Related Terms

• Acetylcholine, amyloid beta precursor protein, APOE, apolipoprotein E, APP, bradycardia, cholinesterase inhibitor, chronic obstructive pulmonary disease, cognition, cognitive, computerized tomography, concussion, COPD, Creutzfeldt-Jakob disease, CT, dementia, eurotoxicity, hemorrhage, hypercholesterolemia, hypertension, inflammation, magnetic resonance imaging, MRI, neuritic, neurons, neurotransmitters, non-steroidal anti-inflammatory drug, NSAID, PET, pneumonia, positron emission tomography, pulmonary embolism, statin, tau, vascular dementia.

Background

• Alzheimer's disease (AD) is an irreversible, progressive disorder in which neurons (brain cells) deteriorate resulting in the loss of cognitive (thought) functions, primarily memory, judgment, reasoning, movement coordination, and pattern recognition. In advanced stages of the disease, all memory and mental functioning may be lost.

• Alzheimer's disease may cause death; it is the eighth leading cause of death in the United States. However, an individual with AD often dies from an additional illness like pneumonia.

• According to the National Institute on Aging (NIA), Alzheimer's disease is the most common form of dementia. Dementia is a group of disorders that impairs mental functioning. Dementia means loss of the ability to think. Alzheimer's is progressive and irreversible. Abnormal changes in the brain worsen over time, eventually interfering with many aspects of brain function. Memory loss is one of the earliest symptoms, along with a gradual decline of other intellectual and thinking abilities, called cognitive functions, and changes in personality or behavior. Other forms of dementia include vascular dementia (due to a lack of blood flow to the brain), mixed dementia (presence of both Alzheimer's and vascular dementia), and Creutzfeldt-Jakob disease (rapidly declining memory and cognition due to consumption of cattle with "mad-cow" disease).

• Alzheimer's advances in stages, progressing from mild forgetfulness and cognitive impairment to widespread loss of mental abilities. In advanced Alzheimer's, people become dependent on others for every aspect of their care. The time course of the disease varies by individual, ranging from five to 20 years. The most common cause of death is infection.

• Age is the most important known risk factor for AD. The number of people with the disease doubles every five years beyond age 65. In the United States, about 10% of people ages 65 and up, and about 50% of people ages 85 and up have AD.

• There are an estimated 24 million people with general dementia worldwide. In the United States, it is estimated that about five million people currently suffer from AD, and about 360,000 people are newly diagnosed every year. Every 72 seconds in the United States, someone develops Alzheimer's. By 2050, the estimated range of Alzheimer's disease prevalence will be 11.3 million to 16 million Americans, with a middle estimate of 13.2 million unless a cure or prevention is found. Medicare and other healthcare insurances help offset the costs for individuals.

• The National Center for Policy Analysis (NCPA) reports that the direct and indirect costs of Alzheimer's and other dementias amount to more than $148 billion annually in the United States alone. The financial cost of caring for someone with Alzheimer's disease can be overwhelming and is estimated to be about $50,000 per year in direct medical expenses.

• There is no known cure for Alzheimer's disease, although researchers have made progress on determining the causes of Alzheimer's.

Risk Factors

• Age: The risk for Alzheimer's disease (AD) increases with each decade of adult life. AD usually affects people older than 65 but rarely, it may affect those younger than 40. Less than five percent of people between 65-74 years old have AD. For people 85 and older, that number jumps to nearly 50%.

• Heredity: The risk of developing AD appears to be slightly higher if a first-degree relative (a parent, sister, or brother) has the disease. Although the genetic link of AD among families remains largely unexplained, researchers have identified a few genetic mutations that greatly increase risk in some families. A clear inherited pattern of AD exists in less than 10% of cases. In addition, one form of the apolipoprotein E (APOE) gene increases the chances of developing late-onset AD. Nearly all individuals with Down's syndrome who live into their 40s develop the disease. Down syndrome (DS) is a condition in which extra genetic material causes delays in the way a child develops and often leads to mental retardation. It affects one in every 800 babies born. Three genetic mutations in DNA are known to cause early-onset Alzheimer's.

• Gender: It is thought that gender plays a role because several clinical studies suggest that women are afflicted with Alzheimer's disease more often than men. This was explained by the life span of women being usually longer than men. However, the evidence is inconsistent and some studies report that the disease is more common in men. Therefore, more research is needed to obtain conclusive evidence regarding prevalence in gender.

• Lifestyle: The same factors that put an individual at risk of heart disease, including hypertension (high blood pressure) and hypercholesterolemia (high cholesterol), may also increase the likelihood that the person will develop AD. Poorly controlled diabetes is another risk factor. Exercise and diet are very important to prevent and control AD. Some clinical studies have suggested that remaining mentally active throughout life, especially in the later years, reduces the risk of AD. Mental activity can be doing crossword puzzles daily, reading the newspaper or books, and increasing social activities.

• Education levels: Clinical studies have found an association between less education and the risk of developing AD. Some researchers theorize that the more an individual uses his/her brain, the more synapses are created, which provide a greater reserve as an individual ages. It remains unclear, however, whether less education and less mental activity create a risk of AD or if it is simply harder to detect AD in individuals who exercise their minds frequently or who have more education. Reading, working, puzzles, and social activities help exercise the mind.

• Toxicity: Another theory is that overexposure to metals (such as lead, mercury, and aluminum) or chemicals may cause AD. For a time, aluminum was thought to increase the likelihood of developing AD. This was due to the findings that more individuals with AD have deposits of aluminum in their brains. After many years of studies, however, no true link to developing AD has been found with aluminum exposure. A study found that workers exposed to aluminum experienced neurotoxicity (nerve damage) and symptoms of early AD, such as decreased cognitive performance. More studies need to be performed to link heavy metals to AD.

• Head injury: The observation that some ex-boxers eventually develop dementia suggests that serious traumatic injury to the head (for example, a concussion with a prolonged loss of consciousness) may be a risk factor for AD. Findings are mixed and more research is needed.

• Hormone replacement therapy: The exact role hormone replacement therapy (HRT) may play in the development of dementia and AD is not yet clear. Early evidence seemed to report that estrogen supplements given after menopause could reduce the risk of dementia and AD. But results from the large-scale Women's Health Initiative Memory Study indicated an increased risk of AD for women taking estrogen after age 65. The verdict is not yet in on whether estrogen affects the risk of dementia and AD if given at an earlier age. More research is needed.

Causes

• Genetic factors: Genetic factors are known to play a role in some cases of Alzheimer's disease (AD). A gene, called the amyloid beta precursor protein (APP) gene, has been linked to the occurrence of AD in Down's syndrome patients who survive beyond 40 years. Some families with a history of early-onset AD also have a mutation on the APP gene. Another gene, the Apo E gene, also has been implicated in the disease. Apo E is a protein found with beta amyloid (a protein found in the brains of AD patients) in neuritic (inflamed nerve) plaques. Together, these genetic mutations account for less than 10% of all AD cases.

• Plaques and tangles: The causes of Alzheimer's disease (AD) are poorly understood, but its effect on brain tissue has been demonstrated clearly. AD damages and kills brain cells. A healthy brain has billions of nerve cells called neurons. Neurons generate electrical and chemical signals that are relayed from neuron to neuron to help an individual think, remember, and feel (physically and emotionally). Brain chemicals called neurotransmitters help these signals flow seamlessly between neurons. Initially in people with AD, neurons in certain locations of the brain begin to die. When they die, lower levels of neurotransmitters are produced, creating signaling problems in the brain. One neurotransmitter, known as acetylcholine, has been found to be deficient in the brains of those with AD. Medication treatment is based around increasing the amount of acetylcholine in the brain.

