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.
Most dementias (see Dementia) are Alzheimer disease. 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 13% of people aged 65 or older and about 45% of those aged 85 or older have Alzheimer disease. It affects more women than men, partly because women live longer. In 2012 in the United States, an estimated 5.4 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 (ε2, ε3, and ε4). People with the ε4 type develop Alzheimer disease more commonly and at an earlier age than other people. In contrast, people with the ε2 type seem to be protected against Alzheimer disease. People with the ε3 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:
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.
The symptoms of Alzheimer disease are similar to those of other dementias, with early, intermediate, and late stages (see Symptoms). They include memory loss, changes in personality, problems using language and doing daily tasks, disorientation, and disruptive behavior. 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 forgetting recent events because forming new memories is difficult. However, the disease sometimes begins with changes in personality. People may become emotionally unresponsive, depressed, or unusually fearful or anxious.
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 may require help with eating, dressing, bathing, and going to the toilet. Disruptive or inappropriate behavior, such as wandering, agitation, irritability, hostility, and physical aggression, is common. 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 falling.
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.
Progression is unpredictable. People live, on average, about 7 years after the diagnosis is made. Most people with Alzheimer disease who can no longer walk live no more than 6 months. However, how long people live varies widely.
Diagnosis of Alzheimer disease is similar to that of other dementias.
Doctors can usually diagnose Alzheimer disease based on the following:
Alzheimer disease can often be distinguished from other dementias because usually, its most noticeable symptom, particularly in the beginning, is forgetting recent events or not being able to form new memories.
If dementia is diagnosed in older people and their memory has gradually deteriorated, doctors consider Alzheimer disease the most likely cause.
Information from the additional tests helps doctors exclude other types and causes of dementia.
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.
Analysis of cerebrospinal fluid (CSF) and positron emission tomography (PET—see see Positron Emission Tomography) are starting to 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 currently, these tests are used mainly in research.
Treatment involves general measures to provide safety and support, as for all dementias (see see Treatment).
The cholinesterase inhibitors donepezil, galantamine, and rivastigmine increase the level of the neurotransmitter acetylcholine in the brain. This level may be low. These drugs may temporarily improve cognitive 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.
Some research tentatively suggests certain measures that may help prevent Alzheimer disease:
Last full review/revision July 2013 by Juebin Huang, MD, PhD