

glutamate, a different messenger chemical involved in learning
and memory.

Memantine:

• Was approved in 2003 for treatment of moderate to severe

Alzheimer's disease.
• Is currently the only drug of its type approved to treat
Alzheimer's.
• Temporarily delays worsening of symptoms for some people.
Many experts consider its degree of benefit is similar to the
cholinesterase inhibitors.

Treatments-at-a-glance

Generic Brand Approved For Side Effects

donepezil Aricept All stages Nausea,
vomiting, loss
of appetite and
increased
frequency of
bowel
movements.
galantamine Razadyne Mild to moderate Nausea,
vomiting, loss
of appetite and
increased
frequency of
bowel
movements.
memantine Namenda Moderate to severe Headache,
constipation,
confusion and
dizziness.
rivastigmine Exelon Mild to moderate Nausea,
 vomiting, loss
of appetite and
increased
frequency of
bowel
movements.
tacrine Cognex Mild to moderate Possible liver
damage,
nausea, and
vomiting.

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Treatments for behavioral and psychiatric

symptoms
For many individuals, Alzheimer's disease affects the way they
feel and act in addition to its impact on memory and other
thought processes. As with cognitive symptoms, the chief
underlying cause is progressive destruction of brain cells. In
different stages of Alzheimer's, people may experience:

• Physical or verbal outbursts

• General emotional distress
• Restlessness, pacing, shredding paper or tissues and yelling
• Hallucinations (seeing, hearing or feeling things that are not
really there)
• Delusions (firmly held belief in things that are not real)

Many diagnosed individuals and their families find these

symptoms the most challenging and distressing effects of the
disease. For more information about behaviors in Alzheimer's
disease, please see the Behaviors section.

There are two approaches to managing behavioral symptoms:

using medications specifically to control the symptoms or non-
drug strategies. Non-drug approaches should always be tried
first.

Non-drug approaches
 Steps to developing successful non-drug treatments include:

• Recognizing that the person is not just "acting mean or

ornery," but is having further symptoms of the disease
• Understanding the cause and how the symptom may relate
to the experience of the person with Alzheimer's
• Changing the person's environment to resolve challenges
and obstacles to comfort, security and ease of mind

Everyone who develops behavioral symptoms should receive a

thorough medical exam, especially if symptoms appear suddenly.
Even though the chief cause of behavioral symptoms is the effect
of Alzheimer's disease on the brain, an exam may reveal
treatable conditions that are contributing to the behavior.

Treatable conditions may include:

Drug side effects. Many people with Alzheimer's take

•
prescription medications for other health problems. Drug
side effects or interactions between drugs can sometimes
affect behavior.
• Physical discomfort. As the disease gets worse, those with
Alzheimer's have more and more difficulty communicating
about their experience. As a result, symptoms of common
illnesses may sometimes go undetected. Pain from
infections of the urinary tract, ear or sinuses may lead to
restlessness or agitation. Discomfort from a full bladder,
constipation, or feeling too hot or too cold may also be
expressed through behavior.
• Uncorrected problems with hearing or vision. These
can contribute to confusion and frustration and foster a
sense of isolation.

Factors in the environment may also trigger behaviors. Events or

changes in a person's surroundings may contribute to a sense of
uneasiness, or increase fear or confusion.

Situations affecting behavior may include:

• Moving to a new residence or nursing home

• Changes in the environment or caregiver arrangements
• Misperceived threats
 • Admission to a hospital
• Being asked to bathe or change clothes
• Fear and fatigue resulting from trying to make sense out of
an increasingly confusing world

Potential solutions

• Monitor personal comfort. Check for pain, hunger, thirst,

constipation, full bladder, fatigue, infections and skin
irritation. Maintain a comfortable room temperature.
• Avoid being confrontational or arguing about facts; instead,
respond to the feeling behind what is being expressed. For
example, if a person expresses a wish to go visit a parent
who died years ago, don't point out that the parent is dead.
Instead, say, "Your mother is a wonderful person. I would
like to see her too."
• Redirect the person's attention. Try to remain flexible,
patient and supportive.
• Create a calm environment. Avoid noise, glare, insecure
space, and too much background distraction, including
television.
• Simplify the environment, tasks and solutions.
• Allow adequate rest between stimulating events.
• Provide a security object or privacy.
• Equip doors and gates with safety locks.
• Remove guns.

Medications for behavioral symptoms

If non-drug approaches fail after they have been applied

consistently, introducing medications may be appropriate when
individuals have severe symptoms or have the potential to harm
themselves or others. Medications can be effective in some
situations, but they must be used carefully and are most effective
when combined with non-drug approaches.

Medications should target specific symptoms so their effects can

be monitored. In general, it is best to start with a low dose of a
single drug. Effective treatment of one core symptom may
sometimes help relieve other symptoms. For example, some
antidepressants may also help people sleep better. Individuals
taking medications for behavioral symptoms must be closely
monitored. People with dementia are susceptible to serious side
 effects, including stroke and an increased risk of death from
antipsychotic medications. Sometimes medications can cause an
increase in the symptom being treated. Without careful
evaluation, some medical providers will increase rather than
decrease the dose, putting the person at greater risk. Risk and
potential benefits of a drug should be carefully analyzed for any
individual.

When considering use of medications, it is important to

understand that no drugs are specifically approved by the U.S.
Food and Drug Administration (FDA) to treat behavioral and
psychiatric dementia symptoms. Some of the examples discussed
here represent “off label” use, a medical practice in which a
physician may prescribe a drug for a different purpose than the
ones for which it is approved.

The decision to use an antipsychotic drug needs to be considered

with extreme caution. A recent analysis shows that atypical
antipsychotics are associated with an increased risk of stroke and
death in older adults with dementia. The FDA has asked
manufacturers to include a “black box” warning about the risks
and a reminder that they are not approved to treat dementia
symptoms. The warning states: “Elderly patients with dementia-
related psychosis treated with atypical antipsychotic drugs are at
an increased risk of death compared to placebo.”

The analysis states that while risperidone and olanzapine are

useful in reducing aggression and risperidone reduces psychosis,
both drugs are associated with severe side effects. Despite some
efficacy, these drugs should not be used routinely with dementia
patients, unless the person is in severe distress or there is a
marked risk of harm.