• Plaques and tangles in brain tissue are considered hallmarks of Alzheimer's disease. Studies of plaques and tangles from the brains of people who have died of AD suggest several possible roles these structures might play in the disease.

• Plaques are made up of beta-amyloid, a normally harmless protein. Although the ultimate cause of neuron death in AD is not known, mounting evidence suggests that a form of beta-amyloid protein may be the cause. The plaque is responsible for memory deterioration in individuals with AD.

• The internal support structure for brain neurons depends on the normal functioning of a protein called tau. In people with AD, threads of tau protein undergo alterations that cause them to become twisted or tangled. Many researchers believe that this may seriously damage neurons, causing them to die.

• Inflammation: Researchers have observed inflammation in the brains of some people with AD. Inflammation is the body's response to injury or infection and a natural part of the healing process. Even as beta-amyloid plaques develop in the spaces between neurons, immune cells are at work getting rid of dead cells and other waste products in the brain. Although research has found that the inflammation occurs before plaques have fully formed, it is not known how this development relates to the disease process. There is also debate about whether inflammation has a damaging effect on neurons or whether it is beneficial in clearing away plaques.

Signs and Symptoms

• Because early symptoms of Alzheimer's disease (AD) progress slowly, diagnosis is difficult and often delayed. The disease's course varies from person to person. Eight years is the average length of time from diagnosis of Alzheimer's to death. Survival begins to decline three years after diagnosis, but some people live more than a decade with the disease.

• Stages of AD: In individuals with AD, changes in the brain may begin 10-20 years before any visible signs or symptoms appear. Some regions of the brain may begin to shrink (found during brain imaging such as positron emission tomography or PET), resulting in memory loss and the first visible sign of AD. Over time, AD progresses through three main stages including mild (early), moderate, and severe.

• Mild symptoms: Individuals with mild symptoms of AD often seem healthy, but mental deterioration, such as memory impairment and confusion, are occurring. Symptoms and early signs of Alzheimer's disease may include: difficulty learning and remembering new information, difficulty with daily tasks (such as managing finances, planning meals, and taking medication on schedule), and depression symptoms (sadness, decreased interest in usual activities, loss of energy). The individual is usually still able to do most activities such as driving a car, but may get lost going to familiar places. People with early and mild symptoms of AD may exhibit mood swings. They may express distrust in others, show increased stubbornness, and withdraw socially. This may be a response to the frustration they feel as they notice uncontrollable changes in their memory. Restlessness also is a common sign. As the disease progresses, people with Alzheimer's may become anxious or aggressive and behave inappropriately.

• Moderate symptoms: In individuals with moderate symptoms of AD, the damaging processes occurring in the brain worsen and spread to other areas that control language, reasoning, sensory processing, and thought. In this stage, symptoms and signs of AD become more severe and behavioral problems may become more obvious. Signs and symptoms of moderate Alzheimer's disease may include forgetting old facts, continually repeating stories, and/or asking the same questions over and over. The individual may make up stories to fill memory gaps. They have difficulty performing tasks such as keeping a checkbook, shopping for groceries, or following written notes. The individual may not shower or go to the toilet as they did previously, and help with these tasks is needed. They become agitated and restless easily. Repetitive movements, such as rocking to and fro or rubbing the hands, are seen. The individual may wander off and needs to be watched closely. Paranoia, delusions, and hallucinations may occur. Deficiencies in intellect and reasoning, along with a lack of concern for appearance, hygiene, and sleep, become more noticeable.

• Severe symptoms: In the advanced stage of AD, damage to the brain's nerve cells is widespread. At this point, full-time care is typically required. The patient is generally bed-ridden. For friends, family, and Alzheimer's caregivers, this can be the most difficult stage. Individuals with severe Alzheimer's disease may have difficulty walking and they often suffer complications from other illnesses such as pneumonia. Signs of severe Alzheimer's disease may include groaning, screaming, mumbling, or speaking gibberish. They refuse to eat and may inappropriately cry out. Individuals with severe or advanced symptoms fail to recognize the faces of family members or caregivers. Apraxia (inability to perform physical tasks such as dressing, eating) and aphasia (loss of ability in comprehension of spoken or written language) are seen. They have great difficulty with all essential activities of daily life.

Diagnosis

• There's no one test to diagnose Alzheimer's disease (AD). Typically, doctors start the diagnostic process by ruling out other diseases and conditions that may also cause memory loss. Small, undetected strokes, which are a lack of oxygen to the brain causing neurological damage, can cause dementia. Individuals with Parkinson's disease, a degenerative nerve disorder, also may develop dementia. Depression can also cause lapses in memory. In addition, many older adults are on multiple medications that may decrease their ability to think clearly.

• Medical history: Questions regarding general health and current medications will be asked. Past medical problems, including diseases and surgeries, will be discussed. Family members will usually be involved in the medical history process.

• Blood tests: Blood tests to determine basic health will be used. A complete blood count (CBC) will determine thyroid problems, electrolyte (such as sodium and potassium) balances, vitamin deficiencies, and immune health.

• Mental status evaluation: A Mental Status Evaluation (MSE) screens memory, problem-solving abilities, attention spans, counting skills, and language skills. Questions such as "what day is it today?" or "who is the president of the United States?" may be asked. Recall tests are another example. Doctors may list familiar objects and then ask a person to repeat them immediately and again five minutes later. The Clock Drawing Test, the Mini-Mental State Examination (MMSE), and the Functional Assessment Staging (FAST) are commonly used mental status evaluation tools for determining if AD is present. On the tests, the final score helps confirm a diagnosis of AD.

• Sometimes doctors will more extensively assess memory, problem-solving abilities, attention spans, counting skills, and language. This is especially helpful in trying to detect AD and other dementias at an early stage. Doctors use formal psychological tests to determine if an individual's mental abilities are as expected for his or her age and education. The patterns of any mental deficits observed during neuropsychological testing can help doctors sort out possible causes of dementia.

• Brain scans: Doctors may want to take a picture of the brain using a brain scan. Several types of brain scans are available including computerized tomography (CT) scan, magnetic resonance imaging (MRI) scan, and positron emission tomography (PET) scan. Doctors can pinpoint visible abnormalities in the brain using these imaging techniques. A CT scan uses x-rays to take many pictures of the brain and then combines the pictures by computer that provides a detailed picture. A CT scan can often show changes in brain structure. MRI's for AD diagnosis display a cross-section of the brain using radio waves and strong magnets instead of radiation. A contrast dye may be injected, although it is used less often with MRI's. PET scans involve the injection of radioactivity into the blood that goes to the brain. Images can then be analyzed for changes in function and structure of the brain. They may take longer than CT scans and the patient is placed inside a confining tube. CT, MRI, and PET are performed at a clinic or hospital. Some individuals will be sedated with mild sedatives (such as alprazolam or Xanax® or midazolam or Versed®). These medications may cause drowsiness and it is not recommended that the individuals drive. The individual should bring a friend or family member with them to the clinic or hospital.

• Genetic testing: Due to the discovery of genes that are associated with developing AD, genetic testing may be used in the future as a routine diagnostic tool for determining the chances of developing AD. Genetic testing is not approved by the U.S. Food and Drug Administration (FDA) for use in AD diagnosis.

Complications

• Mental Illness: Depression is common in patients with Alzheimer's disease (AD), especially during the earlier stages when they may be aware of losing mental functions.

