The disease was first described by the German physician Alois Alzheimer in 1906 after he had cared for a patient with an unusual mental illness. Dr. Alzheimer observed anatomic changes in his patient's brain and described them as abnormal clumps and tangled bundles of fibers. Nearly a century later, these abnormal findings, now described as amyloid plaques and neurofibrillary tangles, along with abnormal clusters of proteins in the brain, are recognized as the characteristic markers of AD.
The disease knows no social or economic boundaries and affects men and women almost equally. According to the Alzheimer's Association (AA), in 2004 as many as 10 percent of people sixty-five years of age and older have AD and nearly 50 percent of people aged eighty-five and older have the disease. AD can strike as early as the thirties and forties, however. Most patients are cared for at home as long as possible, a situation that can be emotionally and physically exhausting for the victims and their families.
The financial consequences of caring for patients with AD also are devastating. The costs of diagnosis, treatment, nursing home care, informal care, and lost wages are estimated by the AA and the National Institute of Aging to be about $100 billion each year. About 75 percent of the total care for people with AD is provided by their families at home. Half of all nursing home residents have AD or a related disorder. In 2004, the cost of one year's stay in a nursing home was estimated to be $42,000 per year, but the cost can exceed $70,000 per year in some areas.
Tax relief is now available for families caring for patients with AD. The Health Insurance Portability and Accountability Act of 1996 (PL 104-191) stipulated that out-of-pocket expenses for long-term care, including personal care, were deductible as medical expenses. The AA offered the example of a patient with AD who still was being cared for in the home by his wife, the primary care-giver. Their 1997 expenses for his care were about $14,700:
- $6,000 for adult day care
- $2,500 for in-home care assistance
- $5,000 for out-of-pocket health expenses, including Medicare copayments, deductibles, and prescription drugs
- $1,200 for premiums for long-term care insurance
The AA estimated that at an annual income of $42,000, approximately $12,000 of these expenses could be deducted under the new law's tax provisions. Previously, medical expenses were deductible only for medical services provided in skilled nursing facilities.
AD has become a disease of particular concern because the nation's older adult population is growing rapidly. According to the U.S. General Accounting Office, the number of cases of AD was expected to increase by more than 12 percent every five years through 2015. By 2050, the number of Americans with AD could range from 11.3 million to sixteen million, according to the AA. Prevalence (the number of people with a disease at a given time) is partially determined by the length of time people with AD survive. Although average survival is eight years after diagnosis, some patients with AD have lived longer than twenty years with the disease. Therefore, improvements in AD care, as well as increased length of life of the older adult population in general, will increase the numbers of patients with AD.
In November 1994 former President Ronald Reagan, age eighty-three, announced that he had developed AD and wanted to make Americans more aware of the disease. Some observers believe that it is theoretically possible that AD had affected Reagan before he left the White House in January 1989. Shortly before Reagan died on June 5, 2004, his wife, Nancy, began to campaign publicly for the lifting of restrictions on the use of human embryos in stem cell research. Advocates of stem cell research believe that successful treatments for many degenerative diseases, including AD, may be discovered through this aspect of stem cell research.
Possible Causes of Alzheimer's Disease
AD is not a normal consequence of growing older, and scientists are continuing to seek its cause. Although most cases appear to have no genetic link, researchers have found some promising genetic clues to the disease. The first breakthrough was reported in the February 1991 issue of the British journal Nature. Researchers reported that they had discovered that a mutation in a single gene could cause this progressive neurologic illness.
Scientists found the defect (mutation) in the gene that directs cells to produce a substance called amyloid protein. Researchers at the Massachusetts Institute of Technology (MIT) have found that low levels of the brain chemical acetylcholine contribute to the formation of hard deposits of amyloid protein that clog the brain tissue of patients with AD. In normal people, the protein fragments are broken down and excreted by the body. Amyloid protein is found in cells throughout the body, and researchers do not know how it becomes a deadly substance in the brain cells of some people and not others.
