Tài liệu khoa học về chữa bệnh Alzheimer bằng cây cỏ (Nguon Natural medicines comprehensive data base) Copy and paste phần nào bạn muốn chuyển ngữ sang tiếng Việt với link chuyển ngữ sau đây https://www.bing.com/translator/?ref=TThis&IG=0DCE10061DD747F59E6D5B0044BB4BBD&IID=SERP.5398&&text=&from=&to=en Alzheimer's disease is named after the physician who first described it, Alois Alzheimer. In 1907, Dr. Alzheimer, Chief of Psychiatry at the Kaiser Wilhelm University in Breslau, Poland, performed an autopsy on a 55-year-old woman who had progressive dementia before death. He described abnormalities in her brain that are now considered the hallmarks of this disease, amyloid plaques and neurofibrillary tangles.93029 Alzheimer's disease is the most common form of dementia in elderly people. Alzheimer's disease affects more than 5 million Americans and is the sixth leading cause of death in the United States.93029,93030 Unlike mild cognitive impairment, the loss of cognitive function associated with Alzheimer's disease is severe enough to affect daily activities and a patient's ability to function independently. The severity of Alzheimer's disease can range from mild to severe, with the most severe cases requiring full-time help to complete basic daily activities.93029 Amyloid plaques and neurofibrillary tangles are considered to be the hallmarks of Alzheimer's disease. Amyloid plaques are insoluble deposits of beta-amyloid protein intermixed with neural debris. In Alzheimer's disease, the amyloid plaques first develop in areas of the brain that control memory and other cognitive functions. It's not clear whether amyloid plaques CAUSE Alzheimer's, or whether they are a by-product of the disease process.93033 Neurofibrillary tangles are found inside neurons. They consist of protein strands that are abnormally twisted. These "tangles" disrupt the intracellular transport system and damage the neuron's ability to communicate with other neurons. This leads to large-scale neuronal death, which is another defining feature of Alzheimer's disease.93033,93034 Since patients with Alzheimer's disease can also present with another form of dementia, it's important to understand other types of dementia. Lewy body dementia is characterized by progressive cognitive decline and the development of parkinsonian motor symptoms. These symptoms result from the build-up of Lewy bodies inside the nuclei of neurons in parts of the brain that control aspects of memory and movement. Lewy bodies are formed by the accumulation of bits of alpha-synuclein protein. In addition to patients with Lewy body dementia, Lewy bodies are also sometimes found in patients with Alzheimer's disease or Parkinson's disease. There is no cure for Lewy body dementia. However, medications may be used to control cognitive and motor symptom decline, and some of these medications are similar to those used for Alzheimer's disease.93043 Vascular dementia is a type of dementia that results from damage to vessels supplying blood to the brain. This damage can be caused by stroke or other blood vessel injuries. In patients with this type of dementia, symptoms begin suddenly and can eventually progress or subside. Some evidence suggests that most dementia patients over the age of 80 years old have both Alzheimer's disease and this type of dementia.93044 Diseases Associated with Dementia Disease Defining features of the disease Cause of disease Alzheimer's disease Progressive cognitive decline Large-scale neuronal death Build-up of amyloid plaques and neurofibrillary tangles Lewy body dementia Progressive cognitive decline Parkinsonian motor symptoms Build-up of Lewy bodies inside brain neuron nuclei Vascular dementia Sudden symptom onset Symptoms either progress or subside Common in Alzheimer's patients >80 years-old Damage to vessels supplying blood to the brain