• Falls and their complications: Individuals with AD may become disoriented, increasing their risk of falls. Falls can lead to bone fractures that require hospitalization, medications, and surgery. Falls may also lead to an increase in the severity of AD symptoms, such as confusion and agitation. In addition, falls are a common cause of serious head injuries, such as brain hemorrhage (bleeding in the brain). Long-term immobilization after surgery and hospitalization may also increase the risk of a pulmonary embolism (blood clot in the lungs), which can be life-threatening.

• Infections: In advanced Alzheimer's disease, people may lose all ability to care for themselves. This can make them more prone to additional health problems such as pneumonia (a bacterial infection of the lungs and respiratory system). They may have difficulty swallowing food and liquids, which may cause individuals with AD to inhale some of what they eat and drink into their airways and lungs, which may then lead to pneumonia.

• Urinary incontinence: Urinary incontinence, or the loss of bladder control causing urine leakage, may require the placement of a urinary catheter, which increases the risk of urinary tract infections (UTIs). UTIs can lead to more serious, life-threatening infections.

Treatment

• The primary symptoms of Alzheimer's disease (AD) include memory loss, disorientation, confusion, and problems with reasoning and thinking. These symptoms worsen as brain cells die and the connections between cells are lost. Progressive loss of brain cells usually occurs. Although current drugs cannot alter the progressive loss of cells, they may help minimize or stabilize symptoms. These medications may also delay the need for nursing home care.

• Cholinesterase inhibitors: The U.S. Food and Drug Administration (FDA) has approved two classes of drugs to treat cognitive symptoms of AD. The first to be approved were cholinesterase inhibitors, which increase the amount of the brain chemical acetylcholine. Three of these drugs that are commonly prescribed include donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®). Tacrine (Cognex®), the first cholinesterase inhibitor, was approved in 1993 but is rarely prescribed today because of associated side effects including possible liver damage. About half of the people who take cholinesterase inhibitors experience a modest improvement in cognitive symptoms, such as memory. Side effects include diarrhea, vertigo (dizziness), drowsiness, fatigue (extreme tiredness), nausea, and vomiting. Individuals with liver disease, peptic ulcer disease, chronic obstructive pulmonary disease (COPD), and slow heart rate should not take these drugs.

• Memantine: Memantine (Namenda®) is a drug approved by the FDA for treatment of moderate to severe Alzheimer's disease. Memantine is the first AD 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. Excess glutamate, on the other hand, may lead to disruption and death of brain cells. Memantine may protect cells against excess glutamate by partially blocking NMDA receptors. Side effects include headache, constipation, confusion, and dizziness.

• Other medications: Medications may be needed to treat the symptoms associated with AD. These symptoms interfere with normal daily activities and sleeping. Depression that occurs during the early stages is commonly treated with antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs) including fluoxetine (Prozac®) and sertraline (Zoloft®), and the tricyclic antidepressants (TCAs) including amitriptyline (Elavil®). Side effects include drowsiness, fatigue, and sedation. TCAs may increase mental confusion. Agitation may be treated with antipsychotic medication, such as haloperidol (Haldol®), risperidone (Risperdal®), olanzapine (Zyprexa®), and quetiapine (Seroquel®). Antipsychotics are not FDA-approved to treat symptoms of AD and may increase the risk for death in elderly dementia patients. Side effects include sedation, confusion, and tardive dyskinesia (an irreversible movement disorder characterized by lip smacking, facial grimacing, and unsteady walking).

• Prognosis: Patients may survive eight to 10 years with AD. Some have been known to live 25 years with the disease. Death usually occurs due to infections (including pneumonia), heart disease, or malnutrition.

Integrative Therapies

• Strong scientific evidence:

• Ginkgo: Ginkgo biloba has been used medicinally for thousands of years. The scientific literature overall does suggest that ginkgo may benefit people with dementia (multi-infarct and Alzheimer's type), and may be as helpful as acetylcholinesterase inhibitor drugs such as donepezil (Aricept®). Well-designed research comparing ginkgo to prescription drug therapies is needed.

• Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Avoid with blood-thinners (like aspirin or warfarin (Coumadin®)) due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Ginkgo should not be used in supplemental doses if pregnant or breastfeeding.

• Good scientific evidence:

• Aromatherapy: Aromatherapy is the use of essential oils from plants for healing purposes. There is suggestive preliminary evidence that aromatherapy using essential oil of lemon balm (Melissa officinalis) may effectively reduce severe agitation in dementia when applied to the face and arms twice daily. Other research reports that steam inhalation of lavender aromatherapy may have similar effects. However, there is a conflicting study that reports no benefits of aromatherapy using lemon balm, Lavender officinalis, sweet orange (Citrus aurantium), or tea tree oil (Malaleuca alternifolia). Overall, the evidence does suggest potential benefits. It is not clear if this is because of anxiety-reducing qualities of these therapies. Additional study is necessary. There is also preliminary research suggesting that aromatherapy used with massage may help to calm people with dementias who are agitated. However, it is not clear if this approach is any better than massage used alone.

• Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving/operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant.

• Bacopa: Bacopa monnieri leaf extract is called brahmi in Ayurvedic medicine (medicine practiced in India) and is widely used in India for enhancing memory, pain relief, and treating epilepsy. Although bacopa is traditionally used in Ayurvedic medicine to enhance cognition, high-quality clinical trials are lacking. Two methodologically weak studies found some evidence that bacopa improves cognition. However, more high-quality and independent research is needed before bacopa can be recommended for enhancing brain function in adults or children.

• Bacopa may interact with medications such as calcium channel blockers (used for arrhythmias and high blood pressure), thyroid medications, phenytoin (Dilantin®), and drugs metabolized by the liver. Use cautiously with drugs or herbs that are metabolized by cytochrome P450 enzymes, thyroid drugs, calcium blocking drugs, and sedatives. Avoid if allergic/hypersensitive to Bacopa monnieri, its constituents or any member of the Srcophulariaceae (figwort) family. Avoid if pregnant or breastfeeding.

• Ginkgo: Multiple clinical trials have evaluated ginkgo for a syndrome called cerebral insufficiency. This condition, more commonly diagnosed in Europe than the United States, may include poor concentration, confusion, absent-mindedness, decreased physical performance, fatigue, headache, dizziness, depression, and anxiety. It is believed that cerebral insufficiency is caused by decreased blood flow to the brain due to clogged blood vessels. Some studies report benefits of ginkgo in patients with these symptoms, but most have been poorly designed without reliable results. Better studies are needed before a conclusion can be made.

• Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Avoid with blood-thinners (like aspirin or warfarin (Coumadin®)) due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Ginkgo should not be used in supplemental doses if pregnant or breastfeeding.

• Music therapy: Music is used to influence physical, emotional, cognitive and social well-being and improve quality of life for healthy people as well as those who are disabled or ill. It may involve either listening to or performing music, with or without the presence of a music therapist. In people with Alzheimer's dementia and other mental disorders in older adults, music therapy has been found to reduce aggressive or agitated behavior, improve mood, and improve cooperation with daily tasks such as bathing. Music therapy may also be beneficial for dementia-associated neuropsychiatric symptoms, such as depression and aggressive behavior. Music therapy may help maintain mental performance in elderly adults undergoing surgical procedures, reduce postoperative confusion and delirium, and increase energy levels.

• Music therapy is generally known to be safe.

