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Alzheimer's disease is a progressive condition of the brain affecting memory, thought and language. The degenerative changes of Alzheimer's disease lead to patches or plaques in the brain and the entanglement of nerve fibers (neurofibrillary tangles). Memory loss and behavioral changes occur as a result of these changes in brain tissue.
Alzheimer's disease is a slow progressive illness. The early behavioral changes may not be noticed, especially difficulty with short-term memory. As the disease progresses, memory loss increases and there are changes in personality, mood and behavior. Disturbances of judgment and concentration occur, along with confusion and restlessness. The type, severity, sequence, and progression of mental changes vary widely. Long periods with little change are common, although occasionally the disease can be rapidly progressive. In addition, some patients may experience weight loss due to complications of eating or remembering to eat.
People with Alzheimer's disease should be given regular physical examinations to detect other organic disorders that may develop. These patients may be unable to communicate clearly regarding the development of new or unrelated symptoms.
Alzheimer's disease is inherited as an autosomal dominant trait in at least 10 percent of the cases. Researchers studying the genetic forms of Alzheimer's disease have located defects causing the disorder on at least three chromosomes. These include genes on chromosomes 1, 14, 19, and 21. It is not understood whether these genetic defects can cause different types of Alzheimer's disease or variations of the same disorder. Researchers have also located a specific gene that is responsible for the early onset form of Alzheimer's disease. In other cases of Alzheimer's disease the cause is unknown.
Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child
Alzheimer's disease frequently occurs in individuals with Down syndrome who live past 35 years of age. Chromosome 21 abnormalities are common to both Down syndrome patients and some of the familial Alzheimer's disease patients.
Some studies suggest that the disease may not be a single illness and that several factors are involved. Researchers at the UCLA Medical School found that 100 percent of men with early Alzheimer's disease (before the age of 60) had the protein HLA-A2 on the surface of their white blood cells, compared to 30 percent of healthy men under the age of 60, and 40 percent of men with late-onset disease. It is suggested that HLA-A2 positive men may be at higher risk for early-onset Alzheimer's disease.
Researchers at the John Hopkins Hospital are studying the brain tissue of deceased Alzheimer's disease patients, and have found nerve cell (neuronal) degeneration. These nerve cells are believed to contain the neurotransmitter acetylcholine. Some patients with Alzheimer's disease have a 90 percent loss of these cells. There may be abnormally low levels of acetylcholine in the brains of Alzheimer's disease patients.
Recent studies suggest that at least four chromosomes carry genes that can lead to the development of Alzheimer's disease. A gene located on the long arm of chromosome 14 (14q) is believed to be responsible for the early onset form of Alzheimer's disease. Another gene, known as the B-amyloid precursor protein gene (APP) is located on the long arm of chromosome 21 (21q). This defective gene is believed to cause a small percentage of people to develop Alzheimer's disease around the age of 50 years. The presence of a specific defective gene on the long arm of chromosome 19 (19q) is an important risk factor for the development of late onset Alzheimer's disease. This gene is known as the APO E2 and APO E4. A fourth gene (STM-2), located on chromosome 1, is thought to be associated with early-onset Alzheimer's disease. This severe form of the disease usually affects people around the age of 40 years.
Researchers believe that brain cells normally produce a soluble form of the amyloid protein. However, people with Alzheimer's disease have insoluble deposits of amyloid (plaques) in their brain. Therefore, an unknown factor may be responsible for the plaque formation. It may not be the amyloid protein that causes Alzheimer's disease, but instead another factor that causes abnormal deposits of amyloid to occur.
Apolipoprotein E (ApoE) is an essential protein that guides cholesterol through the bloodstream. The gene comes in three varieties known as E2, E3, and E4. All genes of the body come in two copies, one donated by the mother and the other by the father. The two copies of the apolipoprotein E gene can be inherited in any combination of either E2, E3, or the E4 variety. Researchers studying the gene for apolipoprotein E (located on chromosome 19) have found that patients with one copy of the E4 gene have double the risk for getting Alzheimer's disease over that of people having no E4 gene at all. Individuals with two copies of the E4 gene have eight times the risk of getting Alzheimer's disease.
Some research indicates that individuals with no copies (alleles) of the APOE-4 gene are affected by Alzheimer's disease at a later age than those who have one or two copies of the defective gene. One study suggests the APOE-4 gene does not increase the risk of Alzheimer's disease but rather influences when an individual will develop Alzheimer's disease. This study suggests individuals with the APOE-4 gene will develop Alzheimer's disease at an earlier age.
