Alzheimer's Disease
Introduction
In 1907, Dr. Alois Alzheimer was the first researcher to link a mental illness in a 55-year-old woman in her last years of life with a pattern of changes that was found in her brain on autopsy after her death. Based on this finding, the mental illness is now known as Alzheimer's disease (AD).
What is it?
Alzheimer's disease is a progressive illness that kills nerve cells and destroys nerve connections in the brain. The disease is marked by mental changes resulting from damage in the brain tissue. Because these changes cannot be visualized until autopsy, diagnosis for the disease is based on symptoms that patients have. Symptoms include gradual loss of awareness, memory, and judgment as well as mood and behavioral disturbances. The lifespan of an Alzheimer's disease victim is generally reduced, although a person may live anywhere from 3 to 20 years after diagnosis. The disease is not reversible, and currently there is no cure. However, drug therapy has been shown to slow the progression of the disease, and there are several options to treat the symptoms.
What causes it?
Researchers have defined two significant changes in the brain that occur in patients with Alzheimer's disease (AD): twisted nerve cell fibers, known as neurofibrillary tangles, and development of protein deposits or clumps, called neuritic plaques. While the exact cause of this disease is still unknown, researchers have found several factors that may contribute to the development of the disease, including an inflammatory response, genetic factors, and environmental influences. Damage to the brain resulting from AD primarily affects the nervous system. The nervous system can be thought of as the body's wiring system for electricity.
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 In Alzheimer's disease, placques and tangles impair the transmission of neurotransmitters. |
Communication between nerve cells in the brain eventually deteriorates. This causes the nerve cells to stop functioning and they inevitably die. The damage generally affects key areas of the brain that are involved in the control of memory, such as the hippocampus (located deep within the brain). Portions of the cerebral cortex, the outer area of the brain that is responsible for functions such as language and reasoning, are also affected.
Possible causes. As previously mentioned, it is believed that the changes in the brain that result from AD could be caused by several different factors described below.
- Inflammatory response: Some researchers think that beta-amyloid may release oxygen free radicals. These are unstable chemicals that are believed to bind to other molecules through a process called oxidation, causing damage to DNA and triggering other harmful processes. The end result is the production of an inflammatory response, in which the immune system overproduces substances used to fight harmful agents in the body. The overproduction results in damage to the body's own cells.
- Genetic factors: An increased risk for Alzheimer's disease has been linked to a gene called ApoE/e4. The presence of this gene is considered a risk factor but not a direct cause of the disease. An increased incidence has also been found for people who have a first-degree relative (parent, brother, or sister) who has had the disease. Three other genes are being researched to see if they have a connection to the development of AD.
- Environmental and other influences: Genetics appears to play a major role, yet it does not offer a complete answer to the occurrence of Alzheimer's disease. A severe head injury may accelerate the development of AD in people who are already susceptible. Additionally, childhood malnutrition may render people more susceptible to mental impairments late in life, including Alzheimer's disease.
Who has it?
About 4 million Americans have Alzheimer's disease. It is estimated that by the year 2050 this number will increase to almost 14 million because the baby boomers will by that year be over the age of 65. Alzheimer's disease is the leading cause of dementia (the loss of healthy mental function) and the eighth leading cause of death in the United States. Death related to Alzheimer's disease is most commonly associated with secondary complications resulting from immobilization, increased risk of infection, and inadequate nutrition.
There are two recognized types of Alzheimer's disease: early onset and late onset. In early onset, symptoms occur before the age of 60 years. This type of Alzheimer's disease runs in families but is only found in 5% to 10% of cases. In late onset, the disease occurs in persons older than 60 years of age. Late onset Alzheimer's disease is not believed to run in families, but these patients may have genetic factors that increase their risk of getting the disease.
The impact of Alzheimer's disease.
A recent study estimates that the cost of providing care for one patient with Alzheimer's disease with severe cognitive impairment is more than $47,000 per year, not including indirect losses in wages or productivity. In the United States alone, approximately $100 billion is spent each year on patients with AD. This includes the cost of medical care as well as lost productivity and personal caretaking. From the time of diagnosis until death, the average patient with Alzheimer's disease accounts for nearly $174,000 in total health care expenditures.
