Alzheimer's disease

Definition

Alzheimer's disease (AD) is an illness of the brain and is a type of dementia. AD causes large numbers of nerve cells in the brain to die. This affects a person's ability to remember things and to think clearly. Doctors do not know what causes the disease. They do know that it usually begins after age 60 and nearly half of people age 85 and older may have Alzheimer's. However, it is not a normal part of aging.

Description

With almost no exceptions, AD is a disease that affects older people and that progresses as the person ages. There is no cure, and only limited treatments were available as of early 2008.

AD is named for German physician Alois Alzheimer (1864–1915). In 1906, Dr. Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental illness. He found abnormal clumps of material (called amyloid plaques) and tangled bundles of fibers (called neurofibrillary tangles). These plaques and tangles in the brain are considered signs of AD. Scientists have found other brain changes in people with AD. Nerve cells die in areas of the brain that are vital to memory and other mental abilities, and connections between nerve cells are disrupted. There also are lower levels of some of the chemicals in the brain that carry messages back and forth between nerve cells. AD may impair thinking and memory by disrupting these messages.

AD often starts slowly. In fact, some people do not know they have Alzheimer's disease. They blame

their forgetfulness on old age. Over time, their memory problems worsen. People with AD lose the ability to drive a car, cook a meal, or even read a newspaper. They may get lost easily and find simple things confusing. Some people become worried, angry, or violent. At some point, people with AD may require others to take care of virtually all their needs, including feeding, bathing, and grooming, either at home or in a care facility.

One of the most notable Americans to develop AD is Ronald Reagan (1911–2004), the 40th president of the United States (1981–1989). He was diagnosed with AD in 1994 and died from complications of the disease in 2004 at the age of 93.

Demographics

The Alzheimer's Association estimates 5.1 million Americans have AD. By 2050, the number could rise to 13.2 million, according to the American Health Assistance Foundation (AHAF). The exact number is difficult to determine since AD is often misdiagnosed as another condition or is not diagnosed until the disease is in its later stages. The AHAF reports that approximately 65,800 people die from AD, and 350,000 new cases of Alzheimer's disease are diagnosed each year in the United States. The disease usually begins after age 60, and risk goes up with age. About 5% of men and women ages 65–74 have AD, and nearly half of those age 85 and older may have the disease. Younger people may develop AD, but much less commonly. Women appear to have a slightly greater risk than males of developing AD. The scope of AD worldwide is not known. AHAF estimates 26 million people worldwide have AD as of 2007 and they project that number will increase to 106 million by 2050.

Causes and symptoms

Scientists do not know what causes AD but they suspect it is caused by multiple factors. The main-stream theory is that AD is brought on when a toxic protein called amyloid accumulates in the brain, causing memory loss and the destruction of brain cells. AD is sometimes a genetic disease, meaning that inherited factors play a role in disease development. It is unclear the extent genetic factors play in developing AD. Some studies indicate more than half of people with AD inherited the disease. Other studies indicate only 25% of AD cases are inherited. People diagnosed with Down Syndrome (DS) are nearly 100% likely to develop AD. The symptoms of AD in patients with DS are the same as in other patients with AD. The primary difference is age at onset. People with DS usually begin to show symptoms of AD around age 40 with nearly 50% displaying symptoms by age 60. Non-inherited AD is referred to as sporadic Alzheimer 's disease. As of 2007, scientists had discovered three genes that, if mutated, can cause early onset AD, and one gene that increases the risk for late onset AD. In 2007, scientists reported they had discovered another gene (SORL 1) that may play a role in the development of late onset AD.

A number of environmental factors have been suggested as causes or triggers of AD. These include aluminum, zinc, viruses, and food-borne toxins. Larger amounts of aluminum are found in autopsy studies of patients with AD compared to patients without AD. However, the origin of the excess aluminum is not yet known. Both low and excess levels of zinc have been cited as potential causes with inconclusive results. Food-borne toxins and viruses have also been studied with no conclusive evidence directly linking them as causes or triggers of AD.

Symptoms

There are seven key warning signs of early onset Alzheimer's disease. They are:

• Asking the same question repeatedly.
• Telling the same story, word for word, repeatedly.
• Forgetting how to do activities that were previously done easily, such as cooking, making repairs, and playing games (cards, checkers, etc.).
• Losing the ability to pay bills or balance a checkbook.
• Getting lost in familiar surroundings, or misplacing commonly used personal or household objects.
• Neglecting personal hygiene, such as not bathing or changing clothes regularly.
• Relying on a spouse or someone else to make decisions or answer questions that a person previously would have done without help.

