The Dartmouth Memory Handbook

Section 3: Alzheimer's Disease
 
 

 

What Is Alzheimer's Disease?

 
From NIH Senior Health
http://nihseniorhealth.gov/alzheimersdisease/whatisalzheimersdisease/01.html
Last Reviewed: May 2015
 
Alzheimer’s disease is a brain disease that slowly destroys memory and thinking skills
and, eventually, the ability to carry out the simplest tasks. It begins slowly and gets
worse over time. Currently, it has no cure.
 
A Common Cause of Dementia
Alzheimer’s disease is the most common cause of dementia among older people.
Dementia is a loss of thinking, remembering, and reasoning skills that interferes with a
person’s daily life and activities. Dementia ranges in severity from the mild stage, when it
is just beginning to affect a person’s functioning, to the severe stage, when the person
must depend completely on others for basic care.
 
Estimates vary, but experts suggest that more than 5 million Americans may have
Alzheimer's disease. Alzheimer’s is currently ranked as the sixth leading cause of death
in the United States, but recent estimates indicate that the disorder may rank third, just
behind heart disease and cancer, as a cause of death for older people
 
Risk Increases With Age
In most people with Alzheimer’s, symptoms first appear in their mid-60s, and the risk of
developing the disease increases with age. While younger people -- in their 30s, 40s,
and 50s -- may get Alzheimer's disease, it is much less common. It is important to note
that Alzheimer's disease is not a normal part of aging.
 
The course of Alzheimer’s disease—which symptoms appear and how quickly changes
occur—varies from person to person. The time from diagnosis to death varies, too. It can
be as little as 3 or 4 years if the person is over 80 years old when diagnosed or as long
as 10 years or more if the person is younger.
 
Memory Problems: One of the First Signs
Memory problems are typically one of the first signs of Alzheimer’s disease, though initial
symptoms may vary from person to person. A decline in other aspects of thinking, such
as finding the right words, vision/spatial issues, and impaired reasoning or judgment,
may also signal the very early stages of Alzheimer’s disease.
 
People with Alzheimer’s have trouble doing everyday things like driving a car, cooking a
meal, or paying bills. They may ask the same questions over and over, get lost easily,
lose things or put them in odd places, and find even simple things confusing. Some
people become worried, angry, or violent.
 
Other Reasons for Memory Issues
Not all people with memory problems have Alzheimer’s disease. Mild forgetfulness can
be a normal part of aging. Some people may notice that it takes longer to learn new
things, remember certain words, or find their glasses. That’s different from a serious
memory problem, which makes it hard to do everyday things.
 
Sometimes memory problems are related to health issues that are treatable. For
example, medication side effects, vitamin B12 deficiency, head injuries, or liver or kidney
disorders can lead to memory loss or possibly dementia. Emotional problems, such as
stress, anxiety, or depression, can also make a person more forgetful and may be
mistaken for dementia.
 
Mild Cognitive Impairment (see also p. 9)
Some older people with memory or other thinking problems have a condition called mild
cognitive impairment, or MCI. MCI can be an early sign of Alzheimer’s, but not everyone
with MCI will develop Alzheimer’s disease. People with MCI have more memory
problems than other people their age, but they can still take care of themselves and do
their normal activities.
 
Signs of MCI may include Losing things often; forgetting to go to events and
appointments; having more trouble coming up with words than other people the same
age, and similar behaviors. If you or someone in your family thinks your forgetfulness is
getting in the way of your normal routine, it’s time to see your doctor. Seeing the doctor
when you first start having memory problems can help you find out what’s causing your
forgetfulness.
 
What Happens to the Brain in Alzheimer’s?
Alzheimer's disease is named after Dr. Alois Alzheimer, a German doctor. In 1906, Dr.
Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual
mental illness. After she died, he examined her brain and found many abnormal clumps
(now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary, or
tau, tangles). Plaques and tangles in the brain are two of the main features of
Alzheimer's disease. Another is the loss of connections between nerve cells (neurons) in
the brain. Neurons send messages between different parts of the brain, and from the
brain to muscles and organs in the body.
 
It seems likely that damage to the brain starts 10 years or more before memory or other
thinking problems become obvious. During the earliest stage of Alzheimer’s, people are
free of symptoms, but harmful changes are taking place in the brain. The damage at first
appears to take place in cells of the hippocampus, the part of the brain essential in
forming memories. Abnormal protein deposits form plaques and tangles in the brain.
Once-healthy nerve cells stop functioning, lose connections with each other, and die. As
more nerve cells die, other parts of the brain begin to shrink. By the final stage of
Alzheimer’s, damage is widespread, and brain tissue has shrunk significantly.
 

Alzheimer's Disease Fact Sheet
From the National Institute on Aging
Alzheimer's Disease Education and Referral Center

https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-fact-sheet
Updated: June 27, 2016
 
Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys
memory and thinking skills and, eventually, the ability to carry out the simplest tasks. In
most people with Alzheimer’s, symptoms first appear in their mid-60s. Estimates vary,
but experts suggest that more than 5 million Americans may have Alzheimer’s.
Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United
States, but recent estimates indicate that the disorder may rank third, just behind heart
disease and cancer, as a cause of death for older people. Alzheimer’s is the most
common cause of dementia among older adults. Dementia is the loss of cognitive
functioning—thinking, remembering, and reasoning—and behavioral abilities to such an
extent that it interferes with a person’s daily life and activities. Dementia ranges in
severity from the mildest stage, when it is just beginning to affect a person’s functioning,
to the most severe stage, when the person must depend completely on others for basic
activities of daily living. The causes of dementia can vary, depending on the types of
brain changes that may be taking place. Other dementias include Lewy body dementia,
frontotemporal disorders, and vascular dementia. It is common for people to have mixed
dementia—a combination of two or more disorders, at least one of which is dementia.
For example, some people have both Alzheimer’s disease and vascular dementia.
 
Alzheimer’s disease is named after Dr. Alois Alzheimer. In 1906, Dr. Alzheimer noticed
changes in the brain tissue of a woman who had died of an unusual mental illness. Her
symptoms included memory loss, language problems, and unpredictable behavior. After
she died, he examined her brain and found many abnormal clumps (now called amyloid
plaques) and tangled bundles of fibers (now called neurofibrillary, or tau, tangles). These
plaques and tangles in the brain are still considered some of the main features of
Alzheimer’s disease. Another feature is the loss of connections between nerve cells
(neurons) in the brain. Neurons transmit messages between different parts of the brain,
and from the brain to muscles and organs in the body.
 
Changes in the Brain
Scientists continue to unravel the complex brain changes involved in the onset and
progression of Alzheimer’s disease. It seems likely that damage to the brain starts a
decade or more before memory and other cognitive problems appear. During this
preclinical stage of Alzheimer’s disease, people seem to be symptom-free, but toxic
changes are taking place in the brain. Abnormal deposits of proteins form amyloid
plaques and tau tangles throughout the brain, and once-healthy neurons stop
functioning, lose connections with other neurons, and die. The damage initially appears
to take place in the hippocampus, the part of the brain essential in forming memories. As
more neurons die, additional parts of the brain are affected, and they begin to shrink. By
the final stage of Alzheimer’s, damage is widespread, and brain volume has shrunk
significantly.
 
