$Unique_ID{BRK03448} $Pretitle{} $Title{Alzheimer's Disease} $Subject{Alzheimer's Disease Presenile Dementia Senility Pick's Disease Binswanger Disease Creutzfeldt-Jakob Disease} $Volume{} $Log{} Copyright (C) 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992 National Organization for Rare Disorders, Inc. 29 Alzheimer's Disease ** IMPORTANT ** It is possible that the main title of the article Alzheimer's Disease is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Presenile Dementia Senility Information on the following diseases can be found in the Related Disorders section of this report: Pick's Disease Binswanger Disease Creutzfeldt-Jakob Disease General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. 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. Symptoms 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. 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. Causes 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 14, 21, and 19. It is not understood whether these genetic defects can cause different types of Alzheimer's Disease or variations of the same disorder. 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. 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. Affected Population Alzheimer's Disease occurs in approximately 2 percent to 3 percent of the general population over 60 years of age. Approximately 2.5 million people in the United States are affected. The disease affects more females than males and a higher percentage of Afro-Americans than Caucasians. Related Disorders 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). Therapies: Standard The treatment of Alzheimer's Disease is symptomatic and supportive. 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 Alzheimer's Disease 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 only drug approved for the treatment of Alzheimer's Disease is Hydergine-LC. Recent tests suggest that this medication may be ineffective in treating Alzheimer's Disease patients. Genetic counseling may be of benefit for patients and their families. Therapies: Investigational Diagnosed Alzheimer's Disease patients who have one or more relatives (living or deceased) also diagnosed with the disease, may participate in a clinical research study being conducted at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, MD. The goal of the study is to identify the gene linked to the type of Alzheimer's Disease that runs in families. Physicians who wish to refer potential candidates from families with many affected individuals should contact: Ms. Linda Nee, M.S.W. or Dr. Ronald Polinsky NIH/National Institute of Neurological Disorders and Stroke (NINDS) Medical Neurology Branch, Bldg. 10, Rm. 5N236 Bethesda, MD 20892 (301) 496-8350 Once the defective gene for Alzheimer's Disease on chromosome 21 is identified, the biochemical abnormality may be defined and researchers may then learn how to correct the defect through drugs, surgery, environmental or genetic manipulation. Studies on the drug tetrahydroaminoacridine (THA or Tacrine) for treatment of Alzheimer's Disease are presently underway. It is hoped that Tacrine may help small amounts of acetylcholine to stay in the brain for longer periods of time. This would not stop the progression of Alzheimer's Disease, but may help temporarily improve symptoms such as memory loss and confusion. Studies published in 1992 indicate that Tacrine may produce slight short-term benefits in a subcategory of Alzheimer's patients, but it can also cause frequent side effects, primarily liver dysfunction and gastrointestinal symptoms. For more information on this drug, please contact: Warner-Lambert Co. 2800 Plymouth Road P.O. Box 1047 Ann Arbor, MI 48106. A study of early onset dementia occurring as a result of Alzheimer's Disease is being conducted by the National Institute of Mental Health (NIMH) and the Neuropsychiatric Research Hospital at Washington, D.C. This study includes a thorough neuropsychological evaluation, brain imaging and evaluation using newly developed biochemical assay techniques. Participants in this study must be under forty-five years of age and not require special medical care. Physicians with patients who are interested should contact: Denise Juliano, MSW Coordinator of Admissions Neuropsychiatric Research Hospital 2700 Martin Luther King Jr. Ave., SE Washington, DC 20032 (202) 373-6100 The narcotic antagonist drug Naltrexone is being tested for treatment of Alzheimer's Disease. This drug may alleviate some symptoms. Further testing is required to determine long-term safety and effectiveness. The drug Desferal administered intramuscularly twice daily is being investigated as a treatment for Alzheimer's Disease. The drug is manufactured by Ciba-Geigy. More study is needed to determine the long-term safety and effectiveness of this treatment. New drugs being developed for the treatment of Alzheimer's Disease by Hoeschst Co. include: Velnacrine (Metane), Suronacrine (HP 128), HP 749, Ebiratide (HOE 427), HOE 065, and CAS 493. The drug linopirine is being tested on Alzheimer's Disease patients. It acts "encourage" brain cells to increase production of acetylcholine that is in short supply in the brains of persons with Alzheimer Disease. Du Pont Merck Pharmaceutical Co. is the manufacturer of this drug. Other drugs in development for the possible treatment of Alzheimer's Disease include: Capoten, SQ 29852, HP290, Nimotop, Guanfacine, Zacopride, Milacemide, Alcar, Oxiracetam, Avan, and Cognex. Research on genetic diseases and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future. This disease entry is based upon medical information available through December 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Alzheimer's Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 203 746-6518 Alzheimer's Disease and Related Disorders Association, Inc. National Headquarters 70 East Lake Street Chicago, IL 60601 (312) 853-3060 (708) 330-0230 (800) 621-0379 (In Illinois) (800) 572-6037 (out of state) NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 NIH/National Institute on Aging (NIA) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-1752 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References THE MERCK MANUAL 15th ed. R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. P. 1337. MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 57-61. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 2075-2079. PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989. Pp. 923-926. LACK OF EFFICACY OF HYDERGINE IN PATIENTS WITH ALZHEIMER'S DISEASE, Thompson, Troy, et al.; N. Eng J Med (August 16, 2990, issue 323 (7)). Pp. 445-448. THERAPEUTIC FRONTIERS IN ALZHEIMER'S DISEASE, S.W. Miller et al.; Pharmacotherapy (1992; 12(3)). Pp. 217-231. DRUG TREATMENT OF ALZHEIMER'S DISEASE, J.K. Cooper; Arch Intern Med (Feb 1991; 151(2)). Pp. 245-249. ALZHEIMER'S DISEASE. RECOGNIZING AND TREATING A FRUSTRATING CONDITION, W.P. Shelton et al.; Postgrad Med (Sept 1991; 90(4)). Pp. 33-34, 37-41. A DOUBLE-BLIND, PLACEBO-CONTROLLED MULTICENTER STUDY OF TACRINE FOR ALZHEIMER'S DISEASE: K.L. Davis, et al.; N Engl J Med, (October 29, 1992; issue 327 (22). Pp. 1253-9.