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Alzheimer disease is a progressive loss of mental function, characterized by degeneration of brain tissue, including loss of nerve cells, the accumulation of an abnormal protein called beta-amyloid, and the development of neurofibrillary tangles.
Forgetting recent events is an early sign, followed by increasing confusion, impairment of other mental functions, and problems using and understanding language and doing daily tasks.
Symptoms progress so that people cannot function, causing them to become totally dependent on others.
Doctors base the diagnosis on symptoms and results of a physical examination, mental status tests, blood tests, and imaging tests.
Treatment involves strategies to prolong functioning as long as possible and may include drugs that may slow the progression of the disease.
How long people live cannot be predicted, but death occurs, on average, about 7 years after the diagnosis is made.
Alzheimer disease is a type of dementia, which is a slow, progressive decline in mental function including memory, thinking, judgment, and the ability to learn.
In 60 to 80% of older people with dementia, Alzheimer disease is the cause. It is rare among people younger than 65. It becomes more common with increasing age. About 11% of people aged 65 or older and about 32% of those aged 85 or older have Alzheimer disease. It affects more women than men, partly because women live longer. In 2015 in the United States, an estimated 5.3 million people had Alzheimer disease. The number of people with Alzheimer disease is expected to greatly increase as the proportion of older people increases.
What causes Alzheimer disease is unknown, but genetic factors play a role: About 5 to 15% of cases run in families. Several specific gene abnormalities may be involved. Some of these abnormalities can be inherited when only one parent has the abnormal gene. That is, the abnormal gene is dominant. An affected parent has a 50% chance of passing on the abnormal gene to each child. About half of these children develop Alzheimer disease before age 65.
One gene abnormality affects apolipoprotein E (apo E)—the protein part of certain lipoproteins, which transport cholesterol through the bloodstream. There are three types of apo E:
Epsilon-4: People with the epsilon-4 type develop Alzheimer disease more commonly and at an earlier age than other people.
Epsilon-2: In contrast, people with the epsilon-2 type seem to be protected against Alzheimer disease.
Epsilon-3: People with the epsilon-3 type are neither protected nor more likely to develop the disease.
(These associations have been studied primarily in whites and may not apply to other races.) However, genetic testing for apo E type cannot determine whether a specific person will develop Alzheimer disease. Therefore, this testing is not routinely recommended.
In Alzheimer disease, parts of the brain degenerate, destroying nerve cells and reducing the responsiveness of the remaining ones to many of the chemical messengers that transmit signals between nerve cells in the brain (neurotransmitters). The level of acetylcholine, a neurotransmitter that helps with memory, learning, and concentration, is low.
Alzheimer disease causes the following abnormalities to develop in brain tissue:
Beta-amyloid deposits: Accumulation of beta-amyloid (an abnormal, insoluble protein), which accumulates because cells cannot process and remove it
Senile or neuritic plaques: Clumps of dead nerve cells around a core of beta-amyloid
Neurofibrillary tangles: Twisted strands of insoluble proteins in the nerve cell
Increased levels of tau: An abnormal protein that is a component of neurofibrillary tangles and beta-amyloid
Such abnormalities develop to some degree in all people as they age but are much more numerous in people with Alzheimer disease. Doctors are not sure whether the abnormalities in brain tissue cause Alzheimer disease or result from some other problem that causes both the dementia and the abnormalities in brain tissue.
Researchers have also discovered that the abnormal proteins in Alzheimer disease (beta-amyloid and tau) resemble the abnormal proteins in prion diseases. That is, they are misfolded and cause other proteins to misfold, causing the disease to progress.
Alzheimer disease causes many of the same symptoms as other dementias, such as the following:
However, Alzheimer disease also differs from other dementias. For example, recent memory is typically affected much more than other mental functions.
Although when symptoms occur varies, categorizing them as early, intermediate, or late symptoms helps affected people, family members, and other caregivers have some idea of what to expect. Personality changes and disruptive behavior (behavior disorders) may develop early or late in Alzheimer disease.
Symptoms develop gradually, so for a while, many people continue to enjoy much of what they enjoyed before developing Alzheimer disease.
Symptoms usually begin subtly. People whose disease develops while they are still employed may not do as well in their jobs. In people who are retired and not very active, the changes may not be as noticeable.
The first and most noticeable symptom may be
Early in the disease, people become less able to use good judgment and think abstractly. Speech patterns may change slightly. People may use simpler words, a general word or many words rather than a specific word, or use words incorrectly. They may be unable to find the right word.
People with Alzheimer disease have difficulty interpreting visual and audio cues. Thus, they may become disoriented and confused. Such disorientation may make driving a car difficult. They may get lost on their way to the store. People may be able to function socially but may behave unusually. For example, they may forget the name of a recent visitor, and their emotions may change unpredictably and rapidly.
Many people with Alzheimer disease often have insomnia. They have trouble falling or staying asleep. Some people become confused about day and night.
At some point, psychosis (hallucinations, delusions, or paranoia) develops in many people with Alzheimer disease.