• Unclear or conflicting scientific evidence:

• Acupressure, shiatsu: Acupressure may decrease verbal and physical agitated behavior in dementia patients. Further study is needed before a conclusion can be made.

• With proper training, acupressure appears to be safe if self-administered or administered by an experienced therapist. Serious long-term complications have not been reported, according to scientific data. Hand nerve injury and herpes zoster ("shingles") cases have been reported after shiatsu massage. Forceful acupressure may cause bruising.

• Acupuncture: Acupuncture has been reported to help improve memory and cognitive performance in the elderly. However, there is currently insufficient available evidence for the use of acupuncture in cognitive disorders and communication disorders. There is also insufficient evidence to recommend the use of acupuncture in the treatment of vascular dementia. More research is necessary.

• Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, and neurological disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics, or with a history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.

• Arginine: There is not enough information available to make a strong recommendation about the use of the amino acid arginine in senile dementia.

• Avoid if allergic to arginine, or with a history of stroke, or liver or kidney disease. Avoid if pregnant or breastfeeding. Use caution if taking blood-thinning drugs (like warfarin or Coumadin®) and blood pressure drugs or herbs or supplements with similar effects. Check blood potassium levels. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control sugar levels.

• Art therapy: Art therapy enables the expression of inner thoughts or feelings when verbalization is difficult or not possible. The aesthetic aspect of the creation of art is thought to lift one's mood, boost self-awareness, and improve self-esteem. Art therapy also allows the opportunity to exercise the eyes and hands, improve eye-hand coordination, and stimulate neurological pathways from the brain to the hands. Art therapy may be an effective means of improving quality of life in the elderly. Art therapy has been used in only a few studies with Alzheimer's disease (AD) patients, with some suggestion of benefit in alleviating negative emotions and minimizing problematic behaviors. However, further studies are needed for definitive conclusions. There is evidence that the non-directed use of visual art (pictures) as a means of encouraging communication among elderly nursing home residents may increase well-being. It may also reduce blood pressure and improve medical health status with regard to reported dizziness, fatigue, pain, and use of laxatives.

• Art therapy may evoke distressing thoughts or feelings. Use under the guidance of a qualified art therapist or other mental health professional. Some forms of art therapy use potentially harmful materials. Only materials known to be safe should be used. Related clean-up materials (like turpentine or mineral spirits) that release potentially toxic fumes should only be used with good ventilation.

• Ayurveda: The herb Brahmi (Bacopa monnieri) is used in many Ayurvedic preparations for a variety of ailments. There is evidence from well-designed studies that it may improve memory and cognitive function in adults. Another study suggests that the herbal preparation Maharishi Amrit Kalash (MAK) -4 may enhance attention capacity or alertness, and thus reverse some of the detrimental cognitive effects of aging. Further research is needed to confirm these results.

• Ayurvedic herbs should be used cautiously because they are potent and some constituents can be potentially toxic if taken in large amounts or for a long period of time. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs may interact with other herbs, foods, and drugs. A qualified healthcare professional should be consulted before use. Use guggul cautiously with peptic ulcer disease. Patients should avoid sour food, alcohol, and heavy exercise with use of this herb. Mahayograj guggul should not be taken for long periods of time. Pippali (Piper longum) should be taken with milk and avoided with asthma. Avoid sweet flag, and avoid amlaki (Emblica officinalis) at bedtime. Avoid Terminalia chebula (harda) if pregnant. Avoid Ayurveda with traumatic injuries, acute pain, advanced disease stages and medical conditions that require surgery.

• Bacopa: Bacopa monnieri leaf extract is called brahmi in Ayurvedic medicine and is widely used in India for enhancing memory, pain relief, and treating epilepsy. However, additional study is needed before a firm conclusion can be drawn.

• Bacopa may interact with medications such as calcium channel blockers (used for arrhythmias and high blood pressure), thyroid medications, phenytoin (Dilantin®), and drugs metabolized by the liver. Use cautiously with drugs or herbs that are metabolized by cytochrome P450 enzymes, thyroid drugs, calcium blocking drugs, and sedatives. Avoid if allergic/hypersensitive to Bacopa monnieri, its constituents, or any member of the Srcophulariaceae (figwort) family. Avoid if pregnant or breastfeeding.

• Beta-carotene: Antioxidants such as beta-carotene may be helpful for increasing cognitive performance and memory. Long-term, but not short-term, beta-carotene supplementation appears to benefit cognition.

• Avoid if sensitive to beta-carotene, vitamin A, or any other ingredients in beta-carotene products.

• Black tea: Several preliminary studies have examined the effects of caffeine, tea, or coffee use on short and long-term memory enhancement. It remains unclear if tea is beneficial for this use. Limited, low-quality research also reports that the use of black tea may improve mental performance/alertness and cognition.

• Black tea contains caffeine, which is a stimulant.Avoid if allergic or hypersensitive to caffeine or tannins. Skin rash and hives have been reported with caffeine ingestion. Use caution with diabetes. Use caution if pregnant. Heavy caffeine intake during pregnancy may increase the risk of SIDS (sudden infant death syndrome). Very high doses of caffeine have been linked with birth defects. Caffeine is transferred into breast milk. Caffeine ingestion by infants can lead to sleep disturbances/insomnia. Infants nursing from mothers consuming greater than 500 milligrams of caffeine daily have been reported to experience tremors and heart rhythm abnormalities. Tea consumption by infants has been linked to anemia, decreased iron metabolism, and irritability.

• Boron: Preliminary human studies report better performance on tasks of eye-hand coordination, attention, perception, short-term memory, and long-term memory with the use of boron. Although boron has not been studied in AD, it may be beneficial in improving cognitive function.

• Avoid if allergic or sensitive to boron, boric acid, borax, citrate, aspartate, or glycinate. Avoid with a history of diabetes, seizure disorder, kidney disease, liver disease, depression, anxiety, high blood pressure, skin rash, anemia, asthma, or chronic obstructive pulmonary disease (COPD). Avoid with hormone-sensitive conditions like breast cancer or prostate cancer. Avoid if pregnant or breastfeeding.

• Chromium: Early research suggests that chromium picolinate may help improve cognitive function in the elderly. Further study is needed in this area. Trivalent chromium appears to be safe because side effects are rare or uncommon. However, hexavalent chromium may be poisonous (toxic).

• Avoid if allergic to chromium, chromate, or leather. Use cautiously with diabetes, liver problems, weakened immune systems (such as HIV/AIDS patients or organ transplant recipients), depression, Parkinson's disease, heart disease, and stroke, and in patients who are taking medications for these conditions. Use cautiously if driving or operating machinery. Use cautiously if pregnant or breastfeeding.

• Coenzyme Q10: Coenzyme Q10, or CoQ10, is produced by the human body and is necessary for the basic functioning of cells. Promising preliminary evidence suggests that CoQ10 supplements may slow down, but not cure, dementia in people with Alzheimer's disease. Additional well-designed studies are needed to confirm these results before a firm conclusion can be made.

• Allergy associated with coenzyme Q10 supplements has not been reported in the available literature, although rash and itching have been reported rarely. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use caution with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke, or with anticoagulants (blood thinners) or antiplatelet drugs (like aspirin or warfarin), blood pressure, blood sugar, cholesterol, or thyroid drugs. Avoid if pregnant or breastfeeding.

• Copper: Copper is a mineral that occurs naturally in many foods including vegetables, legumes, nuts, grains and fruits, as well as shellfish, avocado, and beef (organs such as liver). Conflicting study results report that copper intake may either increase or decrease the risk of developing Alzheimer's disease. Additional research about its effectiveness for Alzheimer's disease prevention is needed.

• Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6mg/L. Use cautiously with anemia, arthralgias, and myalgias. Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The United States Recommended Dietary Allowance (RDA) is 1,000μg for pregnant women. The United States Recommended Dietary Allowance (RDA) is 1,300μg for nursing women.

• Cranberry: Preliminary study results show that cranberry juice may increase overall memory enhancement. Further well-designed clinical trials are needed to confirm these results. It is best not to use sweetened cranberry juice or cranberry juice cocktail due to the high sugar content. The use of 100% cranberry juice products is recommended by healthcare providers.

• Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.

• Creatine: Early studies show that creatine may improve memory in certain populations, such as vegetarians and the elderly. Further research is required before recommendations can be made.

• Avoid if allergic to creatine or with diuretics (like hydrochlorothiazide, furosemide (Lasix®)). Use caution in asthma, diabetes, gout, kidney, liver or muscle problems, stroke or with a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding.

• DHEA: Dehydroepiandrosterone (DHEA) is an endogenous hormone (made in the human body) and secreted by the adrenal gland. DHEA serves as precursor to male and female sex hormones (androgens and estrogens). DHEA levels in the body begin to decrease after age 30 and may need to be taken as supplements. Preliminary evidence, from a controlled trial and a case series, gives conflicting results as to whether DHEA offers benefit to individuals with dementia. Well designed clinical trials, with appropriate endpoints are required before recommendations can be made.

• Avoid if allergic to DHEA. Avoid with a history of seizures. Use with caution in adrenal or thyroid disorders or anticoagulants, or drugs, herbs or supplements for diabetes, heart disease, seizure or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.

• Folate: Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food and folic acid is the synthetic form of this vitamin. Preliminary evidence indicates that low folate concentrations may be related to Alzheimer's disease. Well-designed clinical trials of folate supplementation are needed before a conclusion can be drawn.

• Avoid if allergic or hypersensitive to folate or any folate product ingredients. Use cautiously if receiving coronary stents and with anemia and seizure disorders. It is recommended that pregnant women consume 400 micrograms of folate daily in order to reduce the risk of the fetus developing a defect. Folate is likely safe if breastfeeding.

• Gingko: There is preliminary research showing small improvements in memory and other brain functions with use of ginkgo in patients with age-associated memory impairment (AAMI), although some studies disagree. Overall, there is currently not enough clear evidence to recommend for or against ginkgo for this condition. It remains unclear if ginkgo is effective for memory enhancement in healthy patients. Further well-designed research is needed as existing study results conflict.

• Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Avoid with blood-thinners (like aspirin or warfarin (Coumadin®)) due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Ginkgo should not be used in supplemental doses if pregnant or breastfeeding.

• Ginseng: Early small studies report that Fuyuan mixture, an herbal combination that contains ginseng, may improve symptoms of multi-infarct dementia. The effects of ginseng alone are not clear, and no firm conclusion can be drawn. In addition, the use of ginseng for mental performance has been assessed using standardized measurements of reaction time, concentration, learning, math, and logic. Benefits have been seen both in healthy young people and in older ill patients. Effects have also been reported for the combination use of ginseng with Ginkgo biloba. However, some negative results have also been reported. Therefore, although the sum total of available scientific evidence does suggest some effectiveness of short-term use of ginseng for mental performance, better research is necessary before a strong recommendation can be made.

• Avoid ginseng with known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in ginseng formulations.

• Gotu kola: Ayurveda regards gotu kola (Centella asiatica) as an important rejuvenating herb for nerve and brain cells, believed to be capable of increasing intelligence, longevity, and memory. Asiaticoside derivatives, including asiatic acid and asiaticoside, were shown to reduce hydrogen peroxide-induced cell death, decrease free radical concentrations, and inhibit beta amyloid cell death in vitro, suggesting a possible role for gotu kola in the treatment and prevention of Alzheimer's disease and beta amyloid toxicity. Limited available clinical study investigated a combination product containing gotu kola on cognitive function in the elderly, but did not find any benefit. Additional study is needed to confirm these findings.

• Avoid if allergic to gotu kola, asiaticoside, asiatic acid, or madecassic acid. Avoid with a history of high cholesterol, cancer, or diabetes. Avoid if pregnant or breastfeeding.

• Grapeseed: Grape seed oil is a popular (non scented) carrier oil used in aromatherapy. Although grape seed has been compared to lavender oil and thyme oil to reduce agitation in dementia patients, there is not enough scientific evidence to make a conclusion about its effectiveness.

• Avoid if allergic or hypersensitive to grapes or other grape compounds. Use cautiously if taking blood thinners such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents. Use cautiously with bleeding disorders or if taking drugs that may increase the risk of bleeding. Use cautiously with drugs processed using the liver's cytochrome P450 enzyme system. Use cautiously with blood pressure disorders or if taking ACE inhibitors. Avoid with disorders that increase the risk of bleeding or with active bleeding disorders (stomach ulcers, bleeding into the brain, etc.). Avoid if pregnant or breastfeeding.

• Green tea: Several preliminary studies have examined the effects of caffeine, tea, or coffee use on short and long-term memory and cognition. It remains unclear if tea is beneficial for this use. Limited, low-quality research reports that the use of green tea may improve cognition and mental performance/alertness.

• Green tea contains caffeine, which is a stimulant. Avoid if allergic or hypersensitive to caffeine or tannins. Use cautiously with diabetes or liver disease.

• Guarana: Guarana is a native species of South America and has stimulating properties when taken by mouth. Guarana is also used to enhance athletic performance and to reduce fatigue. Guarana has not been shown to alter cognitive enhancement or arousal in preliminary studies. Caffeine found in guarana may improve simple reaction time, but may not improve immediate memory. Additional study is needed in this area.

• Avoid if allergic/hypersensitivite to guarana (Paullinia cupana), caffeine, tannins, or species of the Sapindaceae family. Avoid with hypertension, psychological or psychiatric disorders, liver impairment, and arrhythmias. Avoid with other stimulatory agents, especially ephedra. Use cautiously with breast disease, impaired kidney function, diabetes, pre-existing mitral valve prolapse, iron deficiency, gastric or duodenal ulcers, bleeding disorders, glaucoma or if at risk for osteoporosis. Use cautiously if undergoing electroconvulsive therapy (ECT). Avoid if pregnant or breastfeeding.

• Guided imagery: The term guided imagery may be used to refer to a number of techniques, including metaphor, story telling, fantasy, game playing, dream interpretation, drawing, visualization, active imagination, or direct suggestion using imagery. Early research suggests that guided imagery of short duration may improve working memory. Further research is needed before a firm conclusion can be drawn.

• Guided imagery is usually intended to supplement medical care, not to replace it, and guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified healthcare provider if mental or physical health is unstable. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that can be brought about by stress, anxiety, or emotional upset because imagery may trigger these symptoms. In patients feeling unusually anxious while practicing guided imagery, or in patients with a history of trauma or abuse, a qualified health care provider should be consulted before practicing guided imagery.

• Jasmine: Odors and memory improvement are considered to be somehow linked in the brain. Two clinical trials using weakly jasmine-scented rooms found that subjects did not have improved recall of a physical environment without the jasmine odor trigger but could remember a word list better when exposed to a jasmine trigger. More research is needed in this area.