Risks and potential benefits of a drug should be carefully

analyzed for any individual. Examples of medications commonly
used to treat behavioral and psychiatric symptoms of Alzheimer's
disease, listed in alphabetical order, include the following:

Antidepressant medications for low mood and irritability:

• citalopram (Celexa)
• fluoxetine (Prozac)
 • paroxeine (Paxil)
• sertraline (Zoloft)
• trazodone (Desyrel)

Anxiolytics for anxiety, restlessness, verbally disruptive behavior

and resistance:

• lorazepam (Ativan)
• oxazepam (Serax)

Antipsychotic medications for hallucinations, delusions,

aggression, agitation, hostility and uncooperativeness:

• aripiprazole (Abilify)
• clozapine (Clozaril)
• haloperidol (Haldol)
• olanzapine (Zyprexa)
• quetiapine (Seroquel)
• risperidone (Risperdal)
• ziprasidone (Geodon)

Research evidence as well as governmental warnings and

guidance regarding the use of antipsychotics indicate that
individuals with dementia should only use these medications
when:

1) their behavioral symptoms are due to mania or psychosis

2) the symptoms present a danger to the resident or others

3) the resident is experiencing inconsolable or persistent distress,

a significant decline in function or substantial difficulty receiving
needed care

Antipsychotic medications should not be used to sedate or

restrain persons with dementia. The minimum dosage should be
used for the minimum amount of time possible. Adverse side
effects require careful monitoring.

Although antipsychotics are the most frequently used medications

for agitation, some physicians may prescribe a seizure
medication/mood stabilizer, such as:

• carbamazepine (Tegretol)
 • divalproex (Depakote)

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Talking with the doctor

Talk to your doctor about what treatment may be right for you or
the person in your care. A medication's effectiveness, and the
side effects it may cause,,can vary from one person to the next.
For one individual, one drug may be more effective but have
greater side effects. For another person, the same drug may be
less effective but have no side effects.

Ask the doctor the following questions when you discuss any
treatments. They will not address all treatment needs, but the
answers to these questions will help you understand the options
and make informed decisions.

• What kind of assessment will you use to determine if the

drug is effective?
• How much time will pass before you will be able to assess
the drug's effectiveness?
• How will you monitor for possible side effects?
• What effects should we watch for at home?
• When should we call you?
• Is one treatment option more likely than another to interfere
with medications for other conditions?
• What are the concerns with stopping one drug treatment
and beginning another?

• At what stage of the disease would you consider it

appropriate to stop using the drug?
Vitamin E

Doctors sometimes prescribe vitamin E to treat Alzheimer’s

disease. One large federally funded study showed that vitamin E
slightly delayed loss of ability to carry out daily activities and
placement in residential care.

Scientists think vitamin E may help because it is an antioxidant, a

substance that may protect nerve cells from certain kinds of
 chemical wear and tear.

No one should use vitamin E to treat Alzheimer’s disease except

under the supervision of a physician. The doses used in the
federal study were relatively high, and vitamin E can negatively
interact with other medications, including those prescribed to
keep blood from clotting.
Treatments for Sleep Changes

• Introduction

• Treatments

Introduction
Many people with Alzheimer’s experience changes in their sleep
patterns. Scientists do not completely understand why this
happens. As with changes in memory and behavior, sleep
changes somehow result from the impact of Alzheimer’s on the
brain.

Many older adults without dementia also notice changes in their

sleep, but these disturbances occur more frequently and tend to
be more severe in Alzheimer’s. There is evidence that sleep
changes are more common in later stages of the disease, but
some studies have also found them in early stages.

Sleep changes in Alzheimer’s may include:

Difficulty sleeping. Many people with Alzheimer’s wake up more

often and stay awake longer during the night. Brain wave studies
show decreases in both dreaming and non-dreaming sleep
stages. Those who cannot sleep may wander, be unable to lie
still, or yell or call out, disrupting the sleep of their caregivers.

Daytime napping and other shifts in the sleep-wake cycle.

Individuals may feel very drowsy during the day and then be
unable to sleep at night. They may become restless or agitated in
the late afternoon or early evening, an experience often called
“sundowning.” Experts estimate that in late stages of Alzheimer’s,
individuals spend about 40 percent of their time in bed at night
awake and a significant part of their daytime sleeping. In extreme
cases, people may have a complete reversal of the usual daytime
wakefulness-nighttime sleep pattern.

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Treatment of sleep changes

A person experiencing sleep disturbances should have a thorough
medical exam to identify any treatable illnesses that may be
contributing to the problem. Examples of conditions that can
make sleep problems worse include:

• Depression
• Restless legs syndrome, a disorder in which unpleasant
“crawling” or “tingling” sensations in the legs cause an
overwhelming urge to move them
• Sleep apnea, an abnormal breathing pattern in which people
briefly stop breathing many times a night, resulting in poor
sleep quality

For sleep changes due primarily to Alzheimer’s disease, there are

non-drug and drug approaches to treatment. Most experts and
the National Institutes of Health (NIH) strongly encourage use of
non-drug measures rather than medication.

Studies have found that sleep medications generally do not

improve overall sleep quality for older adults. Use of sleep
medications is associated with a greater chance of falls and other
risks that may outweigh the benefits of treatment.

Non-drug treatments for sleep changes

Non-drug treatments aim to improve sleep routine and the

sleeping environment and reduce daytime napping. To create an
inviting sleeping environment and promote rest for a person with
Alzheimer’s:

• Maintain regular times for meals and for going to bed and
 getting up
• Seek morning sunlight exposure
• Encourage regular daily exercise, but no later than four
hours before bedtime
• Avoid alcohol, caffeine and nicotine
• Treat any pain
• If the person is taking a cholinesterase inhibitor (tacrine,
donepezil, rivastigmine or galantamine), avoid giving the
medicine before bed
• Make sure the bedroom temperature is comfortable
• Provide nightlights and security objects
• If the person awakens, discourage staying in bed while
awake; use the bed only for sleep
• Discourage watching television during periods of
wakefulness

Medications for sleep changes

In some cases, non-drug approaches fail to work or the sleep

changes are accompanied by disruptive nighttime behaviors. For
those individuals who do require medication, experts recommend
that treatment “begin low and go slow.”