Signs and Symptoms
Memory problems are typically one of the first signs of cognitive impairment related to
Alzheimer’s disease. Some people with memory problems have a condition called mild
cognitive impairment (MCI). In MCI, people have more memory problems than normal
for their age, but their symptoms do not interfere with their everyday lives. Movement
difficulties and problems with the sense of smell have also been linked to MCI. Older
people with MCI are at greater risk for developing Alzheimer’s, but not all of them do.
Some may even go back to normal cognition. The first symptoms of Alzheimer’s vary
from person to person. For many, decline in non-memory aspects of cognition, such as
word-finding, vision/spatial issues, and impaired reasoning or judgment, may signal the
very early stages of Alzheimer’s disease. Researchers are studying biomarkers to see if
they can detect early changes in the brains of people with MCI and in cognitively normal
people who may be at greater risk for Alzheimer’s disease. Studies indicate that such
early detection may be possible, but more research is needed before these techniques
can be relied upon to diagnose Alzheimer’s disease in everyday medical practice.
 
Mild Alzheimer’s Disease
As Alzheimer’s disease progresses, people experience greater memory loss and other
cognitive difficulties. Problems can include wandering and getting lost, trouble handling
money and paying bills, repeating questions, taking longer to complete normal daily
tasks, and personality and behavior changes. People are often diagnosed at this stage.
 
Moderate Alzheimer’s Disease
In this stage, damage occurs in areas of the brain that control language, reasoning,
sensory processing, and conscious thought. Memory loss and confusion grow worse,
and people begin to have problems recognizing family and friends. They may be unable
to learn new things, carry out multistep tasks such as getting dressed, or cope with new
situations. In addition, people at this stage may have hallucinations, delusions, and
paranoia and may behave impulsively.
 
Severe Alzheimer’s Disease
Ultimately, plaques and tangles spread throughout the brain, and brain tissue shrinks
significantly. People with severe Alzheimer’s cannot communicate and are completely
dependent on others for their care. Near the end, the person may be in bed most or all of
the time as the body shuts down.
 
What Causes Alzheimer’s
Scientists don’t yet fully understand what causes Alzheimer’s disease in most people. In
people with early-onset Alzheimer’s, a genetic mutation is usually the cause. Late-onset
Alzheimer’s arises from a complex series of brain changes that occur over decades. The
causes probably include a combination of genetic, environmental, and lifestyle factors.
The importance of any one of these factors in increasing or decreasing the risk of
developing Alzheimer’s may differ from person to person.
 
The Basics of Alzheimer’s
Scientists are conducting studies to learn more about plaques, tangles, and other
biological features of Alzheimer’s disease. Advances in brain imaging techniques allow
researchers to see the development and spread of abnormal amyloid and tau proteins in
the living brain, as well as changes in brain structure and function. Scientists are also
exploring the very earliest steps in the disease process by studying changes in the brain
and body fluids that can be detected years before Alzheimer’s symptoms appear.
Findings from these studies will help in understanding the causes of Alzheimer’s and
make diagnosis easier. One of the great mysteries of Alzheimer’s disease is why it
largely strikes older adults. Research on normal brain aging is shedding light on this
question. For example, scientists are learning how age-related changes in the brain may
harm neurons and contribute to Alzheimer’s damage. These age-related changes
include atrophy (shrinking) of certain parts of the brain, inflammation, production of
unstable molecules called free radicals, and mitochondrial dysfunction (a breakdown of
energy production within a cell).
 
Genetics
Most people with Alzheimer’s have the late-onset form of the disease, in which
symptoms become apparent in their mid-60s. The apolipoprotein E (APOE) gene is
involved in late-onset Alzheimer’s. This gene has several forms. One of them, APOE ε4,
increases a person’s risk of developing the disease and is also associated with an earlier
age of disease onset. However, carrying the APOE ε4 form of the gene does not mean
that a person will definitely develop Alzheimer’s disease, and some people with no
APOE ε4 may also develop the disease. Also, scientists have identified a number of
regions of interest in the genome (an organism’s complete set of DNA) that may
increase a person’s risk for late onset Alzheimer’s to varying degrees.
 
Early-onset Alzheimer’s disease occurs in people age 30 to 60 and represents less than
5 percent of all people with Alzheimer’s. Most cases are caused by an inherited change
in one of three genes, resulting in a type known as early-onset familial Alzheimer’s
disease, or FAD. For others, the disease appears to develop without any specific, known
cause, much as it does for people with late-onset disease.
 
Most people with Down syndrome develop Alzheimer’s. This may be because people
with Down syndrome have an extra copy of chromosome 21, which contains the gene
that generates harmful amyloid.
 
Health, Environmental, and Lifestyle Factors
Research suggests that a host of factors beyond genetics may play a role in the
development and course of Alzheimer’s disease. There is a great deal of interest, for
example, in the relationship between cognitive decline and vascular conditions such as
heart disease, stroke, and high blood pressure, as well as metabolic conditions such as
diabetes and obesity. Ongoing research will help us understand whether and how
reducing risk factors for these conditions may also reduce the risk of Alzheimer’s. A
nutritious diet, physical activity, social engagement, and mentally stimulating pursuits
have all been associated with helping people stay healthy as they age. These factors
might also help reduce the risk of cognitive decline and Alzheimer’s disease. Clinical
trials are testing some of these possibilities.
 
Diagnosis of Alzheimer’s Disease
Doctors use several methods and tools to help determine whether a person who is
having memory problems has “possible Alzheimer’s dementia” (dementia may be due to
another cause) or “probable Alzheimer’s dementia” (no other cause for dementia can be
found). To diagnose Alzheimer’s, doctors may:
 
• Ask the person and a family member or friend questions about overall health,
past medical problems, ability to carry out daily activities, and changes in
behavior and personality
• Conduct tests of memory, problem solving, attention, counting, and language
• Carry out standard medical tests, such as blood and urine tests, to identify other
possible causes of the problem
• Perform brain scans, such as computed tomography (CT), magnetic resonance
imaging (MRI), or positron emission tomography (PET), to rule out other possible
causes for symptoms. These tests may be repeated to give doctors information
about how the person’s memory and other cognitive functions are changing over
time.
 
Alzheimer’s disease can be definitively diagnosed only after death, by linking clinical
measures with an examination of brain tissue in an autopsy. People with memory and
thinking concerns should talk to their doctor to find out whether their symptoms are due
to Alzheimer’s or another cause, such as stroke, tumor, Parkinson’s disease, sleep
disturbances, side effects of medication, an infection, or a non-Alzheimer’s dementia.
Some of these conditions may be treatable and possibly reversible. If the diagnosis is
Alzheimer’s, beginning treatment early in the disease process may help preserve daily
functioning for some time, even though the underlying disease process cannot be
stopped or reversed. An early diagnosis also helps families plan for the future. They can
take care of financial and legal matters, address potential safety issues, learn about
living arrangements, and develop support networks. In addition, an early diagnosis gives
people greater opportunities to participate in clinical trials that are testing possible new
treatments for Alzheimer’s disease or other research studies.
 
Treatment of Alzheimer’s Disease
Alzheimer’s disease is complex, and it is unlikely that any one drug or other intervention
will successfully treat it. Current approaches focus on helping people maintain mental
function, manage behavioral symptoms, and slow or delay the symptoms of disease.
Researchers hope to develop therapies targeting specific genetic, molecular, and
cellular mechanisms so that the actual underlying cause of the disease can be stopped
or prevented.
 
