About Alzheimer ’s disease

About Dementia

Dementia is a general term for a decline in mental ability severe enough to interfere with
daily life. Dementia is not a single disease; it’s the umbrella term for an individual’s
changes in memory, thinking or reasoning. There are many possible causes of dementia,
including Alzheimer’s disease. Disorders grouped under the general term “dementia” are
caused by abnormal brain changes. These changes trigger a decline in thinking skills, also
known as cognitive abilities, severe enough to impair daily life and independent function.
They also affect behavior, feelings and relationships.
Brain changes that cause dementia may be temporary, but they are most often
permanent and worsen, leading to increasing disability and a shortened life span. Survival
can vary widely, depending on such factors as the cause of the dementia, age at diagnosis
and other health conditions of the individual.

Alzheimer’s disease

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, front temporal 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. Once healthy neurons stop functioning and
lose connections with other neurons, they 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.
 Risk Factors

Researchers believe there is not a single cause of Alzheimer’s disease. It likely develops
from multiple factors, such as genetics, lifestyle and environment. Scientists have
identified factors that increase the risk of Alzheimer’s. While some risk factors like age,
family history and genetics can't be changed, emerging evidence suggests there may be
other factors people can influence.

Age
The greatest risk for Alzheimer’s disease is age. After age 65, a person’s risk of
developing the disease increases dramatically. About a third of people age 85 or
older have Alzheimer’s.

Family history
Researchers have learned that people who have a parent, brother or sister with
Alzheimer’s are more likely to develop it than those who do not. The risk increases
if more than one family member has the disease.

Genetics
Two types of genes influence whether a person develops a disease: risk genes and
deterministic genes. Risk genes increase the chance of developing a disease but do
not guarantee it will happen. Deterministic genes cause a disease. This means
anyone who inherits a deterministic gene will develop a disorder.

Rare deterministic genes cause Alzheimer’s in a few hundred extended families

worldwide. Scientists estimate these genes cause less than 1% of cases. Individuals
with these genes usually develop symptoms in their 40s or 50s.

Hispanic people, Black Americans and women

Research shows Black Americans are about twice as likely as White Americans to
have Alzheimer’s or another dementia, and Hispanic Americans are one-and-a-half
 times as likely. Though no one knows the exact reason for these differences,
researchers believe they are related to disparities produced by the historic and
continued marginalization of Black and Hispanic people in the United States —
disparities between older Black and Hispanic populations and older White
populations in life experiences, socioeconomic indicators and, ultimately, health
conditions.

Additionally, women are more likely to develop Alzheimer’s than men. This
difference may be explained, in part, by the fact that women live longer. However,
researchers are exploring how genetic differences may impact Alzheimer’s risk
differently in men and women.

Lowering the risk of cognitive decline

Age, family history and genetics are all risk factors that can’t be changed. However, a
growing body of evidence shows that addressing certain modifiable risk factors and
promoting healthy behaviors can reduce the risk of cognitive decline, possibly reduce the
risk of dementia, and protect cognitive health.

Studies show a strong connection between serious head injury and future risk of
Alzheimer’s. For this reason, it is important to protect against head injury by wearing a
seat belt in the car, wearing a helmet when playing sports and making sure the home is
safe to avoid falls. Research also shows there are lifestyle habits that people can adopt to
help keep their brain healthy and lower their risk of cognitive decline. These include
eating a healthy diet, staying socially active and exercising the body and mind. Not using
tobacco and avoiding excess alcohol is also good for brain health. Science tells us there is
a strong connection between brain health and heart health. The risk of developing
dementia appears to be increased by many conditions that damage the heart and blood
vessels. These include heart disease, diabetes, stroke, high blood pressure and high
cholesterol.
 Symptoms and Signs

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 (biological signs
of disease found in brain images, cerebrospinal fluid, and blood) 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 body shuts down.

What Causes Alzheimer’s

Scientists don’t yet fully understand what causes Alzheimer’s disease in most
people.Inpeople with early-onset Alzheimer’s, a genetic mutation is usually the
cause. Late-on set 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 Apo lipoprotein E (APOE) gene is involved in late-
onset Alzheimer’s. This gene has several forms. One of them, APOE e4, increases a
person’s risk of developing the disease and is also associated with an earlier age of disease
onset. However, carrying the APOE e4 form of the gene does not mean that a person will
definitely develop Alzheimer’s disease, and some people with no APOE e4 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.
Multiple conditions can cause cognitive changes, so it’s essential to obtain a full
medical evaluation to determine whether symptoms are related to Alzheimer’s or
something else. If the cause is not Alzheimer’s or another dementia, it could be a treatable
condition. If it is dementia, there are many benefits to receiving an early and accurate
diagnosis, including an opportunity to plan for the future, access support services and
explore medication that may address some symptoms for a time.

