Alzheimer’s Disease
About 5 percent of men and women ages 65 to 74 have Alzheimer’s disease, and nearly half of those age 85 and older may have the disease. It is important to note, however, that Alzheimer’s disease is not a normal part of aging.
Alzheimer’s disease 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 and tangled bundles of fibers. The clumps are now called amyloid plaques and the tangles are called neurofibrillary tangles. Today, these plaques and tangles in the brain are considered signs of Alzheimer’s disease.
Scientists also have found other brain changes in people with Alzheimer’s disease. There is a loss of nerve cells and pathways 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 complex messages back and forth between nerve cells.
Alzheimer’s disease may disrupt normal thinking and memory by blocking these messages between nerve cells.
Causes and Risk Factors
Scientists do not yet fully understand what causes Alzheimer’s disease. There probably is not one single cause, but several factors that affect each person differently. Age is the most important known risk factor for Alzheimer’s disease. 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 the causes of Alzheimer’s disease. For example, early-onset familial Alzheimer’s disease, a rare form of Alzheimer’s disease that occurs between the ages of 30 and 60, is inherited.
The more common form of Alzheimer’s disease is known as late-onset. It occurs later in life, and no obvious family pattern is seen in most cases. One risk factor for this type of Alzheimer’s disease is a gene that makes one form of a protein called apolipoprotein E, or apoE.
Everyone has apoE, which helps carry cholesterol in the blood. Only about 15 percent of people have the form that increases the risk of Alzheimer’s. It is likely that other genes may also increase the risk of Alzheimer’s or protect against it, but they remain to be discovered.
Scientists still need to learn a lot more about causes and risk factors. In addition to genetics and apoE, they are studying education, diet, environment, and molecular changes in the brain to learn what role they might play in the development of this disease.
Scientists are finding more clues that some of the risk factors for heart disease and stroke — like high blood pressure, high cholesterol, and low levels of the vitamin folate — may also increase the risk of Alzheimer’s. Researchers are also investigating the possibility that physical, mental, and social activities may protect against Alzheimer’s.
Studies have shown that keeping the brain active may be associated with a reduced risk of Alzheimer’s. In a study with nuns, priests, and brothers known as the Religious Orders study, researchers asked more than 700 participants to describe the amount of time they spent in mentally stimulating activities.
These activities included listening to the radio, reading newspapers, playing puzzle games, and going to museums. After following the participants for four years, researchers found that the risk of developing Alzheimer’s was 47 percent lower on average for those who did these mentally stimulating activities most frequently than for those who did them least frequently.
There are no treatments, drugs, or pills that can prevent Alzheimer’s, but people can take some steps that may reduce their risk. These include:
- lowering cholesterol and homocysteine levels
- lowering high blood pressure levels
- controlling diabetes
- exercising regularly
- engaging in activities that stimulate the mind
- A healthy diet is important. Although no special diets or nutritional supplements have been found to prevent or reverse Alzheimer’s disease, a balanced diet helps maintain overall good health.
Research has not shown that these steps will lower your risk for Alzheimer’s, and studies designed to directly test their ability to do so are currently in progress. However, all of these things are good to do anyway because they lower the risk for other diseases and help maintain and improve your overall health and well-being.
Symptoms and Diagnosis
Alzheimer’s disease begins slowly. At first, the only symptom may be mild forgetfulness. People in the early stage of Alzheimer’s disease may have trouble remembering recent events, activities, or the names of familiar people or things. Simple math problems may become hard to solve. Such difficulties may be a bother, but usually they are not serious enough to cause alarm.
However, as the disease goes on, forgetfulness begins to interfere with daily activities. People may forget the way home or find it hard to cope with daily life. Such symptoms are more easily noticed and become serious enough to cause people with Alzheimer’s disease or their family members to seek medical help.
