Alzheimer’s Disease

Alzheimer’s Disease


Definition:

Alzheimer’s disease (AD) is the most common form of dementia, a neurologic disease characterized by loss of mental ability severe enough to interfere with normal activities of daily living, lasting at least six months, and not present from birth. AD usually occurs in old age, and is marked by a decline in cognitive functions such as remembering, reasoning, and planning.

Description:

A person with AD usually has a gradual decline in mental functions, often beginning with slight memory loss, followed by losses in the ability to maintain employment, to plan and execute familiar tasks of daily living, and to reason and exercise judgment. Communication ability, mood, and personality may also be affected. Most people who have AD die within eight years of their diagnosis, although that interval may be as short as one year or as long as 20 years. AD is the fourth leading cause of death in adults after heart disease, cancer, and stroke.Between two and four million Americans have AD; that number is expected to grow to as many as 14 million by the middle of the twenty-first century as the population as a whole ages. While a small number of people intheir 40s and 50s develop the disease (called early-onset AD), AD predominantly affects the elderly. AD affects about 3% of all people between ages 65 and 74, about 19% of those between 75 and 84, and about 47% of those over 85. Slightly more women than men are affected with AD, but this may be because women tend to live longer, leaving a higher proportion of women in the most affected age groups.The cost of caring for a person with AD is considerable, and has been estimated at approximately $174,000 per person over the course of the disease. Most people with AD are cared for at home; the cost of extended nursing home care adds substantially to this estimate.

Causes & symptoms:

The cause or causes of AD are unknown. Some strong leads have been found through recent research, and these have also given some theoretical support to several new experimental treatments.AD affects brain cells, mostly those in brain regions responsible for learning, reasoning, and memory. Autopsies of persons with AD show that these regions of the brain become clogged with two abnormal structures- neurofibrillary tangles and senile plaques. Neurofibrillary tangles are twisted masses of protein fibers inside nerve cells, or neurons. Senile plaques are composed of parts of neurons surrounding a group of brain proteins called beta-amyloid deposits. While it is not clear exactly how these structures cause problems, some researchers now believe that their formation is in fact responsible for the mental changes of AD, presumably by interfering with the normal communication between neurons in the brain.What triggers the formation of plaques and tangles is unknown, although there are several possible candidates. Inflammation of the brain may play a role in their development, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) seems to reduce the risk of developing AD. Restriction of blood flow may be part of the problem, perhaps accounting for the beneficial effects of estrogen that increases blood flow in the brain, among its other effects. Highly reactive molecular fragments called free radicals damage cells of all kinds, especially brain cells, which have smaller supplies of protective antioxidants thought to protect against free radical damage.Several genes have been implicated in AD, including the gene for amyloid precursor protein, or APP, responsible for producing amyloid. Mutations in this gene are linked to some cases of the relatively uncommon early-onset forms of AD. In 2001, scientists discovered a new rare mutation of the APP gene that might lead to new understanding on how the disease develops and new treatment possibilities. Other cases of early-onset AD are caused by mutations in the gene for another protein, called pre-senilin. AD eventually affects nearly everyone with Down syndrome, caused by an extra copy of chromosome 21. Other mutations on other chromosomes have been linked to other early-onset cases.


Potentially the most important genetic link was discovered in the early 1990s on chromosome 19. A gene on this chromosome, called apoE, codes for a protein involved in transporting lipids into neurons. ApoE occurs in at least three forms-apoE2, apoE3, and apoE4. Each person inherits one apoE from each parent, and therefore can either have one copy of two different forms, or two copies of one. Compared to those without ApoE4, people with one copy are about three times as likely to develop late-onset AD, and those with two copies are almost four times as likely to do so. Despite this important link, not everyone with apoE4 develops AD, and people without it can still have the disease. Why apoE4 increases the chances of developing AD is not known.There are several risk factors that increase a person’s likelihood of developing AD. The most significant one is age; older people develop AD at much higher rates than younger ones. Another risk factor is having a family history of AD, Down syndrome, or Parkinson’s disease. People who have had head trauma or hypothyroidism may manifest the symptoms of AD more quickly. No other medical conditions have been linked to an increased risk for AD.Many environmental factors have been suspected of contributing to AD, but population studies have not borne out these links. Among these have been pollutants in drinking water, aluminum from commercial products, and metal dental fillings. To date, none of these factors has been shown to cause AD or increase its likelihood. Further research may yet turn up links to other environmental culprits, although no firm candidates have been identified.The symptoms of AD begin gradually, usually with short-term memory loss. Occasional memory lapses are of course common to everyone, and do not by themselves signify any change in cognitive function. The person with AD may begin with only the routine sort of memory lapse-forgetting where the car keys are-but progress to more profound or disturbing losses, such as forgetting that he or she can even drive a car. Becoming lost or disoriented on a walk around the neighborhood becomes more likely as the disease progresses. A person with AD may forget the names of family members, or forget what was said at the beginning of a sentence by the time he hears the end.As AD progresses, other symptoms appear, including inability to perform routine tasks, loss of judgment, and personality or behavior changes. Some patients have trouble sleeping and may suffer from confusion or agitation in the evening (“sunsetting”). In some cases, people with AD repeat the same ideas, movements, words, or thoughts, a behavior known as perseveration. Some patients may exhibit inappropriate sexual behaviors. In the final stages of the disease, people may have severe problems with eating, communicating, and controlling their bladder and bowel functions.The Alzheimer’s Association has developed a list of 10 warning signs of AD. A person with several of these symptoms should see a physician for a thorough evaluation:- memory loss that affects job skills- difficulty performing familiar tasks- problems with language- disorientation of time and place- poor or decreased judgment- problems with abstract thinking- misplacing things- changes in mood or behavior- changes in personality- loss of initiativeOther types of dementing illnesses, including some that are reversible, can cause similar symptoms. It is important for the person with these symptoms to be evaluated by a professional who can weigh the possibility that his or her symptoms may have another cause. Approximately 20% of those originally suspected of having AD turn out to have some other disorder; about half of these cases are treatable.