Progression

People with Alzheimer's disease progress at different rates, and progression of memory loss varies from person to person. Impaired memory eventually begins to interfere with daily activities. Patients may not be aware that they are experiencing memory failure. Other persons with AD are keenly aware of their memory loss and may become anxious and frustrated, especially in early phases of the disease. Patients with AD may also begin to experience disorientation to place and become confused by changes of environment.

During the middle stage of Alzheimer's disease, a person may not be able to be left alone. The patient can become easily confused and lost. Difficulty in many aspects of language appears at this time. Patients with moderate AD experience problems with comprehension and remembering the names of things in their environment. Their speech may not flow smoothly when they talk and they may have difficulties repeating previousl explained information. Simple mathematical calculations or performing tasks such as dressing or preparing a meal at the correct time may also become impaired. Because there is individual variation in the progression of the disease, some people may still be able to continue routine behavior and engage in general conversation during this phase of the disease. A small number of people may have problems with their vision, although such people with AD frequently deny any vision problems.

In the late stages of AD, a person who can still get out of bed may wander aimlessly. Wandering must be monitored at night because the sleeping patterns of people with AD may change. Walking may become difficult in the late phase of AD because some people experience stiff muscles that cause their movement to be awkward and slow. People with late-stage AD require constant supervision. Rationalizing with patients becomes very difficult at this time because they experience severe mental changes. They are often unable to reason or demonstrate appropriate judgment. Patients may become uninhibited and confrontational. Late-stage AD may lead to delusions, which are false beliefs despite evidence to the contrary. This can include not recognizing a family member or accusing a spouse of infidelity. A patient with AD may also have hallucinations, which are a perception of objects, animals, or people in their environment that are not actually there.

In the end stage of AD, patients may need assistance with basic daily living such as feeding themselves and changing clothes. Most patients are bedridden, their muscles are stiff, and their joints are incapable of bending. Many patients are unable to talk and lose control of their bowel and urinary functions. Abnormal jerking body movements may occur spontaneously, or may be brought on by certain noises or touches. When reflexes are tested, such as tapping the leg below the knee, there are frequently exaggerated responses. Some patients also experience seizures.

Diagnosis

Unfortunately, a definitive diagnosis of Alzheimer's disease can not be confirmed unless an autopsy is performed. Diagnosis before death is based upon the finding of slowly progressive dementia, exclusion of other possible causes for dementia, and brain-imaging studies that show changes in the structure of the brain, usually in the form of shrinkage. Obtaining an accurate medical history is essential in this process. An accurate family history including a history of family members who have had AD and age of onset must be obtained. Physical examination and tests of blood or urine may identify other causes of dementia. Brain-imaging (neuroimaging) refers to the use of positron emission tomography (PET), magnetic resonance imaging (MRI), or computed topography (CT) scans. These are special types of pictures that allow the brain or other internal body structures to be visualized. The earliest changes in the structure of the brain are seen using PET scans. MRI and CT scans are useful in the early phase of the disease to exclude other brain abnormalities that may be causing dementia. As the disease progresses, use of MRI and CT scans can show changes in the structure of the brain tissue that indicate brain cell death. Studies indicate that an MRI scan is statistically accurate in predicting who may or may not develop AD in the future.

The brain of a patient with Alzheimer's has A-beta amyloid neuritic plaques (senile plaques) and intraneuronal neurofibrillary tangles. These are changes in specific proteins and nerve structures of the brain that occur normally as an individual ages, but are greatly increased in patients with AD. These brain changes are similar in sporadic, familial early onset, familial late onset, and patients with Down syndrome-related Alzheimer's disease. A general rule is that the longer a person has AD, the smaller the brain is upon death.

Treatment

There is no cure for AD, but there are medicines that can treat the symptoms of Alzheimer's. Some medicines keep memory loss and other symptoms from worsening for a time. These medicines work best if the disease is found early. Other medicines do not directly treat the disease, but work to help people with AD sleep better or feel less worried and depressed. Treating these symptoms can help patients feel more comfortable in their surroundings. As of early 2008, there were five oral drugs approved by the U.S. Food and Drug Administration (FDA) to control the symptoms of AD and slow its progression. Four of these drugs, called cholinesterase inhibitors, slow the metabolic breakdown of acetylcholine, an important brain chemical involved in nerve cell communication. These drugs make more of this chemical available for communication between cells. This slows the progression of cognitive impairment and can be effective for some patients with mild to moderate symptoms of AD. These four drugs are tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). In 2006, the FDA approved the use of donepezil to treat severe symptoms of AD and in 2007, approved rivastigmine in a patch form that delivers the drug through the skin. The fifth drug, memantine (Namenda), is approved to treat moderate to severe AD. Although the exact mechanism of rivastigmine is not known, it is thought to work by protecting nerve cells in the brain from excess amounts of glutamate, a messenger chemical released in large amounts by AD-damaged brain cells. Adverse side effects of all five drugs include nausea, dizziness, headache, and fatigue.

