Although no cure for Alzheimer’s disease is yet available, medical and behavioral treatments for the disease may ease symptoms for the individual with Alzheimer's.
In addition to treating cognitive and behavioral symptoms, advising patients and their caregivers to initiate health care directives and decisions while the patient still has the capacity to do so can ease the burden for the family as the disease progresses.
· Cognitive Symptoms
· Behavioral Symptoms
· Alternative Treatments
· Monitoring Progression
· Conducting an Assessment
· Involving the Caregiver
· Monitoring Abuse
· Coordinated Care
· End-of-Life Decision
The U.S. Food and Drug Administration (FDA) has approved two classes of drugs to treat cognitive symptoms of Alzheimer’s disease: cholinesterase inhibitors and NMDA receptor antagonists. Vitamin E supplements are frequently prescribed and have become a part of a standard treatment regimen for most people with Alzheimer’s.
The first FDA-approved Alzheimer medications were cholinesterase inhibitors. Three cholinesterase inhibitors are commonly prescribed:
1. donepezil (Aricept), which is approved to treat all stages of Alzheimer’s disease
2. rivastigmine (Exelon), approved for mild to moderate Alzheimer’s
3. galantamine (approved in 2001 under the trade name Reminyl and renamed Razadyne in 2005), also approved for mild to moderate stages
Tacrine (Cognex®), the first drug in this class, was approved in 1993 but is rarely prescribed today because of associated side effects, including possible liver damage.
Cholinesterase inhibitors are designed to increase levels of acetylcholine, a chemical messenger involved in memory, judgment and other thought processes. Acetylcholine is released by certain brain cells to carry messages to other cells. After a message reaches the receiving cell, various other chemicals, including one called acetylcholinesterase, break acetylcholine down so it can be recycled.
Alzheimer’s disease damages or destroys cells that produce and use acetylcholine, reducing amounts available to carry messages. A cholinesterase inhibitor slows the breakdown of acetylcholine by blocking the activity of acetylcholinesterase. By maintaining acetylcholine levels, the drug may help compensate for the loss of functioning brain cells.
Cholinesterase inhibitors may also have other mechanisms that contribute to their effects. Galantamine appears to stimulate the release of acetylcholine and to strengthen the way certain receptors on message-receiving nerve cells respond to it. Rivastigmine may block activity of an additional chemical involved in breaking down acetylcholine.
Cholinesterase inhibitors do not stop the underlying destruction of nerve cells. Their ability to improve symptoms eventually declines as brain cell damage progresses.
What are the benefits of cholinesterase inhibitors?
In clinical trials of all three cholinesterase inhibitors, individuals taking the medications performed better on tests of memory and thinking than those taking a placebo (inactive substance). The degree of benefit was small, and more than half of the recipients showed no improvement at all. In terms of overall effect, most experts believe cholinesterase inhibitors may delay or slow worsening of symptoms in some individuals for about six months to a year, although some may benefit longer.
There is no evidence that combining these drugs would be any more helpful than taking any one of them, and it is likely combining them would result in greater frequency of side effects (discussed below).
There is some evidence that individuals with moderate to severe Alzheimer’s who are taking a cholinesterase inhibitor might benefit slightly more by also taking memantine (Namenda). Memantine is a drug with a different mechanism of action, approved by the FDA in 2003 for symptoms of moderate to severe Alzheimer’s. In clinical trials, memantine showed greater benefit than a placebo, but its effect was modest. Memantine is discussed in more detail below.
How are cholinesterase inhibitors used?
· Donepezil (Aricept®) is a tablet and can be administered once daily. Generally, the initial dose is 5 mg a day(usually given at night). After four to six weeks, if it is well tolerated, the dose is often increased to the therapeutic goal of 10 mg a day.
· Rivastigmine (Exelon®) is available as a capsule or as a liquid. The dosage is gradually increased to minimize side effects. Usually the medication is started at 1.5 mg daily. After two weeks the dosage is increased to 1.5 mg twice a day. The therapeutic goal is to increase the dosage gradually every two weeks to reach 6 to 12 mg a day given in two doses, each equal to half the total. There is a greater frequency of side effects at these higher doses; however, taking drugs with meals may be helpful in reducing the occurrence of side effects.
· Galantamine (Razadyne) is supplied as tablets in strengths of 4, 8 and 12 mg. The recommended starting dose is 4 mg twice a day. If well tolerated after four weeks or more of treatment, the dose is increased to 8 mg twice a day. There was no statistical benefit in clinical trials for 12 mg twice a day over the dose of 8 mg twice a day, but if 8 mg twice a day is well tolerated after four weeks, the dose can be increased to 12 mg twice a day by the physician. Galantamine is also available in an “extended release” form as Razadyne ER that is designed to be taken once a day.
What are the side effects of cholinesterase inhibitors?
Cholinesterase inhibitors are generally well tolerated. If side effects occur, they commonly include nausea, vomiting, loss of appetite, and increased frequency of bowel movements. It is strongly recommended that a physician who is comfortable and experienced in using these medications monitor patients who are taking them and that the recommended guidelines be strictly observed.
It is strongly recommended that a physician who is comfortable and experienced in using these medications monitor patients treated with any of these compounds and that the recommended guidelines be strictly observed. There is no evidence or reason to believe that combining the drugs would be any more beneficial than taking either one alone, and it is likely that combining the drugs would result in greater side effects.
Treatments topic sheet suitable for use as a patient handout.
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Memantine was approved in October 2003 by the FDA for treatment of moderate to severe Alzheimer’s disease. Forest Laboratories Inc., memantine’s U.S. developer, markets the drug under the trade name Namenda®.
Memantine is classified as an uncompetitive low-to-moderate affinity N-methyl-D-aspartate (NMDA) receptor antagonist, the first Alzheimer drug of this type approved in the United States. It appears to work by regulating the activity of glutamate, one of the brain’s specialized messenger chemicals involved in information processing, storage, and retrieval. Glutamate plays an essential role in learning and memory by triggering NMDA receptors to allow a controlled amount of calcium to flow into a nerve cell, creating the chemical environment required for information storage.
