lzheimers disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. In most people with Alzheimers, symptoms first appear after age 60. Estimates vary, but experts suggest that as many as 5.1 million Americans may have Alzheimers disease. Alzheimers disease is the most common cause of dementia among older people. Dementia is the loss of cognitive functioningthinking, remembering, and reasoningand behavioral abilities, to such an extent that it interferes with a persons daily life and activities. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a persons functioning, to the most severe stage, when the person must depend completely on others for basic activities of daily living. Alzheimers 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 tangles). Plaques and tangles in the brain are two of the main features of Alzheimers disease. The third is the loss of connections between nerve cells (neurons) in the brain.
Changes in the Brain in
Alzheimers Disease Although we still dont know how the Alzheimers disease process begins, it seems likely that damage to the brain starts a decade or more before problems become evident. During the preclinical stage of Alzheimers disease, people are free of symptoms 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 begin to work less efficiently. Over
Alzheimers Disease Education & Referral (ADEAR) Center
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time, neurons lose their ability to
function and communicate with each other, and eventually they die.
Very Early Alzheimers
Before long, the damage spreads
to a nearby structure in the brain called the hippocampus, which is essential in forming memories. As more neurons die, affected brain regions begin to shrink. By the final stage of Alzheimers, damage is widespread, and brain tissue has shrunk significantly.
Mild to Moderate Alzheimers
Severe Alzheimers
Very Early Signs and Symptoms
Memory problems are typically one of the first warning signs of cognitive loss, possibly due to the development of Alzheimers disease. 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 are not as severe as those seen in people with Alzheimers disease. Other recent studies have found links between some movement difficulties and MCI. Researchers also have seen links between MCI and some problems with the sense of smell. The ability of people with MCI to perform normal daily activities is not significantly impaired. However, more older people with MCI, compared with those without MCI, go on to develop Alzheimers.
As Alzheimers 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.
vision/spatial issues, and impaired
reasoning or judgment, may also signal the very early stages of Alzheimers disease. Scientists are looking to see whether brain imaging and biomarker studies, for example, of people with MCI and those with a family history of Alzheimers, can detect early changes in the brain like those seen in Alzheimers. Initial studies indicate that early detection using biomarkers and imaging may be possible, but findings will need to be confirmed by other studies before these techniques can be used to help with diagnosis in everyday medical practice.
A decline in other aspects of
cognition, such as word-finding,
These and other studies offer hope
that someday we may have tools that could help detect Alzheimers early, track the course of the disease, and monitor response to treatments.
Near the end, the person may be in
bed most or all of the time as the body shuts down.
Mild Alzheimers Disease
Scientists dont yet fully understand
what causes Alzheimers disease, but it has become increasingly clear that it develops because of a complex series of events that take place in the brain over a long period of time. It is likely that the causes include some mix of genetic, environmental, and lifestyle factors. Because people differ in their genetic make-up and lifestyle, the importance of any one of these factors in increasing or decreasing the risk of developing Alzheimers may differ from person to person.
What Causes Alzheimers
As Alzheimers disease progresses,
memory loss worsens, and changes in other cognitive abilities are evident. Problems can include, for example, getting lost, trouble handling money and paying bills, repeating questions, taking longer to complete normal daily tasks, using poor judgment, and having some mood and personality changes. People often are diagnosed in this stage. Moderate Alzheimers Disease
The Basics of Alzheimers
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 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.
Scientists are conducting studies to
learn more about plaques, tangles, and other features of Alzheimers disease. They can now visualize betaamyloid associated with plaques by imaging the brains of living individuals. Scientists are also exploring the very earliest steps in the disease process. Findings from these studies will help them understand the causes of Alzheimers. One of the great mysteries of Alzheimers disease 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
Severe Alzheimers Disease
By the final stage, plaques and tangles have spread throughout the brain, and brain tissue has shrunk significantly. People with severe Alzheimers cannot communicate and are completely dependent on others for their care.