The risks of sleep-inducing medications for older people who are

cognitively impaired are considerable. They include increased risk
for falls and fractures, confusion, and a decline in the ability to
care for oneself. If sleep medications are used, an attempt should
be made to discontinue them after a regular sleep pattern has
been established.

The type of medication prescribed by a doctor is often influenced

by behaviors that may accompany the sleep changes. Examples
of medications used to treat sleep changes include:

• Tricyclic antidepressants, such as nortriptyline and

trazodone
• Benzodiazepines, such as lorazepam, oxazepam and
temazepam
• “Sleeping pills” such as zolpidem, zaleplon and chloral
hydrate
• “Atypical” antipsychotics such as risperidone, onlanzapine
 and quetiapine

• Older “classical” antipsychotics such as haloperidol

Alternative Treatments

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• Introduction
• Concerns
• Coenzyme Q10
• Coral calcium
• Ginkgo biloba
• Huperzine A
• Omega-3 fatty acids
• Phosphatidylserine

• More information

Introduction
A growing number of herbal remedies, vitamins and other dietary
supplements are promoted as memory enhancers or treatments
for Alzheimer’s disease and related diseases.
Claims about the safety and effectiveness of these products,
however, are based largely on testimonials, tradition and a rather
small body of scientific research. The rigorous scientific research
required by the U.S. Food and Drug Administration (FDA) for the
approval of a prescription drug is not required by law for the
marketing of dietary supplements.

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Concerns about alternative therapies

Although many of these remedies may be valid candidates for
treatments, there are legitimate concerns about using these
drugs as an alternative or in addition to physician-prescribed
therapy:

• Effectiveness and safety are unknown. The maker of a

dietary supplement is not required to provide the FDA with
the evidence on which it bases its claims for safety and
effectiveness.
• Purity is unknown. The FDA has no authority over
supplement production. It is a manufacturer’s responsibility
to develop and enforce its own guidelines for ensuring that
its products are safe and contain the ingredients listed on
the label in the specified amounts.
• Bad reactions are not routinely monitored.
Manufacturers are not required to report to the FDA any
problems that consumers experience after taking their
products. The agency does provide voluntary reporting
channels for manufacturers, health care professionals, and
consumers, and will issue warnings about product when
there is cause for concern.
• Dietary supplements can have serious interactions
with prescribed medications. No supplement should be
taken without first consulting a physician.

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Coenzyme Q10
Coenzyme Q10, or ubiquinone, is an antioxidant that occurs
naturally in the body and is needed for normal cell reactions. This
compound has not been studied for its effectiveness in treating
 Alzheimer’s.

A synthetic version of this compound, called idebenone, was

tested for Alzheimer’s disease but did not show favorable results.
Little is known about what dosage of coenzyme Q10 is considered
safe, and there could be harmful effects if too much is taken.

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Coral calcium
“Coral” calcium supplements have been heavily marketed as a
cure for Alzheimer’s disease, cancer and other serious illnesses.
Coral calcium is a form of calcium carbonate claimed to be
derived from the shells of formerly living organisms that once
made up coral reefs.
In June 2003, the Federal Trade Commission (FTC) and the Food
and Drug Administration (FDA) filed a formal complaint against
the promoters and distributors of coral calcium. The agencies
state that they are aware of no competent and reliable scientific
evidence supporting the exaggerated health claims and that such
unsupported claims are unlawful.

Coral calcium differs from ordinary calcium supplements only in

that it contains traces of some additional minerals incorporated
into the shells by the metabolic processes of the animals that
formed them. It offers no extraordinary health benefits. Most
experts recommend that individuals who need to take a calcium
supplement for bone health take a purified preparation marketed
by a reputable manufacturer.

See also the FDA/FTC press release on the coral calcium

complaint.

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Ginkgo biloba
Ginkgo biloba is a plant extract containing several compounds
that may have positive effects on cells within the brain and the
body. Ginkgo biloba is thought to have both antioxidant and anti-
 inflammatory properties, to protect cell membranes and to
regulate neurotransmitter function. Ginkgo has been used for
centuries in traditional Chinese medicine and currently is being
used in Europe to alleviate cognitive symptoms associated with a
number of neurological conditions.

However, results of a large, multicenter Phase III study published

in the Journal of the American Medical Association (November
19, 2008) showed that gingko was no better than placebo in
delaying changes in memory, thinking and personality and had no
impact on the development of dementia and Alzheimer’s.

The Gingko Evaluation and Memory (GEM) Study enrolled 3,000

individuals age 75 or older who either had no dementia or mild
cognitive impairment. Participants were randomly assigned to
receive twice daily doses of either a placebo or 120 milligrams of
gingko biloba extract. They were followed up every six months for
six years.

Researchers found no statistical difference in dementia or

Alzheimer’s rates between the groups. Among those receiving
gingko, 277 developed dementia. Among those receiving placebo,
246 developed dementia. Mortality rates were also similar.

According to the researchers, an effect may have been observed

if the study was longer because it takes many years to progress
from the initial brain changes of Alzheimer’s to the clinical
symptoms of dementia. The research team intends to conduct a
follow-up analysis of brain function and structure in a subset of
study participants using magnetic resonance imaging and
positron emission tomography scans.

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Huperzine A
Huperzine A (pronounced HOOP-ur-zeen) is a moss extract that
has been used in traditional Chinese medicine for centuries. It
has properties similar to those of cholinesterase inhibitors, one
class of FDA-approved Alzheimer medications. As a result, it is
promoted as a treatment for Alzheimer's disease.
 Evidence from small studies shows that the effectiveness of
huperzine A may be comparable to that of the approved drugs. In
Spring 2004, the National Institute on Aging (NIA) launched the
first large U.S. clinical trial of huperzine A as a treatment for mild
to moderate Alzheimer’s disease.

Because currently available formulations of huperzine A are

dietary supplements, they are unregulated and manufactured
with no uniform standards. If used in combination with FDA-
approved Alzheimer drugs, an individual could increase the risks
of serious side effects.

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Omega-3 fatty acids

Omega-3s are a type of polyunsaturated fatty acid (PUFA).
Research has linked certain types of omega-3s to a reduced risk
of heart disease and stroke.

