Alzheimer’s Disease 

FACT SHEET

memory and thinking skills, and even

Alzheimer’s disease (AD) is an 

irreversible, progressive brain 

disease that slowly destroys 

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tually even the ability to carry out the 

simplest tasks. In most people with AD, 

symptoms first appear after age 60. 

AD is the most common cause of dementia among older people. Dementia 

is the loss of cognitive functioning—

thinking, remembering, and reasoning—to such an extent that it interferes 

with a person’s daily life and activities. 

According to recent estimates, as many 

as 2.4 to 4.5 million Americans are 

living with AD. 

AD 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 tangles). Plaques 

and tangles in the brain are two of the 

main features of AD. The third is the 

loss of connections between nerve cells 

(neurons) in the brain. 

Changes in the Brain in AD

Although we still don’t know what 

starts the AD process, we do know that 

damage to the brain begins as many 

as 10 to 20 years before any problems 

are evident. Tangles begin to develop 

deep in the brain, in an area called the 

entorhinal cortex, and plaques form in 

other areas. As more and more plaques 

and tangles form in particular brain 

areas, healthy neurons begin to work 

less efficiently. Then, they lose their 

ability to function and communicate 

with each other, and eventually they 

die. This damaging process spreads 

to a nearby structure, called the hippocampus, which is essential in forming 

memories. As the death of neurons 

increases, affected brain regions begin 

to shrink. By the final stage of AD, 

damage is widespread and brain tissue 

has shrunk significantly. 

Very Early Signs and Symptoms 

Memory problems are one of the first 

signs of AD. Some people with memory 

problems have a condition called 

amnestic mild cognitive impairment 

(MCI). People with this condition have 

more memory problems than normal 

for people their age, but their symptoms 

Alzheimer’s Disease Education & Referral (ADEAR) Center

A Service of the National Institute on Aging

National Institutes of Health

U.S. Department of Health and Human Services
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are not as severe as those with AD. More 

people with MCI, compared with those 

without MCI, go on to develop AD. 

Other changes may also signal the very 

early stages of AD. For example, recent 

research has found links between some 

movement difficulties and MCI. Researchers also have seen links between some 

problems with the sense of smell and 

cognitive problems. Brain imaging and 

biomarker studies of people with MCI and 

those with a family history of AD are beginning to detect early changes in the brain 

like those seen in AD. These findings will 

need to be confirmed by other studies but 

appear promising. Such findings offer 

hope that some day, we may have tools 

that could help detect AD early, track the 

course of the disease, and monitor response 

to treatments.

Mild AD 

As AD progresses, memory loss continues 

and changes in other cognitive abilities 

appear. Problems can include getting 

lost, trouble handling money and paying 

bills, repeating questions, taking longer 

to complete normal daily tasks, poor 

judgment, and mood and personality 

changes. People often are first diagnosed 

in this stage.

Moderate AD

In this stage, damage occurs in areas of 

the brain that control language, reasoning, 

sensory processing, and conscious thought. 

Memory loss and confusion increase, and 

people begin to have problems recognizing 

family and friends. They may be unable 

to learn new things, carry out tasks that 

involve multiple steps (such as getting 

dressed), or cope with new situations. 

They may have hallucinations, delusions, 

and paranoia, and may behave impulsively.

Severe AD 

By the final stage, plaques and tangles 

have spread throughout the brain and 

brain tissue has shrunk significantly. 

People with severe AD 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 AD 

Scientists don’t yet fully understand what 

causes AD, but it is clear that it develops 

because of a complex series of events that 

As Alzheimer’s disease progresses, neurofibrillary tangles spread throughout the brain 

(shown in blue). Plaques also spread throughout the brain, starting in the neocortex. By 

the final stage, damage is widespread and 

brain tissue has shrunk significantly.
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take place in the brain over a long 

period of time. It is likely that the 

causes include genetic, environmental, 

and lifestyle factors. Because people 

differ in their genetic make-up and lifestyle, the importance of these factors 

for preventing or delaying AD differs 

from person to person. 

The Basics of AD

Scientists are conducting studies to 

learn more about plaques, tangles, and 

other features of AD. They can now 

visualize plaques by imaging the brains 

of living individuals. They are also 

exploring the very earliest steps in the 

disease process. Findings from these 

studies will help them understand the 

causes of AD. 

One of the great mysteries of AD is why 

it largely strikes older adults. Research 

on how the brain changes normally with 

age is shedding light on this question. 

For example, scientists are learning 

how age-related changes in the brain 

may harm neurons and contribute to 

AD damage. These age-related changes 

include inflammation and the production of unstable molecules called free 

radicals.