4 contribute to Alzheimers damage. These age-related changes include atrophy (shrinking) of certain parts of the brain, inflammation, the production of unstable molecules called free radicals, and mitochondrial dysfunction (a breakdown of energy production within a cell).
around the world are searching for
these genes, and have identified a number of common genes in addition to APOE 4 that may increase a persons risk for late-onset Alzheimers. For more about this area of research, see the Alzheimers Disease Genetics Fact Sheet, available at www.nia.nih.gov/Alzheimers.
Genetics Early-onset Alzheimers is a rare form of the disease. It occurs in people age 30 to 60 and represents less than 5 percent of all people who have Alzheimers disease. Most cases of early-onset Alzheimers are familial Alzheimers disease, caused by changes in one of three known genes inherited from a parent.
Environmental/Lifestyle Factors Research also suggests that a host of factors beyond basic genetics may play a role in the development and course of Alzheimers disease. There is a great deal of interest, for example, in associations between cognitive decline and vascular and metabolic conditions such as heart disease, stroke, 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 conditions may help with Alzheimers as well.
Most people with Alzheimers disease
have late-onset Alzheimers, which usually develops after age 60. Many studies have linked the apolipoprotein E (APOE) gene to late-onset Alzheimers. This gene has several forms. One of them, APOE 4, seems to increase a persons risk of getting the disease. However, carrying the APOE 4 form of the gene does not necessarily mean that a person will develop Alzheimers disease, and people carrying no APOE 4 can also develop the disease.
Further, a nutritious diet, physical
activity, social engagement, and mentally stimulating pursuits can all help people stay healthy as they age. New research suggests the possibility that these and other factors also might help to reduce the risk of cognitive decline and Alzheimers disease. Clinical trials of specific interventions are underway to test some of these possibilities.
Most experts believe that additional
genes may influence the development of late-onset Alzheimers. Scientists
Diagnosing Alzheimers Disease
These tests may be repeated to give
doctors information about how the persons memory is changing over time.
Alzheimers disease can be definitively
diagnosed only after death, by linking clinical measures 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 whether a person who is having memory problems has possible Alzheimers dementia (dementia may be due to another cause) or probable Alzheimers dementia (no other cause for dementia can be found).
Early, accurate diagnosis is beneficial
for several reasons. It can tell people whether their symptoms are from Alzheimers or another cause, such as stroke, tumor, Parkinsons disease, sleep disturbances, side effects of medications, or other conditions that may be treatable and possibly reversible. Beginning treatment early on in the disease process can help preserve function for some time, even though the underlying disease 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.
To diagnose Alzheimers, doctors may:
Ask questions about overall health, past medical problems, ability to carry out daily activities, and changes in behavior and personality
In addition, an early diagnosis can
provide greater opportunities for people to get involved in clinical trials. In a typical clinical trial, scientists test a drug or treatment to see if that intervention is effective and for whom it would work best. (See the box for more information.)
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
Treating Alzheimers Disease
Perform brain scans, such as
computed tomography (CT) or magnetic resonance imaging (MRI), to distinguish Alzheimers from other possible causes for symptoms, like stroke or tumor
Alzheimers disease is complex, and it
is unlikely that any one intervention will be found to delay, prevent, or cure it. Thats why current approaches in treatment and research focus on several different aspects, including helping
6 people maintain mental function, managing behavioral symptoms, and slowing or delaying the symptoms of disease.
Participating in Clinical Trials People with Alzheimers disease, those with MCI, those with a family history of Alzheimers, and healthy people with no memory problems and no family history of the disease may be able to take part in clinical trials. Participants in clinical trials for Alzheimers disease help scientists learn about the brain in healthy aging as well as what happens in Alzheimers. Results of clinical trials may lead to improved prevention and treatment approaches. Volunteering to participate in clinical trials is one way to help in the fight against Alzheimers disease.
Maintaining Mental Function
Four medications are approved by the U.S. Food and Drug Administration to treat Alzheimers. Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) are used to treat mild to moderate Alzheimers (donepezil can be used for severe Alzheimers as well). Memantine (Namenda) is used to treat moderate to severe Alzheimers. 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 dont change the underlying disease process, are effective for some but not all people, and may help only for a limited time.