Diagnosis:

Diagnosis of AD is complex, and may require office visits to several different specialists over several months before a diagnosis can be made. While a confident provisional diagnosis may be made in most cases after thorough testing, AD cannot be definitively diagnosed until autopsy examination of the brain for senile plaques and neurofibrillary tangles.

The diagnosis of AD begins with a thorough physical exam and complete medical history. Except in the disease’s earliest stages, accurate history from family members or caregivers is essential. Since there are both prescription and over-the-counter drugs that can cause the same mental changes as AD, a careful review of the patient’s drug, medicine, and alcohol use is important. AD-like symptoms can also be provoked by other medical conditions, including tumors, infection, and dementia caused by mild strokes (multi-infarct dementia). These possibilities must be ruled out as well through appropriate blood and urine tests, brain magnetic resonance imaging (MRI) or computed tomography scans (CT), tests of the brain’s electrical activity (electroencephalographs or EEGs), or other tests.In 2001, researchers demonstrated that postitron emission tomography (PET) scans could help predict who might develop memory impairment. Although PET scanning is a relatively new and expensive technology, it is becoming more readily available. Several types of oral and written tests are used to aid in the AD diagnosis and to follow its progression, including tests of mental status, functional abilities, memory, and concentration. Still, the neurologic exam is normal in most patients in early stages.One of the most important parts of the diagnostic process is to evaluate the patient for depression and delirium, since each of these can be present with AD, or may be mistaken for it. (Delirium involves a decreased consciousness or awareness of one’s environment.) Depression and memory loss are both common in the elderly, and the combination of the two can often be mistaken for AD. Depression can be treated with drugs, although some antidepressants can worsen dementia if it is present, further complicating both diagnosis and treatment.A genetic test for the ApoE4 gene is available, but is not used for diagnosis, because possessing even two copies does not ensure that a person will develop AD.

Treatment:

