Alzheimer’s disease

A topic in the Alzheimer’s Association® series on understanding dementia.

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 not a normal part of aging — it is a progressive brain disease
that causes problems with memory, thinking and behavior. Alzheimer’s is the most
common cause of dementia, contributing to 60% to 80% of dementia cases. Although
there is currently no cure for Alzheimer’s, researchers are paving the way for future
treatments by uncovering new insights into the biology of the disease.

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,
research is offering clues about other risk factors that people may be able to
influence. 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

The symptoms of Alzheimer’s disease are more than simple lapses in memory or age-
related changes. People living with Alzheimer’s disease experience memory loss as
well as difficulties communicating, learning, thinking and reasoning. These are
problems severe enough to interfere with an individual’s work, social activities and
family life.

As the disease progresses, individuals may also experience changes in personality and
behavior, such as anxiety, suspicion or agitation, as well as delusions or
hallucinations.

In collaboration with experts in the field, the Alzheimer’s Association® created a list
of warning signs to help people identify symptoms that may be related to Alzheimer’s
or another form of dementia (alz.org/10signs). It is possible for individuals to
experience one or more of these signs in varying degrees. It is not necessary to
experience every sign in order to raise concern.

If you’re concerned that you or someone you know is displaying any of these signs,
take action. It can be helpful to confide in a friend or family member. For tips on how
to have a conversation, visit alz.org/memoryconcerns.

Diagnosis
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 new 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.

Drugs that change disease progression

Drugs in this category slow disease progression by changing the underlying biology
of the disease process. They aim to 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, visit alz.org/medications.
Amyloid-targeting approaches
Anti-amyloid treatments work by attaching to and removing beta-amyloid, a protein
that accumulates into plaques, from the brain. (These plaques disrupt communication
between nerve cells and may activate immune system cells that trigger inflammation
and devour disabled nerve cells.) Each treatment in progress 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:

● Handling 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 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-e4 gene) that may cause an increased
risk for ARIA. The FDA encourages that testing for APOE-e4 status 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®), a monthly anti-amyloid antibody intravenous (IV)
infusion therapy, 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.

As of January 2024, aducanumab is being discontinued by its manufacturer,

Biogen.

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 levels 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.

Name Approved for Side effects

(Generic/Brand)
Lecanemab Mild cognitive impairment Infusion-related reactions,
Leqembi® and mild dementia due to headache, ARIA
Alzheimer’s disease

Drugs that treat symptoms

Cognitive symptoms (memory and thinking)
These medications are prescribed to treat symptoms related to memory and thinking.
While these drugs cannot stop the damage Alzheimer’s causes to brain cells, they
may help lessen or stabilize symptoms for a limited time by affecting certain
chemicals involved in carrying messages between the brain's nerve cells.
The drugs currently approved to treat cognitive symptoms are cholinesterase
inhibitors and glutamate regulators.

Cholinesterase inhibitors
Cholinesterase (KOH-luh-NES-ter-ays) inhibitors are prescribed to treat symptoms
related to memory, thinking, language, judgment and other thought processes. These
medications prevent the breakdown of acetylcholine (a-SEA-til-KOHlean), a
chemical messenger important for memory and learning. These drugs support
communication between nerve cells.

The cholinesterase inhibitors most commonly prescribed are:

Donepezil (Aricept®): approved to treat all stages of Alzheimer’s disease.

Rivastigmine (Exelon®): approved for mild-to-moderate Alzheimer’s as well
as mild-to-moderate dementia associated with Parkinson’s disease.
Galantamine (Razadyne®): approved for mild-to-moderate stages of
Alzheimer’s disease.

Though generally well-tolerated, if side effects occur, they commonly include nausea,
vomiting, loss of appetite and increased frequency of bowel movements.

Glutamate regulators
Glutamate regulators are prescribed to improve memory, attention, reason, language
and the ability to perform simple tasks. This type of drug works by regulating the
activity of glutamate, a different chemical messenger that helps the brain process
information. This drug is known as:

Memantine (Namenda®): approved for moderate-to-severe Alzheimer’s

disease. Can cause side effects, including headache, constipation, confusion
and dizziness.

Cholinesterase inhibitor + glutamate regulator

This type of drug is a combination of a cholinesterase inhibitor and a glutamate
regulator.
 Donepezil and memantine (Namzaric®): approved for moderate-to-severe
Alzheimer’s disease. Possible side effects include nausea, vomiting, loss of
appetite, increased frequency of bowel movements, headache, constipation,
confusion and dizziness.

Name Approved for Side effects

(Generic/Brand)
Donepezil Mild to severe dementia Nausea, vomiting, loss of
Aricept® due to Alzheimer’s appetite, muscle cramps
and increased frequency of
bowel movements.
Galantamine Mild to moderate dementia Nausea, vomiting, loss of
Razadyne® due to Alzheimer’s appetite and increased
frequency of bowel
movements.
Rivastigmine Mild to moderate dementia Nausea, vomiting, loss of
Exelon® due to Alzheimer’s or appetite and increased
Parkinson’s frequency of bowel
movements.
Memantine Moderate to severe Headache, constipation,
Namenda® dementia due to confusion and dizziness.
Alzheimer’s
Memantine + Donepezil Moderate to severe Nausea, vomiting, loss of
Namzaric® dementia due to appetite, increased
Alzheimer’s frequency of bowel
movements, headache,
constipation, confusion
and dizziness.