Excess glutamate, on the other hand, overstimulates NMDA receptors to allow too much calcium into nerve cells, leading to disruption and death of cells. Memantine may protect cells against excess glutamate by partially blocking NMDA receptors.
Memantine’s action differs from the mechanism of the cholinesterase inhibitors that were previously approved in the United States for treatment of Alzheimer symptoms. Cholinesterase inhibitors temporarily boost levels of acetylcholine, another messenger chemical that becomes deficient in the Alzheimer brain.
What is the evidence that memantine may help Alzheimer symptoms?
Forest submitted evidence in support of memantine’s effectiveness in treating moderate to severe Alzheimer’s disease in a new drug application to the FDA in December 2002, amended in January 2003. In September 2003, the FDA’s Peripheral and Central Nervous System Drug Advisory Committee met to respond to specific questions raised by the FDA regarding application data. Briefing documents and summaries of advisory committee critiques are available on the FDA Web site. At the conclusion of its meeting, the advisory committee voted unanimously that the following data submitted in the new drug application support the safety and effectiveness of memantine in treating moderate to severe Alzheimer’s disease:
1. A 28-week U.S. study enrolling 252 individuals with moderate to severe Alzheimer’s disease and initial scores ranging from 3 – 14 on the Mini-Mental State Examination (MMSE). In this double-blind study, participants were randomly assigned to receive either 10 mg of memantine twice a day or a placebo. Those receiving memantine showed a small but statistically significant benefit in a test of the their ability to perform daily activities and on the Severe Impairment Battery, a test designed to measure cognition in profoundly incapacitated individuals. On the Clinician Interview-Based Impression of Change Plus Caregiver Input, a measure of overall function, memantine recipients also showed a benefit that was significant in one analysis but not in another. In this study, when participants with MMSE scores of less than 10 were considered as a separate group, memantine recipients showed no benefit compared to those who received placebo on either daily activities or overall function.
2. A 24-week U.S. study enrolling 404 individuals with moderate to severe Alzheimer’s disease and initial MMSE scores from 5 – 14 who had been taking donepezil (Aricept®) for at least six months, with a stable dose for at least three months. In this double-blind study, participants were randomly assigned to receive either 10 mg of memantine twice a day or a placebo in addition to their donepezil. Those receiving memantine showed a statistically significant benefit in performing daily activities and on the Severe Impairment Battery, while participants taking donepezil plus placebo continued to decline.
Some advisory committee members considered memantine’s effect modest, similar in scope to the effect seen with cholinesterase inhibitors.
The advisory committee found problems with the design of a third submitted study, conducted in Latvia, because it enrolled individuals with vascular dementia as well as Alzheimer’s disease. An additional issue was that although the data showed a positive effect for memantine on reducing dependence on care, the study lacked an acceptable measure of effect on cognitive function. According to current FDA standards, drugs approved specifically to treat Alzheimer’s disease must show a benefit on cognitive symptoms as well as on overall function, which confirms that the effect on cognition is clinically meaningful.
In June 2003, Forest reported preliminary results from another add-on therapy trial enrolling participants with mild to moderate Alzheimer’s who were also taking any of three commonly prescribed cholinesterase inhibitors — donepezil (Aricept®), galantamine (Razadyne®, formerly Reminyl®) or rivastigmine (Exelon®). Data from this trial were not included in the new drug application seeking approval of memantine for moderate to severe disease. According to the company, the data showed that participants receiving memantine in combination with a cholinesterase inhibitor did not experience significantly greater benefit in cognition or overall function than those who received a cholinesterase inhibitor and a placebo. These preliminary results suggest that memantine may not be as effective in individuals with mild to moderate Alzheimer’s who are taking a cholinesterase inhibitor as it may in more severely ill individuals. This data has not yet been peer reviewed or presented in a professional forum.
How is memantine supplied and prescribed?
Memantine is supplied as an oral medication in 10 mg tablets. Forest is providing prescribing information at www.namenda.com or by calling 1.877.2-NAMENDA (1.877.262.6363). Adverse effects occurring more commonly with memantine than with placebo included headache, constipation, confusion and dizziness.
Treatments topic sheet suitable for use as a patient handout.
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How might vitamin E supplements benefit a person with Alzheimer’s disease?
The normal cell function termed “oxidative metabolism” results in byproducts known as free radicals. Free radicals are highly reactive compounds that quickly “attack” other cell substances, causing damage to the cell wall, metabolic machinery and genetic material (DNA). The cells have natural defenses against this damage, which include the antioxidants vitamins C and E, but with age some of these protective mechanisms decline. Brain cell damage caused by free radicals may play a role in Alzheimer’s disease.
What was the result of the multicenter national study of vitamin E and Alzheimer’s disease?
Research reported in the April 24, 1997, issue of the New England Journal of Medicine investigated the effectiveness of vitamin E and selegiline, a drug with antioxidant properties that is prescribed for treating Parkinson’s disease. The research was part of the Alzheimer’s Disease Cooperative Study, a consortium of academic Alzheimer research centers sponsored by the U.S. National Institute on Aging.
This study suggests that either selegiline or vitamin E delays the occurrence in patients with Alzheimer’s disease to one or more of the following “endpoints”: death, institutionalization, progression from moderate to severe dementia or loss of ability to perform two of three basic activities of daily living (eating, grooming or toileting). When both agents were given together, there was also a delay in progression of Alzheimer’s disease as measured by these endpoints. However, both agents together did not help more than either drug alone. These agents did not improve memory and thinking test scores.
These results are encouraging but as yet have not been confirmed by other studies. We also do not know if these agents would be helpful in milder or severe stages of Alzheimer’s disease. There was no evidence that intellectual deterioration was slowed. Finally, any medication may have side effects or potential interactions with other drugs. For example, it is known that certain doses of selegiline (higher than those used in the study) can lead to serious interactions with some types of foods and certain medications.
Should vitamin E be prescribed?