The mainstay of treatment for a person with AD continues to be the establishment of daily routines and good nursing care, providing both physical and emotional support for the patient. Modifications of the home to increase safety and security are often necessary. The caregiver also needs support. Regular medical care by a practitioner with a non-defeatist attitude toward AD is important so that illnesses can be diagnosed and treated properly.People with AD are also often depressed or anxious, and may suffer from sleeplessness, poor nutrition, and general poor health. Each of these conditions is treatable to some degree. It is important for the person with AD to eat well and continue to exercise. Professional advice from a nutritionist may be useful to provide healthy, easy-to-prepare meals. Finger foods may be preferable to those requiring utensils to be eaten. Regular exercise (supervised for safety if necessary) promotes overall health. A calm, structured environment with simple tools that support orientation (like calendars and clocks) may reduce anxiety and increase safety.
Diet and supplements DIET. The incidence of AD is lower in countries whose citizens have a diet that is lower in fats and calories. There have been a few reports that a diet rich with fish improves mental function in patients with AD or dementia. AD patients treated with essential fatty acids showed greater improvement in mood and mental function than patients on placebo. Because of its disease-preventing properties, red wine in moderation may be beneficial to AD patients.VITAMIN E. Studies have shown that AD patients have lower blood levels of vitamin E than age matched control subjects. A large, two year study of moderately affected AD patients found that taking 2,000 IU of vitamin E daily significantly delayed disease progression as compared to patients taking placebo. This delay was equivalent to that seen with patients taking the drug selegiline. Vitamin E is also thought to delay AD onset. High levels of vitamin E put the patient at higher risk for bleeding disorders.THIAMINE (VITAMIN B,). Several small studies to determine the effectiveness of thiamine (vitamin B1) on AD have been carried out. Daily doses of 3 g for two to three months have improved mental function and AD assessment scores. Other studies have shown that thiamine had no effect on AD patients. Side effects include nausea and indigestion.COBALAMIN (VITAMIN B12). Although results are conflicting, some studies have found that AD patients have lower levels of cobalamin (vitamin B12) than others. Some studies have shown that cobalamin supplementation improves memory and mental function in AD patients whereas other studies have found no effect.ACETYL-L-CARNITINE. Acetyl-L-carnitine is similar in structure to the neurotransmitter acetyl-choline. Studies have shown that 2 g or 3 g of acetyl-L-carnitine daily slows the progression of AD, especially in patients who developed the disease before age 66. Patients who developed disease after 66 years of age worsened with treatment. Side effects include increased appetite, body odor, and rash. DHEA. DHEA (dehydroepiandrosterone) is a steroid hormone. There may be a link between decreasing levels of DHEA in the elderly and development of AD. Studies on the effect, if any, of DHEA on AD are needed. Side effects include acne, hair growth, irritability, insomnia, headache, and menstrual irregularity. MELATONIN. Melatonin is a hormone that helps to regulate mood and sleep cycles. The effect of melatonin treatment on AD is unknown but it may be beneficial in regulating sleep cycles. The usual dose is 3 mg taken one to two hours before bedtime. Side effects are drowsiness, confusion, headache, decreased sex drive, and decreased body temperature.Herbals and Chinese medicine GINKGO. Ginkgo, the extract from the Ginkgo bilo-ba tree is the most commonly used herbal treatment for AD. Several studies have been performed to test the effectiveness of ginkgo for treating AD. The dose range studied were 120-160 mg daily divided into three doses. Although results have been mixed, the evidence suggests that ginkgo is an effective treatment for patients with mild to moderate AD. Side effects are not common but include headache, allergic skin reaction, and gastrointestinal disturbance. Ginkgo also decreases blood coagulation. Individuals with coagulation or platelet disorders should use extreme caution and consult a physician before using ginkgo.PHYTOESTROGENS. Phytoestrogens may be beneficial in the treatment of AD based on the findings that women with AD who are on hormone replacement therapy have improved mental function and mood. Estrogens may prevent AD, therefore, phytoestrogens may have the same effect. Phytoestrogens are mainly found in soy products.CLUBMOSS. Huperzine A is a compound isolated from clubmoss (Huperzia serrata). Studies have shown that taking 0.1-0.4 mg daily improves mental function in AD patients. Side effects are nausea, muscle cramps, vomiting, and diarrhea.TherapiesMusic therapy has been shown to be effective in treating the depression, agitation, wandering, feelings of isolation, and memory loss associated with AD. AD patients have benefited from listening to favorite music or participating in musical activity. Participation in a music therapy group was more effective at improving memory and decreasing agitation than being part of a verbal (talking) group.A wide variety of other therapies have been beneficial in the treatment of the psychologic symptoms of AD. These include:- Light therapy in the evening to improve sleep cycle disturbances.- Supportive therapy through touch, compliments, and displays of affection.- Sensory stimulation through massage and aromatherapy.- Socio-environmental therapies use activities fitted to previous interests, favorite foods, and pleasant surroundings.- Cognitive therapy to reduce negative perceptions and learn coping strategies.- Insight-oriented psychotherapy addresses the patient’s awareness of his or her disease.- Dance therapy.- Validation therapy.- Reminiscence therapy.- Reality-oriented therapy.Nursing care and safetyThe nursing care required for a person with AD is easy to learn. Caregivers will usually need to spend increasing amounts of time grooming the patient as the disease progresses. The patient may require assisted feeding early on to make sure that he or she is taking in enough nutrients. Later on, as movement and swallowing become difficult, a feeding tube may be placed into the stomach through the abdominal wall. A feeding tube requires more attention, but is generally easy to care for if the patient is not resistant to its use. Incontinence becomes the most difficult problem to deal with at home, and is a principal reason for pursuing nursing home care. In the early stages, limiting fluid intake and increasing the frequency of toileting can help. Careful attention to hygiene is important to prevent skin irritation and infection from soiled clothing.In all cases, a person diagnosed with AD should not be allowed to drive, because of the increased potential for accidents and the increased likelihood of wandering very far from home while disoriented. In the home, simple measures such as grab bars in the bathroom, bed rails on the bed, and easily negotiable passageways can greatly increase safety. Electrical appliances should be unplugged and put away when not in use. Matches, lighters, knives, or weapons should be stored safely out of reach. The hot water heater temperature may be set lower to prevent accidental scalding. A list of emergency numbers, including the poison control center and the hospital emergency room, should be posted by the phone.Care for the caregiver
Family members or others caring for a person with AD have an extremely difficult and stressful job that becomes harder as the disease progresses. It is common for caregivers to develop feelings of anger, resentment, guilt, and hopelessness, in addition to the sorrow they feel for their loved one and for themselves. Depression is an extremely common consequence. Becoming a member of an AD caregivers’ support group can be one of the most important things a family member does, not only for him or herself, but for the person with AD as well. The location and contact numbers for AD caregiver support groups are available from the Alzheimer’s Association; they may also be available through a local social service agency, the patient’s physician, or pharmaceutical companies that manufacture the drugs used to treat AD. Medical treatment for depression may be an important adjunct to group support.Outside help, nursing homes, andgovernmental assistanceMost families eventually need outside help to relieve some of the burden of around-the-clock care for a person with AD. Personal care assistants, either volunteer or paid, may be available through local social service agencies. Adult daycare facilities are becoming increasingly common. Meal delivery, shopping assistance, or respite care may be available as well. Many families consider nursing home care when AD advances to the late-stage.Several federal government programs may ease the cost of caring for a person with AD, including Social Security Disability, Medicare, and Supplemental Security Income. Each of these programs may provide some assistance for care, medication, or other costs, but none of them will pay for nursing home care indefinitely. Medicaid is a state-funded program that may provide for some or all of the cost of nursing home care, although there are important restrictions. Details of the benefits and eligibility requirements of these programs are available through the local Social Security or Medicaid office, or from local social service agencies.