Noncognitive symptoms (behavioral and psychological symptoms)

Alzheimer’s affects more than just memory and thinking. A person’s quality of life
may be impacted by a variety of behavioral and psychological symptoms that
accompany dementia, such as sleep disturbances, agitation, hallucinations and
delusions. Some medications focus on treating these noncognitive symptoms for a
time, though it is important to try non-drug strategies to manage behaviors before
adding medications.

The FDA has approved one drug to address symptoms of insomnia that has been
tested in people living with dementia and one that treats agitation.
Orexin receptor antagonist
Prescribed to treat insomnia, this drug inhibits the activity of orexin, a type of
neurotransmitter involved in the sleep-wake cycle:

Suvorexant (Belsomra®): approved for treatment of insomnia and has been

shown in clinical trials to be effective for people living with mild to moderate
Alzheimer’s disease. Possible side effects include, but are not limited to: risk
of impaired alertness and motor coordination (including impaired driving),
worsening of depression or suicidal thinking, complex sleep behaviors (such
as sleep-walking and sleep-driving), sleep paralysis and compromised
respiratory function.

Atypical antipsychotics
Atypical antipsychotics are a group of antipsychotic drugs that target the serotonin
and dopamine chemical pathways in the brain. These drugs are largely used to treat
schizophrenia and bipolar disorder and as add-on therapies for major depressive
disorder. The FDA requires that all atypical antipsychotics carry a safety warning that
the medication has been associated with an increased risk of death in older patients
with dementia-related psychosis.

Many atypical antipsychotic medications are used "off-label" to treat dementia-related

behaviors, and there is currently only one FDA-approved atypical antipsychotic to
treat agitation associated with dementia due to Alzheimer's. It is important to try non-
drug strategies to manage non-cognitive symptoms — like agitation — before adding
medications.

Brexpiprazole (Rexulti®): approved for the treatment of agitation associated

with dementia due to Alzheimer's disease. Possible side effects include, but
are not limited to: weight gain, sleepiness, dizziness, common cold symptoms,
and restlessness or feeling like you need to move. Warning for serious side
effects: increased risk of death in older adults with dementia-related
psychosis. Rexulti is not approved for the treatment of people with dementia-
related psychosis without agitation that may happen with dementia due to
Alzheimer's disease.
 Name Indicated for Common side effects
(Generic/Brand)
Brexpiprazole Agitation associated with Weight gain, sleepiness,
Rexulti® dementia due to dizziness, common cold
Alzheimer's disease symptoms, and
restlessness or feeling like
you need to move.

Warning for serious side

effects: increased risk of
death in older adults with
dementia-related
psychosis. Rexulti is not
approved for the treatment
of people with dementia-
related psychosis without
agitation that may happen
with dementia due to
Alzheimer's disease.
Suvorexant Insomnia in people living Impaired alertness and
Belsomra® with mild to moderate motor coordination,
Alzheimer’s disease worsening of depression or
suicidal thinking, complex
sleep behaviors, sleep
paralysis, compromised
respiratory function.

Progression
Alzheimer’s disease progresses in stages with a range of symptoms that increase in
severity over time. Because the disease affects people in different ways, the rate of
progression will vary. On average, a person with Alzheimer’s may live four to eight
years after diagnosis, but some people live as long as 20 years. Stages of Alzheimer’s
may overlap, which can make it difficult to know which stage a person is in.
There are five stages of the disease:

Asymptomatic
On the earliest end of the continuum are people who are asymptomatic (i.e., without
symptoms). This means that they may have the biological changes of the disease in
their brain but do not show any cognitive symptoms.

Mild cognitive impairment (MCI) due to Alzheimer’s

Mild cognitive impairment (MCI) is an early stage of memory loss or other loss of
cognitive ability in individuals who can still independently perform activities of daily
living. MCI can develop for multiple reasons, and some individuals living with MCI
may go on to develop dementia while others will not. MCI can be an early stage of
Alzheimer’s disease if hallmark changes in the brain, such as beta-amyloid buildup,
are present.

Mild dementia due to Alzheimer’s disease (early)

If hallmark changes in the brain are present, the person may progress into dementia
due to Alzheimer’s disease. A person with mild dementia due to Alzheimer’s
(sometimes referred to as the early stage) will typically start to experience symptoms
that interfere with some daily activities.

Moderate dementia due to Alzheimer’s disease (middle)

For those with moderate dementia due to Alzheimer’s disease (sometimes referred to
as the middle stage), biological changes in the brain continue to progress, and
symptoms are more pronounced and will interfere with many of the person’s daily
activities. This is typically the longest stage of the disease and can last for many
years.

Severe dementia due to Alzheimer’s disease (late)

In this stage (sometimes referred to as the late stage), biological changes in the brain
continue to progress. Symptoms are severe and will interfere with most daily
activities. People in this stage lose the ability to carry on a conversation, respond to
the environment, and, eventually, control movement. Assistance or supervision is
required to complete most daily personal care.
Current Alzheimer’s statistics
● More than 6 million Americans are living with Alzheimer’s disease.
● Alzheimer’s kills more than breast cancer and prostate cancer combined.
● One in 3 seniors dies with Alzheimer’s disease.

TS-0035 | Updated February 2024