There is no single diagnostic test that can determine if a person has Alzheimer’s
disease. However, diagnostic tools and criteria make it possible for physicians to make a
diagnosis of Alzheimer’s with about 90% accuracy. The diagnostic process may involve a
thorough medical history, mental status and mood testing, a physical and neurological
exam, and tests (such as blood tests and brain scans) to rule out other causes of dementia-
like symptoms. This process may take more than one day or visit. To learn more about
the diagnostic process, visit alz.org/evaluatememory.
 Treatments

Progress in Alzheimer’s and dementia research is creating promising treatments for

people living with the disease.

The U.S. Food and Drug Administration (FDA) has approved medications that fall into two
categories: drugs that change disease progression in people living with Alzheimer’s, and
drugs that may temporarily mitigate some of the symptoms of the disease.

When considering any treatment, it is important to have a conversation with a health care
professional to determine whether it is appropriate. A physician who is experienced in
using these types of medications should monitor people who are taking them and ensure
that the recommended guidelines are strictly observed.

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

Several medications are approved by the U.S. Food and Drug Administration 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 each
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.
 Drugs That Change Disease Progression

Drugs in this category slow disease progression. They slow the decline of memory
and thinking, as well as function, in people living with Alzheimer’s disease.
The treatment landscape is rapidly changing. For the most up-to-date information on
FDA-approved treatments for Alzheimer’s disease.

Amyloid-targeting approaches
Anti-amyloid treatments work by removing beta-amyloid, a protein that
accumulates into plaques, from the brain. Each works differently and targets beta-
amyloid at a different stage of plaque formation.

These treatments change the course of the disease in a meaningful way for people in the
early stages, giving them more time to participate in daily life and live independently.
Clinical trial participants who received anti-amyloid treatments experienced reduction in
cognitive decline observed through measures of cognition and function.

Examples of cognition measures include:

● Memory.
● Orientation.

Examples of functional measures include:

● Conducting personal finances.
● Performing household chores such as cleaning.

Anti-amyloid treatments do have side effects. These treatments can cause serious allergic
reactions. Side effects can also include amyloid-related imaging abnormalities (ARIA),
infusion-related reactions, headaches and falls.

ARIA is a common side effect that does not usually cause symptoms but can be serious. It
is typically a temporary swelling in areas of the brain that usually resolves over time. Some
people may also have small spots of bleeding in or on the surface of the brain with the
swelling, although most people with swelling in areas of the brain do not have symptoms.
Some may have symptoms of ARIA such as headache, dizziness, nausea, confusion and
vision changes.
Some people have a genetic risk factor (ApoE ε4 gene carriers) that may cause an
Increased risk for ARIA. The FDA encourages that testing for ApoE ε4 status should be
Performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to
testing, doctors should discuss with patients the risk of ARIA and the implications of
genetic testing results.

These are not all the possible side effects, and individuals should talk with their doctors
to develop a treatment plan that is right for them, including weighing the benefits and
risks of all approved therapies.

Aducanumab (Aduhelm®)
Aducanumab (Aduhelm) is an anti-amyloid antibody intravenous (IV) infusion therapy
that is delivered every four weeks. It has received accelerated approval from the FDA to
treat early Alzheimer's disease, including people living with mild cognitive impairment
(MCI) or mild dementia due to Alzheimer's disease whohave confirmation of elevated
beta-amyloid in the brain.

Aducanumab was the first therapy to demonstrate that removing beta-amyloid from the
brain reduces cognitive and functional decline in people living with early Alzheimer’s.

Aducanumab is being discontinued by its manufacturer, Biogen. The company stated that
people who are now receiving the drug as part of a clinical trial will continue to have
access to it until May 1, 2024, and that people who are now receiving it by prescription
will have it available to them until Nov. 1, 2024.
Donanemab (Kisunla™)
Donanemab (Kisunla) is an anti-amyloid antibody intravenous (IV) infusion therapy
delivered every four weeks. It has received traditional approval from the FDA to treat
early Alzheimer's disease, including people living with mild cognitive impairment (MCI) or
mild dementia due to Alzheimer's disease who have confirmation of elevated beta-
amyloid in the brain. There is no safety or effectiveness data on initiating treatment at
earlier or later stages of the disease than were studied. Donanemab was the third therapy
to demonstrate that removing beta-amyloid from the brain reduces cognitive and
functional decline in people living with early Alzheimer's

Lecanemab (Leqembi®)
Lecanemab (Leqembi) is an anti-amyloid antibody intravenous (IV) infusion therapy that
is delivered every two weeks. It has received traditional approval from the FDA to treat
early Alzheimer's disease, including people living with mild cognitive impairment (MCI) or
mild dementia due to Alzheimer's disease who have confirmation of elevated beta-
amyloid in the brain. There is no safety or effectiveness data on initiating treatment at
earlier or later stages of the disease than were studied. Lecanemab was the second
therapy to demonstrate that removing beta-amyloid from the brain reduces cognitive and
functional decline in people living with early Alzheimer's.
 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.