The U.S. Food and Drug Administration (FDA) permits

supplements and foods to display labels with “a qualified health
claim” for two omega-3s called docosahexaneoic acid (DHA) and
eicosapentaenoic acid (EPA). The labels may state, “Supportive
but not conclusive research shows that consumption of EPA and
DHA omega-3 fatty acids may reduce the risk of coronary heart
disease,” and then list the amount of DHA or EPA in the product.
The FDA recommends taking no more than a combined total of 3
grams of DHA or EPA a day, with no more than 2 grams from
supplements.

Research has also linked high intake of omega-3s to a possible

reduction in risk of dementia or cognitive decline. The chief
omega-3 in the brain is DHA, which is found in the fatty
membranes that surround nerve cells, especially at the
microscopic junctions where cells connect to one another.

A Jan. 25, 2006, literature review by the Cochrane Collaboration

found that published research does not currently include any
clinical trials large enough to recommend omega-3 supplements
to prevent cognitive decline or dementia. But the reviewers found
enough laboratory and epidemiological studies to conclude this
 should be a priority area for further research.

According to the review, results of at least two larger clinical trials

are expected in 2008. The Cochrane Collaboration is an
independent, nonprofit organization that makes objective
assessments of available evidence on a variety of issues in
treatment and health care.

Theories about why omega-3s might influence dementia risk

include their benefit for the heart and blood vessels; anti-
inflammatory effects; and support and protection of nerve cell
membranes. There is also preliminary evidence that omega-3s
may also be of some benefit in depression and bipolar disorder
(manic depression).

A report in the April 2006 Nature described the first direct

evidence for how omega-3s might have a helpful effect on nerve
cells (neurons). Working with laboratory cell cultures, the
researchers found that omega-3s stimulate growth of the
branches that connect one cell to another. Rich branching creates
a dense “neuron forest,” which provides the basis of the brain’s
capacity to process, store and retrieve information.

See also the 2004 FDA press release announcing extension of the
qualified health claim for omega-3s and coronary heart disease
from supplements to foods.

Back to top

Phosphatidylserine
Phosphatidylserine (pronounced FOS-fuh-TIE-dil-sair-een) is a
kind of lipid, or fat, that is the primary component the
membranes that surround nerve cells. In Alzheimer’s disease and
similar disorders, nerve cells degenerate for reasons that are not
yet understood. The theory behind treatment with
phosphatidylserine is its use may shore up the cell membrane
and possibly protect cells from degenerating.

The first clinical trials with phosphatidylserine were conducted

 with a form derived from the brain cells of cows. Some of these
trials had promising results. However, most trials were with small
samples of participants.

This line of investigation came to an end in the 1990s over

concerns about mad cow disease. There have been some animal
studies since then to see whether phosphatidylserine derived
from soy may be a potential treatment. A report was published in
2000 about a clinical trial with 18 participants with age-
associated memory impairment who were treated with
phosphatidylserine. The authors concluded that the results were
encouraging but that there would need to be large carefully
controlled trials to determine if this could be a viable treatment.

1. Three pounds, three parts

Your brain is your most powerful

organ, yet weighs only about three
pounds. It has a texture similar to firm
jelly.

It has three main parts:

1. The cerebrum fills up most

of your skull. It is involved in
remembering, problem solving,
thinking, and feeling. It also controls
movement.
2. The cerebellum sits at the
back of your head, under the
cerebrum. It controls coordination
and balance.

3. The brain stem sits beneath

your cerebrum in front of your
cerebellum. It connects the brain to
the spinal cord and controls
automatic functions such as
breathing, digestion, heart rate and
blood pressure.
 2. Supply lines

Your brain is nourished by one of

your body's richest networks of
blood vessels.

With each heartbeat, arteries carry

about 20 to 25 percent of your
blood to your brain, where billions
of cells use about 20 percent of the
oxygen and fuel your blood carries.

When you are thinking hard, your

brain may use up to 50 percent of
the fuel and oxygen.

The whole vessel network

includes veins and capillaries in
addition to arteries.

3. The cortex: "Thinking wrinkles"

Your brain’s wrinkled surface is a spe
outer layer of the cerebrum called the
Scientists have “mapped” the cortex b
identifying areas strongly linked to ce
functions.

Specific regions of the cortex:

• Interpret sensations from you

body, and sights, sounds and smell
the outside world.

• Generate thoughts, solve

problems and make plans.

• Form and store memories.

• Control voluntary movemen

4. Left brain/right brain
Your brain is divided into r
left halves. Experts are not
how the "left brain" and "ri
brain" may differ in functio
except:

• The left half contr

movement on the body's
side.

• The right half con

the body's left side.

• In most people, th
language area is chiefly o
the left.

Link
Brain Basics Alzheimer's Disease and the Brain Act
Brain Tour 1234567 8 9 10 11 12 13 14 15 16 17
Cre

5. The neuron forest

The real work of your brain goes on in

individual cells. An adult brain contains
about 100 billion nerve cells, or neurons,
with branches that connect at more than
100 trillion points. Scientists call this dense,
branching network a "neuron forest."

Signals traveling through the neuron

forest form the basis of memories,
thoughts, and feelings.

Neurons are the chief type of cell destroyed

by Alzheimer's disease.
© 2009 Alzheimer's Association. All rights reserved.
www.alz.org | 800.272.3900
If you are a member of the media and want to request permission to

reproduce images, contact media@alz.org. If you are a member of the

general public, contact brandhelp@alz.org.

6. Cell signaling
Signals that form memories and
thoughts move through an
individual nerve cell as a tiny
electrical charge.

Nerve cells connect to one

another at synapses. When a
charge reaches a synapse, it may
trigger release of tiny bursts of
chemicals called
neurotransmitters. The
neurotransmitters travel across
the synapse, carrying signals to
other cells. Scientists have
identified dozens of
neurotransmitters.

Alzheimer's disease disrupts both

the way electrical charges travel
within cells and the activity of
neurotransmitters.