Maintaining Mental Function
The U.S. Food and Drug Administration has approved to treat symptoms of Alzheimer’s.
Donepezil (Aricept¨), rivastigmine (Exelon¨), and galantamine (Razadyne¨) are used
to treat mild to moderate Alzheimer’s (donepezil can be used for severe Alzheimer’s as
well). Memantine (Namenda¨) is used to treat moderate to severe Alzheimer’s. These
drugs work by regulating neurotransmitters, the brain chemicals that transmit messages
between neurons. They may help maintain thinking, memory, and communication skills,
and help with certain behavioral problems. However, these drugs don’t change the
underlying disease process. They are effective for some but not all people and may help
only for a limited time.
 
Managing Behavior
Common behavioral symptoms of Alzheimer’s include sleeplessness, wandering,
agitation, anxiety, and aggression. Scientists are learning why these symptoms occur
and are studying new treatments—drug and nondrug— to manage them. Research has
shown that treating behavioral symptoms can make people with Alzheimer’s more
comfortable and makes things easier for caregivers. Looking for New Treatments
Alzheimer’s disease research has developed to a point where scientists can look beyond
treating symptoms to think about addressing underlying disease processes. In ongoing
clinical trials, scientists are developing and testing several possible interventions,
including immunization therapy, drug therapies, cognitive training, physical activity, and
treatments used for cardiovascular disease and diabetes.
 
Support for Families and Caregivers
Caring for a person with Alzheimer’s disease can have high physical, emotional, and
financial costs. The demands of day-to-day care, changes in family roles, and decisions
about placement in a care facility can be difficult. There are several evidence-based
approaches and programs that can help, and researchers are continuing to look for new
and better ways to support caregivers. Becoming well informed about the disease is one
important strategy. Programs that teach families about the various stages of Alzheimer’s
and about ways to deal with difficult behaviors and other caregiving challenges can help.
Good coping skills, a strong support network, and respite care are other ways that help
caregivers handle the stress of caring for a loved one with Alzheimer’s disease. For
example, staying physically active provides physical and emotional benefits. Some
caregivers have found that joining a support group is a critical lifeline. These support
groups allow caregivers to find respite, express concerns, share experiences, get tips,
and receive emotional comfort. Many organizations sponsor in-person and online
support groups, including groups for people with early-stage Alzheimer’s and their
families.
 
Participating in Clinical Trials
Everybody—those with Alzheimer’s disease or mild cognitive impairment as well as
healthy volunteers with or without a family history of Alzheimer’s—may be able to take
part in clinical trials and studies. Participants in Alzheimer’s clinical research help
scientists learn how the brain changes in healthy aging and in Alzheimer’s. Currently, at
least 70,000 volunteers are needed to participate in more than 150 active clinical trials
and studies that are testing ways to understand, diagnose, treat, and prevent
Alzheimer’s disease. Volunteering for a clinical trial is one way to help in the fight against
Alzheimer’s disease. Studies need participants of different ages, sexes, races, and
ethnicities to ensure that results are meaningful for many people. The National Institute
on Aging (NIA) at the National Institutes of Health (NIH) leads the Federal Government’s
research efforts on Alzheimer’s. NIA-supported Alzheimer’s Disease Centers throughout
the United States conduct a wide range of research, including studies of the causes,
diagnosis, and management of Alzheimer’s. NIA also sponsors the Alzheimer’s Disease
Cooperative Study (ADCS), a consortium of leading researchers throughout the United
States and Canada who conduct clinical trials.
 
To find out more about Alzheimer’s clinical trials and studies:
• Talk to your health care provider about local studies that may be right for you.
• Visit the ADEAR Center website at www.nia.nih.gov/alzheimers/volunteer.
• Contact Alzheimer’s disease centers or memory or neurology clinics in your
community.
• Search the ADEAR Center clinical trials finder for a trial near you or to sign up for
email alerts about new trials: www.nia.nih.gov/alzheimers/clinical-trials.
 

Frequently Asked Questions About Alzheimer’s Disease

 
From NIH Senior Health
http://nihseniorhealth.gov/alzheimersdisease/faq/faqlist.html#a3
Updated May, 2015
 
1. What is Alzheimer's disease?
Alzheimer’s disease is a brain disease that slowly destroys memory and thinking skills
and, eventually, the ability to carry out the simplest tasks. It begins slowly and gets
worse over time. Currently, it has no cure. Alzheimer’s disease is the most common
cause of dementia in older people.
 
2. What is dementia?
Dementia is a loss of thinking, remembering, and reasoning skills that interferes with a
person’s daily life and activities. Alzheimer’s disease is the most common cause of
dementia among older people. Dementia ranges in severity from the mild stage, when it
is just beginning to affect a person’s functioning, to the severe stage, when the person
must depend completely on others for care.
 
3. How many people in the United States have Alzheimer's disease?
Estimates vary, but experts suggest that more than 5 million Americans may have
Alzheimer's disease. Alzheimer’s is currently ranked as the sixth leading cause of death
in the United States, but recent estimates indicate that the disorder may rank third, just
behind heart disease and cancer, as a cause of death for older people.
 
4. What is mild cognitive impairment?
Mild cognitive impairment, or MCI, is a condition that can be an early sign of Alzheimer’s
disease—but not everyone with MCI will develop Alzheimer’s. People with MCI can still
take care of themselves and do their normal activities. Signs of MCI may include: losing
things often; forgetting to go to events and appointments; having more trouble coming
up with words than other people the same age, and similar behaviors.
 
5. What is typically the first sign of Alzheimer's disease?
Memory problems are typically one of the first signs of Alzheimer’s disease, though
different people may have different initial symptoms. A decline in other aspects of
thinking, such as finding the right words, vision/spatial issues, and impaired reasoning or
judgment, may also signal the very early stages of Alzheimer’s disease.
 
6. What are the stages in the development of Alzheimer's disease?
Alzheimer's disease has three stages: early (also called mild), middle (moderate),
and late (severe).
A person in the early stage of Alzheimer’s may:
• Find it hard to remember things
• Ask the same questions over and over
• Get lost in familiar places
• Lose things or put them in odd places
• Have trouble handling money and paying bills
• Take longer than normal to finish daily tasks.
 
As Alzheimer’s disease progresses to the middle stage, memory loss and confusion
grow worse, and people may have problems recognizing family and friends. Other
symptoms are this stage include:
-Difficulty learning new things and coping with new situations
-Trouble carrying out tasks that involve multiple steps, like getting dressed
-Impulsive behavior
-Forgetting the names of common things
-Hallucinations, delusions, or paranoia
-Wandering away from home.
 
As Alzheimer’s disease becomes more severe, people lose the ability to communicate.
They may sleep more, lose weight, and have trouble swallowing. Often they are
incontinent—they cannot control their bladder and/or bowels. Eventually, they need total
care.
 
7. What changes in the brain happen to people with Alzheimer's disease?
Although we still don’t know how Alzheimer’s disease begins, it seems likely that
damage to the brain starts 10 years or more before problems become obvious. During
the earliest stage of Alzheimer’s, people are free of symptoms, but harmful changes are
taking place in the brain. Abnormal protein deposits form amyloid plaques and
neurofibrillary tangles in the brain. Once-healthy nerve cells lose their ability to function
and communicate with each other, and eventually they die. As nerve cells in the brain die, parts of the brain begin to shrink. By the final stage of Alzheimer’s, damage is widespread, and brain tissue has shrunk significantly.
 