Genetics 

In a very few families, people develop 

AD in their 30s, 40s, and 50s. These 

people have a mutation, or permanent 

change, in one of three genes that they 

inherited from a parent. We know that 

these gene mutations cause AD in these 

“early-onset” familial cases. 

However, most people with AD have 

“late-onset” AD, which usually develops 

after age 60. Many studies have linked a 

gene called APOE to late-onset AD. This 

gene has several forms. One of them, 

APOE e4, increases a person’s risk of 

getting the disease. About 40 percent 

of all people who develop late-onset AD 

carry this gene. However, carrying the 

APOE e4 form of the gene does not 

necessarily mean that a person will 

develop AD, and people carrying no 

APOE e4 forms can also develop AD. 

Scientists think that other risk-factor 

genes exist as well. A possible new one, 

SORL1, was discovered in 2007. Largescale genetic research studies are looking to find other genes. For more about 

this area of research, see the Alzheimer’s 

Disease Genetics Fact Sheet, available at 

www.nia.nih.gov/Alzheimers. 

Lifestyle Factors 

A nutritious diet, exercise, social engagement, and mentally stimulating 

pursuits can all help people stay healthy. 

New research suggests the possibility 

that these factors also might help to 

reduce the risk of cognitive decline and 

AD. Scientists are investigating associations between cognitive decline and 

heart disease, high blood pressure, 

diabetes, and obesity. Understanding 

these relationships and testing them in 

clinical trials will help us understand 

whether reducing risk factors for these 

diseases may help with AD as well. 

How AD Is Diagnosed

AD can be definitively diagnosed only 

after death by linking clinical course 

with an examination of brain tissue and 

pathology in an autopsy. But doctors 

now have several methods and tools to 

help them determine fairly accurately 
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whether a person who is having 

memory problems has “possible AD” 

(the symptoms may be due to another 

cause) or “probable AD” (no other cause 

for the symptoms can be found). To 

diagnose AD, doctors:

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ask questions about the person’s 

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 medical tests, such as tests 

of blood, urine, or spinal fluid 

perform brain scans, such as a computerized tomography (CT) scan or 

a magnetic resonance imaging (MRI) 

test

These tests may be repeated to give 

doctors information about how the 

person’s memory is changing over 

time. 

Early diagnosis is beneficial for several 

reasons. Having an early diagnosis and 

starting treatment in the early stages 

of the disease can help preserve function for months to years, even though 

the underlying AD process cannot be 

changed. Having an early diagnosis 

also helps families plan for the future, 

make living arrangements, take care 

of financial and legal matters, and 

develop support networks. 

In addition, an early diagnosis can 

provide greater opportunities for people 

to get involved in clinical trials. In a 

clinical trial, scientists test drugs or 

treatments to see which are most effective and for whom they work best. (See 

the box, below, for more information.)

Participating in 

Clinical Trials

People with AD, those with MCI, those 

with a family history of AD, and healthy 

people with no memory problems and no 

family history of AD may be able to take 

part in clinical trials. Study volunteers 

help scientists learn about the brain in 

healthy aging as well as what happens in 

AD. Results of AD clinical trials are used 

to improve prevention and treatment 

approaches. Participating in clinical trials 

is an effective way to help in the fight 

against AD.

NIA, which is part of the National 

Institutes of Health (NIH), leads the 

Federal Government’s research efforts 

on AD. NIA-supported Alzheimer’s 

Disease Centers located throughout the 

United States conduct many clinical trials 

and carry out a wide range of research, 

including studies of the causes, diagnosis, and management of AD. NIA 

also sponsors the Alzheimer’s Disease 

Cooperative Study (ADCS), a consortium 

of leading AD researchers throughout 

the U.S. and Canada who conduct clinical 

trials on promising AD treatments.

To find out more about AD clinical trials, 

talk to your health care provider or contact NIA’s ADEAR Center at 1-800-438-

4380. Or, visit the ADEAR Center clinical 

trials database at www.nia.nih.gov/

Alzheimers/ResearchInformation/

ClinicalTrials. You also can sign up for 

email alerts that let you know when new 

clinical trials are added to the database. 

More information about clinical trials 

is available at www.ClinicalTrials.gov.
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How AD Is Treated

AD is a complex disease, and no single 

“magic bullet” is likely to prevent or cure 

it. That’s why current treatments focus on 

several different aspects, including helping 

people maintain mental function; managing behavioral symptoms; and slowing, 

delaying, or preventing AD.