People in the middle stages of Alzheimer’s disease may forget how to do basic tasks, like brushing their teeth or combing their hair. They can no longer think clearly. They begin to have problems speaking, understanding, reading, or writing. Later on, people with Alzheimer’s disease may become anxious, agitated or aggressive, or wander away from home. Eventually, patients need total care.
An early, accurate diagnosis of Alzheimer’s disease helps patients and their families plan for the future. It gives them time to discuss care options while the patient can still take part in making decisions. And even though no drug can slow the onset or the progression of Alzheimer’s, early diagnosis offers the best chance to treat the symptoms of the disease.
Today, the only definite way to diagnose Alzheimer’s disease is to find out whether there are plaques and tangles in brain tissue. To look at brain tissue, 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” Alzheimer’s disease while the person is still alive. At specialized centers, doctors can diagnose Alzheimer’s disease correctly up to 90 percent of the time.
Doctors use several tools to diagnose “probable” Alzheimer’s disease:
- A complete medical history with questions about the person’s general health, past medical problems, and any difficulties carrying out daily activities.
- Medical tests, such as tests of blood, urine or spinal fluid.
- Tests to measure memory, problem solving, attention, counting, and language.
- Brain scans that allow the doctor to look at a picture of the brain to see if anything does not look normal.
Sometimes, 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 symptoms similar to those of Alzheimer’s. Some of these other conditions can be treated successfully.
Recently, scientists have focused on a type of memory change called mild cognitive impairment, or MCI. MCI is different from both Alzheimer’s disease and age-related memory change. People with MCI have ongoing memory problems but do not have noticeable problems in other areas like confusion, attention problems, and difficulty with language.
Treatments and Research
There is no known cure for Alzheimer’s, but there are treatments that can prevent some symptoms from getting worse for a limited time. Ongoing research offers clues to the way Alzheimer’s develops and the reasons it starts. It also offers hope that some day it may be possible to delay the onset of Alzheimer’s, slow its progress, or even prevent it altogether.
Alzheimer’s disease develops slowly, starting with mild memory problems and ending in death. The course the disease takes and how fast changes occur vary from person to person. The time from diagnosis to end of life varies. It can be as little as 3 years if the person is over 80 when diagnosed. Or it may be as long as 10 years or more if the person is younger.
A person with Alzheimer’s should be under a doctor’s care and may see a neurologist, psychiatrist, family doctor, internist, or geriatrician — a specialist who treats older adults. The doctor can treat the person’s physical and behavioral problems and answer the many questions that the person or the family may have.
No treatment can stop Alzheimer’s disease. However, for some people in the early and middle stages of the disease, the drugs Aricept, Exelon or Razadyne — previously known as Reminyl — may help prevent some symptoms from becoming worse for a limited time. Aricept is also approved for severe symptoms of Alzheimer’s. Another drug, Namenda, is approved for use in moderate to severe forms of the disease, although it is also limited in its effects.
Also, some medicines may help control behavioral symptoms of Alzheimer’s disease such as sleeplessness, agitation, wandering, anxiety, and depression. Treating these symptoms often makes patients more comfortable and makes their care easier for caregivers.
Family members and friends can assist people in the early stages of Alzheimer’s in continuing their daily routines, physical activities, and social contacts. People with Alzheimer’s should be kept up-to-date about the details of their lives, such as the time of day, where they live, and what is happening at home or in the world.
Memory aids may help in the day-to-day living of patients in the earlier stages of Alzheimer’s. Some families find that a big calendar, a list of daily plans, notes about simple safety measures, and written directions describing how to use common household items are very useful aids.
Treatments and Research – Research
The National Institute on Aging (NIA) is part of the National Institutes of Health, and it is the lead federal agency for research on Alzheimer’s disease. NIA coordinates the National Institutes of Health’s Alzheimer’s Disease Prevention Initiative.
The Alzheimer’s Disease Prevention Initiative is designed to
- understand why Alzheimer’s disease occurs and who is at greatest risk for developing it.