In 1995 three more genes linked to AD were identified. One gene appears to be related to the most devastating form of AD, which can strike people in their thirties. When defective, the gene may prevent brain cells from correctly processing a substance called beta amyloid precursor protein. The second gene is linked to another early-onset form of AD that strikes before age sixty-five. This gene also appears to be involved in producing beta amyloid. Researchers believe that the discovery of these two genes will allow them to narrow their search for the proteins responsible for early-onset AD and give them clues to the causes of AD in older people.
The third gene, known as apolipoprotein E (apoE), actually was reported as associated with AD in 1993, but its role in the body was not known at that time. Researchers have found since then that the gene plays several roles. Within the body, it regulates lipid metabolism within the organs and helps to redistribute cholesterol. In the brain, apoE participates in repairing nerve tissue that has been injured. There are three forms (alleles) of the gene: apoE-2, apoE-3, and apoE-4. Until recently, people with two copies of apoE-4, one from each parent, were thought to have a greatly increased risk of developing AD before age 70. From one-half to one-third of all AD patients have at least one apoE-4 gene, whereas only 15 percent of the general population have an apoE-4 gene. In 1998, however, researchers discovered that the apoE-4 gene seems to affect when a person may develop AD, not whether the person will develop the disease.
Another newly discovered gene, A2M-2, seems to affect whether a person will develop AD. Of Americans, 30 percent may carry A2M-2, a genetic variant that more than triples the risk of developing late-onset AD compared to siblings with the normal version of the A2M gene. The discovery of A2M-2 opens up the possibility of developing a drug that mimics the A2M gene's normal function. This has the potential to protect susceptible persons against brain damage or perhaps even reverse it.
Symptoms of Alzheimer's Disease
AD begins slowly. The symptoms include difficulty with memory and a loss of cognitive function (intellectual abilities). The patient with AD also may experience confusion; language problems, such as trouble finding words; impaired judgment; disorientation in place and time; and changes in mood, behavior, and personality. How quickly these changes occur varies from person to person, but eventually the disease leaves its victims unable to care for themselves. In their terminal stages, patients with AD require care twenty-four hours a day. They no longer recognize family members or themselves, and they need help with such daily activities as eating, dressing, bathing, and using the toilet. Eventually, they may become incontinent, blind, and unable to communicate. Finally, their bodies may "forget" how to breathe or make the heart beat. Many patients die from pneumonia.
Testing for Alzheimer's Disease
A complete physical, psychiatric, and neurologic evaluation usually can produce a diagnosis of AD that is about 90 percent accurate. For many years, the only sure way to diagnose the disease was to examine brain tissue under a microscope, which was not possible while the AD victim was still alive. An autopsy of someone who has died of AD reveals a characteristic pattern that is the hallmark of the disease—tangles of fibers (neurofibrillary tangles) and clusters of degenerated nerve endings (neuritic plaques) in areas of the brain that are crucial for memory and intellect. Also, the cortex of the brain is shrunken.
In 1996 a San Francisco biotechnology firm developed a diagnostic test for AD. The test, which involves analysis of blood and spinal fluid, produced conclusive results in 60 percent of older patients with dementia.
In 2000 researchers at Brigham and Women's Hospital in Boston found that the use of MRI techniques could measure the volume of brain tissue in areas of the brain used for memory, organizational ability, and planning. In addition, the use of these measurements could accurately identify persons with AD and predict which people would develop AD. That same year, scientists at New York University Medical Center, the Mayo Clinic, and the National Hospital for Neurology and Neurosurgery in London reported using MRI to identify parts of the brain affected by AD before symptoms appear and measure brain atrophy to monitor the progression of AD.
Other investigators are looking at biologic markers, such as blood tests, for AD and neuropsychological tests, which measure memory, orientation, judgment, and problem-solving. They hope to see if they can accurately predict whether healthy, unaffected older adults will develop AD or whether those with mild cognitive impairment will go on to develop AD.