Treatment of Alzheimer’s Disease There are no interventions that can cure Alzheimer's disease. Instead, interventions for this condition aim to help patients maintain cognitive function and slow symptom progression. Because there are many theories about what exactly causes the cognitive defects associated with Alzheimer's disease, different treatments focus on different targets. Which natural medicines are your patients taking? Start a conversation on Natural Medicines Colleagues Interact. Commonly Used Conventional and Natural Medicines for Alzheimer's Disease* Cholinergic Agents Conventional Medicines Acetylcholinesterase Inhibitors Donepezil (Aricept) Galantamine (Razadyne) Memantine / Donepezil (Namzaric) Rivastigmine (Exelon) Cholinergic Receptor Agonists Bethanechol (Urecholine) Natural Medicines Acetylcholinesterase Inhibitors Butea superba Evodia Huperzine A Ginkgo leaf (Ginkgo biloba) Acetylcholine Precursors Acetyl-L-carnitine Alpha-GPC Choline DMAE (dimethylaminoethanol) Lecithin Phosphatidylcholine Phosphatidylserine NMDA Inhibitors Conventional Medicines Memantine (Namenda) Memantine / Donepezil (Namzaric) Natural Medicines Huperzine A Antioxidants Conventional Medicines Selegiline (Eldepryl) Natural Medicines Beta-carotene Ginkgo leaf (Ginkgo biloba) Vitamin C Vitamin E Anti-inflammatory Agents Conventional Medicines NSAIDs Aspirin Natural Medicines Evening primrose oil (Oenothera biennis) Fish oil Gamma linolenic acid Ginkgo leaf (Ginkgo biloba) Hormonal Agents Dehydroepiandrosterone (DHEA) Miscellaneous Cat's claw (Uncaria tomentosa) Caprylic acid Coconut oil (Cocos nucifera) Folic acid Gotu kola (Centella asiatica) Homotaurine Medium chain triglycerides (MCTs) Niacin Pyridoxine Turmeric Vinpocetine Vitamin B12 *Note: Many natural medicines are tried for Alzheimer's disease. Inclusion in this list does not necessarily suggest effectiveness.

The Role of Acetylcholine Acetylcholine is a neurotransmitter produced by the enzyme choline acetyltransferase. Acetylcholine plays a role in both the peripheral and central nervous system. In the brain, acetylcholine influences certain physiological processes, including attention, learning, memory, and sleep. Since acetylcholine plays a role in cognitive processes, its deficit is considered to be a factor in Alzheimer's disease and other forms of dementia.93051 In patients with Alzheimer's disease, the activity of choline acetyltransferase is significantly reduced. Consequently, patients with Alzheimer's disease show decreased levels of acetylcholine in the brain.93036 Therefore, most pharmacologic approaches target acetylcholine. Conventional and natural medicines that target acetylcholine do so in one of three ways. Some of these medicines inhibit the breakdown of endogenous acetylcholine. Others supply acetylcholine precursors to boost acetylcholine production. Finally, some medicines "mimic" acetylcholine action at postsynaptic cholinergic receptors. Learn more about conventional treatments for Alzheimer's disease: Cholinesterase inhibitors or memantine are beneficial for Alzheimer's disease. Targeting acetylcholine: Inhibiting the breakdown of endogenous acetylcholine. Acetylcholinesterase inhibitor (AChEI) drugs are the first-line treatments for Alzheimer's. These include donepezil, rivastigmine, and galantamine. These drugs reversibly inhibit the acetylcholinesterase (AChE) enzyme, which breaks down acetylcholine. By inhibiting the breakdown of acetylcholine, they INCREASE acetylcholine levels.44,15640,15641 AChEI drugs are started early on in patients with mild to moderate Alzheimer's disease and are often used for years.15641 They all modestly improve cognitive function and seem to delay the need for nursing home placement. However, they can be difficult to tolerate due to significant side effects such as nausea, vomiting, and diarrhea.44 Some natural medicines also inhibit AChE activity. Before a patient is started on a conventional AChEI drug, do you ask about supplements the patient may already be using? Do you know of any natural medicine(s) that may need to be discontinued prior to starting an AChEI drug? Huperzine A is an alkaloid isolated from Huperzia serrata (Chinese club moss).3082 It is now on store shelves in brand-name products with enticing names such as Alpha Brain, Extension IQ, Memorall, and Memory Mate. Huperzine A reversibly inhibits AChE for up to three hours. It produces a variable degree of acetylcholine elevation in different areas of the brain, with maximal effects in the frontal and parietal cortex.3141 It seems to be more specific for AChE and have a longer duration of action than prescription AChE inhibitors such as donepezil.3131,3132 Huperzine A might also have another beneficial effect for Alzheimer's patients. It seems to have N-methyl-D-aspartate (NMDA) receptor antagonist properties. Theoretically