Another study has suggested that there is a genetic cause for the sporadic form of Alzheimer's disease. Most people with the disease have no apparent family history. A majority of the patients in the study had at least one of the suspected genes for late onset familial Alzheimer's disease. Researchers indicate that the disease may be related to other causes in those individuals without the suspected gene. More study is needed before the possible genetic causes for this disease can be more fully understood.
A study by the U.S. Alzheimer's Disease Collaborative Group suggests that people who inherit two defective copies of the presenilin-1 (PS-1) gene may have double the risk for developing the disease. This defective gene may be responsible for up to 20 percent of the cases of Alzheimer's disease.
One very preliminary study showed individuals who consumed a high fat diet have a higher chance of developing Alzheimer's disease.
Researchers believe they have discovered another gene that is responsible for the development of late onset Alzheimer's disease. The gene, known as K variant, is located on chromosome 3. The K variant gene is believed to interact with the E4 variant gene, increasing the risk of developing late onset Alzheimer's disease. Researchers hope the discovery of the possible interaction of these two genes may help lead to a drug that will interfere with the disease process.
Researchers believe they have discovered a molecule called endoplasmic-reticulum-associated binding protein (ERAB) that may be responsible for the development of Alzheimer's disease.
A gene, called tau, believed to cause a form of dementia may also be involved in Alzheimer's disease.
Researchers have discovered gene that is believed to be responsible for the development of late onset Alzheimer's disease. The gene, known as alpha-2-macroglobulin (A2M), is located on chromosome 12. A mutation in the A2M gene is believed to break down beta amyloid protein. Individuals with a mutation in the A2M gene are more than three times as likely to develop late onset Alzheimer's disease.
Alzheimer's disease occurs in approximately 3 percent of the general population over 65 years of age. Approximately, half of individuals over the age of 85 are believed to be at risk for Alzheimer's disease. Approximately 4.5 million people in the United States are affected. The disease affects more females than males and a higher percentage of Americans of African descent than those of European ancestry.
It is possible that the incidence of Alzheimer's disease may be higher than the estimates cited above. The National Institute on Aging has estimated that, for each five-year age group beyond 65, the percentage of people with Alzheimer's disease doubles.
Alzheimer's disease is primarily a disease affecting the elderly, but there is an early-onset form that can strike people in their 30s.
One study demonstrated that individuals who do not marry have a two to three times, greater risk of developing Alzheimer's disease or another form of dementia than those who do marry.
Symptoms of the following disorders can be similar to those of Alzheimer's Disease. Comparisons may be useful for a differential diagnosis:
Pick's Disease is a degenerative neurological disorder that affects the frontal and temporal lobes of the brain. The symptoms of Pick's Disease closely resemble those of Alzheimer's Disease. In the early stages, memory is still intact and there is a high degree of disorientation. In the later stages of this disorder, there is a loss of motor control and language skills. There may also be severe dementia. (For more information on this disorder, choose "Pick's Disease" as your search term in the Rare Disease Database.)
Binswanger Disease is a form of senile dementia that is associated with degenerative changes in the white matter of the brain. The major symptoms include the loss of short-term memory, difficulty coping with unusual events, self-centeredness and childish behavior. Other symptoms may include urinary incontinence, difficulty walking, tremor and depression. (For more information on this disorder, choose "Binswanger " as your search term in the Rare Disease Database.)
Creutzfeldt-Jakob Disease is a rare, degenerative disease of the brain that is characterized by the progressive degeneration of the central nervous system and by neuromuscular disturbances. The early symptoms include a marked loss of memory, behavioral changes, difficulty in concentration and visual disturbances. Sporadic, shock-like contractions of muscles (myoclonus) may also be present. The illness progresses to mental deterioration, sensory disturbances and the progressive wasting away of muscle. (For more information on this disorder, choose "Creutzfeldt-Jakob" as your search term in the Rare Disease Database.)
The only way to conclusively diagnose Alzheimer's disease is through examination of the brain after death. However, physicians are able to make a probable diagnosis based upon a complete medical history, neurological and psychological tests, a physical exam with blood and urine laboratory tests, and a brain-imaging scan.
