Alzheimer's Disease
Alzheimer's Disease, progressive brain disorder that causes a gradual and
irreversible decline in memory, language skills, perception of time and space,
and, eventually, the ability to care for oneself. First described by German
psychiatrist Alois Alzheimer in 1906, Alzheimer's disease was initially thought
to be a rare condition affecting only young people, and was referred to as
presenile dementia. Today late-onset Alzheimer's disease is recognised as the
most common cause of the loss of mental function in those aged 65 and over.
Alzheimer's in people in their 30s, 40s, and 50s, called early-onset
Alzheimer's disease, occurs much less frequently, accounting for less than 10
percent of the estimated 4 million Alzheimer's cases in the United States.
Although Alzheimer's disease is not a normal part of the aging process, the
risk of developing the disease increases, as people grow older. About 10
percent of the United States population over the age of 65 is affected by
Alzheimer's disease, and nearly 50 percent of those over age 85 may have the
disease.
Alzheimer's disease takes a devastating toll, not only on the patients, but
also on those who love and care for them. Some patients experience immense fear
and frustration as they struggle with once commonplace tasks and slowly lose
their independence. Family, friends, and especially those who provide daily
care suffer immeasurable pain and stress as they witness Alzheimer's disease
slowly take their loved one from them.
The onset of Alzheimer's disease is usually very gradual. In the early stages,
Alzheimer's patients have relatively mild problems learning new information and
remembering where they have left common objects, such as keys or a wallet. In
time, they begin to have trouble recollecting recent events and finding the
right words to express themselves. As the disease progresses, patients may have
difficulty remembering what day or month it is, or finding their way around
familiar surroundings. They may develop a tendency to wander off and then be
unable to find their way back. Patients often become irritable or withdrawn as
they struggle with fear and frustration when once commonplace tasks become
unfamiliar and intimidating. Behavioural changes may become more pronounced as
patients become paranoid or delusional and unable to engage in normal conversation.
Eventually Alzheimer's patients become completely incapacitated and unable to
take care of their most basic life functions, such as eating and using the
bathroom. Alzheimer's patients may live many years with the disease, usually
dying from other disorders that may develop, such as pneumonia. Typically the
time from initial diagnosis until death is seven to ten years, but this is
quite variable and can range from three to twenty years, depending on the age
of onset, other medical conditions present, and the care patients receive.
The brains of patients with Alzheimer's have distinctive formations—abnormally
shaped proteins called tangles and plaques—that are recognised as the hallmark
of the disease. Not all brain regions show these characteristic formations. The
areas most prominently affected are those related to memory.
Tangles are long, slender tendrils found inside nerve cells, or neurons.
Scientists have learned that when a protein called tau becomes altered, it may
cause the characteristic tangles in the brain of an Alzheimer's patient. In
healthy brains, tau provides structural support for neurons, but in Alzheimer's
patients this structural support collapses.
Plaques, or clumps of fibres, form outside the neurons in the adjacent brain
tissue. Scientists found that a type of protein, called amyloid precursor
protein, forms toxic plaques when it is cut in two places. Researchers have
isolated the enzyme beta-secretase, which is believed to make one of the cuts
in the amyloid precursor protein. Researchers also identified another enzyme,
called gamma secretase that makes the second cut in the amyloid precursor
protein. These two enzymes snip the amyloid precursor protein into fragments
that then accumulate to form plaques that are toxic to neurons.
Scientists have found that tangles and plaques cause neurons in the brains of
Alzheimer's patients to shrink and eventually die, first in the memory and
language centers and finally throughout the brain. This widespread neuron
degeneration leaves gaps in the brain's massaging network that may interfere
with communication between cells, causing some of the symptoms of Alzheimer's
disease.
Alzheimer's patients have lower levels of neurotransmitters, chemicals that
carry complex messages back and forth between the nerve cells. For instance,
Alzheimer's disease seems to decrease the level of the neurotransmitter
acetylcholine, which is known to influence memory. A deficiency in other
neurotransmitters, including somatostatin and corticotropin-releasing factor,
and, particularly in younger patients, serotonin and norepinephrine, also
interferes with normal communication between brain cells.
The causes of Alzheimer's disease remain a mystery, but researchers have found
that particular groups of people have risk factors that make them more likely
to develop the disease than the general population. For example, people with a
family history of Alzheimer's are more likely to develop Alzheimer's disease.
Some of the most promising Alzheimer's research is being conducted in the field
of genetics to learn the role a family history of the disease has in its
development. Scientists have learned that people who are carriers of a specific
version of the apolipoprotein E gene (apoE gene), found on chromosome 19, are
several times more likely to develop Alzheimer's than carriers of other
versions of the apoE gene. The most common version of this gene in the general
population is apoE3. Nearly half of all late-onset Alzheimer's patients have
the less common apoE4 version, however, and research has shown that this gene
plays a role in Alzheimer's disease. Scientists have also found evidence that
variations in one or more genes located on chromosomes 1, 10, and 14 may
increase a person's risk for Alzheimer's disease. Scientists have identified
the gene variations on chromosomes 1 and 14 and learned that these genes
produce mutations in proteins called presenilins. These mutated proteins
apparently trigger the activity of the enzyme gamma secretase, which splices the
amyloid precursor protein.