8. What causes Alzheimer's disease?
Scientists do not yet fully understand what causes Alzheimer's disease in most people.
In early-onset Alzheimer’s, which occurs in people between the ages of 30 and 60, a
genetic mutation is usually the cause. Late-onset Alzheimer’s, which usually develops
after age 60, arises from a complex series of brain changes that occur over decades.
The causes probably include a mix of genetic, environmental, and lifestyle factors.
These factors affect each person differently. Increasing age is the most important known
risk factor for Alzheimer's disease. Lifestyle factors, such as diet and physical exercise,
and long-term health conditions, like high blood pressure and diabetes, might also play a
role in the risk of developing Alzheimer’s disease.
 
9. If a family member has Alzheimer's disease, will I get it, too?
Just because a family member has Alzheimer's disease does not mean that you will get
it, too. A rare form of Alzheimer's disease, called early-onset familial Alzheimer's, is
inherited. It occurs in people between the ages of 30 and 60 and is caused by mutations,
or changes, in certain genes. Most cases of Alzheimer's are late-onset. They occur after
age 60 and usually have no obvious family pattern. However, genetic factors appear to
increase a person's risk of developing late-onset Alzheimer's.
 
10. If you become forgetful as you get older, does that mean you will get
Alzheimer’s disease?
Not all memory problems are caused by Alzheimer’s disease. Mild forgetfulness can be
a normal part of aging. Sometimes memory problems are related to health issues that
are treatable. For example, these conditions may cause memory loss or possibly
dementia:
Medication side effects
Vitamin B12 deficiency
Chronic alcoholism
Tumors or infections in the brain.
 
Thyroid, liver or kidney disorders also can lead to memory loss. Emotional problems,
such as stress, anxiety, or depression, can also make a person more forgetful and may
be mistaken for dementia. The confusion and forgetfulness caused by emotions usually
are temporary and go away when the feelings fade.
 
If you or someone in your family thinks your forgetfulness is getting in the way of your
normal routine, it’s time to see your doctor. He or she can find out what’s causing these
problems.
 
11. How is Alzheimer's disease diagnosed?
The only definitive way to diagnose Alzheimer's disease is to find out whether plaques
and tangles exist in brain tissue. To look at brain tissue, doctors perform a brain autopsy,
an examination of the brain done after a person dies.
 
Doctors can only make a diagnosis of "possible" or “probable” Alzheimer’s disease while
a person is alive. Doctors with special training can diagnose Alzheimer's disease
correctly up to 90 percent of the time. Doctors who can diagnose Alzheimer’s include
geriatricians, geriatric psychiatrists, and neurologists. A geriatrician specializes in the
treatment of older adults. A geriatric psychiatrist specializes in mental problems in older
adults. A neurologist specializes in brain and nervous system disorders.
 
To diagnose Alzheimer's disease, doctors may ask questions about overall health, past
medical problems, ability to carry out daily activities, and changes in behavior and
personality; conduct tests to measure memory, problem solving, attention, counting, and
language skills; carry out standard medical tests, such as blood and urine tests; and
perform brain scans to look for anything in the brain that does not look normal.
 
12. Why is early diagnosis of Alzheimer’s important?
An early, accurate diagnosis of Alzheimer's disease helps people and their families plan
for the future. It gives them time to discuss care options, find support, and make legal
and financial arrangements while the person with Alzheimer’s can still take part in
making decisions. Also, even though no medicine or other treatment can stop or slow
the disease, early diagnosis offers the best chance to treat the symptoms.
 
13. How long do people live after getting diagnosed with Alzheimer's?
The time from diagnosis of Alzheimer’s disease to death varies. It can be as little as 3 or
4 years if the person is over 80 years old when diagnosed or as long as 10 years or
more if the person is younger.
 
14. Are there any medicines to treat Alzheimer's disease?
Currently, no treatment can stop Alzheimer's disease. However, four medications are
used to treat its symptoms. These medicines may help maintain thinking, memory, and
speaking skills for a limited time. They work by regulating certain brain chemicals. Most
of these medicines work best for people in the early or middle stages of the disease.
 
For people with mild or moderate Alzheimer's, donepezil (Aricept¨), rivastigmine
(Exelon¨), or galantamine (Razadyne¨) may help. Donepezil is also approved to treat
symptoms of moderate to severe Alzheimer's. Another drug, memantine (Namenda¨), is
used to treat symptoms of moderate to severe Alzheimer's, although it also has limited
effects. All of these medicines have possible side effects.
 
Certain medicines and other approaches can help control the behavioral symptoms of
Alzheimer's disease. These symptoms include sleeplessness, agitation, wandering,
anxiety, anger, and depression.
 
15. Is there anything I can do to prevent Alzheimer's disease?
Currently, no medicines or treatments are known to prevent Alzheimer's disease, but
scientists are studying many possibilities. These possibilities include lifestyle factors
such as exercise and physical activity, a healthy diet, and mentally stimulating activities.
In addition to lifestyle factors, scientists have found clues that some long-term health
conditions, like heart disease, high blood pressure, and diabetes, are related to
Alzheimer's disease. It’s possible that controlling these conditions will reduce the risk of
developing Alzheimer’s.
 
16. Can exercising prevent Alzheimer’s disease?
Research suggests that exercise may play a role in reducing risk for Alzheimer’s
disease. Animal studies show that exercise increases both the number of small blood
vessels that supply blood to the brain and the number of connections between nerve
cells in older rats and mice. In addition, researchers have found that exercise raises the
level of a nerve growth factor (a protein key to brain health) in an area of the brain that is
important to memory and learning.
 
17. Can controlling certain diseases protect against Alzheimer's?
Age-related diseases and conditions—such as vascular disease, high blood pressure,
heart disease, and diabetes—may increase the risk of Alzheimer’s. Many studies are
looking at whether this risk can be reduced by preventing or controlling these diseases
and conditions.
 
For example, one clinical trial is looking at how lowering blood pressure to or below
current recommended levels may affect cognitive decline and the development of MCI
(mild cognitive impairment) and Alzheimer’s disease. Participants are older adults with
high systolic (upper number) blood pressure who have a history of heart disease or
stroke, or are at risk for those conditions.
 
Diabetes is another disease that has been linked to Alzheimer’s. Past research suggests
that abnormal insulin production contributes to Alzheimer’s-related brain changes.
(Insulin is the hormone involved in diabetes.) Diabetes treatments have been tested in
people with Alzheimer’s, but the results have not been conclusive.
 
18. Can eating certain foods prevent Alzheimer’s disease?
A number of studies suggest that eating certain foods may help keep the brain healthy—
and that others can be harmful. Researchers are looking at whether a healthy diet—one
that includes lots of fruits, vegetables, and whole grains and is low in fat and added
sugar—can help prevent Alzheimer’s.
 
19. Can you prevent Alzheimer's by keeping your brain active?
Keeping the mind sharp—through social engagement or intellectual stimulation—is
associated with a lower risk of Alzheimer’s disease. Activities like working, volunteering,
reading, going to lectures, and playing computer and other games are being studied to
see if they might help prevent Alzheimer’s. But we do not know with certainty whether
these activities can actually prevent Alzheimer’s.
 