. Signal coding
 100 billion nerve cells… 100
trillion synapses… dozens of
neurotransmitters… This
“strength in numbers” provides
your brain’s raw material. Over
time, our experiences create
patterns in signal type and
strength. These patterns of
activity explain how, at the
cellular level, our brains code our
thoughts, memories, skills and
sense of who we are.

The positron emission

tomography (PET) scan on the
left shows typical patterns of
brain activity associated with:

• Reading words

• Hearing words

• Thinking about words

• Saying words

Activity is highest in red areas

and then decreases through the
other colors of the rainbow from
yellow to blue-violet.

Specific activity patterns change

throughout life as we meet new
people, have new experiences and
acquire new skills. The patterns
also change when Alzheimer’s
disease or a related disorder
disrupts nerve cells and their
connections to one another.

8. Alzheimer’s changes the

whole brain
Alzheimer’s disease leads to
nerve cell death and tissue loss
throughout the brain. Over
time, the brain shrinks
dramatically, affecting nearly
all its functions.
 These images show:

• A brain without the

disease

• A brain with
advanced Alzheimer’s

• How the two brains

compare

. More brain changes

Here is another view of how

massive cell loss changes the whole
brain in advanced Alzheimer's
disease. This slide shows a
crosswise "slice" through the
middle of the brain between the
ears.

In the Alzheimer brain:

• The cortex shrivels up,

damaging areas involved in
thinking, planning and
remembering.

• Shrinkage is especially
severe in the hippocampus, an
area of the cortex that plays a
key role in formation of new
memories.

• Ventricles (fluid-filled
spaces within the brain) grow
larger.

10. Under the microscope

 Scientists can also see the terrible
effects of Alzheimer's disease
when they look at brain tissue
under the microscope:

• Alzheimer tissue has

many fewer nerve cells and
synapses than a healthy brain.

• Plaques, abnormal
clusters of protein fragments,
build up between nerve cells.

• Dead and dying nerve

cells contain tangles, which
are made up of twisted strands
of another protein.

Scientists are not absolutely sure

what causes cell death and tissue
loss in the Alzheimer brain, but
plaques and tangles are prime
suspects.

11. More about plaques

Plaques form when protein

pieces called beta-amyloid
(BAY-tuh AM-uh-loyd) clump
together. Beta-amyloid comes
from a larger protein found in the
fatty membrane surrounding
nerve cells.

Beta-amyloid is chemically
"sticky" and gradually builds up
into plaques.

The most damaging form of

beta-amyloid may be groups of
a few pieces rather than the
plaques themselves. The small
clumps may block cell-to-cell
signaling at synapses. They may
also activate immune system
 cells that trigger inflammation
and devour disabled cells.

12. More about tangles

Tangles destroy a vital cell

transport system made of
proteins. This electron
microscope picture shows a cell
with some healthy areas and
other areas where tangles are
forming.

In healthy areas:

• The transport system is

organized in orderly parallel
strands somewhat like railroad
tracks. Food molecules, cell
parts and other key materials
travel along the “tracks.”
• A protein called tau
(rhymes with wow) helps the
tracks stay straight.

In areas where tangles are

forming:

• Tau collapses into

twisted strands called
tangles.
• The tracks can no
longer stay straight. They fall
apart and disintegrate.

• Nutrients and other

essential supplies can no longer
move through the cells, which
eventually die.

13. Progression through the brain

 Plaques and tangles (shown in
the blue-shaded areas) tend to
spread through the cortex in a
predictable pattern as
Alzheimer’s disease progresses.

The rate of progression varies

greatly. People with Alzheimer’s
live an average of eight years, but
some people may survive up to
20 years. The course of the
disease depends in part on age at
diagnosis and whether a person
has other health conditions.

• Earliest Alzheimer's –
changes may begin 20 years
or more before diagnosis.

• Mild to moderate
Alzheimer stages – generally
last from 2 - 10 years.

• Severe Alzheimer’s –
may last from 1 - 5 years.

14. Earliest Alzheimer stages

 In the earliest stages, before
symptoms can be detected with
current tests, plaques and tangles
begin to form in brain areas
involved in:

• Learning and memory

• Thinking and planning

15. Mild to moderate

Alzheimer's
In mild to moderate stages, brain
regions important in memory and
thinking and planning develop
more plaques and tangles than
were present in early stages. As a
result, individuals develop
problems with memory or
thinking serious enough to
interfere with work or social life.
They may also get confused and
have trouble handling money,
expressing themselves and
organizing their thoughts. Many
people with Alzheimer’s are first
diagnosed in these stages.

Plaques and tangles also spread to

areas involved in:

• Speaking and
understanding speech

• Your sense of where

your body is in relation to
objects around you
 As Alzheimer’s progresses,
individuals may experience
changes in personality and
behavior and have trouble
recognizing friends and family
members.

16. Severe Alzheimer's disease

In advanced Alzheimer’s
disease, most of the cortex is
seriously damaged. The brain
shrinks dramatically due to
widespread cell death.
Individuals lose their ability to
communicate, to recognize
family and loved ones and to
care for themselves.

Clinical Studies

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• Introduction
• Consider participating
• How clinical trials work
• How to find a study

• More information

Introduction
Over the last 15 years, scientists have made enormous strides in
understanding how Alzheimer’s disease affects the brain. Many of
these recent insights point toward promising new strategies for
treatment, prevention and diagnosis.

Following successful laboratory work or animal studies, new

treatments must undergo clinical studies (testing in human
volunteers, also called clinical trials). More than 100 clinical
studies are now recruiting participants with and without
Alzheimer’s disease, related diseases or memory loss to help test
these exciting new approaches.

Back to top

Reasons to consider participating

You can make a difference! Clinical studies are the engine that
powers medical progress. Scientists work constantly to find better
ways to treat diseases. Improved treatments can never become a
reality without testing in human volunteers. No one ever chooses
to become ill, but anyone can consider helping to advance
knowledge about an illness affecting them or someone close to
them.

There is reason for optimism about experimental

 treatments. No investigational treatment advances to clinical
testing unless there is strong evidence indicating it will be as
good or better than currently available therapies

Every study matters. Every clinical study contributes valuable

knowledge, whether or not the treatment works as hoped.