Vitamin E worked at least as well as selegiline on Alzheimer’s progression in this study and had fewer side effects. vitamin E also costs less. For these reasons it is preferred over selegiline in Alzheimer’s disease treatment. Vitamin E is considered to be a “benign” medication and most people can take it without side effects. However, any change in medications should first be discussed with your primary care physician because all medication can cause side effects or interactions with other medications. People taking “blood-thinners” like warfarin (Coumadin®), ticlopidine (Ticlid®), and others may not be able to take vitamin E or will need to be monitored closely by their physician if they are taking vitamin E.
What dose of vitamin E is best?
Exactly what dose of vitamin E is the “best” is not known. The doses of vitamin E in the study were 1,200 IU twice daily. Other doses need to be studied to answer this question confidently. Many doctors recommend 400 IU twice daily because they believe this dosage to be safe for most individuals and it should have the antioxidant effect desired in the brain.
Prepared by John C. Morris, M.D., professor of neurology at Washington University at St. Louis
When Alzheimer’s disrupts memory, language, thinking and reasoning, these effects are referred to as “cognitive symptoms” of the disease. The term “behavioral and psychiatric symptoms” describes a large group of additional symptoms that occur to at least some degree in many, but by no means all, individuals with Alzheimer’s.
In early stages of the disease, people may experience personality changes such as irritability, anxiety or depression. In later stages, other symptoms may occur, including sleep disturbances; agitation (physical or verbal outbursts, general emotional distress, restlessness, pacing, shredding paper or tissues, yelling); delusions (firmly held belief in things that are not real); or hallucinations (seeing, hearing or feeling things that are not there).
Many individuals with Alzheimer’s and their families find behavioral and psychiatric symptoms to be the most challenging and distressing effects of the disease. These symptoms are often a determining factor in a family’s decision to place a loved one in residential care. They also often have an enormous impact on care and quality of life for individuals living in long-term care facilities.
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A person exhibiting behavioral and psychiatric symptoms should receive a thorough medical evaluation, especially when symptoms come on suddenly. Treatment depends on a careful diagnosis, determination of the possible causes, and the types of agitated behavior the person is experiencing. With proper treatment and intervention, significant reduction or stabilization of the symptoms can often be achieved.
Symptoms often reflect an underlying infection or medical illness. The pain or discomfort caused by pneumonia or a urinary tract infection can result in agitation. An untreated ear or sinus infection can cause dizziness and pain that affect behaviors.Uncorrected problems with hearing or vision may also have an impact. Side effects of prescription medication are another common contributing factor to behavioral symptoms. Side effects are especially likely to occur when individuals are taking multiple medications for several health conditions, creating a potential for drug interactions.
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Non-drug treatment strategies
There are two distinct types of treatments for behavioral and psychiatric symptoms: non-drug strategies and prescription medications. Non-drug interventions should be tried first. In general, steps to managing symptoms include (1) identifying the behavior, (2) understanding its cause and (3) adapting the caregiving environment to remedy the situation.
Correctly identifying what has triggered symptoms can often help in selecting the best approach. Often the trigger is some sort of change in the person’s environment:
- change in caregiver
- change in living arrangements
- presence of houseguests
- being asked to change clothing
A key principle of intervention is redirecting the person's attention, rather than arguing, disagreeing or being confrontational. Additional strategies include the following:
- simplify the environment
- simplify tasks and routines
- allow adequate rest between stimulating events
- use labels to cue or remind the person
- equip doors and gates with safety locks
- remove guns
- reduce risk of fires with extra smoke alarms and control access to the stove
- use lighting to reduce confusion and restlessness at night
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Medications to treat behavioral symptoms
Medications can be effective in some situations, but they must be used carefully and are most effective when combined with non-drug approaches. Medications should target specific symptoms so their effect can be monitored. In general, it is best to start with a low dose of a single drug. Effective treatment for one core symptom may sometimes help relieve other symptoms. Thoughtful choice of a drug may also maximize its benefit. For exampe, some antidepressants may also help people sleep better.
People with dementia are susceptible to serious side effects, including a slightly increased risk of death from antipsychotic medications. Risk and potential benefits of a drug should be carefully analyzed for any individual.
Some examples of medications commonly used to treat behavioral and psychiatric dementia symptoms are listed below. These lists do not include every drug used for these purposes. Doctors base their choice of medication on many factors, including the underlying cause of dementia and an individual's symptoms, living situation, caregiving arrangement and coexisting health conditions.
Antidepressant medications for low mood and irritability
- citalopram (Celexa®)
- fluoxetine (Prozac®)
- paroxetine (Paxil®)
- sertraline (Zoloft®)
- trazodone (Desyrel®)
Anxiolytics for anxiety, restlessness, verbally disruptive behavior and resistance
- lorazepam (Ativan®)
- oxazepam (Serax®)
Antipsychotic medications for hallucinations, delusions, aggression, hostility and uncooperativeness
- newer "atypical" agents such as aripiprazole (Abilify®); olanzapine (Zyprexa®); quetiapine (Seroquel®); risperidone(Risperdal®); and ziprasidone (Geoden®)
- older first-generation drugs such as haloperidol (Haldol®)
The decision to use an antipsychotic drug needs to be considered with special care. Recent studies have shown that these drugs are associated with slightly increased risk of death in older adults with dementia. The FDA has labeled drugs with a warning about the risk and a reminder that they are not approved to treat dementia symptoms.
To maximize the chances of effectiveness, the choice of a particular drug, how long it should be used and when it should be discontinued all need to be carefully tailored to an individual's symptoms and circumstances. The underlying cause of a person's dementia may also influence the selection of a drug. For example, it is generally considered inadvisable for individuals with dementia with Lewy bodies (DLB) to take antipsychotic drugs.
Although antipsychotics are among the most frequently used medications for treating agitation, some physicians may prescribe an anticonvulsant/mood stabilizer, such as divalpoex (Depakote®), for hostility or aggression.
Many experts recommend that use of drugs to treat agitation, aggression, hallucinations and delusions in persons with dementia be managed by a physician with experience and interest in this area.