20. What is basic research and why is it an important part of Alzheimer's
disease research?
Basic research helps scientists gain new knowledge about a disease process, including
how and why it starts and progresses. In Alzheimer’s disease, basic research seeks to
identify the cellular, molecular, and genetic processes that lead to the disease. For
example, scientists are studying the ways in which plaques and tangles damage nerve
cells in the brain; the very earliest brain changes in the disease process; the role of
Alzheimer’s risk-factor genes in the development of the disease; how risk-factor genes
interact with other genes and lifestyle or environmental factors to affect Alzheimer’s risk.
 
21. What is translational research and why is it an important part of
Alzheimer's disease research?
Translational research grows out of basic research. It creates new medicines, devices,
or behavioral interventions aimed at preventing, diagnosing, or treating a disease. An
important goal of Alzheimer’s translational research is to increase the number and
variety of potential new medicines and other interventions that are approved for testing
in humans. Scientists also examine medicines approved to treat other diseases to see
they might be effective in people with Alzheimer’s.
 
The most promising interventions are tested in test-tube and animal studies to make
sure they are safe and effective. Currently, a number of different substances are under
development that may one day be used to treat the symptoms of Alzheimer’s disease or
mild cognitive impairment.
 
22. What is clinical research and why is it an important part of Alzheimer's
disease research?
Clinical research is medical research involving people. It includes clinical studies, which
observe and gather information about large groups of people. It also includes clinical
trials, which test a medicine, therapy, medical device, or intervention in people to see if it
is safe and effective.
 
Clinical trials are the best way to find out whether a particular intervention actually slows,
delays, or prevents Alzheimer’s disease. Trials may compare a potential new treatment
with a standard treatment or placebo (mock treatment). Or, they may study whether a
certain behavior or condition affects the progress of Alzheimer’s or the chances of
developing it.
 
23. How can people help test possible new treatments for Alzheimer’s
People with Alzheimer's disease, those with mild cognitive impairment, those with a
family history of Alzheimer’s, and healthy people with no memory problems who want to
help scientists test new treatments may be able to take part in clinical trials. Participants
in clinical trials help scientists learn about the brain in healthy aging as well as what
happens in Alzheimer’s. Results of these trials are used to improve prevention and
treatment methods.
 
To find out more about Alzheimer’s clinical trials, talk to your health care provider or
contact the Alzheimer’s Disease Education and Referral (ADEAR) Center at 1-800-
438-4380
 

Stages of Alzheimer’s Disease

 
Adapted from Santulli RB:
The Alzheimer’s Family: Helping Caregivers Cope
New York: WW Norton, 2011
 
Alzheimer’s disease is a progressive illness. From diagnosis (often several years after
symptoms have begun) until death, anywhere from 2 to 20 years can elapse. The typical
person with Alzheimer’s has symptoms for about 10 years, although the actual duration
can depend on numerous factors such as the person’s age at the time of disease onset,
general health, the quality and intensity of medical care throughout the disease, and
other factors.
 
It is useful to talk about stages of Alzheimer’s disease, just as doctors will stage other
long-term illnesses such as cancer or heart disease. It is important to remember,
however, that there is great variability from one individual to the next. While certain
characteristics may be typical of a person at, for example, the moderate stage of the
disease, features of more advanced illness as well as more mild symptoms may be
present in the same individual at the same time. Staging is useful for clinicians and
others, as a shorthand way to communicate some information about a given person
without having to describe every symptom or disability. But staging is only a rough
approximation.
 
The most common and useful staging system has just three stages. In this system,
people with Alzheimer’s are classified as being in the mild, moderate, or severe stage of
the disease. In practice, specialists also speak frequently of persons with mild-tomoderate
or moderate-to-severe disease, when features of both stages are present; the
term end-stage disease refers to the final sub-stage of severe dementia.
 
Mild Stage
Typical features of mild or early-stage Alzheimer’s disease include the following:
  1. Disorientation to time and place.
  2. Loss of initiative (apathy).
  3. Mood and personality changes may occur.
  4. Impairment of judgment in decision making.
  5. Difficulty managing money, paying bills, and other instrumental activities of daily living
 
Impact on Day-to-Day Life
To meet criteria for a diagnosis of Alzheimer’s disease or other form of dementia, there
needs to be evidence that the impairments have an impact on daily life. This is a gray
area. For example, just how much difficulty remembering names is beyond the
boundaries of normal aging or MCI and therefore qualifies instead for a diagnosis of
Alzheimer’s? For example, impairment in functioning may be present if someone
refuses to go to social events or lunches at the senior center because they can no longer
reliably remember anyone’s name there.
 
Another example of memory impairment impacting daily life is someone who develops
adverse medication effects from taking his or her daily medications more frequently than
prescribed, because of forgetfulness, or not taking the medications at all for several days in a row.
When difficulties of this kind are present, persons with mild Alzheimer’s disease
generally need some supervision or assistance from others on a daily basis. Usually,
however, they are able to live in the community with family, or even alone with sufficient,
regular caregiver support and assistance.
 
The mild stage of Alzheimer’s disease usually lasts two to four years, although there is
great variability, and will depend on how early the diagnosis as made.
 
Moderate Stage
Persons with moderate-stage disease typically display the following characteristics:
  1. Increasing memory loss and confusion
  2. Difficulty recognizing friends and family (usually not the spouse or primary 
    care partner, although this varies)
  3. Significant difficulty with reading, writing, and finding words
  4. Loss of impulse control
  5. Reluctance or refusal to bathe
  6. Difficulty with dressing and other ADLs, but not yet in need of total assistance 
    with these
  7. Significant mood or behavioral problems (see p. 117)
 
Moderate-stage Alzheimer’s disease covers a wide range of functions and impairments.
Someone in the early-moderate stages of disease may need some help with cueing to
get dressed, whereas someone in the late-moderate stages may need near total
assistance with ADLs. Similarly, speech may be only mildly disturbed, or it may be
almost completely incoherent. Persons with moderate Alzheimer’s disease may live at
home, with considerable help from others. Usually, they do not live alone unless
someone is assisting them for at least some period of time every day, and that is not an
ideal situation in most cases. Other individuals with moderate dementia may reside in a
memory care unit of an assisted living facility, or possibly even a nursing home,
depending on their degree of dependency or concurrent medical problems. The
moderate stage of the disease can last anywhere from two to ten years.
 
Severe Stage
By the time an individual reaches the severe stages of Alzheimer’s, he or she has
usually have been ill for many years. Typical symptoms at this stage include:
  1. Little or no short-term memory;
  2. in need of complete assistance with all basic activities of daily living
    (eating, bathing, dressing, toileting, ambulating, and continence);
  3. language, both expressive (speaking) and receptive
    (understanding what someone else is saying) is extremely impaired, if still present at all; 
  4. usually incontinent of both urine and bowel.
 
Individuals in the severe stage of dementia are frequently in a nursing home, due to their
impairment in all ADLs and incontinence. If the person still lives at home, they need
nearly continuous care for survival as they are literally unable to do anything for
themselves.
 