In October 2006, the Food and Drug Administration (FDA) approved donepezil hydrochloride (Aricept) for the treatment of severe dementia in patients with AD. Aricept had previously been approved for mild to moderate dementia. It is now the first drug to be approved for all degrees of severity of the disease.
In general, the treatment of Alzheimer's disease is symptomatic and supportive. The goal of most treatment options is to slow the loss of memory and cognitive function in affected individuals and to allow them to maintain an independent lifestyle.
Tranquilizers may decrease agitation, anxiety or unusual behaviors. The depression often accompanying this illness may be treated with various antidepressant drugs. Proper diet and fluid intake are important. Special diets or food supplements may or may not be of benefit. Exercise and physical therapy may be helpful for some patients. Patients with AD should avoid drinking alcoholic beverages since alcohol can add to the confused mental state. The daily routine of a patient should be maintained as normally as possible. Continuation of social activities should be encouraged.
The FDA has approved the following prescription drugs for people with mild-to-moderate Alzheimer's disease: tacrine (Cognex), rivastigmine (Exelon), and galantamine (Reminyl). These drugs increase the level in the brain of acetylcholine, a chemical that facilitates communication between nerves. These drugs inhibit an enzyme called cholestinerase that breaks down the acetylcholine.
Another drug, memantine (Namenda) has been approved by the FDA to treat people with moderate-to-severe Alzheimer's disease. This drug is thought to work by blocking the action of glutamate, a brain chemical that may be overactive in people with Alzheimer's disease.
Genetic counseling may be of benefit for some affected individuals and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
As of December 2006, more than 100 clinical studies related to Alzheimer's disease were listed on the www.clinicaltrials.gov site. These studies investigate the causes of, and possible treatments for, this disease. The death of former President Ronald Reagan after his lengthy battle with AD has further spotlighted this condition. Efforts are being made to investigate stem cell replacement as a treatment. Other research is based upon the amyloid hypothesis. This hypothesis is that AD starts with the accumulation of amyloid plaques, and that limiting this accumulation will change the course of the disease.
Other lines of investigation include the following:
Vascular drugs that fall in the category of statins (Lipitor, Bryostatin, Simvastatin, etc.), generally associated with lowering cholesterol are being examined for their potential in preventing the buildup of beta-amyloid plaque on the brain, which may be the root cause of AD. Some researchers believe this plaque may be formed by high cholesterol.
In several studies, researchers are investigating whether ingesting non-steroidal, anti-inflammatory drugs (NAISDs), vitamins, or folic acid may reduce the risk of developing Alzheimer's disease or slow its progression. NAISDs include common pain relief drugs. The vitamins being studied include E, B12, and B6.
Researchers are investigating the possible role of estrogen as a memory enhancer for post-menopausal women with AD.
A Phase III study of the drug VP4896 (Leuprolide) is in progress (2006). This study is based on the hypothesis that luteinizing hormone is the cause of Alzheimer's disease. This drug blocks production of luteinizing hormone. It is manufactured by Voyager Pharmaceutical Corp. Patients are being recruited in the United States, Canada, and South America. For information, contact Connie Powers at (919) 846-4880 (email@example.com) or go to www.clinicaltrials.gov.
Memory Pharmaceuticals Corp. has three drugs in beginning phases (2005) of development for the treatment of Alzheimer's disease. For information, contact the company at:
Memory Pharmaceuticals Corp.
100 Philips Parkway
Montvale, NJ 07645
Phone: (201) 802-7100
Fax: (201) 802-7190
Phase III clinical trials have been launched in testing centers across North America for the drug Alzhemed. This drug is being studied for its potential effectiveness in improving cognitive function in patients with mild-to-moderate Alzheimer's disease. It is designed to prevent beta-amyloid formation and deposition in the brain. These trials are not presently listed within the NIH information. For information on the clinical trials and Alzemed contact its manufacturer, Neurochem, at:
Phone: (450) 680-4500
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Home page: http://www.jdfaf.org
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800 #: 800-352-9424
Home page: http://www.ninds.nih.gov/
31 Center Drive, MSC 2292
Bethesda, MD 20892
Phone #: 301-496-1752
800 #: 800-222-2225
Home page: http://www.nih.gov/nia
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San Francisco, CA 94117
Phone #: 415-476-6880
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Home page: http://www.memory.ucsf.edu
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FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:1043000; Last Update:8/20/99.
Report last updated: 2007/01/08 00:00:00 GMT+0