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.
Strong scientific evidence
Ginkgo: Ginkgo biloba has been used medicinally for thousands of years. The scientific literature overall does suggest that ginkgo benefits people with early stage Alzheimer's disease and multi-infarct dementia, and may be as helpful as acetylcholinesterase inhibitor drugs such as donepezil (Aricept®). Well-designed research comparing ginkgo to prescription drug therapies is needed. Ginkgo may cause bleeding, especially in sensitive individuals such as those taking medications for bleeding disorders (including warfarin or Coumadin®).
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) can effectively reduce agitation in people with severe 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.
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.
Ginseng: Several clinical studies report that ginseng (Panax ginseng) can modestly improve thinking or learning. 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 in this area, better research is necessary before a strong recommendation can be made.
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.
Unclear or conflicting scientific evidence
Acupuncture: Acupuncture has been reported to help improve memory and cognitive performance in the elderly. However, there is insufficient available evidence for the use of acupuncture in cognitive and communication disorders. More research is necessary.
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. 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.
Boron: Boron is a mineral that is essential for health. 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 memory.
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.
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 is needed.
Cranberry: Preliminary study results show that cranberry juice may increase overall ability to remember. 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 are recommended by healthcare providers.
Melatonin: Melatonin is a naturally occurring hormone that helps regulate the 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.
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.
Folic acid: 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 might be related to Alzheimer's disease. Well-designed clinical trials of folate supplementation are needed before a conclusion can be drawn.
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 performance. Further research is needed before a firm conclusion can be drawn.
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 functioning. More studies are needed to determine if these techniques can reliably be used to improve cognitive performance and possibly aid in treating cognitive and nervous system disorders.
Lemon balm: Clinical data suggest that the use of standardized lemon balm (Melissa officinalis) extract has some effect on particular self-reported measures of mood and cognition. 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.
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.
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 disease, 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.
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.
Vitamin B1: Because thiamin (vitamin B1) deficiency can result in a form of dementia (Wernicke-Korsakoff syndrome, a neurological condition), 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.
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.
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®).
Other supplements that have unclear or conflicting scientific evidence include black and green tea (Camellia sinensis), iodine, iron, omega-3 fatty acids (fish oils), policosanol (sugar cane wax), soy (Glycine max), and yoga.
Historical or theoretical uses lacking sufficient evidence
Integrative therapies used in Alzheimer's disease treatment that have historical or theoretical uses but lack sufficient clinical evidence include: 5-HTP (5-hydroxytryptophan), ashwagandha (Withania somnifera), astaxanthin, cat's claw (Uncaria tomentosa), cordyceps (Cordyceps sinensis), garlic (Allium sativum), gotu kola (Centella asiatica), hypnosis, muira puama (Ptychopetalum olacoides), rosemary (Rosmarinus officinalis), taurine, turmeric (Curcuma longa), and zinc.
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.