it might protect neurons against toxic levels of glutamate.3131 Patients with Alzheimer's disease seem to have higher central nervous system (CNS) levels of glutamate. The excess glutamate binds to NMDA receptors and causes postsynaptic Ca2+ influx and subsequent neuronal degeneration. By blocking NMDA receptors, huperzine A may inhibit glutamate-induced neurotoxicity. This is similar to the Alzheimer's drug memantine (Namenda).3129 Even though huperzine A blocks NMDA receptors like memantine, it might not be as beneficial as memantine. Huperzine A has low affinity for NMDA receptors.3137 No clinical research has evaluated huperzine A in patients with moderate to severe Alzheimer's disease. There is some clinical evidence that taking huperzine A can improve memory, cognitive function, and behavioral function in patients with Alzheimer's disease.3138,3140,3171,4624,55613,55703,55704,55705,55706,55709 However, an analysis of clinical trials shows that huperzine A improves cognitive function in Alzheimer's patients when using some scales, but not others55674 More evidence from higher-quality trials, as well as the long-term safety data is needed. If a patient tries huperzine A, caution them about potential adverse effects. Huperzine A will likely cause similar side effects as conventional AChEI drugs. These effects include nausea, vomiting, diarrhea, cramps, sweating, blurred vision, muscle twitching, increased saliva, and increased urination.3140,3172 High doses can cause bronchospasm, seizures, bradycardia, and arrhythmias. In general, these drugs and huperzine A should be used with caution in patients with asthma, chronic obstructive pulmonary disease (COPD), cardiovascular disease, intestinal or urogenital tract obstruction, peptic ulcer disease, or seizures. Practice Pearl Tell patients who are already taking a conventional AChEI drug not to also take huperzine A. Combining huperzine A with a conventional AChEI drug might increase the chance of toxicity.3131 Ginkgo biloba is one of the most popular supplements used to treat symptoms of Alzheimer's disease and dementia. Ginkgo can inhibit AChE activity.93037 In addition to inhibiting AChE activity, ginkgo leaf extract might be helpful for Alzheimer's disease due to inhibition of toxicity and cell death induced by beta-amyloid peptides.6494 It might also increase acetylcholine levels in portions of the brain associated with cognitive function.93052 However, these latter effects have not yet been demonstrated in humans. Some evidence shows that taking ginkgo leaf extract modestly improves symptoms of Alzheimer's disease and other dementias. Studies lasting from three months to one year show that ginkgo leaf extract can stabilize or improve some measures of cognitive function and social functioning in patients with Alzheimer's disease.1514,1515,2666,6224,6225,6490,11981,17191,17717,87823,87855,87866,89703,89713 Higher daily doses of ginkgo (240 mg) seem to have a greater effect on cognitive function than lower daily doses (120 mg).87855,87866 However, due to poor study quality, there are concerns that positive results observed in some of the early ginkgo studies may not be reliable. Although most clinical trials show benefit, there are some conflicting findings suggesting inconsistent and unpredictable effects.5720,16636,16637,87726,87848,88006,89710 Most clinical studies have not compared ginkgo leaf extract to conventional AChEI drugs. Two preliminary comparative studies show that taking a specific ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 160 to 240 mg daily for 22 to 24 weeks is comparable to donepezil 5 mg daily for mild to moderate Alzheimer's dementia.14499,87826 However, indirect comparisons suggest that ginkgo leaf extract might be less effective than some AChEI drugs, including donepezil.6224,6490,11981,89710 Ginkgo has also been evaluated for the prevention of Alzheimer's disease or dementia. Epidemiologic research shows that taking ginkgo extract is not associated with a decreased risk of developing Alzheimer's disease or dementia in elderly patients with memory impairment. However, it might be associated with a decreased risk of overall mortality.14812 Also, three large-scale clinical trials show that taking ginkgo extract 120 mg twice daily does not reduce the risk of developing all-cause dementia or Alzheimer's disease in