Alzheimer's disease is already a major public health problem. However, the implications for the future are even more serious as Americans are living longer. The major costs associated with AD are related to supportive care. Because of the expense of institutionalized care, more than half of the people who suffer from AD are cared for at home by relatives or friends. This number can be expected to grow significantly as the number of people with AD increases.
Caregivers, most of whom are women, often try to balance the responsibilities of work and family life with providing care for a relative with AD. This can prove to be extraordinarily burdensome in many ways. Caregivers are thought to spend an average of $12,500 of their own funds caring for a patient with AD. Some may even leave the workforce to provide full-time care for a loved one with the disease.
What are the risk factors?
The following factors put people at risk for Alzheimer's disease:
- Age - scientists believe the incidence of Alzheimer's disease doubles every 5 years after the age of 65 years
- Genetic abnormalities - genes such as Apo lipoprotein E4 (ApoE4)
- Family history of the disease - especially a primary relative (parents or siblings)
- Gender - women are more likely to have the disease than men
Potential risk factors being examined:
- Down's syndrome - patients may be at risk for developing Alzheimer's disease at an earlier age
- Mental or physical inactivity during midlife
- Severe head injury
- Stroke
- History of alcohol abuse
What are the symptoms?
Simple day-to-day tasks such as paying bills, picking up groceries, and using the telephone become impossible for the person who has advanced Alzheimer's disease. People with this illness may eventually lose their ability to recognize family and friends and often become unable to care for themselves. Some symptoms of Alzheimer's disease include the following:
- Loss of memory
- Impairment of reasoning and thinking skills
- Increased irritability
- Anxiety
- Depression
- Frustration
- Impaired judgment or concentration
- Wandering
- Suspiciousness or paranoia
- Delusions
- Disruptive behavior
- Hallucinations
- Aggression
- Agitation
During the earliest stages of Alzheimer's disease, mild forgetfulness is typical. Anxiety and depression also commonly occur at an early stage of Alzheimer's disease.
The next stage is usually marked by poor concentration, trouble with speech and language, and wandering. Later, memory problems become more severe. Many people who have Alzheimer's disease deny the significance of their symptoms. As the disease advances, they may need help with daily activities, such as food preparation and bathing.
In the final stages, they can become incapacitated and disoriented to the point of not knowing their own name and not recognizing loved ones.
Unlike a stroke, where changes occur within minutes or hours, the mental changes seen with Alzheimer's disease progress over an average of 8 to 10 years from the time the symptoms first appear. The disease has, however, been known to progress over a period of 20 years. How quickly these changes occur varies from person to person. Patients may be able to hide symptoms by becoming withdrawn and less social. It is important to make sure that a person's decline in mental function is not due to something else. Other causes for change in mental status include the following:
- Medications
- Infection
- Depression
- Alcohol abuse
- Liver or kidney disease
- Heart or circulatory problems
- Hypothyroidism - a deficiency of the thyroid secretion
- Vitamin B12 deficiency
- Tumors
An early and accurate diagnosis provides additional time to address legal, financial, and medical issues that can occur during the course of the disease. Early diagnosis may provide an opportunity to treat Alzheimer's disease with medications at an initial stage and slow its rate of development.
How is it treated?
Currently, there is no cure for Alzheimer's disease (AD). However, there are medications available to slow the progression of the disease and research is continuing in hopes to find a cure. Treatment is mainly aimed at alleviating or improving symptoms of the disease.
Since the main symptoms of AD include memory loss, confusion, and cognitive alterations (e.g. impaired reasoning or thinking), medications specifically aimed at improving these symptoms are needed. Cholinesterase inhibitors are commonly prescribed because they have been shown to minimize and stabilize these symptoms of AD. To learn more about these medications, click on the drug class link below.
Other common symptoms of AD include agitation and disruptive behavior. To improve these symptoms, medications such as antidepressants [like fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil), and sertaline (Zoloft)], sedatives [like lorazepam (Ativan), temazepam (Restoril)], and antipsychotic drugs [like olanzapine (Zyprexa) or risperidone (Risperdal)] may be needed.