As of early 2008, a number of drugs were undergoing clinical trials or were in development to treat AD, none of which would cure the disease. An interesting and controversial theory about AD surfaced in 2006 when a small clinical trial reported that the diabetes drug rosiglitazone (Avandia) may slow the progression of AD. This has led a handful of researchers to suggest AD may be a type of diabetes. A number of previous studies have shown that brain cells of people with AD are resistant to insulin . This, in turn, deprives neurons of glucose (sugar) that is needed for energy. If insulin resistance in the brain is shown to be the cause of AD, it would be a monumental shift in the understanding of the disease. A new study of Avandia in 3,400 people with AD began in 2007 and results were expected to be available in 2009. If the insulin-AD connection is proven true, it could lead to tests capable of detecting insulin resistance in the brain early on allowing corrective action to be taken that could delay or prevent onset of AD later in life.

Nutrition/Dietetic concerns

Several studies have found that high fat and high calorie diets may increase the risk of developing AD. Other possible high risk factors include alcohol, salt, and refined carbohydrates . In addition, several studies found that fish consumption reduced the incidence of AD in European and North American countries. Scientists speculate that Omega-3 fatty acids in fish may delay the onset of AD. Anti-inflammatory agents, such as antioxidants , have shown some effectiveness in treating the disease. A diet that includes antioxidants such as Vitamin C, Vitamin E , selenium, green tea, and ginkgo biloba extract may be beneficial. Ginkgo biloba, in addition to its antioxidant properties, increases blood and oxygen flow to the brain perhaps boosting brain function. It is recommended that patients with AD avoid environmental toxins, such as tobacco smoke.

Therapy

There are no specific therapies associated with AD. A person with AD should be encouraged to exercise as much as their symptoms or physical limitations allow. Daily supervised walks are a good general exercise for people with AD.

Prognosis

On average, Alzheimer's disease lasts eight to ten years. Death is most frequently related to malnutrition , secondary infection (infection that is not the initial medical problem) such as pneumonia or heart disease . Malnutrition is a state in which not enough calories are taken in to support the normal functions of the human body. Malnourished people are also more prone to infections. There is no evidence that links AD to heart disease, however, the rate for both increases as people age.

Prevention

As of 2008, there was no known way to prevent AD. A number of studies in laboratory mice indicate that a Mediterranean-style diet low in sugar and saturated animal fat, and high in fruits, vegetables, and whole-grains, may reduce the risk of developing the disease. Several studies also suggest that a glass of red wine once a day may provide protection against AD.

Caregiver concerns

Caring for a person with AD at home is a difficult task and can become overwhelming at times. Each day may bring new challenges as the caregiver copes with changing levels of ability and new patterns of behavior. Research has shown that caregivers themselves are at increased risk for depression and illness, especially if they do not receive adequate support from family, friends, and the community.

One of the biggest struggles caregivers face is dealing with the difficult behaviors of the patient. Basic activities of daily living, such as dressing, bathing, and eating often become difficult to manage for both the person with AD and the caregiver. Having a daily plan can help caregivers cope. Many caregivers find it helpful to use strategies for dealing with difficult behaviors and stressful situations. Each person with AD is unique and responds differently, and each person changes over the course of the disease. Caregivers need to remain calm and offer reassurance to the patient. Community organizations that offer help should be sought. Support groups for caregivers can provide a place to express their feelings and help in anticipating future problems.

QUESTIONS TO ASK YOUR DOCTOR

• Are there tests available that can determine if I have Alzheimer?s disease?
• If I have AD, how can I expect it to progress?
• Is there anything that can be done to slow the progression?
• Are there any new or experimental treatments available?
• Would I be eligible for any clinical trials?
• When must a person with AD stop driving or doing other risky activities?

KEY TERMS

Antioxidant —A substance that inhibits the destructive effects of oxidation in the body.

Computed topography (CT) scan —A scan in which detailed images of a part of the body are formed by x rays together with a computer.

Delusion —A persistent false belief held in the face of strong contradictory evidence.

Dementia —A usually progressive deterioration of intellectual functions, such as memory, that can occur while other brain functions, such as those controlling movement and the senses, are retained.

Down syndrome —A genetic disorder characterized by a broad skull, blunt facial features, short stature, and learning difficulties. It is caused by the presence of an extra copy of a specific chromosome.

Genetic disease —A disease inherited from one or both parents.

Magnetic resonance imaging (MRI) —An imaging technique that uses electromagnetic radiation together with a computer to obtain detailed images of the body's soft tissues, such as the brain.