Participants receive a high standard of care. All participants

receive regular care related to the study and opportunities to talk
to study staff. Research shows that people involved in studies
tend to do somewhat better than people in a similar stage of their
disease who are not enrolled, regardless of whether the
experimental treatment works. Scientists believe this advantage
may be due to the general high quality of care provided during
clinical studies.

Back to top

How clinical trials work

Studies proceed in “phases”

The U.S. Food and Drug Administration (FDA) has established a

rigorous sequence of testing for experimental drugs. The system
gradually builds evidence for a drug’s effectiveness and
determines that a drug has an acceptable “safety profile” (that is,
the risks associated with its use are reasonable, given its
potential benefit). Experimental drugs must perform well enough
in each phase to be allowed to progress to the next one.

• Preclinical studies in laboratories establish a scientific

basis for believing a drug is reasonably safe and may be
effective.
• Phase I trials, the first stage of human testing, typically
enroll fewer than 100 volunteers. These studies are
primarily concerned with assessing risks and side effects
associated with a drug.
• Phase II trials enroll up to a few hundred volunteers with
the condition the drug is designed to treat. These studies
provide further information about safety and focus on
determining the best dose of a drug. Scientists also watch
for signs of effectiveness, but Phase II trials are generally
 too small to provide clear evidence about benefit.
• Phase III trials enroll several hundred to thousands of
volunteers, often at multiple study sites nationwide. They
provide the chief evidence for safety and effectiveness that
the FDA will consider in deciding whether to approve a drug.
• Phase IV trials, also called post-marketing studies, are
often required by FDA after a drug is approved. The trial
sponsor must monitor the health of individuals taking the
drug to gain further insight into its long-term safety and
effectiveness and the best way to use it.

Back to top

Designed for accuracy

Scientists have learned that people can sometimes feel better,
and even have improved results on medical tests, just because
they believe a treatment is helping them. Doctors can also
convince themselves a treatment is working because they care
about their patients and want to help them get better.

There are two main strategies to reduce the likelihood that hopes
and beliefs will affect the outcome of clinical studies:

1) Trials are “placebo-controlled.” This means that some

study participants are randomly chosen by a computer to receive
the experimental treatment and some receive a “placebo” (an
inactive, look-alike treatment).

2) Trials are “double-blinded.” This means that both

participants and study staff are “blind” (unaware) about who is
getting the drug and who is getting the placebo.

Some studies are designed so the group of participants getting

the treatment is larger than the group receiving the placebo. And
some studies can be designed so all participants get the
treatment for part of the study.

Back to top

Safety behind the scenes

 Although participants and study staff don’t know who’s getting
the drug and who’s getting the placebo, most trials have a
separate, independent Data Safety and Monitoring Committee
with access to this information. Committee members regularly
analyze data behind the scenes and step in if they notice any
worrisome patterns of serious side effects in drug recipients.

Back to top

Informed consent
Participating in research is a big step. Informed consent is the
process of learning key facts about a study before deciding
whether to volunteer. The FDA requires potential participants to
be given complete information about the study in writing. Study
staff also meet personally with each potential participant to
explain risks and possible benefits and answer any questions.
People who decide to join the study must sign the informed
consent form.

Individuals who are invited to participate in a study are not

required to do so. Participants are also free to leave a study at
any time.

Back to top

Matching participants to studies

Enrolling the right participants helps researchers maximize the
likelihood of accurately measuring the effect of an experimental
treatment. Some drugs, like antibiotics for an infection, have an
obvious effect that is easy to detect.

It is often more challenging to assess the impact of drugs for

chronic, serious diseases, including Alzheimer’s and related
diseases. To eliminate certain factors that make it harder to
assess a treatment, researchers define “inclusion and exclusion
criteria” for each clinical study. Examples of these criteria include:

• Limiting participants to a certain age range

• Requiring participants to be in a certain stage of the disease
• Not allowing health conditions other than the one being
 studied
• Not permitting use of certain other medications
• Requiring participation of a caregiver or “study partner”

Back to top

How to find a study near you

If you would like to consider participating in research, please see
our Clinical Trials Index. Your local Alzheimer’s Association may
be aware of additional opportunities. You may also call our 24/7
Helpline at 1.800.272.3900.

2007: The Year in Alzheimer Science

• Introduction
• Promoting research and supporting
individuals with Alzheimer's
• Focus on prevention
• Research advances span the spectrum
• Caring for the caregiver
• Association expands research funding

• More information

Introduction
The year 2007 entered the history books as a period of
tremendous advances in Alzheimer research. These advances
occurred on all fronts, encompassing areas as diverse as genetic
risk factors for Alzheimer's, imaging studies to identify
Alzheimer's in the living brain and blood tests that may one day
be used to diagnose Alzheimer's.

As the largest private, nonprofit funding organization for

Alzheimer research, the Alzheimer's Association played a key and
highly visible role in nurturing research. This role included not
only providing more than $21 million in funding for research
grants, but also launching the Clinical Studies Initiative to explore
ways to improve recruitment and retention of clinical study
participants. In addition, the Association brought together
 researchers from around the world at the International
Conference on Prevention of Dementia and convened two
Research Roundtable meetings to spur collaborations in the field.

These research efforts paint only part of the picture of the

Association's accomplishments in 2007. Many of the Association's
other accomplishments, such as the introduction of the
Champions Campaign and publication of the inaugural issue of
Alzheimer's Disease Facts and Figures, feed into the Association's
broader research efforts by increasing awareness of both the
impact of the disease and the urgent need for escalated national
funding to combat it.

Back to top

Promoting research and supporting individuals

with Alzheimer's who help make it possible
Clinical studies are the basis for advancement of knowledge in all
areas of medicine, but these studies are sometimes hampered by
difficulty in recruiting individuals to participate. To better
understand the issues at play when clinical study participation is
being considered, the Alzheimer's Association in April 2007
launched the Clinical Studies Initiative.