- improve the accuracy of diagnosis and the ability to identify those at risk.
- discover, develop, and test new treatments and ways to prevent Alzheimer’s.
- discover treatments for behavioral problems in patients with Alzheimer’s disease.
People with Alzheimer’s disease and those with mild cognitive impairment, or even healthy people who want to help scientists test new treatments may be able to take part in clinical trials. Clinical trials are studies done with people to find out if a new drug or treatment is both safe and effective.
New therapies are tested on people only after laboratory and animal studies show that the therapy is safe and has promising results. The Food and Drug Administration sets strict rules to make sure that people who agree to be in the studies are treated as safely as possible.
People who take part in clinical trials say that the biggest benefit is having regular contact with experts who have lots of practical experience and a broad understanding about the disease. They also feel they are making a valuable contribution to knowledge that will help people who develop Alzheimer’s in the future.
Scientists funded by NIA are testing a number of drugs in clinical trials to see if they prevent Alzheimer’s disease, slow the disease, or help reduce behavioral symptoms. Many drugs and therapies are tested in clinical trials. Some ideas that seem promising turn out to have little or no benefit when they are carefully studied in a clinical trial.
There is evidence that inflammation in the brain may contribute to the damage caused by Alzheimer’s disease. Some studies have suggested that drugs such as nonsteroidal anti-inflammatory drugs, or NSAIDs, might help slow the progression of Alzheimer’s. So far, however, clinical trials have not shown a benefit from these drugs.
A clinical trial studying two of these drugs, Vioxx and Aleve, showed that they did not delay the progression of Alzheimer’s in people who already had the disease. In another trial, testing whether the NSAIDs Celebrex and Aleve could prevent Alzheimer’s in healthy older people at risk for the disease, the drugs were stopped, although subjects continue to be followed for safety. New reports showed that Celebrex was linked to an increased risk for heart disease and a preliminary review of the data on Aleve from the trial suggested a possible increased risk for heart disease and stroke.
Researchers are continuing to look for ways to test how other anti-inflammatory drugs might affect the development or progression of Alzheimers.
Recent research has suggested a link between Alzheimer’s disease and factors that increase the risk for heart disease. Medicines already used to help reduce the risk of heart disease may help lower the chances of developing Alzheimer’s disease or may slow its progression. Clinical trials of drugs known as statins, commonly used to lower cholesterol, have begun to see if they might help slow down the progression of Alzheimer’s disease.
Studies have shown that people with Alzheimer’s often have higher levels of an amino acid called homocysteine in their blood. High levels of homocysteine are known to increase the risk of heart disease. Folic acid and vitamins B6 and B12 can reduce levels of homocysteine in the blood, and scientists are conducting clinical trials to see whether these substances can also slow rates of mental decline.
Recently, scientists have focused on a type of memory change called mild cognitive impairment, or MCI. MCI is different from both Alzheimer’s disease and age-related memory change. People with MCI have ongoing memory problems but do not have noticeable problems in other areas like confusion, attention problems, and difficulty with language.
Scientists funded by the National Institute on Aging recently completed a clinical trial — the Memory Impairment Study — to learn whether treatment of MCI might prevent or slow further memory loss, including the development of Alzheimer’s.
This 3-year trial compared the drug donepezil or vitamin E to a placebo in people with MCI to see if the drug or vitamin might delay or prevent the development of Alzheimer’s. The study found that taking vitamin E did not prevent or delay Alzheimer’s in a person with MCI. It is possible that vitamin E may not help after memory loss has already started. However, donepezil, also known as Aricept, did seem to delay the onset of Alzheimer’s, but only during the first year of treatment, providing no clear guidance to doctors about prescribing donepezil for people with MCI.