elderly patients with normal cognitive function or in those with mild cognitive impairment.16634,87848,87904 In addition, evidence from a larger analysis suggests that, although taking ginkgo extract may improve cognition in patients with Alzheimer's disease, it does not prevent disease progression.89713 Overall, taking ginkgo extract does not seem to prevent or slow the progression of Alzheimer's disease. However, taking ginkgo extract might improve cognitive function in patients with Alzheimer's disease. If patients with mild to moderate Alzheimer's disease are considering ginkgo, suggest that they use EGb 761 or LI 1370, as these two products have been studied the most extensively. However, let the patients know that a conventional AChEI might work better. Practice Pearl Most of the clinical studies on the effectiveness of ginkgo leaf for Alzheimer's disease and other types of dementia have used the standardized extracts EGb 761 (Dr. Willmar Schwabe Pharmaceuticals and Ipsen) and LI 1370 (Lichtwer Pharma). These two extracts are similar and prepared to contain approximately 24% to 25% flavone glycosides and 6% terpene lactones. Other products with similar ingredients include Ginkgold (Nature's Way) and Tebonin Konzent (Dr. Willmar Schwabe Pharmaceuticals). There are a number of other dietary supplements that seem to work like AChEI drugs, but there isn't enough reliable information to know if these supplements are safe and effective. For instance, there is some interest in evodia for Alzheimer's disease and other dementias. Evodia extract has shown AChE inhibitory effects in cell culture studies. This effect appears to be due to the constituent dehydroevodiamine. Also, in an animal model, evodia extract appears to decrease experimentally induced memory impairment.15250 However, evodia has not been evaluated in clinical research, and it's too soon to know if evodia is safe. Therefore, it's too soon to recommend. There is also interest in using Butea superba for Alzheimer's disease. Butea superba is a vine native to India, Thailand, China, and Vietnam. It is most commonly used as an aphrodisiac or to treat erectile dysfunction.14920 However, some preliminary research suggests that Butea superba can inhibit AChE by about 55% in cell cultures.14919 Theoretically, this might be beneficial in dementia patients. However, Butea superba has not been evaluated in patients with Alzheimer's disease, and it's too soon to know if it is safe. Therefore, it's too soon to recommend. Have any of your patients tried other natural medicines they heard might work like AChEI drugs? Targeting acetylcholine: Supplying acetylcholine precursors to increase acetylcholine production. There are no conventional drugs that are used as acetylcholine precursors. However, lots of natural medicines take this approach. Lecithin is a phospholipid that is of interest for treating Alzheimer's disease or other dementias due to its potential for increasing acetylcholine levels.5156 Lecithin can increase serum choline, which is a precursor to acetylcholine.14822,14836,14838 As a source of choline, there was hope that lecithin could increase acetylcholine and help alleviate symptoms of Alzheimer's disease. However, clinical research shows that taking lecithin 1.2 to 45 grams daily alone or in combination with tacrine (Cognex, discontinued) or ergoloid mesylates does not significantly improve cognitive function in patients with Alzheimer's disease.5149,5150,5151,5152,14817,14823,14826,14837,14838,15703,19208 Taking lecithin also does not seem to affect the progression of Alzheimer's dementia when taken for up to six months.14825 Lecithin is made up of several phosphatidyl esters, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Some of these derivatives of lecithin have also been evaluated for Alzheimer's disease. Clinical research shows that taking phosphatidylserine orally 100 mg three times daily can increase cognitive function, global improvement rating scales, and improve behavioral rating scales over six to 12 weeks of treatment.2255,2437,2438,2439,7114,7118 Phosphatidylserine seems to be most effective in patients with less severe symptoms.2437,2439 However, phosphatidylserine might lose its effectiveness with extended use. After 16 weeks of treatment, progression of Alzheimer's disease seems to overcome any benefit of