Introduction
Dementia is a brain disorder that seriously affects a person's ability to carry out daily activities. The most common form of dementia among older people is Alzheimer's disease (AD), which involves the parts of the brain that control thought, memory, and language. Although scientists are learning more every day, right now they still do not know what causes AD, and there is no cure.

Scientists think that as many as 4.5 million Americans suffer from AD. The disease usually begins after age 60, and risk goes up with age. While younger people also may get AD, it is much less common. About 5 percent of men and women ages 65 to 74 have AD, and nearly half of those age 85 and older may have the disease. It is important to note, however, that AD is not a normal part of aging.

AD 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. He found abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles). Today, these plaques and tangles in the brain are considered signs of AD.

Scientists also have found other brain changes in people with AD. Nerve cells die in areas of the brain that are vital to memory and other mental abilities. There also are lower levels of some of the chemicals in the brain that carry messages back and forth between nerve cells. AD may impair thinking and memory by disrupting these messages.

What Causes AD?
Scientists do not yet fully understand what causes AD. There probably is not one single cause, but several factors that affect each person differently. Age is the most important known risk factor for AD. The number of people with the disease doubles every 5 years beyond age 65.

Family history is another risk factor. Scientists believe that genetics may play a role in many AD cases. For example, familial AD, a rare form of AD that usually occurs between the ages of 30 and 60, is inherited. The more common form of AD is known as late-onset. It occurs later in life, and no obvious inheritance pattern is seen. However, several risk factor genes may interact with each other to cause the disease. The only risk factor gene identified so far for late-onset AD, is a gene that makes one form of a protein called apolipoprotein E (apoE). Everyone has apoE, which helps carry cholesterol in the blood. It is likely that other genes also may increase the risk of AD or protect against AD, but they remain to be discovered. The National Institute on Aging (NIA), part of the National Institutes of Health, is sponsoring the AD Genetics Initiative to recruit families with AD to learn more about risk factor genes. To participate in this study, families should contact the National Cell Repository for AD toll-free at 1-800-526-2839 or send an e-mail to: alzstudy@iupui.edu.

Scientists still need to learn a lot more about what causes AD. In addition to genetics and apoE, they are studying education, diet, and environment to learn what role they might play in the development of this disease. Scientists are finding increasing evidence that some of the risk factors for heart disease and stroke, such as high blood pressure, high cholesterol, and low levels of the vitamin folate, may predispose people to AD. Evidence for physical, mental, and social activities as protective factors against AD is also increasing.

What Are the Symptoms of AD?
AD begins slowly. At first, the only symptom may be mild forgetfulness. In this stage, people may have trouble remembering recent events, activities, or the names of familiar people or things. They may not be able to solve simple math problems. Such difficulties may be a bother, but usually they are not serious enough to cause alarm.

However, as the disease goes on, symptoms are more easily noticed and become serious enough to cause people with AD or their family members to seek medical help. For example, people in the middle stages of AD may forget how to do simple tasks, like brushing their teeth or combing their hair. They can no longer think clearly. They begin to have problems speaking, under-standing, reading, or writing. Later on, people with AD may become anxious or aggressive, or wander away from home. Eventually, patients need total care.

How is AD Diagnosed?
An early, accurate diagnosis of AD helps patients and their families plan for the future. It gives them time to discuss care while the patient can still take part in making decisions. Early diagnosis will also offer the best chance to treat the symptoms of the disease.

Today, the only definite way to diagnose AD is to find out whether there are plaques and tangles in brain tissue. To look at brain tissue, how-ever, doctors must wait until they do an autopsy, which is an examination of the body done after a person dies. Therefore, doctors can only make a diagnosis of "possible" or "probable" AD while the person is still alive.

At specialized centers, doctors can diagnose AD correctly up to 90 percent of the time. Doctors use several tools to diagnose "probable" AD, including:

• questions about the person’s general health, past medical problems, and the history of any difficulties the person has carrying out daily activities,
• tests of memory, problem solving, attention, counting, and language,
• medical tests—such as tests of blood, urine, or spinal fluid, and
• brain scans.

Some of these test results help the doctor find other possible causes of the person’s symptoms. For example, thyroid problems, drug reactions, depression, brain tumors, and blood vessel disease in the brain can cause AD-like symptoms. Some of these other conditions can be treated successfully.