• Use cautiously during pregnancy, based on traditional use. Use cautiously in patients allergic to jasmine, jasmine oil, or other fragrances. Use cautiously during lactation as jasmine flowers applied to the breasts have been used as a lactofuge. Avoid oral consumption of essential oils, including jasmine essential oil, as they are extremely potent and can be poisonous.

• Jojoba: Jojoba oil is traditionally used as a carrier or massage oil. There is currently not enough available evidence to recommend for or against the use of jojoba oil for dementia.

• Avoid if allergic or hypersensitive to jojoba, its constituents, or members of the Simmondsiaceae family. Avoid oral consumption of jojoba products. Avoid if pregnant or breastfeeding.

• Khat: Khat is a flowering evergreen plant that has been grown for use as a stimulant for centuries. Khat has been evaluated for its benefits for cognitive function; however, the results are mixed with some studies showing benefit and others showing negative effects. Additional study is needed to clarify these findings.

• When taken by mouth, it is unknown whether khat is physically addictive. However, it is linked to psychological dependence and is illegal in the United States. Avoid if allergic to the Celastraceae family (staff vine family). Use cautiously if taking amoxicillin, ampicillin or stimulants. Use cautiously with a history of high blood pressure, fast heartbeat (tachycardia), depression, or motor tics (Tourette's syndrome). Avoid with glaucoma or mental illness. Avoid driving or operating heavy machinery after using khat. Avoid holding khat in the cheek for a long time. Avoid if pregnant or breastfeeding.

• Kundalini yoga: Kundalini yoga is one of many traditions of yoga that share common roots in ancient Indian philosophy. It is comprehensive in that it combines physical poses with breath control exercises, chanting (mantras), meditations, prayer, visualizations, and guided relaxation. Breathing exercises are an important part of Kundalini yoga. There is some evidence from studies with healthy volunteers that use of certain breathing techniques (such as breathing solely through one nostril or the other) may improve different aspects of cognitive function. More studies are needed to determine if these techniques can reliably be used to improve cognitive function and possibly aid in treating cognitive and nervous system disorders.

• Avoid exercises that involve stoppage of breath, with heart or lung problems, insomnia, poor memory, or concentration. Avoid certain inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Use cautiously with mental disorders as some techniques may cause an altered state of consciousness. Kundalini Yoga is considered safe and beneficial for use during pregnancy and lactation when practiced under the guidance of expert instruction. Lamaze techniques are based on yogic breathing. If started early in the pregnancy, it may be possible to master the ability of breathing to reduce stress and aid in labor. Teachers of yoga are generally not medically qualified and should not be regarded as sources of medical advice for management of clinical conditions.

• Lavender: Small studies of patients with severe dementia in nursing homes have found that lavender aromatherapy or pinning a cloth to the patient with lavender oil on it may help to decrease agitated behavior. Although lavender is a sedative-type aroma, use during recess periods in a work environment after accumulation of fatigue seemed to prevent deterioration of cognitive performance in subsequent work sessions. Small trials investigating the effects of lavender aromatherapy on agitation and behavior in patients with Alzheimer's dementia report conflicting results. Further well-designed studies are needed before a conclusion can be drawn.

• Avoid if allergic or hypersensitive to lavender. Avoid with history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.

• L-Carnitine: Early evidence suggests the effectiveness of L-carnitine and/or acetyl-L-carnitine for Alzheimer's disease. However, the evidence is mixed. Most of the studies related to dementia suffer from various weaknesses. Although preliminary evidence is promising, there is insufficient available evidence to recommend for or against this use. There are also a limited number of studies relevant to the use of carnitine for memory. Carnitine does not appear to have any effect on memory. Additional study is needed before a conclusion can be made.

• Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.

• Lemon balm: Limited data is available supporting the use of lemon balm as a treatment for agitation in dementia patients. Additional study is necessary before a conclusion can be drawn. Clinical data suggest that the use of standardized lemon balm (Melissa officinalis) extract has some effect on particular self-reported measures of mood and cognitive performance. More rigorous studies need to be conducted using patient-relevant outcomes to better assess the validity of these results as they apply to patient care.

• Based on available research, lemon balm taken by mouth has been reported to be relatively well tolerated when taken for up to eight weeks. Evidence for topical administration of lemon balm cream suggested minimal side effects for up to 10 days of application. Avoid if allergic or hypersensitive to lemon balm. Avoid with Grave's disease or thyroid hormone replacement therapy. Use cautiously in glaucoma because lemon balm may increase eye pressure. Use caution when operating heavy machinery. Lemon balm preparations may contain trace amounts of lead. Avoid if pregnant or breastfeeding.

• Macrobiotic diet: Macrobiotics is a predominantly vegetarian, whole-foods diet that emphasizes whole grains (especially brown rice), vegetables, fruits, legumes, and seaweeds. The evidence is mixed as to whether or not a macrobiotic diet helps, hinders, or has no effect on cognitive function in children.

• There is a risk of nutrition deficiencies with use of an exclusive macrobiotic diet; however, this can be avoided with appropriate menu planning. Use cautiously with cancer or other medical conditions without expert planning or supplementation. Macrobiotic diets are not recommended in children or adolescents without professional guidance or appropriate supplementation, and are also not recommended in pregnant or lactating women due to potential deficiencies, unless properly supplemented.

• Massage: Massage with or without essential oils has been used in patients with dementia in chronic care facilities to assess effects on behavior. There is compelling early evidence that aromatherapy with essential oils may reduce agitation in patients with dementia, although the effects of massage itself are not clear.

• Avoid with bleeding disorders, low platelet counts, or if on blood-thinning medications (such as heparin or warfarin/Coumadin®). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with a history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

• Meditation: Some forms of meditation may have positive effects on cognitive function. However, there is not enough clear evidence that any specific form of meditation can support or enhance cognitive function.

• Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

• Melatonin: Melatonin is a naturally occurring hormone that helps regulate sleep/wake cycles (circadian rhythm). There is limited study of melatonin for improving sleep disorders associated with Alzheimer's disease (including nighttime agitation or poor sleep quality in patients with dementia). It has been reported that natural melatonin levels are altered in people with Alzheimer's disease, although it remains unclear if supplementation with melatonin is beneficial. Further research is needed in this area before a firm conclusion can be reached.

• Based on available studies and clinical use, melatonin is generally regarded as safe in recommended doses for short-term use. Melatonin should be avoided in patients using warfarin, and possibly in patients taking other blood-thinning medications or with clotting disorders. Melatonin may cause drops in blood pressure. Caution is advised in patients with high cholesterol levels, atherosclerosis, those at risk for cardiovascular disease, diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Mild gastrointestinal distress commonly occurs, including nausea, vomiting, or cramping. Patients with glaucoma taking melatonin should be monitored by a healthcare professional. Melatonin should be avoided in women who are pregnant or attempting to become pregnant; high levels of melatonin during pregnancy may increase the risk of developmental disorders. In men, decreased sperm motility and decreased sperm count are reported with use of melatonin.

• Music therapy: Music therapy may reduce feelings of agitation and anxiety in patients with moderately severe and severe Alzheimer's disease. More research is needed to confirm these results.

• Music therapy is generally known to be safe.

• Niacin: Dementia can be caused by severe niacin insufficiency, but it is unclear whether variation in intake of niacin in the usual diet is linked to Alzheimer's disease (AD) or cognitive decline. Further research is needed before a conclusion can be drawn.

• Avoid niacin/vitamin B3 if allergic to niacin or niacinamide. Avoid with a history of liver disease or dysfunction, irregular heartbeats (arrhythmia), heart disease, blood clotting, bleeding disorders, asthma, anxiety, panic attacks, thyroid disorders, stomach ulcers, gout or diabetes. Avoid if pregnant or breastfeeding.