phosphatidylserine.2255 Phosphatidylcholine is another phosphatidyl ester of lecithin that has been considered for treating Alzheimer's disease. Phosphatidylcholine is the largest reservoir of choline in the body.5228 Since phosphatidylcholine might increase acetylcholine, there is interest in using it for improving memory and for conditions such as Alzheimer's disease. While some preliminary research shows that a single dose of phosphatidylcholine 25 grams can improve some measures of memory in healthy college students,5228 it has not be evaluated in patients with Alzheimer's disease. Alpha-GPC is a breakdown product of phosphatidylcholine. Like phosphatidylcholine, it is thought to work for Alzheimer's disease by increasing the production of acetylcholine. It might also improve neuronal functioning by improving neuronal membrane fluidity.12101 Preliminary clinical research suggests that taking alpha-GPC 1,200 mg/day significantly improves cognitive function in Alzheimer's patients after three and six months of treatment.12176 However, it's too soon to know if alpha-GPC is effective when used long-term. More research is needed before alpha-GPC can be recommended. Dimethylaminoethanol (DMAE, deanol) is a precursor to choline and therefore might increase acetylcholine levels. It's naturally found in seafood products such as sardines. However, clinical research shows that taking DMAE supplements doesn't improve symptoms of Alzheimer's.1680,1681 Tell patients not to count on DMAE supplements. In addition to evaluating choline precursors for treating Alzheimer's disease, some research has evaluated choline itself. Choline is readily available in the typical diet. It is found in foods such as liver, muscle meats, fish, nuts, beans, peas, eggs, wheat germ, spinach, and others.5139 However, oral choline does not appear to increase acetylcholine in the brain, and clinical trials show that taking choline supplements, alone or in combination with lecithin, does not reduce symptoms of Alzheimer's disease.5170,5175,42309 Targeting acetylcholine: Supplying agents that "mimic" acetylcholine action at the postsynaptic cholinergic receptors. This approach is promising in theory, but most drugs are disappointing in practice. Postsynaptic cholinergic receptor agonists, such as bethanechol (Urecholine), cause significant cholinergic side effects or they require impractical intracranial administration.12276,12277,12278,12279 Some natural medicines also take this approach. Acetyl-L-carnitine is structurally related to acetylcholine and might act as an analog of acetylcholine in patients with Alzheimer's disease. People take acetyl-L-carnitine (sometimes found on store shelves as L-acetylcarnitine or LAC) or a precursor, the amino acid L-carnitine. L-carnitine will not cross the blood-brain barrier until it is converted to acetyl-L-carnitine. Once inside the central nervous system, acetyl-L-carnitine promotes acetylcholine release and increases choline acetyltransferase activity.44 Some studies show that acetyl-L-carnitine provides Alzheimer's patients some benefit in memory, behavioral performance, and a delayed progression of deterioration as measured by cognitive testing.42,1595,1598,1599,3600 However, other research shows that acetyl-L-carnitine does not slow the progression of cognitive decline.1594 The latest thinking is that acetyl-L-carnitine is more likely to show some benefit in patients less than 66 years of age with early onset and a fast rate of disease progression.1594,1595,1596,1597,1598,1599,9105,10391 If a patient wants to try it, suggest that they aim for a dose of 1,500 to 4,000 mg divided into two or three doses daily. Acetyl-L-carnitine is usually well-tolerated. However, explain that in some cases it can cause nausea, vomiting, and agitation. There are also reports of depression, mania, confusion, and aggression in Alzheimer's patients who take acetyl-L-carnitine.1594,1595,1596,1597,1598,1599,9105,10391 Practice Pearl Help patients keep the carnitine products straight. If they want to use one for Alzheimer's, guide them toward acetyl-L-carnitine. L-carnitine is a precursor of L-acetylcarnitine, but only a small portion of it is converted. There are also some products with DL-carnitine or D-carnitine. These deplete L-carnitine and lead to more side effects such as myasthenia syndrome and muscle wasting.