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Medications for sleep problems
Some medications are approved specifically by the U.S. Food and Drug Administration (FDA) as “sleeping pills.” Most physicians tend to avoid prescribing “sleeping pills” for older adults with dementia, since in this group these drugs may have serious side effects, including incontinence, problems with balance, falls or increased agitation.
- one widely used alternative is the antidepressant trazodone (Desyrel®), which tends to make people sleepy
- anti-anxiety medications are also sometimes used
Physicians also recommend that individuals with dementia avoid over-the-counter sleep remedies. The active ingredient in many of these preparations is diphenhydramine (Benadryl®), an antihistamine that tends to make people feel drowsy. Diphenhydramine further suppresses the activity of one of the main brain cell messenger chemicals whose activity is reduced by Alzheimer’s disease.
Examples of over-the-counter sleep aids containing diphenhydramine that should be avoided include:
- Compoz®, Nytol®, Sominex® and Unisom®
- diphenhydramine is also an ingredient in many “nighttime” or “PM” versions of popular pain relievers and cold and sinus remedies
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Helpful hints during an episode of agitation
Do: back off and ask permission, use calm positive statements, reassure, slow down, use visual or verbal cues, add light, offer guided choices between two options, focus on pleasant events, offer simple exercise options, or limit stimulation.
Do not: raise voice, take offense, corner, crowd, restrain, rush, criticize, ignore, confront, argue, reason, shame, demand, condescend, force, explain, teach, show alarm, or make sudden movements out of the person’s view.
Say: May I help you? Do you have time to help me? You’re safe here. Everything is under control. I apologize. I’m sorry that you are upset. I know it’s hard. I will stay until you feel better.
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Helpful hints to prevent agitation
Create a calm environment: remove stressors, triggers or danger; move person to a safer or quieter place; change expectations; offer security object, rest or privacy; limit caffeine use; provide opportunity for exercise; develop soothing rituals; and use gentle reminders.
Avoid environmental triggers: noise, glare, insecure space, and too much background distraction, including television.
Monitor personal comfort: check for pain, hunger, thirst, constipation, full bladder, fatigue, infections, and skin irritation; ensure a comfortable temperature; be sensitive to fears, misperceived threats, and frustration with expressing what is wanted.
This content was developed by the Alzheimer’s Association Medical and Scientific Advisory Council.
Miracle drugs for diseases such as Alzheimer’s are heavily promoted in the news, in magazines and especially on the Internet. Several products claim to cure Alzheimer's and even prevent it from ever occurring.
Many of these products claim to be herbal or all natural. However, these claims do not mean the products are safe. In most cases there is not enough scientific evidence backing these products — neither proving their effectiveness nor disproving the existence of harmful side effects.
Products currently promoted as Alzheimer treatments include Ginkgo biloba, Hyuperzine A, Coenzyme Q10 and Phosphatidyl serine.
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Ginkgo biloba is a plant extract containing several compounds that may have positive effects on cells within the brain and the body. Ginkgo biloba is thought to have both antioxidant and anti-inflammatory properties, to protect cell membranes, and to regulate neurotransmitter function. Ginkgo has been used for centuries in traditional Chinese medicine and currently is being used in Europe to alleviate cognitive symptoms associated with a number of neurological conditions.
In a study published in the Journal of the American Medical Association (October 22/29, 1997), Pierre L. Le Bars, M.D., Ph.D., of the New York Institute for Medical Research, and colleagues found ginkgo biloba to have a positive effect in individuals with Alzheimer’s disease.
This 52-week study initially involved 309 patients suffering from mild to moderately severe dementia, caused by either Alzheimer’s disease or multi-infarct dementia (MID, or vascular dementia). These patients were divided into two groups; participants in one group were administered 120 mg of ginkgo biloba extract each day, and participants in the second group received a placebo (sugar pill).
At the end of the study, data from only 202 of the participants were used to determine the efficacy of using ginkgo in the treatment of Alzheimer’s disease due to a significant dropout rate of participants during the course of the treatment. Participants were tested for improvement in cognition, daily living and social behavior, and overall impairment. Researchers found that modest improvements took place in cognition, activities of daily living (such as eating and dressing), and social behavior — but no measurable difference was noticed in overall impairment.
Results from this study show that ginkgo may help some individuals with Alzheimer’s disease slightly, but further research is needed in order to determine the exact mechanisms by which ginkgo works in the body. Also, results from this study are considered preliminary because of the low number of participants involved and methodological issues associated with the research.
Further study of ginkgo biloba is necessary to fully understand its potential therapeutic value in treating individuals with Alzheimer’s. Few side effects are associated with the use of ginkgo as a dietary supplement, although it is known to reduce the ability of blood to clot, potentially leading to more serious conditions, such as hemorrhaging. This possibility of hemorrhaging may increase if ginkgo biloba is taken in combination with other anticoagulants, such as aspirin.
The National Center for Complementary and Alternative Medicine of the U.S. National Institutes of Health has launched a large, multicenter study to determine if ginkgo biloba may help prevent Alzheimer's disease. Recruitment for this trial closed in 2002 and the trial will run for five years, so results will not be available until some time after 2007.
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Huperzine (HOOP-ur-zeen) is an herbal supplement derived from the club moss Huperzia serrata. It has been used for centuries in Chinese traditional medicine as a treatment for swelling, fever and blood disorders. Recent clinical trials in China have reportedly shown that huperzine also offers some benefit in Alzheimer’s disease.
Research suggests that huperzine A (HupA) functions as a cholinesterase inhibitor and that it may also have chemical properties that help protect nerve cells, but large-scale clinical trials are needed to confirm that huperzine is effective in treating Alzheimer’s disease. In spring 2004, the National Institute on Aging (NIA) launched the first U.S. trial of huperzine as a treatment for mild to moderate Alzheimer’s.
If trials document any benefit for huperzine, consumers will need access to a standardized formulation that offers consistent dosing and guaranteed purity.