Alternative therapies have been studied such as gingko biloba. While a few small studies have shown gingko biloba to help treat AD, more research is needed to substantiate this claim. Plus, herbal supplements are not regulated by the federal Food and Drug Administration (FDA) and thus are not put through the rigorous testing that the FDA requires for prescription medications. Given this, much care must be taken when choosing an herbal supplement. This should be discussed with a physician prior to use of the supplement.
Helping Yourself
If you are a caregiver to a person who has Alzheimer's Disease, remember that it is important for that person to perform as many regular daily activities as possible. Any independence retained in performing the necessary activities of daily living will help improve quality of life and maintain self-esteem. Other important self-help activities include:
- Physical exercise
- Social activity
- Proper nutrition
- Health maintenance
- A calm and well-structured environment
Other helpful caregiver tips include:
- Simplify the home environment--keep the home and contents in it organized; keep things in the same place (e.g. don't reorganize the kitchen cabinets). Use labels or cue cards to remind the person.
- Maintain simple routines and tasks--don't give the person with AD complicated chores or tasks and provide a structured daily routine.
- Allow for adequate rest between stimulating events--don't over-exhaust the person; allow for quiet time or naps during hectic days or activities.
- Maintain a safe environment--equip doors and gates with safety locks and remove guns from the home.
Many local and national organizations have prepared information for people with Alzheimer's Disease and their loved ones. The national office of the Alzheimer's Disease and Related Disorders Association (ADRDA) is a good place to start. For information, contact the ADRDA at 70 E. Lake Street, Chicago, IL 60601.
What is on the horizon?
Because there are so few known certainties regarding Alzheimer's disease, research is underway in almost every aspect of the disease. However, much of this research focuses on easing mental and behavioral symptoms. The following is a brief description of what's new in Alzheimer's disease research:
- Damage to parts of the brain involved in memory may be seen on brain scans before symptoms of Alzheimer's disease occur. Researchers are looking at such changes in a large study, the AD Neuroimaging Initiative, to determine if brain imaging can help predict the onset or possibly monitor the progression of AD.
- The enzyme Cdk5 helps form the neurofibrillary tangles that are characteristic of AD. Researchers believe that inhibiting Cdk5 might prevent formation of the neurofibrillary tangles and are now testing a variety of compounds against the enzyme.
- Folate may decrease the risk of developing Alzheimer's disease, according to a recent report. Researchers found that those patients who had a higher intake of both dietary folate and folate supplements had a reduced risk of developing AD. However, the authors concluded that although this is a positive finding, the decision to increase folate intake to prevent AD should await further reports and clinical trials.
- Gene therapy is being studied by a group of investigators at the University of California. A group of researchers from Indiana University are also attempting to identify the exact genes that are responsible for causing AD.
- A popular cholesterol-lowering medication, Zocor, has been studied for its possible benefits in slowing the progression of AD. It has been shown to have a mild reduction in beta amyloid production for patients in early stages of AD. Lipitor is currently being studied for its possible benefits in AD as well.
- Another cholinesterase inhibitor, physostigmine, may improve memory in healthy subjects by decreasing the time normally needed to complete tasks and by improving activity in a specific part of the brain. However, side effects of this drug, including nausea and vomiting, may limit its usefulness.
- Research is underway for a nasal vaccine that theoretically would decrease the amount of plaques developed with Alzheimer's disease and would ultimately lead to continued communication in the brain. The vaccine is inhaled through the nose, in a manner similar to the way many asthma and allergy medications are used.
- Researchers are also studying the effects of selegiline (Eldepryl, Somerset) and vitamin E in treating Alzheimer's disease. The oxidation of brain cells is considered a possible mechanism of the disease, and both vitamin E and selegiline are considered to have antioxidant properties. So far, studies have shown that selegiline and vitamin E may delay disease progression. Today, many physicians use Vitamin E in combination with other treatment options for AD.