The first stage of the initiative was the implementation of a nine-

month pilot program conducted at five Alzheimer's Association
chapters (Providence, R.I.; Atlanta, Ga.; Indianapolis, Ind.;
Tulsa, Okla.; and Mountain View, Calif.). The program included
physician market research, physician outreach and efforts to
increase consumer awareness. Because physicians' opinions
about clinical studies can greatly influence individuals' decisions
about participation, market research assessed physicians'
attitudes toward studies, their knowledge of the local research
environment and reasons for previous reluctance to refer
individuals to clinical studies. Based on market research data, the
Association began physician outreach efforts to foster positive
attitudes toward clinical studies and generate increased referrals
to studies. At the end of 2007, data collection was being
completed and analysis of data undertaken.
 While the scientific community recognizes the pivotal role that
research participants play in advancing knowledge, the
Alzheimer's Association's commitment extends beyond promoting
that role to supporting the myriad needs of individuals with
Alzheimer's. Beginning July 28, 2007, the Association hosted the
first of four town hall meetings across the country to give people
living with the early stages of the disease the opportunity to
discuss issues they face and share helpful resources, programs
and services. Part of the Association's Early Stage Initiative,
these town hall meetings gave the Association and wider public
the opportunity to learn from those who are still able to advocate
for themselves. A "virtual" town hall meeting Web site was
developed to ensure the widest possible access to the valuable
perspectives shared.

The Alzheimer's Association took its commitment to individuals

with Alzheimer's even further in 2007 when it asked the U.S.
Food and Drug Administration (FDA) to give those directly
affected by Alzheimer's a more active role in the review and
approval of new drugs. In November the FDA expanded its
Patient Consultant and Patient Representative Programs to
include individuals in the early stages of Alzheimer's disease and
their caregivers. "People who are living with this terrible disease
have much to offer to the pharmaceutical industry, researchers
and government regulators, and their voices must be heard," said
Harry Johns, Alzheimer's Association president and CEO.

Back to top

Conference and brain health 'Road Map' focus on

prevention
More than 1,000 scientists, physicians and policymakers gathered
in Washington, D.C., June 9–12, 2007, at the second Alzheimer's
Association International Conference on Prevention of Dementia.
The 250-plus presentations addressed topics including emerging
diagnostic strategies, drug discovery, risk factors and
experimental therapies in clinical trials. During the conference the
Centers for Disease Control and Prevention (CDC) and the
Alzheimer's Association released the first National Public Health
 Road Map to Maintaining Cognitive Health.

Road Map
The Road Map highlights the importance of maintaining and
improving cognitive health to the overall health of the nation.
CDC Director Julie L. Gerberding, M.D., M.P.H., told the
gathering, "By embracing cognitive health as a priority issue,
legislators and the public health community would be mobilized to
study, identify and implement effective interventions that
preserve it. Our challenge is to offer a coordinated and unified
national effort. The Road Map meets that challenge by laying out
a shared vision that builds on the foundation of the work done to
date and shapes the work of the future."

The Road Map, available at http://www.cdc.gov/, provides

strategies for assessing public perceptions about cognitive health,
recommends particular actions to be taken to support cognitive
health and calls for additional research to better understand the
risk factors for cognitive decline and to design interventions to
prevent it.

Treatment horizon
In the meantime, updates on research under way were much
anticipated highlights of the conference. Many of the updates
focused on anti-amyloid therapies. These are therapies that either
reduce the production of the protein beta-amyloid that forms the
hallmark plaques of Alzheimer's or that increase the clearance of
beta-amyloid from the brain.

The makers of Alzhemed (Neurochem) announced that the U.S.

clinical trial of the drug had been halted due to high data
variations among trial sites that had invalidated the statistical
model for evaluating the drug, which was designed to block
aggregation of beta-amyloid into plaques. The clinical trial had
been carried out at 67 sites and involved 1,052 individuals with
Alzheimer's. Neurochem hoped to develop a new statistical model
to lessen the impact of site variations, but in late August revealed
that the FDA had deemed trial results inconclusive. The European
trial, however, was continued until November, when it too was
halted.

Myriad, the makers of Flurizan, reported results of a 12-month

follow-on study to a Phase II trial. Flurizan reduces beta-amyloid
by changing the activity of an enzyme involved in its production.
After 24 months of treatment, people in the mildest stages of
Alzheimer's who received the highest drug dose showed
significant stabilization or improvement in cognition and function.
Phase III studies were begun.

A Phase III study was also planned for LY450139, made by Lilly.
Results of Phase II studies showed that the gamma-secretase
inhibitor decreased beta-amyloid levels in both blood and spinal
fluid.

Conference attendees also heard an update on AAB-001

(Bapineuzumab), made by Elan and Wyeth. Development of the
drug was informed by preceding trials of the companies' drug AN-
1792, the first anti-amyloid drug to reach clinical trials. A Phase
II trial of AN-1792, delivered as a vaccine, was stopped in 2002
when 6 percent of study participants experienced brain
inflammation. Researchers continued to collect data on
participants and found that those who developed the highest
levels of anti-amyloid antibodies appeared to have benefited from
the vaccine. While AN-1792 was an "active vaccine" designed to
stimulate production of beta-amyloid antibodies in participants,
Bapineuzumab is a "passive vaccine" that delivers antibodies
against beta-amyloid. The drug is expected to move into Phase
III trials in 2008.

Back to top

Alzheimer research advances span the spectrum of

approaches
In addition to the research news presented at the International
Conference on Prevention of Dementia, 2007 yielded advances
that underscore the vast number of approaches taken by
investigators to better understand Alzheimer's.

SORL1
In the January 14, 2007, online Nature Genetics, researchers
 described results of a study implicating the gene SORL1 in late-
onset Alzheimer's disease. The gene, also known as SORLA
(sortilin-related, low-density lipoprotein receptor class A repeat-
containing protein), is one of several involved in a cellular sorting
process that sends amyloid precursor protein (APP) down one of
two paths: a path in which it is recycled or a path that moves it
to cell structures called endosomes where the enzymes beta- and
gamma-secretase cut it apart, freeing the beta-amyloid peptide
component of APP to leave the brain cell, combine with additional
beta-amyloid and potentially form the amyloid plaques of
Alzheimer's.

When researchers investigated the genes involved in APP sorting,

only SORL1 was associated with an increased risk of Alzheimer's.
The association between SORL1 and Alzheimer's was statistically
significant in six of nine cohorts. The study results were based on
genetic information from more than 6,800 individuals, 48 percent
of whom had Alzheimer's. Researchers used single-letter changes
in gene sequence (called SNPs for single nucleotide
polymorphisms) to track SORL1 genes and found that Caucasians
with Alzheimer's had one SNP, while African-Americans, Hispanics
and Israeli Arabs with Alzheimer's had a different one. Their next
step is to examine the areas around the SNPs to try to identify
specific genetic variations that might lead to Alzheimer's.