• Omega-3 fatty acids, fish oil, alpha-linolenic acid: Well-designed clinical trials are needed before omega-3 fatty acids can be recommended for the prevention of cognitive impairment or dementia.

• Avoid if allergic or hypersensitive to fish, omega-3 fatty acid products that come from fish, nuts, or linolenic acid or omega-3 fatty acid products that come from nuts. Avoid during active bleeding. Use cautiously with bleeding disorders, diabetes, low blood pressure or drugs, herbs or supplements that treat any such conditions. Use cautiously before surgery. The Environmental Protection Agency (EPA) recommends that intake be limited in pregnant/nursing women to a single 6-ounce meal per week, and in young children to less than 2 ounces per week. For farm-raised, imported, or marine fish, the U.S. Food and Drug Administration recommends that pregnant/nursing women and young children avoid eating types with higher levels of methylmercury and less than 12 ounces per week of other fish types. Women who might become pregnant are advised to eat 7 ounces or less per week of fish with higher levels of methylmercury or up to 14 ounces per week of fish types with about 0.5 parts per million (such as marlin, orange roughy, red snapper, or fresh tuna).

• Pet therapy: In the institutionalized elderly, there is evidence that pet therapy may reduce depression and blood pressure, reduce irritability, reduce agitation, and increase social interaction. In Alzheimer's dementia, there is evidence that the presence of a companion animal may increase social behaviors such as smiles, laughs, looks, leans, touches, verbalizations, or name-calling.

• Avoid if allergic to animal dander. Use only animals that have had veterinary screening, particularly in situations involving young children, frail elderly, or patients with immune disorders or medical conditions making them vulnerable to infection. Do not provide unsupervised use of animals with the severely mentally ill and very young children. Avoid with a fear of animals or traumatic history with animals.

• Physical therapy: Various physical therapy approaches, including activity-specific exercise programs, resistance training, and other physiotherapy or motor interventions have been studied for elderly patients with cognitive impairment, Alzheimer's disease, or related dementia. Physical therapy has also been studied for brain injury, nerve disorders, neurological disorders, and geriatric rehabilitation. Healthcare providers may suggest home-based physical therapy or similar exercise programs for patients with cognitive impairment. Overall, results are mixed and more high quality research is needed in this area.

• Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported, although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy and although reports of major adverse effects are lacking in the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed healthcare provider before initiation.

• Policosanol: The effects of policosanol supplementation on reactivity and related brain activity have been examined. Although there is early compelling evidence, further research is necessary before a clear conclusion can be made.

• Avoid if allergic or hypersensitive to policosanol. Use cautiously if taking aspirin or blood pressure medications. Use cautiously with high blood pressure. Use cautiously if pregnant or breastfeeding.

• Polypodium leucotomos extract and anapsos: Extracts of the polypodium fern have been used for many health conditions. It is commonly found in South America and Europe. The South American species Polypodium leucotomos L. is also known as "calaguala." Extracts of this species are called "anapsos." Limited scientific information is available about the effectiveness of polypodium in the treatment of dementia and Alzheimer's disease.

• Avoid if allergic or hypersensitive to ferns from the family Polypodiaceae. Use cautiously with heart disease or with use of blood pressure drugs. Avoid operating any heavy machinery when taking polypodium. Avoid if pregnant or breastfeeding.

• Reiki: Early research suggests that Reiki therapy may improve behavioral and memory problems in patients with mild cognitive disorders or mild Alzheimer's disease. However, additional studies are needed to confirm these findings.

• Reiki is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Use cautiously with psychiatric illnesses.

• Rhodiola: Early human study suggests that rhodiola may benefit learning, memory, and mental performance. Well-designed studies are needed before a recommendation may be made.

• Avoid if allergic or sensitive to Rhodiola. Use cautiously in people with diabetes, cardiovascular disease, or neurological or psychiatric disorders. Rhodiola is not recommended for use during pregnancy or breastfeeding.

• Rhubarb: Preliminary study has investigated rhubarb along with other herbs in the treatment of age-associated memory impairment (AAMI). Studies of rhubarb alone are needed to discern rhubarb's effect on aging and memory.

• Avoid if allergic/hypersensitive to rhubarb, its constituents, or related plants from the Polygonaceae family. Avoid using rhubarb for more than two weeks because it may induce tolerance in the colon, melanosis coli, laxative dependence, pathological alterations to the colonic smooth muscles, and substantial loss of electrolytes. Avoid with atony, colitis, Crohn's disease, dehydration with electrolyte depletion, diarrhea, hemorrhoids, insufficient liver function, intestinal obstruction or ileus, irritable bowel syndrome, menstruation, pre-eclampsia, renal disorders, ulcerative colitis, and urinary problems. Avoid handling rhubarb leaves, as they may cause contact dermatitis. Avoid rhubarb in children under age 12 due to water depletion. Use cautiously with bleeding disorders, cardiac conditions, coagulation therapy, constipation, history of kidney stones, or thin or brittle bones. Use cautiously if taking anti-psychotic drugs or oral drugs, herbs or supplements (including calcium, iron, and zinc). Avoid if pregnant or breastfeeding.

• Riboflavin: Adequate nutrient supplementation with riboflavin (vitamin B2) may be required for the maintenance of adequate cognitive function. Treatment with B-vitamins including riboflavin has been reported to improve scores of depression and cognitive function in patients taking tricyclic antidepressants. This may be related to tricyclic-caused depletion of riboflavin levels.

• Avoid if allergic or hypersensitive to riboflavin. Since the amount of riboflavin a human can absorb is limited, riboflavin is generally considered safe. Riboflavin is generally regarded as safe during pregnancy and breastfeeding. The U.S. Recommended Daily Allowance (RDA) for riboflavin in pregnant women is higher than for non-pregnant women, and is 1.4 milligrams daily (1.6 milligrams for breastfeeding women).

• Sage: Sage has long been suggested as a possible therapy for memory and cognitive improvement. Several trials provide evidence for the use of sage for this indication. Early evidence also suggests that sage oil may be useful in the treatment of Alzheimer's disease. Additional study is needed to confirm these findings and determine the best dose.

• Avoid if allergic or hypersensitive to sage species, their constituents, or to members of the Lamiaceae (mint) family. Use cautiously with hypertension (high blood pressure). Use sage essential oil or tincture cautiously in patients with epilepsy. Avoid if pregnant or breastfeeding.

• Soy: It is unclear if soy isoflavone supplementation in postmenopausal women may improve cognitive function. Results from studies are mixed.

• Avoid if allergic to soy. Breathing problems and rash may occur in sensitive people. Soy, as a part of the regular diet, is traditionally considered to be safe during pregnancy and breastfeeding, but there is limited scientific data. The effects of high doses of soy or soy isoflavones in humans are not clear, and therefore are not recommended. There has been a case report of vitamin D deficiency rickets in an infant nursed with soybean milk (not specifically designed for infants). People who experience intestinal irritation (colitis) from cow's milk may experience intestinal damage or diarrhea from soy. It is not known if soy or soy isoflavones share the same side effects as estrogens, like increased risk of blood clots. The use of soy is often discouraged in patients with hormone-sensitive cancers, such as breast, ovarian, or uterine cancer. Other hormone-sensitive conditions such as endometriosis may also be worsened. Patients taking blood-thinning drugs like warfarin should check with a doctor and pharmacist before taking soy.