Oxidative Stress and Inflammation A number of natural supplements are promoted as "antioxidants" or "anti-inflammatories." Which ones might benefit patients with Alzheimer's disease? What are the potential adverse effects of these supplements? There is increasing evidence that free radical damage to brain phospholipids, carbohydrates, proteins, and DNA is involved in neuron death in Alzheimer's disease. Oxidative stress refers to the burden in the human body caused by the production of free radicals. There are oxidative stress by-products in the neurofibrillary tangles and amyloid plaques found in Alzheimer's. Beta-amyloid protein itself can be neurotoxic by inducing oxidative stress.12283 Inflammatory response markers are present in the brain in Alzheimer's disease.12284,12285 Overall, oxidative stress and the inflammatory cascade, working together, seem to be important in the pathogenesis of Alzheimer's disease. This suggests that therapeutic efforts aimed at both these mechanisms might be beneficial.12285,12286 A variety of antioxidants including vitamin C, vitamin E, and beta-carotene have been promoted for use in Alzheimer's disease. Plasma levels of vitamin C and beta-carotene seem to correlate with memory performance.12287 Also, some epidemiological research suggests that long-term use of vitamin C and vitamin E supplements, in combination and in higher doses than typically found in multivitamins, is associated with a reduced prevalence and incidence of Alzheimer's disease.11390 However, clinical research shows that consuming vitamin C from dietary sources, or taking vitamin C as a supplement, does not reduce the risk of developing Alzheimer's disease.4636,9824,10131,13165,83339 Similarly, intake of dietary or supplemental beta-carotene does not have any effect on Alzheimer's disease risk.10131,34597,34624 Vitamin E has also been evaluated for treating and/or preventing Alzheimer's disease, but results are conflicting. Observational and clinical research shows that supplemental vitamin E does not decrease the risk of developing Alzheimer's disease.4636,13060,13165 However, there has been some interesting work on how vitamin E might help slow its progression when used alone or in combination with prescription drugs. Here's a quick summary of the findings: Vitamin E (synthetic, all-rac-alpha-tocopherol) 2000 IU daily can delay the progression of disease from the moderate stage to the severe stage by about 6 months. That's about the same delay seen when patients receive selegiline 10 mg daily.4635 Vitamin E, taken alone or with selegiline, doesn't seem to improve cognition in Alzheimer's patients with poor baseline cognition, possibly because of the severity of their disease.4635 Social function and behavior also seem to improve when patients take BOTH vitamin E and selegiline. But taking just one or the other doesn't seem to help.4635 Taking vitamin E alone, or with selegiline, seems to reduce the need for supervision and improves the patient's ability to perform activities of daily living.4635 Taking vitamin E alone, selegiline alone, or vitamin E and selegiline together seems to delay admission to nursing home care compared to no treatment. Taking vitamin E alone causes the biggest delay (about 230 days); then comes selegiline (215 days), followed by the combination (145 days).4635 Long-term combination therapy with donepezil 5 mg and vitamin E 1000 IU/day also might help slow cognitive decline in patients with Alzheimer's disease.11472 Taking vitamin E 2000 IU/day along with memantine 20 mg daily does not slow the progression of mild to moderate Alzheimer's disease compared to memantine alone.19060 This evidence is encouraging for vitamin E. However, there now is also evidence that unhealthy people who take vitamin E in high doses have an increased risk of all-cause mortality.12212,13036,15305 This makes assessing the risk vs. benefit of using vitamin E for these patients a challenge. Evening primrose oil provides significant amounts of gamma linolenic acid (GLA) and linoleic acid. Supplementation with GLA improves the dihomogamma-linolenic acid (DGLA) to arachidonic acid ratio, and this seems to inhibit production of inflammatory metabolites, including leukotrienes.2039,6036 However, there is no evidence that evening primrose oil can reduce the symptoms of Alzheimer's disease. Fish oil is a popular supplement that has often been referred to as a "brain food." Consequently, there is interest in using fish oil to treat or prevent Alzheimer's disease or other dementias. Fish oil is thought to be beneficial for many conditions due to its anti-inflammatory effects. In patients with Alzheimer's disease, levels of certain proteins called specialized proresolving mediators (SPMs) appear to decrease over time. These proteins help resolve inflammation by downregulating pro-inflammatory signals and promoting tissue regeneration. Some clinical research suggests that intake of omega-3 fatty acids found in fish oil can prevent the decline in SPMs in patients