Helping People with AD Maintain 

Mental Function 

Four medications are approved by the 

U.S. Food and Drug Administration to treat 

AD. Donepezil (Aricept®), rivastigmine 

(Exelon®), and galantamine (Razadyne®) 

are used to treat mild to moderate AD 

(donepezil can be used for severe AD as 

well). Memantine (Namenda®) is used to 

treat moderate to severe AD. These drugs 

work by regulating neurotransmitters (the 

chemicals that transmit messages between 

neurons). They may help maintain thinking, memory, and speaking skills, and 

help with certain behavioral problems. 

However, these drugs don’t change the 

underlying disease process and may help 

only for a few months to a few years.

Managing Behavioral Symptoms 

Common behavioral symptoms of AD include sleeplessness, agitation, wandering, 

anxiety, anger, and depression. Scientists 

are learning why these symptoms occur 

and are studying new treatments—drug 

and non-drug—to manage them. Treating 

behavioral symptoms often makes people 

with AD more comfortable and makes their 

care easier for caregivers.

Slowing, Delaying, or Preventing AD

AD research has developed to a point 

where scientists can look beyond treating 

symptoms to think about addressing the 

underlying disease process. In ongoing 

AD clinical trials, scientists are looking 

at many possible interventions, such as 

cardiovascular treatments, antioxidants, 

immunization therapy, cognitive training, 

and physical activity. 

Supporting Families and 

Caregivers

Caring for a person with AD can have high 

physical, emotional, and financial costs. 

The demands of day-to-day care, changing 

family roles, and difficult decisions about 

placement in a care facility can be hard 

to handle. Researchers are learning a lot 

about AD caregiving, and studies are helping experts develop new ways to support 

caregivers.

Becoming well-informed about AD is one 

important long-term strategy. Programs 

that teach families about the various stages 

of AD and about flexible and practical 

strategies for dealing with difficult caregiving situations provide vital help to those 

who care for people with AD.

Developing good coping skills and a strong 

support network of family and friends also 

are important ways that caregivers can 

help themselves handle the stresses of caring for a loved one with AD. For example, 

staying physically active provides physical 

and emotional benefits. 

Some AD caregivers have found that 

participating in an AD support group is 

a critical lifeline. These support groups 

allow caregivers to find respite, express 

concerns, share experiences, get tips, and 

receive emotional comfort. The Alzheimer’s 

Association, Alzheimer’s Disease Centers, 

and many other organizations sponsor 
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in-person and online AD support groups 

across the country. There are a growing 

number of groups for people in the early 

stage of AD and their families. Support 

networks can be especially valuable 

when caregivers face the difficult decision of whether and when to place a 

loved one in a nursing home.

Advancing Our Understanding

Thirty years ago, we knew very little 

about AD. Since then, scientists have 

made many important advances. 

Research supported by NIA and other 

organizations has expanded knowledge 

of brain function in healthy older people, 

identified ways we might lessen normal 

age-related declines in mental function, 

and deepened our understanding of AD. 

Many scientific and clinical fields are 

now working together to untangle the 

genetic, biological, and environmental 

factors that, over many years, ultimately 

result in AD. This effort is bringing us 

closer to the day when we will be able 

to manage successfully or even prevent 

this devastating disease.

For More Information

To learn about support groups, services, 

research centers, research studies, and 

publications about AD, contact the 

following resources:

Alzheimer’s Disease Education 

and Referral (ADEAR) Center

P.O. Box 8250

Silver Spring, MD 20907-8250

800-438-4380 (toll-free)

www.nia.nih.gov/Alzheimers 

A service of the National Institute on 

Aging (NIA), the ADEAR Center offers 

information and publications for families, 

caregivers, and professionals on diagnosis, treatment, patient care, caregiver 

needs, long-term care, education and 

training, and research related to AD. 

Staff members answer telephone, email, 

and written requests and make referrals 

to local and national resources. The 

ADEAR website provides free, online 

publications in English and Spanish; 

email alert and online Connections

newsletter subscriptions; an AD clinical 

trials database; the AD Library database; 

and more.

Alzheimer’s Association 

225 N. Michigan Avenue, Floor 17 

Chicago, IL 60601-7633 

800-272-3900 (toll-free) 

866-403-3073 (TDD/toll-free) 

www.alz.org

Alzheimer’s Foundation of America 

322 Eighth Avenue, 7th Floor 

New York, NY 10001 

866-AFA-8484 (866-232-8484; toll-free) 

www.alzfdn.org

Eldercare Locator 

800-677-1116 (toll-free) 

www.eldercare.gov

Family Caregiver Alliance 

180 Montgomery Street, Suite 1100 

San Francisco, CA 94104 

800-445-8106 (toll-free) 

www.caregiver.org

NIHSeniorHealth

www.nihseniorhealth.gov

NIH Publication No. 08-6423 November 2008