End Stage
The final phase of severe dementia is referred to as the end stage. Persons in end stage
dementia often show the following characteristics: Weight loss; increasing difficulty with
eating or reluctance to eat; inability to recognize even close family members; minimal or
no language; minimal to no interaction with the environment; automatic reactions, only,
to stimulation
 
The severe and end stages of Alzheimer’s disease, together, can last for many years,
depending on a number of factors including the person’s overall state of physical health.
Persons in the end stage of Alzheimer’s are eligible for hospice care through Medicare.
 

Early-Onset Alzheimer’s Disease

 
Robert B. Santulli, M.D.
(added September, 2016)
 
While Alzheimer’s disease most commonly occurs in individuals over the age of 65,
about 5% of all cases begin earlier. When the disease begins before age 65, it is
referred to as “Early-Onset Alzheimer’s Disease” (EOAD). The more typical form of the
disease is referred to as “Late-Onset Alzheimer’s Disease” (LOAD).
 
Familial Early-Onset Alzheimer’s Disease (FAD)
About half of individuals with EOAD have a genetic mutation that has caused the
disease. A genetic mutation is a permanent alteration in the DNA sequence that
characterizes the gene. These occur for reasons that are unknown. In people with
familial early-onset Alzheimer’s disease (FAD), there is usually a parent who has earlyonset
Alzheimer’s disease, and that person’s siblings and children have a 50% chance
of inheriting the disease.
 
The genetic mutation responsible for FAD occurs in one of three genes: APP, on
chromosome 21; presenilin-1 on chromosome 14; or presenilin-2 on chromosome 1.
Of the three, presenilin-1 is by far the most common cause of FAD. Each of these
genes influences the production of beta-amyloid protein that is thought by many to be
important in the causation of Alzheimer’s disease. In addition, there may be several
other genes that cause FAD, but these have not yet been identified.
 
Research on Familial Early-Onset Alzheimer’s Disease
The Dominantly Inherited Alzheimer Network (DIAN) is a research partnership involving
a number of institutions in the United States and abroad. Individuals who come from
families with inherited forms of Alzheimer’s disease (whether or not they, themselves,
have the disease or the gene) are studied intensively by this group, in the hopes that this
will lead to a better understanding of the disease, and will help develop new treatments.
Eligible individuals may find out more about the DIAN at http://www.dian-info.org/. Other
research studies of early-onset Alzheimer’s disease are also ongoing. This is particularly
important since many studies of LOAD exclude individuals younger than 65.
 
Sporadic (Non-Familial) Early-Onset Alzheimer’s Disease
About half of those with EOAD have no identified genetic causes. These persons may or
may not have direct relatives with the disease, just as is the case in those who develop
late-onset Alzheimer’s. It is not known why the disease begins early in these individuals,
although this is an active area of research.
 
Age of Onset
In the non-familial form of early-onset Alzheimer’s, the disease typically begins in the
50’s or early 60’s, whereas the genetic form of the disease often has an earlier age of
onset. It has been reported to occur in the 30’s although that is exceedingly uncommon.
 
Clinical Similarity to Late-Onset Alzheimer’s Disease
Other than the age at which the illness begins, there appear to be no notable differences
in the disease pathology (the actual appearance of the brain tissue, when viewed at
autopsy both grossly and under a microscope) between EOAD and LOAD. Symptoms
and overall course of the illnesses are likewise very similar, although there are some
reports that persons with early-onset Alzheimer’s disease may have more non-memory
symptoms, such as apraxias or visuospatial dysfunction. Likewise, anti-dementia
medication treatment has about the same overall degree of effectiveness in each group.
Because EOAD is similar in so many respects to the LOAD, most of what is written in
this Handbook applies to these individuals, as well.
 
Making the Diagnosis
Particularly for those with early-onset Alzheimer’s who have no family history of the
disease, making the diagnosis can be very difficult; often, symptoms have been present
for many years before an accurate diagnosis is ultimately made. This is due to two
factors: (1) the rarity of Alzheimer’s in the years before 65; and (2) the presentation of
the disease in both young and old is often very insidious, with initial symptoms that could
easily be mistaken for other conditions.
 
Typically, individuals may present in their fifties or very early sixties with vague
complaints, such as new difficulties at work; trouble concentrating; low mood; social
withdrawal; personality changes, and the like. With hindsight, it might be obvious that
this array of symptoms fits the pattern for EOAD, but it is certainly not the first diagnosis
that individuals themselves or their physicians are likely to consider when the person
presents with these difficulties at a relatively early age. Often, patients are seen as
merely being under “stress”; having a “midlife crisis” or marital difficulties, or possibly
using excessive amounts of alcohol or other drugs. Another common misdiagnosis is
depression; of course, depression can be a presenting feature of Alzheimer’s disease at
any age, but a careful exploration may reveal that other symptoms are also present,
when the depression is a component of dementia rather than a condition existing by
itself. Similarly, apathy commonly occurs in early Alzheimer’s and can easily be
mistaken for depression.
 
Other Dementias Can Appear Before Age 65:
Early-onset Alzheimer’s disease is the most common form of dementia that occurs
before the age of 65. However, other dementias can also occur at an early age. The
most common of these is fronto-temporal dementia (see p. 97). FTD typically begins in
the 50’s, although it can have an onset that is earlier or later. Most other types of
dementia presenting before age 65 are exceedingly rare.
 
The Impact on Working Life
Of the many challenges associated with early-onset dementia, the impact on work is one
of the most significant. Since the disease begins so insidiously, and since diagnosis can
be delayed for so many years, symptoms can significantly interfere with the person’s
ability to perform adequately at his or her job before the cause of this change in work
performance is identified. While it is illegal to simply fire someone because they have
early-onset dementia, if this diagnosis is not known, employers may simply feel that the
individual is not performing well on the job for other reasons, and it is not rare that
persons lose their employment because of performance issues before it is clear that they
are suffering from early –onset dementia. This humiliation only adds to the enormous
psychological and, especially, financial burden of the disease.
 
The Social Security Administration considers early-onset Alzheimer’s and frontotemporal
dementia to be conditions that are eligible for the “Compassionate Allowance”
program. This permits expedited review for eligibility for Social Security Disability
Insurance (SSDI) or Supplemental Security Income (SSI). While these are certainly
valuable benefits for chronically ill individuals, the remuneration rarely equals that which
someone earned prior to developing Alzheimer’s disease. More information about the
Compassionate Allowance program is available at the following website:
https://www.ssa.gov/compassionateallowances/.
 
For these reasons, it is especially important to attempt to obtain a definitive diagnosis as
soon as possible, particularly if developing symptoms are causing difficulties on the job
and threatening continued employment.
 
The Impact on the Family
One of the particular burdens of EOAD is that the individual often has young children at
home. Not only is the afflicted individual progressively less able to provide appropriate
care for his or her offspring, but also, living with a demented parent can be extremely
traumatic for children. It is important to talk openly with children (in an age-appropriate
fashion) about the disease, sooner rather than later. See p. 267 for a list of books and
other resources to help children understand and cope with the illness. Most of these
resources, not surprisingly, are oriented toward dealing with the illness in a grandparent,
rather than a parent, but they can be quite helpful nevertheless. It may be very useful
for children to speak with a counselor or a therapist about the situation.
 