The National Institute on Aging (NIA),
part of the National Institutes of Health (NIH), leads the Federal Governments research efforts on Alzheimers. NIAsupported Alzheimers 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 Alzheimers. NIA also sponsors the Alzheimers Disease Cooperative Study (ADCS), a consortium of leading researchers throughout the U.S. and Canada who conduct clinical trials on promising Alzheimers treatments.
Managing Behavioral Symptoms
Common behavioral symptoms of Alzheimers include sleeplessness, agitation, wandering, anxiety, anger, and depression. Scientists are learning why these symptoms occur and are studying new treatmentsdrug and non-drugto manage them. Treating behavioral symptoms often makes people with Alzheimers more comfortable and makes their care easier for caregivers.
To find out more about Alzheimers clinical
trials, talk to your health care provider or contact NIAs ADEAR Center at 1-800438-4380. Or, visit the ADEAR Center clinical trials database at www.nia.nih.gov/ Alzheimers/Clinical-Trials. 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. Also see Participating in Alzheimers Disease Clinical Trials and Studies at www.nia.nih.gov/Alzheimers.
with Alzheimers disease. For example,
staying physically active provides physical and emotional benefits.
Slowing, Delaying, or Preventing
Alzheimers Disease Alzheimers 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 looking at many possible interventions, such as immunization therapy, cognitive training, physical activity, antioxidants, and the effects of cardiovascular and diabetes treatments.
Some Alzheimers caregivers have found
that participating in 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, such as those listed in the For More Information section, sponsor in-person and online support groups across the country. There are a growing number of groups for people in the early stage of Alzheimers 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 or assisted living facility. For more information about at-home caregiving, see Caring for a Person with Alzheimers Disease: Your Easy-to-Use Guide from the National Institute on Aging at www.nia.nih.gov/Alzheimers.
Supporting Families and Caregivers Caring for a person with Alzheimers disease 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 have learned much about Alzheimers caregiving, and studies are helping to develop new ways to support caregivers.
Advancing Understanding
Becoming well-informed about the
disease is one important long-term strategy. Programs that teach families about the various stages of Alzheimers and about flexible and practical strategies for dealing with difficult caregiving situations provide vital help to those who care for people with Alzheimers.
Thirty years ago, we knew very little
about Alzheimers disease. Since then, scientists have made 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 the disease. Many scientists and physicians are now working together to untangle the genetic, biological, and
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
8 environmental factors that, over many years, ultimately result in Alzheimers. This effort is bringing us closer to
better managing and, ultimately,
preventing this devastating disease.
For More Information
Alzheimers Association 225 N. Michigan Avenue, Floor 17 Chicago, IL 60601-7633 1-800-272-3900 (toll-free) 1-866-403-3073 (TDD/toll-free) www.alz.org
To learn about support groups,
services, research centers, research studies, and publications about Alzheimers disease, contact the following resources:
Alzheimers Foundation of America 322 Eighth Avenue, 7th Floor New York, NY 10001 1-866-AFA-8484 (1-866-232-8484; toll-free) www.alzfdn.org
Alzheimers Disease Education
and Referral (ADEAR) Center P.O. Box 8250 Silver Spring, MD 20907-8250 1-800-438-4380 (toll-free) www.nia.nih.gov/Alzheimers The National Institute on Agings ADEAR Center offers information and publications for families, caregivers, and professionals on diagnosis, treatment, patient care, caregiver needs, longterm care, education and training, and research related to Alzheimers disease. 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 alerts; an Alzheimers disease clinical trials database; the Alzheimers Disease Library database; and more.
NIH Publication No. 11-6423
Eldercare Locator 1-800-677-1116 (toll-free) www.eldercare.gov Family Caregiver Alliance 180 Montgomery Street, Suite 900 San Francisco, CA 94104 1-800-445-8106 (toll-free) www.caregiver.org NIHSeniorHealth www.nihseniorhealth.gov/ alzheimersdisease/toc.html