Galantamine (Razadyne®, formerly Reminyl®), one of the FDA-approved cholinesterase inhibitors, was originally derived from the snowdrop Galanthus nivalis, although it is now made synthetically.
Pending results of large-scale trials, most experts recommend against use of huperzine A because there are cholinesterase inhibitors approved by the U.S. Food and Drug Administration (FDA) available. Under no circumstances should an individual who is already taking an FDA-approved cholinesterase inhibitor begin taking huperzine A in addition to the prescribed drug.
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Omega-3 fatty acids
Omega-3s are a type of polyunsaturated fatty acid (PUFA). Research has linked certain types of omega-3s to a reduced risk of heart disease and stroke.
The U.S. Food and Drug Administration (FDA) permits supplements and foods to display labels with “a qualified health claim” for two omega-3s called docosahexaneoic acid (DHA) and eicosapentaenoic acid (EPA). The labels may state, “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease,” and then list the amount of DHA or EPA in the product. The FDA recommends taking no more than a combined total of 3 grams of DHA or EPA a day, with no more than 2 grams from supplements.
Research has also linked high intake of omega-3s to a possible reduction in risk of dementia or cognitive decline. The chief omega-3 in the brain is DHA, which is found in the fatty membranes that surround nerve cells, especially at the microscopic junctions where cells connect to one another.
A Jan. 25, 2006, literature review by the Cochrane Collaboration found that published research does not currently include any clinical trials large enough to recommend omega-3 supplements to prevent cognitive decline or dementia. But the reviewers found enough laboratory and epidemiological studies to conclude this should be a priority area for further research.
According to the review, results of at least two larger clinical trials are expected in 2008. The Cochrane Collaboration is an independent, nonprofit organization that makes objective assessments of available evidence on a variety of issues in treatment and health care.
Theories about why omega-3s might influence dementia risk include their benefit for the heart and blood vessels; anti-inflammatory effects; and support and protection of nerve cell membranes. There is also preliminary evidence that omega-3s may also be of some benefit in depression and bipolar disorder (manic depression).
A report in the April 2006 Nature described the first direct evidence for how omega-3s might have a helpful effect on nerve cells (neurons). Working with laboratory cell cultures, the researchers found that omega-3s stimulate growth of the branches that connect one cell to another. Rich branching creates a dense “neuron forest,” which provides the basis of the brain’s capacity to process, store and retrieve information.
See also the 2004 FDA press release announcing extension of the qualified health claim for omega-3s and coronary heart disease from supplements to foods.
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Coenzyme Q10, or ubiquinone, is an antioxidant that occurs naturally in the body and is needed for normal cell reactions to occur. This compound has not been studied for its effectiveness in treating Alzheimer’s.
A synthetic version of this compound, called idebenone, was tested for Alzheimer’s disease but did not show favorable results. Little is known about what dosage of coenzyme Q10 is considered safe, and there could be harmful effects if too much is taken.
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Phosphatidylserine (pronounced FOS-fuh-TIE-dil-sair-een) is a kind of lipid, or fat, that is the primary component of cell membranes of neurons. In Alzheimer’s disease and similar disorders, neurons degenerate for reasons that are not yet understood. The strategy behind the possible treatment with phosphatidylserine is to shore up the cell membrane and possibly protect cells from degenerating.
The first clinical trials with phosphatidylserine were conducted with a form derived from the brain cells of cows. Some of these trials had promising results. However, most trials were with small samples of participants.
This line of investigation came to an end in the 1990s over concerns about mad cow disease. There have been some animals studies since then to see whether phosphatidylserine derived from soy may be a potential treatment. A report was published in 2000 about a clinical trial with 18 participants with age-associated memory impairment who were treated with phosphatidylserine. The authors concluded that the results were encouraging but that there would need to be large carefully controlled trials to determine if this could be a viable treatment.
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“Coral” calcium supplements have been heavily marketed as a cure for Alzheimer’s disease, cancer and other serious illnesses. Coral calcium is a form of calcium carbonate claimed to be derived from the shells of formerly living organisms that once made up coral reefs.
In June 2003, the Federal Trade Commission (FTC) and the Food and Drug Administration (FDA) filed a formal complaint against the promoters and distributors of coral calcium. The agencies state that they are aware of no competent and reliable scientific evidence supporting the exaggerated health claims and that such unsupported claims are unlawful.
“Coral” calcium differs from ordinary calcium supplements only in that it contains traces of some additional minerals incorporated into the shells by the metabolic processes of the animals that formed them. It offers no extraordinary health benefits. Most experts recommend that individuals who need to take a calcium supplement for bone health take a purified preparation marketed by a reputable manufacturer.
During a patient’s initial visit (often during the diagnostic evaluation), you should make an assessment using tests such as the Mini-Mental State Examination (MMSE) or Physical Self-Maintenance Scale (PSMS) to establish baseline cognition and functional ability. You should also ask questions regarding behavioral symptoms, such as agitation, psychosis, anxiety and depression to assess the patient’s response to treatment. You can then compare future assessments to the baseline to track any changes in cognition, function or behavior that may have occurred since a previous visit.
The MMSE and PSMS are often used in clinical settings because they tend to take less time to administer than some of the longer, more involved assessments. The MMSE needs to be completed by a physician or other health care professional. In some cases, the PSMS can be given to the caregiver to complete in the waiting room. Once you choose a particular assessment test, you should repeat the same test during each subsequent visit in order to compare a patient’s current scores to his or her previous scores.
After a diagnosis of Alzheimer’s disease is made and a treatment plan implemented, patients should return for evaluation approximately three months after the start of medication and, subsequently, twice per year. In some cases, patients may need to return more frequently, depending on the medication prescribed. You should administer the MMSE and PSMS, or other assessment, at each visit in order to monitor improvement, stabilization or worsening of cognitive and behavioral symptoms and to better follow the progression of the disease.
Both cognitive and behavioral symptoms of dementia tend to change as the disease progresses, so regular visits can ensure adaptation of treatment strategies to current needs. More frequent visits are often required for patients exhibiting more severe behavioral symptoms, such as depression, agitation, hallucinations, or delirium, who may be taking medications specific to those conditions.