Spouses who previously stayed at home to raise their young children may be compelled
back into the workforce for financial reasons. Additionally, spouses who work outside of
the home need to consider how to provide proper supervision and care for the individual
with EOAD who is now at home full-time. Some members of this “sandwich generation”
had also been caring for elderly parents, in addition to young children, and now have a
spouse with dementia who needs care as well; these are burdens that no one person
can manage alone, and outside help from other family and/or community resources is
essential.
 
Aside from these practical realities, there are, of course, the enormous emotional
burdens of losing a loved one, gradually, to dementia. Spouses of any age must cope
with this, but it can be particularly devastating for those who are younger (see Santulli
RB and Blandin K, The Emotional Journey of the Alzheimer’s Family, for a more
thorough discussion of the emotional losses experienced by the spouse and other family
members when someone has dementia).
 
The Eventual Need for Care in a Facility
Because of their younger age, many people who develop EOAD will live for an
exceptionally long time with the disease, often spending years in the later stages of the
illness. Many people with early-onset Alzheimer’s resist going to adult day programs for
dementia care, since they may be decades younger than the majority of other clients in
the program.
 
Unlike those with the more common LOAD, where both the patient and spouse are likely
to be retired, the spouse of the younger-onset individual may well be working full-time.
Children are still in school and often too young to provide significant amounts of care for
the ill parent. For all of these reasons, care in a facility (assisted living or nursing home)
is a frequent necessity, eventually. This is, of course, a wrenching move for everyone.
Some nursing facilities have units for younger residents, but these are mostly found in
urban areas. Persons with early-onset Alzheimer’s may have greater physical strength
and vitality than most facilities are accustomed to in their residents, and if there is
aggressive behavior or wandering, continued stay in the facility can be threatened. This
may also be the case for individuals with fronto-temporal dementia.
 

Alzheimer’s Disease Genetics Fact Sheet
From the National Institute on Aging
Alzheimer’s Disease Education and Referral Center

https://www.nia.nih.gov/alzheimers/publication/
alzheimers-disease-genetics-fact-sheet
Page Last Updated: April 8, 2016
 
Scientists believe that many factors influence when Alzheimer's disease begins and how
it progresses. The more they study this devastating disease, the more they realize that
genes play an important role. Research conducted and funded by the National Institute
on Aging (NIA) at the National Institutes of Health (NIH) and others is advancing our
understanding of Alzheimer's disease genetics.
 
The Genetics of Disease
Some diseases are caused by a genetic mutation, or permanent change in one or more
specific genes. If a person inherits from a parent a genetic mutation that causes a
certain disease, then he or she will usually get the disease. Sickle cell anemia, cystic
fibrosis, and early-onset familial Alzheimer's disease are examples of inherited genetic
disorders.
 
In other diseases, a genetic variant may occur. A single gene can have many variants.
Sometimes, this difference in a gene can cause a disease directly. More often, a variant
plays a role in increasing or decreasing a person's risk of developing a disease or
condition. When a genetic variant increases disease risk but does not directly cause a
disease, it is called a genetic risk factor.
 
Identifying genetic variants may help researchers find the most effective ways to treat or
prevent diseases such as Alzheimer's in an individual. This approach, called precision
medicine, takes into account individual variability in genes, environment, and lifestyle for
each person.
 
Alzheimer’s Disease Genetics
Alzheimer's disease is an irreversible, progressive brain disease. It is characterized by
the development of amyloid plaques and neurofibrillary, or tau, tangles; the loss of
connections between nerve cells (neurons) in the brain; and the death of these nerve
cells. There are two types of Alzheimer's—early-onset and late-onset. Both types have a
genetic component.
 
What Are DNA, Chromosomes, and Genes?
Genetic mutations in a cell can lead to abnormal proteins and, in turn, diseases such as
early-onset Alzheimer’s.
 
The nucleus of almost every human cell contains a “blueprint” that carries the
instructions a cell needs to do its job. The blueprint is made up of DNA
(deoxyribonucleic acid), which is present in long strands that would stretch to nearly 6
feet in length if attached end to end. The DNA is packed tightly together
with proteins into compact structures called chromosomes. Normally, each cell has 46
chromosomes in 23 pairs, which are inherited equally from a person's biological parents.
The DNA in nearly all cells of an individual is identical.
 
Each chromosome contains many thousands of segments, called genes. People inherit
two copies of each gene from their parents, except for genes on the X and Ychromosomes,
which, among other functions, determine a person's sex. The genes “instruct” the cell to
make unique proteins that, in turn, dictate the types of cells made.
 
Genes also direct almost every aspect of the cell's construction, operation, and repair.
Even slight changes in a gene can produce a protein that functions abnormally, which
may lead to disease. Other changes in genes may increase or decrease a person's risk
of developing a particular disease.
 
Early-Onset Alzheimer's Disease
(see also p. 63)
 
Early-onset Alzheimer's disease occurs in people age 30 to 60 and represents less than
5 percent of all people with Alzheimer's. Most cases are caused by an inherited change
in one of three genes, resulting in a type known as early-onset familial Alzheimer's
disease, or FAD. For others, the disease appears to develop without any specific, known
cause.
 
A child whose biological mother or father carries a genetic mutation for early-onset FAD
has a 50/50 chance of inheriting that mutation. If the mutation is in fact inherited, the
child has a very strong probability of developing early-onset FAD.
 
Early-onset FAD is caused by any one of a number of different single-gene mutations on
chromosomes 21, 14, and 1. Each of these mutations causes abnormal proteins to be
formed. Mutations on chromosome 21 cause the formation of abnormal amyloid
precursor protein (APP). A mutation on chromosome 14 causes abnormal presenilin 1 to
be made, and a mutation on chromosome 1 leads to abnormal presenilin 2.
Each of these mutations plays a role in the breakdown of APP, a protein whose precise
function is not yet fully understood. This breakdown is part of a process that generates
harmful forms of amyloid plaques, a hallmark of the disease.
 
Critical research findings about early-onset Alzheimer's have helped identify key steps in
the formation of brain abnormalities typical of the more common late-onset form of
Alzheimer's. Genetics studies have helped explain why the disease develops in people
at various ages.
 
NIA-supported scientists are continuing research into early-onset disease through
the Dominantly Inherited Alzheimer Network (DIAN), an international partnership to
study families with early-onset FAD. By observing the Alzheimer's-related brain changes
that occur in these families long before symptoms of memory loss or cognitive issues
appear, scientists hope to gain insight into how and why the disease develops in both its
early- and late-onset forms.
 
In addition, a clinical trial in Colombia, South America, supported by the NIA, is testing
the effectiveness of an amyloid-clearing drug in symptom-free volunteers at high risk of
developing early-onset FAD.
 
Late-Onset Alzheimer's Disease
Most people with Alzheimer's have the late-onset form of the disease, in which
symptoms become apparent in the mid-60s and later. The causes of late-onset
Alzheimer's are not yet completely understood, but they likely include a combination of
genetic, environmental, and lifestyle factors that affect a person's risk for developing the
disease.
 
Researchers have not found a specific gene that directly causes the late-onset form of
the disease. However, one genetic risk factor—having one form of the apolipoprotein E
(APOE) gene on chromosome 19—does increase a person's risk. APOE comes in
several different forms, or alleles:
 
• APOE ε2 is relatively rare and may provide some protection against the disease.
If Alzheimer's disease occurs in a person with this allele, it usually develops later
in life than it would in someone with the APOE ε4 gene.
• APOE ε3, the most common allele, is believed to play a neutral role in the
disease—neither decreasing nor increasing risk.
• APOE ε4 increases risk for Alzheimer's disease and is also associated with an
earlier age of disease onset. A person has zero, one, or two APOE ε4 alleles.
Having more APOE ε4 alleles increases the risk of developing Alzheimer's.
 