with Alzheimer's disease.93041 In some population research, higher fish and fish oil intake has been linked to a decreased risk of developing Alzheimer's disease.15040,15041,65817 Other epidemiological research suggests that elderly people who eat fish at least once weekly have a lower risk of developing dementia than people who eat fish less often.65595 However, not all studies have shown positive results. Some epidemiological research suggests that there is no correlation between fish consumption and risk of dementia in elderly individuals.65962 The reason for the conflicting results it not entirely clear. However, some population research suggests that eating fish as part of the diet is associated with a reduced risk of Alzheimer's disease and dementia in only elderly individuals who are apolipoprotein E (ApoE) epsilon-4 carriers.65817 The epsilon-4 allele of ApoE is a strong genetic risk factor for Alzheimer's disease and has been associated with an increased prevalence of Alzheimer's disease as well as an early age of onset.93040 This suggests that eating fish as part of the diet may reduce the risk of Alzheimer's disease in high-risk patients. However, this needs to be confirmed by additional studies. Very little clinical research has evaluated the effect of fish oil supplements on symptoms or progression of Alzheimer's disease. In one study in patients with existing mild to moderate Alzheimer's disease, taking a specific fish oil supplement (EPAX 1050 TG, Pronova Biopharma ASA) providing the omega-3 fatty acids docosahexaenoic acid (DHA) 1.7 grams and eicosapentaenoic acid (EPA) 0.6 grams daily for six months did not significantly delay cognitive decline. However, there is some evidence that taking this fish oil supplement might slow cognitive decline in a subgroup of patients with very mild cognitive dysfunction at baseline.15024

Beta-Amyloid Protein Beta-amyloid protein is thought to lead to the death of neurons, a major hallmark of Alzheimer's disease. Aging seems to make the brain more vulnerable to this effect.1594,4844 Some investigators are trying to identify agents that can block the formation or deposition of beta-amyloid protein. The theory is that blocking beta-amyloid could prevent Alzheimer's. Cat's claw is one prospect. Some preliminary data show that a specific cat's claw extract called PTI-00703 might prevent formation and deposition of beta-amyloid plaques like those found in Alzheimer's disease.93038 PTI-00703 is found in supplements like CognoBlend Advanced Formula by Unicity International. However, so far the only research has been done in animals. Don't recommend it until there are more reliable data. Gotu kola is the common name for Centella asiatica, a plant grown in India and southern Africa. Interest in gotu kola as an anti-Alzheimer's agent was renewed when a Korean report identified three asiaticoside derivatives as having neuroprotective effects. In cell culture research, these derivatives - asiatic acid, asiaticoside 6, and SM2 - are able to block cell death induced by beta-amyloid.1889 However, there is still no evidence that gotu kola helps patients with Alzheimer's disease. Until more is known, don't recommend gotu kola for patients with Alzheimer's disease or other types of dementia. Homotaurine is an amino acid which is not involved in protein synthesis. Homotaurine is used in supplements like ViviMind by OVOS Natural Health. There is interest in using homotaurine for treatment of Alzheimer's disease because of its effect on amyloid protein. Amyloid proteins can build up to form amyloid plaques in the brain. When amyloid precursor protein is cleaved at a particular site, it produces beta-amyloid, the main component of amyloid plaques.12295,17061,17065 The amyloid-beta peptides vary in length, but the most common forms contain 40 or 42 amino acids (amyloid-beta40 and amyloid-beta42). Amyloid-beta42 is the more hydrophobic form, and is more likely to aggregate into oligomers, meaning small assemblies or aggregates, and insoluble amyloid fibrils, which are neurotoxic precursors to plaque formation.17061,17062,17065 Fibril formation involves polymerization and a change in amyloid-beta conformation from random coils to beta-sheets, which is promoted by sulfated glycosaminoglycans (GAGs).17061,17062,17065 These GAGs also protect the formed fibrillar proteins from proteolysis.17061 Homotaurine binds to soluble amyloid-beta peptides, interfering with the binding of GAGs. This prevents amyloid-beta peptides from forming into insoluble fibers called amyloid-beta fibrils. By blocking the formation of amyloid-beta fibers, homotaurine prevents the formation of amyloid plaques.17061,17062,17064,17065 This mechanism of action suggests that homotaurine is most likely to slow progression of Alzheimer's disease, and is more likely to be effective in early disease, before large amounts of amyloid plaque have been formed.17062,17064 Cell culture and animal studies have demonstrated that homotaurine can prevent amyloid-beta peptides from