• TENS: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive technique in which a low-voltage electrical current is delivered through wires from a small power unit to electrodes located on the skin. TENS is often used to treat pain, as an alternative or addition to pain medications. Preliminary research suggests that TENS may be of benefit with some symptoms of Alzheimer's disease, including mood, memory, and cycles of daily rest and activity. Additional human study is necessary before a firm conclusion can be drawn.

• Avoid with implantable devices, like defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation, like neuropathy, and with seizure disorders. Avoid if pregnant or breastfeeding.

• Therapeutic touch: Studies suggest that therapeutic touch may reduce behavioral symptoms of dementia such as searching and wandering, tapping and banging, anxiety, agitation, and vocalization in people with Alzheimer's dementia. Well-designed studies are needed before a firm conclusion can be drawn.

• Therapeutic touch is believed to be safe for most people. Therapeutic touch should not be used for potentially serious conditions in place of more proven therapies. Avoid with fever or inflammation, and on body areas with cancer.

• Thiamin: Because thiamin deficiency can result in a form of dementia (Wernicke-Korsakoff syndrome), its relationship to Alzheimer's disease and other forms of dementia has been investigated. Whether thiamin supplementation is of benefit in Alzheimer's disease remains controversial. Further evidence is necessary before a firm conclusion can be reached.

• Thiamin is generally considered to be safe and relatively nontoxic. Avoid if allergic or hypersensitive to thiamin. Rare hypersensitivity/allergic reactions have occurred with thiamin supplementation. Skin irritation, burning, or itching may rarely occur at injection sites. Large doses may cause drowsiness or muscle relaxation. Use cautiously if pregnant or breastfeeding.

• Traditional Chinese medicine: Traditional Chinese medicine (TCM) herbal combinations have been used for the treatment of dementia and reportedly improve cognitive function and activities of daily living. More studies of better design are needed before recommendations can be made.

• Acupuncture is generally considered safe. Avoid with valvular heart disease, infections, bleeding disorders or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, and neurologic disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics or with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.

• Turmeric: Curcumin has been shown to have antioxidant and anti-inflammatory properties and to reduce beta-amyloid and plaque burden in lab studies. However, there is currently not enough evidence to suggest the use of curcumin for cognitive function.

• Avoid if allergic or hypersensitive to turmeric, curcumin, yellow food colorings, or plants belonging to the Zingiberaceae (ginger) family. Use cautiously with a history of bleeding disorders, immune system deficiencies, liver disease, diabetes, hypoglycemia, or gallstones. Use cautiously with blood-thinners, such as warfarin (like Coumadin®), and blood sugar-altering medications. Avoid in medicinal amounts if pregnant or breastfeeding. Turmeric should be stopped prior to scheduled surgery.

• Vitamin B12: Some patients diagnosed with Alzheimer's disease have been found to have abnormally low vitamin B12 (cyanocobalamin) levels in their blood. However, vitamin B12 deficiency itself often causes disorientation and confusion and thus mimics some of the prominent symptoms of Alzheimer's disease. Well-designed clinical trials are needed.

• Avoid vitamin B12 supplements if allergic or hypersensitive to cobalamin, cobalt, or any other vitamin B12 product ingredients. Avoid with coronary stents (mesh tube that holds clogged arteries open) and Leber's disease. Use cautiously if undergoing angioplasty and with anemia. Vitamin B12 is generally considered safe when taken in amounts that are not higher than the Recommended Dietary Allowance (RDA). There is not enough scientific data available about the safety of larger amounts of vitamin B12 during pregnancy and/or breastfeeding.

• Vitamin E: Vitamin E has been proposed and evaluated for the prevention or slowing of dementia (including Alzheimer's type), based on antioxidant properties and findings of low vitamin E levels in some individuals with dementia. There is some evidence that all-rac-alpha-tocopherol (synthetic vitamin E) is similar in effects to a commonly used drug for AD, selegiline (Eldepryl®), in slowing cognitive function decline in patients with moderately severe Alzheimer's disease. No additive effect was observed when used in combination with selegiline. Retrospective data suggests that long-term combination therapy with donepezil (Aricept®) may help slow cognitive decline in patients with Alzheimer's disease. Overall, the evidence remains inconclusive in this area. Other research suggests that vitamin E from dietary sources or supplements does not affect the risk of developing Alzheimer's disease or vascular dementia.

• Vitamin E may cause bleeding, especially in sensitive individuals such as those taking medications for bleeding disorders (including warfarin or Coumadin®). Avoid if allergic or hypersensitive to vitamin E. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders or if taking blood thinners. Avoid use above the recommended daily level in pregnant and breastfeeding women.

• Yoga: There is limited human study of yoga for memory improvement. Better studies are needed before a recommendation can be made.

• Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

• Fair negative scientific evidence:

• Beta-carotene: Intake of dietary or supplemental beta-carotene has not been shown to have an effect on Alzheimer's disease risk.

• Bitter orange: Bitter orange has been used in aromatherapy, although it does not appear to reduce combative, resistive behaviors in individuals with dementia. Currently, evidence supporting the use of bitter orange for dementia and behavioral challenges is lacking.

• DHEA: Studies of the effects of dehydroepiandrosterone (DHEA) on memory have produced complex and inconsistent results. Additional study is warranted in this area.

• Gingko: The results of limited available study investigating the effect of Ginkgo biloba on post-prandial mental performance are unclear. Ginkgo may benefit some but not all endpoints. Further clinical trials are required before a conclusion can be made.

• Psychotherapy: Based on limited available study, brief psychotherapeutic approaches may not help improve cognitive function and overall well-being in Alzheimer's disease patients. More studies are needed in this area.

Prevention

• Healthy aging: Some of the most recent research indicates that taking steps to improve cardiovascular (heart) health, such as losing weight, exercising, and controlling hypertension (high blood pressure) and high cholesterol, may also help prevent Alzheimer's disease (AD).

• Nonsteroidal anti-inflammatory drugs (NSAIDs): Several clinical studies have reported that the NSAIDs ibuprofen (Advil® or Motrin®), naproxen sodium (Aleve®), and indomethacin (Indocin®, a prescription drug) may reduce the risk of developing Alzheimer's. This may be because inflammation appears to play a role in Alzheimer's. Because NSAIDs can cause stomach and intestinal bleeding and kidney problems, clinical trials need to be completed before it's clear whether individuals should take NSAIDs solely to prevent Alzheimer's.

• Statins: Statin drugs are used to lower cholesterol levels. They include atorvastatin (Lipitor®) and simvastatin (Zocor®). Recent studies have reported that "statin" drugs may reduce the risk of AD. More studies are being done to determine exactly what role, if any, statins may have in Alzheimer's prevention. Researchers believe that statins help improve blood flow to the brain by decreasing particles in the blood such as cholesterol and triglycerides.

• Selective estrogen receptor molecules (SERMs): A drug called a selective estrogen receptor molecule (SERM, including raloxifene or Evista®) is used to protect against the bone loss associated with osteoporosis. It also appears to lower the risk of developing mild cognitive impairment, a memory disorder that often precedes Alzheimer's. The mechanism is not known.

• Mental fitness: Maintaining mental fitness may delay onset of dementia. Some researchers believe that lifelong mental exercise and learning may promote the growth of additional synapses, the connections between neurons, and delay the onset of dementia. Other researchers argue that advanced education gives a person more experience with the types of memory and thinking tests used to measure dementia. Doing crossword puzzles, reading books, and increasing social activities are recommended by healthcare providers.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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