As Alzheimer disease progresses, people have trouble remembering events in the past. They start to forget the names of friends and relatives. They may require help with eating, dressing, bathing, and going to the toilet. All sense of time and place is lost: People with Alzheimer disease may even get lost on their way to the bathroom at home. Their increasing confusion puts them at risk of wandering and falling.
Disruptive or inappropriate behavior, such as wandering, agitation, irritability, hostility, and physical aggression, is common.
Eventually, people with Alzheimer disease cannot walk or take care of their personal needs. They may be incontinent and unable to swallow, eat, or speak. These changes put them at risk of undernutrition, pneumonia, and pressure sores (bedsores). Memory is completely lost.
Ultimately, coma and death, often due to infections, result.
Because people are less capable of controlling their behavior, they sometimes act inappropriately or disruptively (for example, by yelling, throwing, hitting, or wandering). These actions are called behavior disorders.
Several effects of Alzheimer disease contribute to this behavior:
Because they have forgotten the rules of proper behavior, they may act in socially inappropriate ways. When hot, they may undress in public. When they have sexual impulses, they may masturbate in public, use off-color or lewd language, or make sexual demands.
Because people with Alzheimer disease have difficulty understanding what they see and hear, they may misinterpret an offer of help as a threat and may lash out. For example, when someone tries to help them undress, they may interpret it as an attack and try to protect themselves, sometimes by hitting.
Because their short-term memory is impaired, they cannot remember what they are told or have done. They repeat questions and conversations, demand constant attention, or ask for things (such as meals) they have already received. They may become agitated and upset when they do not get what they ask for.
Because they cannot express their needs clearly or at all, they may yell when in pain or wander when lonely or frightened.
Whether a particular behavior is considered disruptive depends on many factors, including how tolerant the caregiver is and what sort of situation the person with Alzheimer disease is living in.
When people with Alzheimer disease cannot sleep, they may wander, yell, or call out.
Diagnosis of Alzheimer disease is similar to that of other dementias.
Doctors must determine whether a person has dementia and, if so, whether the dementia is Alzheimer disease.
Doctors can usually diagnose Alzheimer disease based on the following:
Symptoms, which are identified by asking the person and family members or other caregivers questions
Results of a physical examination
Results of a mental status test
Results of additional tests, such as blood tests, computed tomography (CT), or magnetic resonance imaging (MRI)
Mental status testing, consisting of simple questions and tasks (see Table: Mental Status Testing), helps doctors determine whether people have dementia.
Sometimes more detailed testing (called neuropsychologic testing) is needed. This testing covers all the main areas of mental function, including mood, and usually takes 1 to 3 hours. This testing helps doctors distinguish dementia from other conditions that can cause similar symptoms, such as age-associated memory impairment, mild cognitive impairment, and depression.
Information from the above sources can usually help doctors rule out delirium as the cause of symptoms (see Table: Comparing Delirium and Dementia). Doing so is essential because delirium, unlike dementia, can often be reversed if promptly treated. Differences between the two include the following:
Alzheimer disease is suspected when the following are present:
The diagnosis of dementia has been confirmed.
Usually, the most noticeable symptom, particularly in the beginning, is forgetting recent events or not being able to form new memories.
Memory and other mental functions have gradually deteriorated and are continuing to deteriorate.
The dementia began after age 40 and usually after age 65.
Some symptoms can help doctors distinguish Alzheimer disease from other dementias. For example, visual hallucinations (seeing things or people that are not there) are more common and occur earlier in Lewy body dementia than in Alzheimer disease. Also, people with Alzheimer disease are often better-groomed and neater than people with other dementias.
Information from additional tests helps doctors confirm the diagnosis of Alzheimer disease and exclude other types and causes of dementia.
Analysis of cerebrospinal fluid (CSF), obtained during a spinal tap, and positron emission tomography (PET) may be used to help diagnose Alzheimer disease. If CSF analysis detects a low level of beta-amyloid and if PET scans show amyloid deposits, the diagnosis is more likely to be Alzheimer disease. However, these tests are not routinely available.
The diagnosis of Alzheimer disease can be confirmed only when a sample of brain tissue is removed (after death, during an autopsy) and examined under a microscope. Then, the characteristic loss of nerve cells, neurofibrillary tangles, and senile plaques containing beta-amyloid can be seen throughout the brain, particularly in the area of the temporal lobe that is involved in forming new memories.
Some research tentatively suggests certain measures that may help prevent Alzheimer disease:
Controlling cholesterol levels: Some evidence suggests that having high cholesterol levels may be related to developing Alzheimer disease. Thus, people may benefit from a diet low in saturated fats and, if needed, drugs (such as statins) to lower cholesterol and other fats (lipids).
Controlling high blood pressure: High blood pressure may damage blood vessels that carry blood to the brain and thus reduce the brain’s oxygen supply, possibly disrupting connections between nerve cells.
Exercising: Exercising helps the heart function better and, for unclear reasons, may help the brain function better.