- It has been suggested that the decline of estrogen production in postmenopausal women may place women at greater risk for developing Alzheimer's disease. Results of a recently completed trial did not support the use of estrogen replacement therapy in the treatment of Alzheimer's disease. However, future studies are underway to determine if estrogen has a role in preventing or delaying the onset of AD.
- Evoxac, an agent approved by the FDA to treat dry mouth in Sjogren's Syndrome (an autoimmune disease that affects moisture-producing glands such as salivary and sweat glands) has been shown to reduce levels of the protein beta-amyloid in Alzheimer patients. The effects of this medication on thought process and long-term disease progression are currently being assessed.
References
Agency for Health Care Policy and Research. Early Alzheimer's disease: recognition and assessment; Clinical Practice Guideline, No. 19. U.S. Department of Health and Human Services, Public Health Service. Available at: http://www.ahcpr.gov/clinic/alzover.htm. Accessed January 2008.
Alzheimer's Association. Public Policy FAQs. Available at: http://www.alz.org/. Accessed January 2008.
Alzheimer's disease Education and Referral Center. National Institutes of Health's National Institute of Aging. Available at: http://www.nia.nih.gov/alzheimers. Accessed January 2008.
Alzheimer?s Disease.com. Available at: http://www.exelonpatch.com/info/about/alzheimers/alzheimers-explained.jsp?WT.svl=FM. Accessed January 2008.
Alzheimer?s Disease Fact Sheet. National Institutes of Health?s National Institute of Aging. Available at: http://www.nia.nih.gov/Alzheimers/Publications/adfacts.htm. Accessed February 2007.
Alzheimer?s Disease Neuroimaging Initiative. National Institutes of Health?s National Institute of Aging. Available at: http://www.nia.nih.gov/Alzheimers/ResearchInformation/ClinicalTrials/ADNI.htm. Accessed January 2008.
Beal MF, Richardson EP, Martin JB. Alzheimer's disease and other dementias. In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL, eds. Harrison's Principles of Internal Medicine. 13th Ed. New York: McGraw-Hill; 1994.
Faulkner JD, Bartlett J, Hick P. Alzheimer's disease. In: Pharmacotherapy: A Pathophysiologic Approach. 6th Ed. New York: McGraw-Hill; 2005: pages 1157-1173.
FDA approved Reminyl for the treatment of mild to moderate Alzheimer's disease [press release]. March 5, 2001. Alzheimer Research Forum Web site. Available at: http://www.alzforum.org/. Accessed January 2008.
Frazin, N. Drug Screening Study Suggests New Treatments for Alzheimer?s. National Institute of Neurological Disorders and Stroke. Available at: http://www.ninds.nih.gov/news_and_events/news_articles/news_article_Alzheimer_Cdk5_inhibitors_092605.htm. Accessed January 2008.
Luchsinger, J et al. Relation of higher folate intake to lower risk of Alzheimer disease in elderly. Arch Neurol. 2007; 64: 86-92. [Abstract]. Available at: http://archneur.ama-assn.org/cgi/content/short/64/1/86. Accessed January 2008.
Mozes, Alan. Nasal Vaccine Might Slow Alzheimer?s. Available at: http://www.medicinenet.com/script/main/art.asp?articlekey=52934. Accessed March 2006.
Namenda Package Insert. St. Louis, MO: Forest Pharmaceuticals, Inc; 2003 October. Available at: http://www.namenda.com. Accessed January 2008.
New drug therapies delay effects of Alzheimer's disease. New England Journal of Medicine April 24, 1997. Alzheimer's disease Education and Referral Center, National Institute on Aging web site. Available at: http://www.alzheimers.org/nianews12.html.
Ropper AH, Brown RH. Alzheimer?s Disease. In: Principles of Neurology. 8th. New York: McGraw-Hill; 2005: pages 898-906. Standaert DG, Young AB. Treatment of Alzheimer?s Disease. Goodman and Gilman?s -The Pharmacological Basis of Therapeutics -11th ed. McGraw & Hill; 2006: pages 538-540.
Alzheimer's Disease Health Condition Last Updated: March 2008
Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.