Several years ago, a clinical trial showed that vitamin E slowed the progress of some consequences of Alzheimer’s disease by about seven months. Other studies are considering whether antioxidants — such as vitamin E and C — can slow Alzheimer’s. One clinical trial is examining whether vitamin E and/or selenium supplements can prevent Alzheimer’s or stop mental decline. More studies on other antioxidants are ongoing or being planned.
Studies have linked keeping the brain active with a reduced risk of Alzheimer’s disease. In a study of healthy older people and people with possible or probable Alzheimer’s, scientists found that the healthy people had taken part in more mentally stimulating activities in their early and middle adulthood years than those who later developed Alzheimer’s. The healthy group also spent more hours in these types of activities.
A growing body of research suggests that the more formal education a person has, the better his or her memory and learning ability will be, even if the brain turns out to have the type of plaques associated with Alzheimer’s disease.
Some studies have suggested that estrogen used by women to treat the symptoms of menopause also protects the brain. Experts also wondered whether using estrogen could reduce the risk of Alzheimer’s or slow the disease.
However, clinical trials to test estrogen have not shown that it can slow the progression of Alzheimer’s in women who have already been diagnosed with the disease. And one study found that women over the age of 65 who used estrogen with a progestin were at greater risk for dementia, including Alzheimer’s. The study also showed that older women who used only estrogen could increase their risk of developing dementia.
Scientists believe that more research is needed to find out if estrogen may play some role in Alzheimer’s. They would like to know whether starting estrogen therapy around the time of menopause, rather than at age 65 or older, will protect memory or prevent Alzheimer’s disease, and an NIH clinical trial is testing this possibility.
Early studies suggested that extracts from the leaves of the ginkgo biloba tree might be of some help in treating symptoms of Alzheimer’s disease. There is no evidence yet that gingko biloba will cure or prevent Alzheimer’s. Scientists are now trying to find out in a clinical trial whether ginkgo biloba can delay mental decline or prevent Alzheimer’s disease or other types of dementia in older people.
Will a vaccine someday prevent Alzheimer’s disease? Early vaccine studies in mice successfully reduced beta-amyloid plaques in the brain and improved the way mice performed on memory tests. But when the studies were conducted in humans, they had to be stopped because some participants experienced side effects. However, scientists are continuing to study variations of the vaccine approach in the hope that they will reduce beta-amyloid in the brain while minimizing harmful side effects.
Scientists have come a long way in their understanding of Alzheimer’s disease. Findings from years of research have begun to clarify differences among age-related memory changes, mild cognitive impairment, and Alzheimer’s disease. Scientists also have made great progress in defining the changes that take place in the Alzheimer’s disease brain. This allows them to pinpoint possible targets for treatment.
Treatments and Research – Participating in Research
People with Alzheimer’s disease and those with mild cognitive impairment, or even healthy people who want to help scientists test new treatments may be able to take part in clinical trials. Clinical trials are studies done with people to find out if a new drug or treatment is both safe and effective.
To make it easier for people to find out about studies, the National Institute on Aging, or NIA, maintains the Alzheimer’s Disease Clinical Trials Database. It lists clinical studies for Alzheimer’s disease that are sponsored by the federal government and private companies.
Two major studies currently underway are the AD Genetics Study and the Neuroimaging Study.
The AD Genetics Study is collecting genetic material from individuals with more than two living brothers or sisters who have late-onset Alzheimer’s disease. This valuable resource will allow researchers to speed up the discovery of genes that increase the risk for late-onset Alzheimer’s.
The AD Neuroimaging Initiative uses imaging techniques like magnetic resonance imaging, or MRI, and positron emission tomography, or PET scans, to measure the structure and function of the brain. One day, these measurements may be able to identify people who are at risk of getting Alzheimer’s before they develop symptoms. Imaging techniques may also help doctors see how well patients are responding to treatment.
To find out more about these and other studies, or more about Alzheimer’s disease in general, contact the NIA’s ADEAR Center at 1-800-438-4380 or visit the ADEAR Center web site at www.alzheimers.org/trials/index.html.