Regular visits are also important in monitoring patients for treatable conditions that may contribute to distress, discomfort and agitation, such as constipation, urinary tract infections and chronic pain.
The patient’s primary caregiver is an invaluable and essential source of information during follow-up visits. Patients will most likely not be reliable in assessing whether an improvement in symptoms has resulted from use of a particular medication. Moreover, since Alzheimer patients regularly have “good days” and “bad days,” a clinician’s evaluation in one brief visit may not be as valuable or reliable as a caregiver’s report of the patient’s condition over several days or weeks.
Follow-up visits should include a basic physical exam to determine if any decline in physical health has taken place and a detailed interval history obtained from the patient and his or her caregiver. The detailed history should contain information about any extraordinary disruption in the patient’s daily living situation that may have occurred since the last visit, (e.g., moving into a new home, hospitalization, drastic change in routine). It is also helpful to ask the caregiver to bring in or “brown-bag” all medications the patient may be taking at the time of the visit, to determine whether existing symptoms can be attributed to side effects or interactions between prescribed and over-the-counter medication.
When assessing treatment efficacy in patients with Alzheimer’s, it is important to remember that improvement may be minimal and temporary stabilization in cognitive decline is more likely. Typically, less decline is observed in the early stages of the disease, with more rapid degeneration accompanying the later stages. Regardless of treatment, the disease will continue to progress, and you should advise patients and their families to plan ahead for future treatment and care options.
As assessments are being conducted, and a treatment plan determined, explain to the patient and his or her caregiver the limitations of current medications for Alzheimer’s disease. Clarify that existing treatments cannot reverse or stop the progression of Alzheimer’s disease, yet they may be able to help affected individuals maintain their independence for a longer period of time and may even delay the need for professional care and institutionalization.
Conducting an Assessment
Medications currently approved for treatment of Alzheimer’s all work primarily by inhibiting breakdown of acetylcholine, a neurotransmitter that becomes deficient in the Alzheimer brain as nerve cells degenerate and die. Although these drugs do not slow progression of the underlying disease process, they may temporarily stabilize or delay worsening of memory problems and other cognitive symptoms. But even temporary stabilization can be valuable to patients as well as to their caregivers and families.
Evaluating treatment efficacy in patients with Alzheimer’s disease can be complicated, particularly because treatments may benefit several types of function. Symptoms associated with the disease are primarily cognitive, but there are often other behavioral or physical conditions, making it difficult to assess problems in one area of functioning. Symptoms also vary by individual and stage of the disease process and require diversified assessments of treatment efficacy.
Current assessment tools
Current assessment tools are designed to evaluate several areas of function, including:
- functional capacity
- general physical health
- quality of life
Most assessment tools are designed to be completed either by the patient (in the early stages of disease), the caregiver or the patient’s primary health care provider. Most often, a combination of tests is needed to complete an evaluation of the patient’s overall condition. Assessments given by the primary caregiver often evaluate not only the patient’s condition but also the caregiver’s own well-being, which can be an important factor in deciding whether a particular treatment strategy has proven beneficial.
For patients with Alzheimer’s disease or a related dementia, there is no single test that can simultaneously assess all areas of functioning. The aim of such tests is to better understand the actual efficacy of treatments and to develop a comprehensive, practical assessment that can be administered quickly by a clinician. Numerous assessment tools have been developed, and several others are being studied:
Alzheimer’s Disease Assessment Scale, cognitive subsection (ADAS-cog)
Blessed Information-Memory-Concentration Test (BIMC)
Clinical Dementia Rating Scale (CDR)
Mini-Mental State Examination (MMSE)*
Functional Assessment Questionnaire (FAQ)*
Instrumental Activities of Daily Living (IADL)
Physical Self-Maintenance Scale (PSMS)*
Progressive Deterioration Scale (PDS)
Clinical Global Impression of Change (CGIC)
Clinical Interview-Based Impression (CIBI)
Global Deterioration Scale (GDS)
Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD)
Neuropsychiatric Inventory (NPI)*
*Used most often in clinical settings
Involving the Caregiver
A solid relationship with the family or caregiver of a patient with Alzheimer’s disease is an essential component of providing effective treatment and care. Once a treatment plan is decided upon, it is the caregiver, or another close family member, who will be responsible for timely administration of the medication and for providing accurate updates on the patient’s condition and behavior.
Alzheimer's affects the entire family
In treating Alzheimer’s disease, it is common practice to include the caregiver and family. Alzheimer’s affects entire families, especially as the disease progresses and affected individuals become more dependent upon their primary caregivers. Caregivers often experience feelings of depression, anxiety, stress and helplessness that need to be assessed by a clinician. Some of these symptoms can be alleviated by appropriate treatment.
Measure caregiver stress
A novel approach to evaluating treatment efficacy in patients with Alzheimer’s disease is to measure caregiver burden and stress, which should decrease as a direct result of good patient care and treatment. A patient who is doing well under a specific treatment regime often requires less assistance and supervision from his or her caregiver, which allows more time for caregivers to care for themselves. A few assessment tools are available for caregivers, and several others are being studied.
Maintain a positive relationship
When working with patients, their caregivers and families, explain that improvements may take time to become apparent and can be defined more accurately as a stabilization of symptoms versus a reversal of cognitive decline. Maintaining a positive and open relationship with caregivers can help them anticipate what may lie ahead and plan realistically for the future. As a patient’s condition progresses, caregivers and families may have questions and may need additional support. Referrals to local chapters of the Alzheimer’s Association and other health care professionals may be helpful for families who need assistance while caring for their loved ones.
Making the most out of doctor visits
To help caregivers and patients make the most out of their doctor visits with you, refer them to the Alzheimer's Association's Partnering With Your Doctor workshop. It is designed for individuals with memory loss and their caregivers who want to learn strategies for improving their relationship and interactions with their physicians.