Recently, scientists have focused on a type of memory change called mild cognitive impairment (MCI), which is different from both AD and normal age-related memory change. People with MCI have ongoing memory problems, but they do not have other losses like confusion, attention problems, and difficulty with language. Scientists funded by the NIA are studying information collected from the Memory Impairment Study to learn whether early diagnosis and treatment of MCI might prevent or slow further memory loss, including the development of AD.

Scientists are finding that damage to parts of the brain involved in memory, such as the hippocampus, can sometimes be seen on brain scans before symptoms of the disease occur. The NIA will be funding the AD Neuroimaging Initiative, a study that will find out whether brain scans can diagnose AD early. These brain scans and other potential "biomarkers" have the potential for speeding the testing of drugs for MCI and AD.

How is AD Treated?
AD is a slow disease, starting with mild memory problems and ending with severe brain damage. The course the disease takes and how fast changes occur vary from person to person. On average, AD patients live from 8 to 10 years after they are diagnosed, though the disease can last for as many as 20 years.

No treatment can stop AD. However, for some people in the early and middle stages of the disease, the drugs tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), or galantamine (Reminyl) may help prevent some symptoms from becoming worse for a limited time. Also, some medicines may help control behavioral symptoms of AD such as sleeplessness, agitation, wandering, anxiety, and depression. Treating these symptoms often makes patients more comfortable and makes their care easier for caregivers.

Developing new treatments for AD is an active area of research. Scientists are testing a number of drugs to see if they prevent AD, slow the disease, or help reduce symptoms.

There is evidence that inflammation in the brain may contribute to AD damage. Some scientists believe that drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) might help slow the progression of AD, although recent studies of two of these drugs, rofecoxib (Vioxx) and naproxen (Aleve), have shown that they did not delay the progression of AD in people who already have the disease. Now, scientists are studying the NSAIDs celecoxib (Celebrex) and naproxen to find out if they can slow the onset of the disease.

Research has shown that vitamin E slows the progress of some consequences of AD by about 7 months. Scientists now are studying vitamin E to learn whether it can prevent or delay AD in patients with MCI.

Recent research suggests that ginkgo biloba may be of some help in treating AD symptoms. There is no evidence that ginkgo will cure or prevent AD. Scientists now are trying to find out whether ginkgo biloba can delay or prevent dementia in older people.

Recent findings from the Women’s Health Initiative (WHI) highlight the importance of clinical trials, which are studies to find out whether a treatment is both safe and effective. Earlier studies had suggested that the hormone replacement therapy that millions of women take after menopause may be protective against AD. However, the WHI clinical trial found an increased risk of AD in women taking hormones as compared with those taking an inactive pill. The trial used a commonly pre-scribed pill combining estrogens and progesterone. Further studies on estrogen alone and other hormone preparations, such as the estrogen patch, continue.

People with AD and those with MCI who want to help scientists test possible treatments may be able to take part in clinical trials. Healthy people also can help scientists learn more about the brain and AD. The NIA and the Food and Drug Administration (FDA) are working together to maintain the AD Clinical Trials Database, which lists AD clinical trials sponsored by the Federal government and private companies. To find out more about these studies, contact the NIA’s Alzheimer’s Disease Education and Referral (ADEAR) Center at 1-800-438-4380, or visit the ADEAR Center Web site at www.alzheimers.org. You also can sign up for e-mail alerts on new clinical trials that have been added to the database.

Many of these studies are being done at NIA-supported Alzheimer's Disease Centers located throughout the United States. These centers carry out a wide range of research, including studies of the causes, diagnosis, treatment, and management of AD. To get a list of these centers, contact the ADEAR Center.

Is There Help for Caregivers?
Most often, spouses or other family members provide the day-to-day care for people with AD. As the disease gets worse, people often need more and more care. This can be hard for caregivers and can affect their physical and mental health, family life, job, and finances.

The Alzheimer’s Association has chapters nationwide that provide educational programs and support groups for caregivers and family members of people with AD. For more information, contact the Alzheimer’s Association listed at the end of this fact sheet.

Research
Scientists have come a long way in their understanding of AD. Findings from years of research have begun to clarify differences between normal age-related memory changes, MCI, and AD. Scientists also have made great progress in defining the changes that take place in the AD brain, which allows them to pinpoint possible targets for treatment. These advances are the foundation for the National Institutes of Health (NIH) Alzheimer’s Disease Prevention Initiative, which is designed to:
 

• understand why AD occurs and who is at greatest risk of developing it;
• improve the accuracy of diagnosis and the ability to identify those at risk;
• discover, develop, and test new treatments;
• discover treatments for behavioral problems in patients with AD.