APOE ε4 is called a risk-factor gene because it increases a person's risk of developing
the disease. However, inheriting an APOE ε4 allele does not mean that a person will
definitely develop Alzheimer's. Some people with an APOE ε4 allele never get the
disease, and others who develop Alzheimer's do not have any APOE ε4 alleles.
Using a relatively new approach called genome-wide association study (GWAS),
researchers have identified a number of regions of interest in the genome (an
organism's complete set of DNA, including all of its genes) that may increase a person's
risk for late-onset Alzheimer's to varying degrees. By 2015, they had confirmed 33
regions of interest in the Alzheimer's genome.
 
A method called whole genome sequencing determines the complete DNA sequence of
a person's genome at a single time. Another method called whole exome sequencing
looks at the parts of the genome that directly code for the proteins. Using these two
approaches, researchers can identify new genes that contribute to or protect against
disease risk. Recent discoveries have led to new insights about biological pathways
involved in Alzheimer's and may one day lead to effective interventions.
 
Genetic Testing
A blood test can identify which APOE alleles a person has, but results cannot predict
who will or will not develop Alzheimer's disease. It is unlikely that genetic testing will ever
be able to predict the disease with 100 percent accuracy, researchers believe, because
too many other factors may influence its development and progression.
 
Currently, APOE testing is used in research settings to identify study participants who
may have an increased risk of developing Alzheimer's. This knowledge helps scientists
look for early brain changes in participants and compare the effectiveness of treatments
for people with different APOE profiles. Most researchers believe that APOE testing is
useful for studying Alzheimer's disease risk in large groups of people but not for
determining any one person's risk.
 
Genetic testing is used by researchers conducting clinical trials and by physicians to
help diagnose early-onset Alzheimer's disease. However, genetic testing is not
otherwise recommended.
 
Epigenetics: Nature Meets Nurture
Scientists have long thought that genetic and environmental factors interact to influence
a person's biological makeup, including the predisposition to different diseases. More
recently, they have discovered the biological mechanisms for those interactions. The
expression of genes (when particular genes are “switched” on or off) can be affected—
positively and negatively—by environmental factors at any time in life. These factors
include exercise, diet, chemicals, or smoking, to which an individual may be exposed,
even in the womb.
 
Epigenetics is an emerging science focused on how and when particular genes are
turned on or off. Diet and exposure to chemicals in the environment, among other
factors, can alter a cell's DNA in ways that affect the activity of genes. That can make
people more or less susceptible to developing a disease.
 
There is emerging evidence that epigenetic mechanisms contribute to Alzheimer's
disease. Epigenetic changes, whether protective, benign, or harmful, may help explain,
for example, why one family member develops the disease and another does not.
Scientists are learning more about Alzheimer's-related epigenetics, with the hope of
developing individualized treatments based on epigenetic markers and their function.
 
Research Questions
Discovering all that we can about the role of Alzheimer's disease genetic risk and
protective factors is an important area of research. Understanding more about the
genetic basis of the disease will help researchers to answer a number of basic
questions: (1) Determine what makes the disease process begin? (2) Understand why
do some people with memory and other thinking problems develop Alzheimer's while
others do not? (3) Determine how genetic risk and protective factors may interact with
other genes and lifestyle or environmental factors to affect Alzheimer's risk in any one
person; (4) Identify people who are at high risk for developing Alzheimer's so they can
benefit from new interventions and treatments as soon as possible; and (5) Focus on
new prevention and treatment approaches.
 
Major Alzheimer's Genetics Research Efforts Underway
The National Institute on Aging supports several major genetics research programs:
 
(1) The Alzheimer's Disease Sequencing Project (ADSP) is an innovative
collaboration between NIA and the National Human Genome Research Institute, both
part of NIH. The first phase of the project determined the order of all 3 billion letters in
the individual genomes of 580 participants. It also generated whole exome sequencing
data for an additional 11,000 volunteers.
 
(2) The Alzheimer's Disease Genetics Consortium is a collaborative effort to collect
and analyze genetic data from thousands of families around the world to identify genes
associated with an increased risk of developing late-onset Alzheimer's.
 
(3) The Late-Onset Alzheimer's Disease Genetics Study is gathering and analyzing
genetic and other information from 1,500 or more families in the United States with two
or more members who have late-onset Alzheimer's.
 
(4) The International Genomic Alzheimer's Project (IGAP) is comprised of four
consortia in the United States and Europe that have been working together since 2011
on genome-wide association studies (GWAS) involving thousands of DNA samples and
shared data sets. In a study of more than 74,000 individuals, IGAP recently reported the
identification of 19 novel regions of interest that are associated with the disease.
 
(5) The Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is a national
genetics data repository that gives investigators access to data to study the genetics of
late-onset Alzheimer's disease.
 
(6) The National Cell Repository for Alzheimer's Disease (NCRAD) is a national
resource that helps researchers find genes that increase the risk of Alzheimer's by
providing biological samples and data.
 
Volunteers are critical to Alzheimer's disease genetics research. The more genetic
information that researchers can gather and analyze from individuals and families—both
healthy volunteers and those who may be at risk—the more clues they will have for
finding additional risk-factor genes.
 
Glossary
 
Allele—A form of a gene. Each person receives two alleles of a gene, one from
each biological parent. This combination is one factor among many that influence
a variety of processes in the body. On chromosome 19, the apolipoprotein E
(APOE) gene has three common alleles: ε2, ε3, and ε4.
 
Apolipoprotein E (APOE) gene—A gene on chromosome 19 involved in making
a protein that helps carry cholesterol and other types of fat in the bloodstream.
The APOE ε4 allele is the major known risk-factor gene for late-onset Alzheimer's
disease.
 
Chromosome — A compact structure containing DNA and proteins present in
nearly all cells of the body. Chromosomes carry genes, which direct the cell to
make proteins and direct a cell's construction, operation, and repair. Normally,
each cell has 46 chromosomes in 23 pairs. Each biological parent contributes
one of each pair of chromosomes.
 
DNA (deoxyribonucleic acid)—The hereditary material in humans and almost
all other organisms. Almost all cells in a person's body have the same DNA. Most
DNA is located in the cell nucleus.
 
Gene—A basic unit of heredity. Genes direct a cell to make proteins and guide
almost every aspect of a cell's construction, operation, and repair.
 
Genetic mutation—A permanent change in a gene that can be passed on to
children. The rare, early-onset familial form of Alzheimer's disease is associated
with mutations in genes on chromosomes 21, 14, and 1.
 
Genetic risk factor—A change in a gene that increases a person's risk of
developing a disease.
 
Genetic variant—A change in a gene that may increase or decrease a person's
risk of developing a disease or condition.
 
Genome—An organism's complete set of DNA, including all of its genes. Each
genome contains all of the information needed to build and maintain that
organism.
 
Protein—A substance that determines the physical and chemical characteristics
of a cell and therefore of an organism. Proteins are essential to all cell functions
and are created using genetic information.