Participants learn how to prepare for a doctor's visit, what to expect, questions to ask and tips for follow-up visits. They will also learn how to use care logs to track changes in health, mood, memory and behaviors-information you need to help provide the best care and treatment for the individual. In addition, participants will learn how to use medication and appointment logs.
People with Alzheimer’s are vulnerable to abuse by people close to them. They may also fall prey to strangers who take advantage of their cognitive impairment.
Types of abuse
· Physical — causing physical pain or injury
· Emotional — verbal assaults, threats of abuse, harassment and intimidation
· Neglect — failure to provide necessities, including food, clothing, shelter or medical care
· Confinement — restraining or isolating the person
· Financial — the misuse or withholding of the person’s resources to his or her disadvantage or the advantage of someone else
· Sexual abuse — touching, fondling or any sexual activity when the person is unable to understand, unwilling to consent, or threatened or physically forced
· Willful deprivation — willfully denying the person medication, medical care, food, shelter, or physical assistance, and thereby exposing the individual with Alzheimer’s to the risk of physical, mental or emotional harm
American Medical News (1992), vol. 35, no. 46
Coping with stress
Caregivers — both family and professionals — are most often the abusers of older people. In many cases, stress and frustration may provoke unintentional violent feelings in caregivers. Family caregivers may feel isolated, depressed, and resentful toward their loved as the disease progresses and may become abusive without realizing it. Other issues, such as substance abuse, emotional problems and dependency, may also lead to mistreatment.
If you are having difficulty dealing with stress related to caregiving, it is important to get the support you need through a counselor, clergy or Association-sponsored support group. Find your local Alzheimer's Association.
To report an incident of elder abuse, call the Elder Care Locator at 1.800. 677.1116. For more information about elder abuse, visit the Elder Rights and Resources page of the Administration on Aging Web site.
What is coordinated care?
The chief goal of coordinated care is to develop cost-effective strategies to make health care systems more responsive to the needs of people with complex chronic illnesses such as Alzheimer’s disease.
Current systems often fail to meet those needs. Care is fragmented, with little communication among different professionals providing treatment. Follow-up and monitoring are poorly planned. Health professionals are often rushed, with barely enough time to address the pressing reason for a visit and none left over to provide support, education, or referrals to community resources.
Fragmentation and lack of follow-up, education and support all put chronically ill patients at risk of costly health crises, such as emergency room visits and unplanned hospitalizations.
Coordinated care aims to improve health outcomes, avoid crises and reduce costs by:
· identifying medical, functional, emotional and social needs
· meeting those needs through integration of medical services and education and support of patients and families
· monitoring patients for early signs of problems
Since 1995, the Alzheimer's Association has partnered with health care organizations to develop, implement and evaluate models of coordinated medical care and supportive services for people with Alzheimer's disease and other dementias.
Several of these partnerships produced the Guidelines and Tools posted below.
The projects discussed here all had care managers to assist with care coordination. Some care managers were based in the partnering health organization, some were in local Alzheimer’s Association chapters, and some were in another community agency.
One indicator of success in these initiatives was the proportion of people with dementia and family caregivers who received Alzheimer’s Association chapter services. To encourage referral and timely use of services, the projects instituted a process in which the health professional asked the person and family for permission to give their names and contact information to the local chapter so the chapter could initiate a relationship.
Guidelines and tools
· Clinical Practice Guidelines for Dementia Care from Kaiser Permanente
America’s oldest and largest integrated health care organization, with more than 8 million members in 9 states and the District of Columbia.
· The U.S. Department of Veterans Affairs (VA) provides medical care and other benefits to America’s 25 million living veterans. The Partners in Dementia Care program was an innovative partnership between the VA in upstate New York (VISN 2) and four Alzheimer’s Association chapters in that region.
Partners in Dementia Care Executive Summary (2 pages)
Partners in Dementia Care Report (30 pages)
Partners in Dementia Care Appendices (34 pages)
· Tools for Early Identification, Assessment and Treatment for People with Alzheimer's Disease and Dementia (40 pages)
A Publication of the Chronic Care Networks for the Alzheimer’s Disease, a joint initiative of the Alzheimer's Association and the National Chronic Care Consortium.
Medicare provides health benefits to 40 million elderly and disabled Americans. Medicare beneficiaries can choose to enroll in a Medicare HMO or to remain in regular, fee-for-service Medicare.
In the 1990s, the number of Medicare beneficiaries who enrolled in Medicare HMOs increased very rapidly, growing from 1.8 million in 1993 to 6.3 million (16% of all Medicare beneficiaries) in 1999. In 1995, in response to this rapid growth in Medicare HMO enrollment, the Alzheimer's Association began an initiative to improve care for people with Alzheimer's disease and other dementias who are enrolled in Medicare HMOs.
The initiative involved the Alzheimer's Association national office and more than 25 local chapters. It has resulted in strong working relationships between chapters and health care systems and providers in their local communities. It has also provided the Association with valuable information about how to coordinate health care and chapter services and how to improve physician knowledge and practices in dementia care.
Partnership with Kaiser Permanente
Since 1995, 10 Alzheimer's Association chapters have worked with the Kaiser Permanente health care system in their community to test ways to improve care for Kaiser members with Alzheimer's disease and other dementias.
Association chapters in Los Angeles, Cleveland, Denver, Hawaii, Portland, Oregon, Sacramento, San Diego, San Francisco, Albany and Washington D.C. have participated in studies that included training for Kaiser staff about Alzheimer's disease and dementia, increasing referrals from Kaiser to the chapter, and joint efforts to provide information, care consultation, and supportive services for the members and their family caregivers.
Highlight here are three partnerships with the Kaiser Permanente system:
Los Angeles: In 1995, the Alzheimer's Association, Los Angeles began working with Kaiser Permanente in Southern California to develop a partnership to improve care for Kaiser Permanente members with dementia and their family caregivers. Nationwide, this partnership was the first joint venture between a managed care organization and a local Alzheimer's Association chapter. The project provided standardization in the diagnosis and management of the disease. It also created a model for collaboration between a Kaiser Permanente region and a community service organization.