Physicians and neuroscientists have long been eager for a simple and accurate test that can distinguish people with AD from those with cognitive problems or dementias arising from other causes. An accurate test would allow the detection of AD early enough for the use of experimental medications to slow the progression of the disease and would identify people at risk of developing AD. However, the availability of tests raises ethical and practical questions: Do patients really want to know their risk of developing AD? Will health insurers use test results to deny insurance coverage?
Treatments for Alzheimer's Disease
There is still no cure or prevention for AD, and treatment focuses on managing symptoms. Medication can reduce some of the symptoms, such as agitation, anxiety, unpredictable behavior, and depression. Physical exercise and good nutrition are important, as is a calm and highly structured environment. The object is to help the patient with AD maintain as much comfort, normalcy, and dignity as possible.
There are two FDA-approved classes of drugs to treat cognitive symptoms of AD. The first to be approved were cholinesterase inhibitors, which are drugs designed to prevent the breakdown of acetylcholine. Cholinesterase inhibitors keep levels of the chemical messenger high, even while the cells that produce the messenger continue to become damaged or die. About half of the people who take cholinesterase inhibitors see modest improvement in cognitive symptoms. Until 1996 tacrine (marketed as Cognex) was the nation's only AD medication, but tacrine rarely is prescribed today because of associated side effects, including possible liver damage. However, there are three other cholinesterase inhibitors currently used that produce some delay in the deterioration of memory and other cognitive skills—donepezil (Aricept), approved in 1996; rivastigmine (Exelon), approved in 2000; and galantamine (Reminyl), approved in 2001.
Memantine (Namenda) was approved by the FDA in October 2003 for treatment of moderate to severe AD. It is classified as an uncompetitive low-to-moderate affinity N-methyl-D-aspartate (NMDA) receptor antagonist, and it is the first Alzheimer drug of this type approved in the United States. According to the AA, it seems to work by regulating the activity of glutamate, one of the brain's specialized messenger chemicals involved in information processing, storage, and retrieval.
National Institutes of Health affiliates, pharmaceutical companies, and the AA are involved in clinical trials of new drugs to treat AD. All of the drugs being tested are intended to improve the symptoms of AD and slow its progression, but none are expected to "cure" AD. The investigational drugs aim to address three aspects of AD—improve cognitive function in people with early AD; slow or postpone the progression of the disease; and control behavioral problems such as wandering, aggression, and agitation of patients with AD.
Other research under way in 2004 involves the use of NSAIDs, such as ibuprofen or naproxen, to reduce the risk of developing AD because AD involves inflammatory processes in the brain. Another National Institute on Aging–funded study is trying to find out whether antioxidants, such as vitamin E, can prevent persons with mild memory impairment from progressing to AD.
Research to see if estrogen reduces the risk of AD or slows the disease has been done, and one study showed that estrogen does not slow the progression of already diagnosed disease. Also, a study on combination hormone therapy (estrogen and progestin) showed that women older than age sixty-five participating in the study had twice the rate of dementia, including AD, compared with women who did not take the medication. Substances already used to reduce cardiovascular risk factors, such as statin drugs and folic acid, also are being studied to determine whether they also reduce AD risk.
Second Victims
The suffering of a patient with AD is only part of the devastating emotional, physical, and financial trauma of AD. People who care for loved ones with AD are considered "second victims" of the disease. Caregivers often neglect their own needs, including their health and social lives, and the needs of other family members. As a result, they may develop more stress-related illnesses and are at greater risk for depression.
Many professionals recommend support groups for caregivers of patients with AD, made up of family members, friends, and health care professionals. These groups encourage members to share information and ideas, give and receive mutual support, and exchange coping skills with each other. A study of 206 spouses of patients with AD found that caregivers benefited greatly from support groups and counseling. Those who received this kind of support were able to care for the patients at home for almost one year longer than caregivers who lacked support.
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