PET-PIB
An established technology for identifying Alzheimer's in the living
brain will be an invaluable tool for early diagnosis of the disease
and monitoring the effects of drugs designed to stop or slow its
progression. Study results published in the March 2007 issue of
Archives of Neurology demonstrated that significant strides are
being made toward that goal. The article describes the first
postmortem study of an individual with dementia who, before
death, had undergone positron emission tomography (PET) after
injection of Pittsburgh compound B (PIB), a radioactive dye.
Because Alzheimer's can now only be definitively diagnosed on
autopsy, a postmortem comparison of amyloid distribution was
necessary to confirm the accuracy of PET-PIB. The study showed
that the distribution of amyloid at autopsy matched the overall
distribution on PET-PIB. If the accuracy of PET-PIB is replicated in
additional, large studies, it could enable a definitive diagnosis of
 Alzheimer's in the living brain.

Protein patterns
The impact of an even simpler test for Alzheimer's, such as a
blood test, would be enormous. Researchers reported taking a
step in that direction in an article appearing October 15, 2007, in
the online Nature Medicine. They studied 120 proteins involved in
cell-to-cell communication, looking for patterns that differed
between people with and without Alzheimer's. They found that as
few as 18 proteins were needed to identify an Alzheimer's-specific
pattern. Among the 92 study volunteers, the protein pattern
identified with 90 percent accuracy those who had clinically
diagnosed Alzheimer's. In 47 volunteers with mild cognitive
impairment, the pattern accurately identified 91 percent of
volunteers who would go on to develop Alzheimer's during the
follow-up period.

This is only one of several tests of this type in development.

Further research is needed to determine their accuracy in large,
diverse patient populations. But with every study, whether it
revolves around genetics, imaging, blood tests or an array of
other approaches, the scientific community takes a step closer to
uncovering the causes of and potential treatments for
Alzheimer's.

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Caring for the caregiver

While most basic science and clinical research in Alzheimer's
focuses on individuals with the disease, a distinct body of
research has developed around Alzheimer caregivers as well.
Among the journals publishing articles on caregivers in 2007 were
the Journal of Immunology and American Journal of Geriatric
Psychiatry. In its September 15 issue, the former included an
article describing the physical toll of being an Alzheimer
caregiver. Comparing 41 caregivers with 41 noncaregivers,
researchers found that Alzheimer caregivers had shorter
telomeres than noncaregivers. Telomeres are the genetic material
at the end of chromosomes that promote error-free cell division.
Shortening of telomeres is a natural part of aging, but caregivers'
 telomeres were shortened to an extent comparable to four to
eight years of aging beyond the shortening found in the control
group. They also had fewer immune system T cells and more
inflammation-promoting proteins.

Geriatric Psychiatry published results of a study testing an

intervention for Alzheimer caregivers. In its September issue, the
journal describes the effect of extra counseling and support
versus standard support in 406 caregivers. Half the caregivers
had six sessions of individual and family counseling, participated
in support groups and received telephone counseling as needed.
The other half received help when they asked for it, but not
formal counseling sessions. Those in the first group reported
better physical health than did those in the second group. The
effect began within four months of the start of the study and
continued for more than a year.

Throughout its 27-year history, the Alzheimer's Association has

led the way in supporting and educating individuals with
Alzheimer's and caregivers alike, and 2007 was no exception.
From August 26 to 29, 2007, the Association held its 15th annual
Dementia Care Conference, providing care professionals with the
opportunity to connect with peers from around the country, learn
from renowned aging experts and participate in educational
programs tailored to their unique needs. During the conference
the Association released its Dementia Care Practice
Recommendations for Assisted Living Residences and Nursing
Homes: Phase 3, End-of-Life Care, the third in a series of
recommendations. These most recent recommendations focus on
improving the end-of-life experience for people with Alzheimer's
and other forms of dementia by offering concrete suggestions for
addressing issues pertinent to this population. The
recommendations were the results of collaborations among
Association staff members, representatives of more than 30
national associations and other experts.

"Underlying the…recommendations is a person-centered approach

to dementia care, which involves tailoring care to the abilities and
changing needs of each resident," said Peter Reed, Ph.D., senior
director of programs for the Association. Added Jane Tilly,
Dr.P.H., director of quality care advocacy for the Association,
"Our highly collaborative, consensus-based process ensures that
the recommendations represent the best dementia care practices
and…are practical so nursing homes and assisted living
residences can incorporate them into the daily care routines of
their residents."

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Alzheimer's Association expands research funding

In the face of decreased federal funding for Alzheimer research,
the Alzheimer's Association stepped up its efforts to provide
financial support to investigators through its 2007 grants
program. The Association awarded more than $21 million for 109
research projects from a competitive field of 639 applications
from 42 states and 27 countries. Since the grants program began
in 1982, it has provided more than $220 million for Alzheimer
research. The grants program offers several types of awards,
including the Zenith Award, which in 2007 provided an additional
$200,000 per grant awarded, an increase from $250,000 to
$450,000.

In July 2007 evidence of the Association's commitment to funding

research grew when the Association, Cure Alzheimer's Fund and
Lou Ruvo Brain Institute announced that they had joined forces to
establish the Tomorrow's Leaders in Alzheimer's Disease
Research Awards. The annual award program provides $100,000
to each of three outstanding new M.D. or Ph.D. investigators who
have made pivotal contributions to basic understanding, early
detection, treatment or prevention of Alzheimer's. The first
awards will be given in 2008.

To speed research advances, the Association hosted two Research

Roundtable meetings in Washington, D.C. The Roundtable
facilitates collaborations between researchers in academia and
industry. The May 30–31 meeting convened more than 90
members and invited guests to explore the academic-industry
interface for Alzheimer's drug discovery, while the November 12–
14 meeting focused on the latest diagnostic tools for early-risk
assessment. This unique forum for the sharing of information
continues to grow in popularity, with industry membership
expanding in 2007