Positron emission tomography (PET) —A method of medical imaging capable of displaying the metabolic activity of organs in the body. It is useful in investigating brain disorders.

Tomography —A technique to produce a focused image of the structures at a specific depth within the body, while blurring details at other depths.

People with AD must be monitored closely during times when they are unable to determine their own care. Financial assets and plans for the ongoing management of the disease should be addressed before this advanced stage is reached. Nursing home or care home placement is an option for people with AD who do not have caregivers in their own homes, or for patients who become unmanageable in the home.

Dealing with the diagnosis

Finding out a loved one has AD can be a stressful, frightening, and overwhelming. Upon learning of the diagnosis, it is helpful to:

• Discuss any questions about AD with the patient's doctor. Find out what treatments might work best to relieve symptoms and address changes in behavior.
• Contact organizations such as the Alzheimer's Association for information on the disease, treatment options, and caregiving resources. Some community groups may offer classes that teach caregiving skills.
• Find a local support group for caregivers. Often, other members of support groups can offer useful ideas and suggestions based on their own experiences.
• Try to develop a daily routine to make caregiving go more smoothly. Take into account times of day when the person with AD is less confused or more cooperative.
• Make time for the caregivers to take an occasional break by using an adult day care service or respite services for the person with AD.
• Plan for the future by getting financial and legal documents in order, exploring longterm care options, and investigating what services are available through health insurance, Medicare, and state agencies.

Resources

BOOKS

Pearce, Nancy. Inside Alzheimer's: How to Hear and Honor Connections With a Person Who Has Dementia. Taylors, SC: Forrason Press, 2007.

Pitzer, Jean. You Too Can Survive: My Journey as an Alzheimer's Caregiver. Lincoln, NE: iUniverse, 2007.

Sabbagh, Marwan. The Alzheimer's Answer: Reduce Your Risk and Keep Your Brain Healthy. Hoboken, NJ: Wiley, 2008.

Whitehouse, Peter J., and Daniel George. The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Diagnosis. New York: St. Martin's Press, 2008.

PERIODICALS

Arnst, Catherine. “Is Alzheimer's a Form of Diabetes? If So, an Insulin-Centered Treatment Could Alter the Course of the Disease.” Business Week (December 17, 2007): 54.

Ault, Alicia. “Debate Continues Over Early Cognition Screening: Some Argue That Obtaining a Timely Baseline Could Offset Subsequent Delays in Diagnosing Alzheimer's.” Family Practice News (December 15, 2007): 27.

Christensen, Daniel D., and Peter Lin. “Practical Treatment Strategies for Patients with Alzheimer's Disease.” Journal of Family Practice (December 2007): 17-23.

Feldman, Stephen A., and Barry W. Rovner. “Competence and Capacity in Alzheimer's Disease.” The Legal Intelligencer (January 11, 2008).

Grady, Denise. “Finding Alzheimer's Before a Mind Fails.” New York Times (December 26, 2007): A1+.

Johnson, Kate. “Tailored Interventions Relieve Stress for Alzheimer's Caregivers.” Internal Medicine News (April 1, 2006): 27.

Pomerantz, Jay M. “Pharmacological Approaches to Alzheimer's Disease.” Drug Benefit Trends (December 1, 2007): 495.

ORGANIZATIONS

Alzheimer's Association, 225 N. Michigan Ave., 17th Floor, Chicago, IL, 60601-7633, (312) 335-8700, (800) 272-3900, (866) 699-1246, [email protected], http://www.alz.org.

Alzheimer's Disease Education and Referral Center, P.O. Box 8250, Silver Spring, MD, 20907-8250, (800) 438-4380, (301) 495-3334, [email protected], http://www.nia.nih.gov/alzheimers.

Alzheimer's Foundation of America, 322 8th Ave., 6th Floor, New York, NY, 10001, (866) 232-8484, (646) 638-1546, [email protected], http://www.alzfdn.org.

American Health Assistance Foundation, 22512 Gateway Center Dr., Clarkburg, MD, 20871, (301) 948-3244, (800) 437-2423, (301) 258-9454, [email protected], http://www.ahaf.org.

Alzheimer's Australia, P.O. Box 4019, Hawker, ACT,, Australia, 2614, (612) 6254-4233, (800) 100-500 (Australia only), http://www.alzheimers.org.au.

European Alzheimer's Disease Consortium, Dept. of Internal Medicine and Clinical Gerontology, Toulouse University Hospital, 170 Avenue de Casselardit, Toulouse,, France, 31300, 33-5-6177-7649, 33-5-6149-7109, [email protected], http://www.eadc.alzheimer-europe.org.

Ken R. Wells