Keeping mentally active: People are encouraged to continue doing activities that challenge the mind, such as learning new skills, doing crossword puzzles, and reading the newspaper. These activities may promote the growth of new connections (synapses) between nerve cells and thus help delay dementia.
Drinking alcohol in modest amounts: In modest amounts (not more than 3 drinks a day), alcohol may help lower cholesterol and maintain blood flow. Alcohol may even help with thinking and memory by stimulating the release of acetylcholine and causing other changes in nerve cells in the brain. However, there is no convincing evidence that people who do not drink alcohol should start drinking to prevent Alzheimer disease. Once dementia develops, abstaining from alcohol is usually best because it can make symptoms of dementia worse.
Treatment of Alzheimer disease involves general measures to provide safety and support, as for all dementias (see Dementia : Treatment of Dementia). Also, certain drugs can help for a while. The person with Alzheimer disease, family members, other caregivers, and the health care practitioners involved should discuss and decide on the best strategy for that person.
Pain and any other disorders or health problems (such as a urinary tract infection or constipation) are treated. Such treatment may help maintain function in people with dementia.
Creating a safe and supportive environment can be very helpful.
Generally, the environment should be bright, cheerful, safe, stable, and designed to help with orientation. Some stimulation, such as a radio or television, is helpful, but excessive stimulation should be avoided.
Structure and routine help people with Alzheimer disease stay oriented and give them a sense of security and stability. Any change in surroundings, routines, or caregivers should be explained to people clearly and simply.
Following a daily routine for tasks such as bathing, eating, and sleeping helps people with Alzheimer disease remember. Following a regular routine at bedtime may help them sleep better.
Activities scheduled on a regular basis can help people feel independent and needed by focusing their attention on pleasurable or useful tasks. Such activities should include physical and mental activities. Activities should be broken down in small parts or simplified as the dementia worsens.
The cholinesterase inhibitorsdonepezil, galantamine, and rivastigmine increase the level of the neurotransmitter acetylcholine in the brain. This level may be low in people with Alzheimer disease. These drugs may temporarily improve mental function, including memory, but they do not slow the progression of the disease. Only some of the people who have Alzheimer disease benefit from these drugs. For these people, the drugs may effectively turn the clock back 6 to 9 months. These drugs are most effective in people with mild to moderate disease. The most common side effects include nausea, vomiting, weight loss, and abdominal pain or cramps.
Memantine appears to slow the progression of Alzheimer disease. Memantine can be used with a cholinesterase inhibitor.
Researchers continue to study drugs that may prevent or slow the progression of Alzheimer disease—for example, substances that may reduce the amount of amyloid deposited. Estrogen therapy for women, nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen or naproxen), and ginkgo biloba are being studied. But none has consistently proved to be effective. Moreover, estrogen appears to do more harm than good.
Vitamin E is an antioxidant that theoretically might help protect nerve cells from damage or help them function better. Whether vitamin E is useful is unclear. Before people take any dietary supplement, they should discuss the risks and benefits with their doctor.
Caring for people with Alzheimer disease is stressful and demanding, and caregivers may become depressed and exhausted, often neglecting their own mental and physical health. The following measures can help caregivers:
Learning about how to effectively meet the needs of people with Alzheimer disease and what to expect from them: Caregivers can get this information from nurses, social workers, organizations, and published and online materials.
Seeking help when it is needed: Caregivers can talk to social workers (including those in the local community hospital) about appropriate sources of help, such as day-care programs, visits by home nurses, part-time or full-time housekeeping assistance, and live-in assistance. Counseling and support groups can also help.
Caring for self: Caregivers need to remember to take care of themselves. They should not give up their friends, hobbies, and activities.
Planning for the future is essential because Alzheimer disease is progressive. Long before a person with Alzheimer disease needs to be moved to a more supportive and structured environment, family members should plan for this move and evaluate the options for long-term care. Such planning usually involves the efforts of a doctor, a social worker, nurses, and a lawyer, but most of the responsibility falls on family members.
Decisions about moving a person with Alzheimer disease to a more supportive environment involve balancing the desire to keep the person safe with the desire to maintain the person’s sense of independence as long as possible.
Some long-term care facilities specialize in caring for people with Alzheimer disease. Staff members are trained to understand how people with Alzheimer disease think and act and how to respond to them. These facilities have routines that make the residents feel secure and provide appropriate activities that help them feel productive and involved in life. Most facilities have appropriate safety features. Finding a facility that has the appropriate safety features is important.
Before people with Alzheimer disease become too incapacitated, decisions should be made about medical care, and financial and legal arrangements should be made. These arrangements are called advance directives. People should appoint a person who is legally authorized to make treatment decisions on their behalf (a health care proxy). They should discuss their health care wishes with this person and their doctor (see Legal and Ethical Concerns at the End of Life). Such issues are best discussed with all concerned long before decisions are necessary.
As Alzheimer disease worsens, treatment tends to be directed at maintaining the person’s comfort rather than at attempting to prolong life.
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