Researchers have made similar strides in the investigation of early-onset
Alzheimer's disease. A series of genetic mutations in patients with early-onset
Alzheimer's has been linked to the production of amyloid precursor protein, the
protein in plaques that may be implicated in the destruction of neurons. One
mutation is particularly interesting to geneticists because it occurs on a gene
involved in the genetic disorder Down syndrome. People with Down syndrome
usually develop plaques and tangles in their brains as they get older, and
researchers believe that learning more about the similarities between Down
syndrome and Alzheimer's may further our understanding of the genetic elements
of the disease.
Some studies suggest that one or more factors other than heredity may determine
whether people develop the disease. One study published in February 2001
compared residents of Ibadan, Nigeria, who eat a mostly low-fat vegetarian
diet, with African Americans living in Indianapolis, Indiana, whose diet
included a variety of high-fat foods. The Nigerians were less likely to develop
Alzheimer's disease compared to their U.S. counterparts. Some researchers
suspect that health problems such as high blood pressure, atherosclerosis
(arteries clogged by fatty deposits), high cholesterol levels, or other
cardiovascular problems may play a role in the development of the disease.
Other studies have suggested that environmental agents may be a possible cause
of Alzheimer's disease; for example, one study suggested that high levels of
aluminium in the brain may be a risk factor. Several scientists initiated
research projects to further investigate this connection, but no conclusive
evidence has been found linking aluminium with Alzheimer's disease. Similarly,
investigations into other potential environmental causes, such as zinc
exposure, viral agents, and food-borne poisons, while initially promising, have
generally turned up inconclusive results.
Some studies indicate that brain trauma can trigger a degenerative process that
results in Alzheimer's disease. In one study, an analysis of the medical
records of veterans of World War II (1939-1945) linked serious head injury in
early adulthood with Alzheimer's disease in later life. The study also looked
at other factors that could possibly influence the development of the disease
among the veterans, such as the presence of the apoE gene, but no other factors
were identified.
Alzheimer's disease is only positively diagnosed by examining brain tissue
under a microscope to see the hallmark plaques and tangles, and this is only
possible after a patient dies. As a result, physicians rely on a series of
other techniques to diagnose probable Alzheimer's disease in living patients.
Diagnosis begins by ruling out other problems that cause memory loss, such as
stroke, depression, alcoholism, and the use of certain prescription drugs. The
patient undergoes a thorough examination, including specialised brain scans, to
eliminate other disorders. The patient may be given a detailed evaluation
called a neuropsychological examination, which is designed to evaluate a
patient's ability to perform specific mental tasks. This helps the physician
determine whether the patient is showing the characteristic symptoms of Alzheimer's
disease—progressively worsening memory problems, language difficulties, and
trouble with spatial direction and time. The physician also asks about the
patient's family medical history to learn about any past serious illnesses,
which may give a hint about the patient's current symptoms.
There is no known cure for Alzheimer's disease, and treatment focuses on
lessening symptoms and attempting to slow the course of the disease. Drugs that
increase or improve the function of brain acetylcholine, the neurotransmitter
that affects memory, have been approved by the United States Food and Drug
Administration (FDA) for the treatment of Alzheimer's disease. Called
acetylcholinesterase inhibitors, these drugs have had modest but clearly
positive effects on the symptoms of the disease. These drugs can benefit
patients at all stages of illness, but they are particularly effective in the
middle stage. This finding corresponds with new evidence that low acetylcholine
levels in patients with Alzheimer's disease may not be present in the earliest
stage of the illness.
Evidence shows that there is inflammation in the brains of Alzheimer's
patients, which may be associated with the production of amyloid precursor
protein. Studies are under way to find drugs that prevent this inflammation, to
possibly slow or even halt the progress of the disease. Other promising
approaches center on mechanisms that manipulate amyloid precursor protein
production or accumulation. Drugs are in development that may block the
activity of the enzymes that cut the amyloid precursor protein, halting amyloid
production. Other studies in mice suggest that vaccinating animals with amyloid
precursor protein can produce a reaction that clears amyloid precursor protein
from the brain. Physicians have started vaccination studies in humans to
determine if the same potentially beneficial effects can be obtained. There is
still much to be learned, but as scientists better understand the genetic
components of Alzheimer's, the roles of the amyloid precursor protein and the
tau protein in the disease, and the mechanisms of nerve cell degeneration, the
possibility that a treatment will be developed is more likely.
The responsibility for caring for Alzheimer's patients generally falls on their
spouses and children. Care givers must constantly be on guard for the
possibility of an Alzheimer's patient wandering away or becoming agitated or
confused in a manner that jeopardises the patient or others. Coping with a
loved one's decline and inability to recognise familiar faces causes enormous
pain.
The increased burden faced by families is intense, and the life of the
Alzheimer's care giver is often called a 36-hour day. Not surprisingly, care
givers often develop health and psychological problems of their own as a result
of this stress. The Alzheimer's Association, a national organisation with local
chapters throughout the United States, was formed in 1980 in large measure to
provide support for Alzheimer's care givers. Today, national and local chapters
are a valuable source for information, referral, and advice.