· Establishing Partnerships Between Managed Care and Aging Service Organizations (143 pages)
A replication manual that highlights important issues to consider when establishing partnerships; includes lessons learned and useful tools. The manual is based on the Alzheimer’s Association-Kaiser Permanente Metropolitan Los Angeles Dementia Care Project.
Cleveland: The Cleveland Alzheimer's Managed Care Demonstration began with a premise that "by initiating contact with individuals with memory problems and their families, Alzheimer's Association Care Consultants will help them address current and future caregiving challenges, thus averting more costly and stressful crises". Over the study period, 210 memory impaired Kaiser members and their families were enrolled. The results testify to the multifaceted impact of the Alzheimer's Association care consultation during just one year of a family's caregiving journey. Not only was patient utilization impacted, reducing use of hospital and emergency room services, but also both patient and caregiver well-being and relationship strain improved.
San Francisco and Albany, NY: In 1996, the Alzheimer's Association launched the Chronic Care Networks for Alzheimer's Disease (CCN/AD) project in partnership with the National Chronic Care Consortium (NCCC). The project's intent is to implement and evaluate a model of coordinated primary and acute health care and supportive services for people with Alzheimer's disease and dementia. In six sites across the country, Alzheimer's Association chapters, and local managed care organizations or other integrated health care systems are working together to implement the project model and improve the care provided for people with these conditions. Once again, Kaiser Permanente has been a major player. Two of the six sites involved a Kaiser health care system - San Francisco and Troy/Albany, NY.
Kaiser Permanente Dementia Care Program
Using ideas and tools developed through these partnerships and other projects conducted by Kaiser Permanente health systems, the Kaiser Permanente Care Management Institute (KP-CMI) developed its Dementia Care Program. This program includes guidelines and recommendations on how dementia care should be provided to Kaiser members. The new program is an informational resource only and is not a substitute for clinical judgment based on the individual needs of patients.
The program includes:
· Nine "key principles" on diagnosing and caring for patients with dementia and support for their caregivers. These principles include early identification and diagnosis, connecting caregivers to vital community resources, developing a care plan and monitoring and adjusting medication use.
· Measures for assessing care performance and progress in caring for people with dementia.
· Valuable forms, tools and lists of resources that will help care providers implement the guideline's recommendations.
For an individual with Alzheimer’s disease, advance planning is essential to fulfilling end-of-life wishes. The physicians and care team play an important role in initiating discussion with the individual and family regarding these wishes.
Even though Alzheimer’s disease can run a course of up to 20 years, it is terminal. Ideally, the physician and care team should discuss values and preferences related to death and dying with all older persons on a regular basis. Early discussion will help to clarify the individual’s wishes before the onset of dementia.
Individuals have a moral and legal right to limit or forgo medical or life sustaining treatment (including the use of artificial feeding, mechanical ventilators, cardiopulmonary resuscitation, antibiotics, dialysis and other invasive technologies). Individuals who lack decision-making capacity have the right to have surrogates use advance directives to assure this right.
The two common forms of advance directives are a living will and a durable power of attorney for health care. A living will states the individual’s choices for future medical care decisions. The durable power of attorney allows the individual to designate a surrogate, usually a trusted family member, to make specific treatment decisions for them. The surrogate should make decisions consistent with what they think the individual’s wishes would have been. In the absence of written advance directives, care providers should try to learn about the individual’s wishes from family members as a basis for making their decisions.
Every state now legislatively recognizes advance directives. State legislation creates procedural mechanisms to effectuate rights that are guaranteed by the federal constitution. Both the living will and durable power of attorney for health care are authorized in most states and the District of Columbia. However, issues within the statutes regarding the use or withdrawal of artificial nutrition and hydration vary from state to state.
If there is an identified surrogate, families should be contacted and involved in the decision-making process. Care providers should work closely with the family, in cases where a substitute judgment must be made, to interpret advance directives. If there is a lack of knowledge about the individual, care providers should base a decision on what they feel is in the best interest for that individual. If necessary, the importance of respecting the individual’s wishes should be clarified for the family. Clinical ethics consultants or the facility’s ethics committee may offer assistance in facilitating consensus.
An individual’s right to refuse or withdraw any treatment, including treatment for life-threatening illness (infections, hemorrhaging, heart attacks, etc.), is not the same as assisted suicide or euthanasia. In fact, aggressive medical treatment may seem torturous to the individual because of his or her lack of orientation to the surroundings and lack of understanding of the intentions of care providers.
During the final stages of Alzheimer’s disease, hospice care can be particularly beneficial to individuals with Alzheimer’s disease and their family members. Hospice, which is normally offered to individuals who are expected to live less than six months, includes comprehensive palliative care and support services, including bereavement counseling for family members.
Aggressive life-sustaining treatments such as artificial nutrition and hydration, antibiotics and cardiopulmonary resuscitation are not normally recommended for hospice patients. However, it is important to assess the person’s need for pain medication, since many persons with Alzheimer’s disease may be unable to verbally communicate their discomfort.
Hospice care is a benefit paid, for those eligible, by Medicare and Medicaid, and often by private insurance. Most hospice patients are cared for in the home, but some reside in long-term care settings. Despite the appropriateness and benefit for persons with Alzheimer’s disease and their families, and their eligibility for the Medicare hospice benefit, very few persons with Alzheimer’s disease receive hospice care. Physicians, care professionals and families can change this by generating awareness of the importance of hospice to the individual in the final stages of Alzheimer’s disease.
The care providers should:
· Facilitate early communication with older patients to understand their end-of-life wishes.
· Respect the end-of-life wishes of the individual.
· If these wishes conflict with the care provider’s personal beliefs, consideration should be given to the transfer of care to another provider
· Confer with ethics consultants or ethics committees in cases where there is no consensus with the family.
· Refer families to the Alzheimer’s Association for services such as support groups and information about local programs and services.
Internet Citation: http://www.alz.org/professionals_and_researchers_cognitive_symptoms.asp