Allopathic treatment:

The only two drugs approved for AD, tacrine hydrochloride (Cognex) and donepezil hydrochloride (Ari-cept), increase the brain levels of the neurotransmitteracetylcholine, thereby increasing the communication ability of the remaining neurons. These drugs can modestly increase cognition and improve the ability to perform normal activities of daily living. The most significant side effect of tacrine is an increase in the liver enzyme alanine aminotransferase (ALT). Patients taking tacrine must have a weekly blood test to monitor their ALT levels. Other frequent side effects include nausea, vomiting, diarrhea, abdominal pain, indigestion, and skin rash. Donepezil has two advantages over tacrine: fewer side effects and once daily dosing. Donepezil does not appear to affect liver enzymes and the frequency of abdominal side effects is lower.Estrogen, the female sex hormone, is widely prescribed for post-menopausal women to prevent osteoporosis. Several preliminary studies have shown that women taking estrogen have lower rates of AD, and those who develop AD have a slower progression and less severe symptoms.

Preliminary studies have also suggested a reduced risk for developing AD in older people who regularly use nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen (Advil), and naproxen (Aleve), although not acetaminophen. A 2001 study reported that those subjects who used NSAIDs for at least two years were up to 80% less likely to develop Alzheimer’s. Further study on the effects of NSAIDs on AD are underway.Selegiline, a drug used in the treatment of Parkinson’s disease, appears to slow the development of AD. Selegiline is thought to act as an antioxidant, preventing free radical damage. However, it also acts as a stimulant, making it difficult to determine whether the delay in onset of AD symptoms is due to protection from free radicals or to the general elevation of brain activity from the stimulant effect.Psychiatric symptoms, such as depression, anxiety, hallucinations (seeing or hearing things that aren’t there), and delusions (false beliefs) may be treated with drugs if necessary.

Expected results:

While Alzheimer’s disease may not be the direct cause of death, the generally poorer health of a person with AD increases the risk of life-threatening infection, including pneumonia. In addition, other diseases common in old age (cancer, stroke, and heart disease) may lead to more severe consequences in a person with AD. On average, people with AD live eight years past their diagnosis, with a range from 1-20 years.

Prevention:

There is currently no sure way to prevent Alzheimer’s disease, though some of the drug treatments discussed .above may eventually be proven to reduce the risk of developing the disease. The most likely current candidates are estrogen, phytoestrogens, NSAIDs, vitamin E, and selegiline. In 2001, researchers found preliminary indications that onest of Alzheimer’s might be tied to cholesterol levels. Although results must be confirmed by other scientists, lowering cholesterol in the diet might help prevent onset of the disease.

KEY TERMS:

Acetylcholine -One of the substances in the body that helps transmit nerve impulses.
Dementia-Impaired intellectual function that interferes with normal social and work activities.
Neurofibrillary tangle -Twisted masses of protein inside nerve cells that develop in the brains of people with AD.
Neuron-A nerve cell.
Senile plaque -Structures composed of parts of neurons surrounding brain proteins called beta-amyloid deposits and found in the brains of people with AD.