forming into amyloid-beta fibers. Homotaurine can also decrease cell death induced by amyloid-beta42, the amyloid-beta peptide that tends to aggregate into insoluble amyloid fibers and cause amyloid deposition.17061,17064,17065 In animals, homotaurine reduces brain amyloid plaque load and decreases plasma and cerebral levels of the two most common forms of amyloid-beta peptides.17061,17064,17065 All of this sounds promising, but the effect of homotaurine on Alzheimer's disease in humans is still unclear. Preliminary clinical research has compared homotaurine 50 mg, 100 mg, or 150 mg twice daily to placebo in patients over age 50 with mild to moderate Alzheimer's disease. After three months there were dose-dependent reductions in cerebrospinal fluid (CSF) levels of amyloid-beta42, but no change in cognitive or clinical measures of the disease.17062,17064,17065 The decrease in amyloid-beta42 levels was greater in people with mild disease than in those with moderate disease at entry into the study.17062 In an extension of this study, homotaurine 150 mg twice daily was taken for up to 36 months.17062,17064 Twenty-four patients were treated for at least 20 months, with stabilization of cognitive function scores in 70% of these patients.17065 However, in contrast, a large-scale, placebo-controlled clinical trial involving 1052 patients taking homotaurine was not significantly more effective than placebo.17066,17067 So far, despite promising preliminary findings, the best evidence shows no benefit. For now, advise patients not to rely on homotaurine. Medium chain triglycerides (MCTs) have gotten some attention as a potential treatment for Alzheimer's disease. Some research suggests that Alzheimer's disease is associated with a decreased rate of glucose metabolism in certain parts of the brain. This effect seems to occur at early stages of the disease, often prior to cognitive decline. Although the brain uses glucose as its primary energy substrate, it can also use ketone bodies such as beta-hydroxybutyrate, acetoacetate, and acetone. Theoretically ketone bodies may supplement the brain's normal reliance on glucose in cases of decreased cerebral glucose metabolism. Taking MCTs increases levels of ketone bodies. Therefore, it is theorized that taking MCTs might improve energy metabolism in the brain and improve symptoms of Alzheimer's disease.17028 Ketone bodies produced by consuming MCTs might also inhibit beta-amyloid damage in the brain.17029 Clinical research evaluating MCTs has involved a specific medical food called Axona by Accera, Inc. This product contains MCTs in the form of caprylic acid. One preliminary clinical trial shows that taking Axona 20 grams daily does not significantly improve cognitive function in patients with mild to moderate Alzheimer's disease compared to placebo after 90 days of treatment. However, in a subgroup of these patients with the APOE4 gene variant, taking this product did significantly improve cognitive scores compared to placebo.17028 Another preliminary clinical study shows that a single dose of this same MCT-containing product improves measures of cognitive function in patients with the APOE4 gene variant, but not in patients without the gene variant.17029 Along with caprylic acid, coconut oil is also a rich source of MCTs, so there is a lot of interest in using it for Alzheimer's disease. However, there is currently no reliable information about its effectiveness. Explain to patients that there is not enough reliable evidence for MCTs or supplements containing MCTs for preventing or treating Alzheimer's disease. There is also interest in using turmeric for treating or preventing Alzheimer's disease. Turmeric is a spice commonly used in Asian food. It is derived from the root of the turmeric plant.11140 Recently, turmeric has gained significant popularity for use in people with osteoporosis or cancer. Some early research has also assessed the effects of turmeric for Alzheimer's disease. One of the major active constituents of turmeric is the curcuminoid curcumin.80405,80434,80599,80642,80691 Early research suggests that curcumin may have beneficial effects in treating or preventing Alzheimer's disease. In animal models, curcumin has been shown to induce disaggregation of amyloid beta, and decreased brain amyloid protein, plaque, and oxidized protein levels.17096,79074,79941,80080,80534 Cell culture research suggests that curcumin reduces beta-amyloid production by inhibiting the upregulation of beta-site APP-cleaving enzyme-1 (BACE-1). BACE-1 is the rate-limiting enzyme for beta-amyloid production.80368,80409 Other cell culture research suggests that curcuminoids increase the clearance of amyloid beta from mononuclear cells and enhance the uptake of amyloid beta by macrophages from patients with Alzheimer's disease.79941,80144,80520 In addition to reducing the production and increasing the clearance of amyloid beta, cell culture and animal studies also suggest that curcuminoids from turmeric protect against impairment by, or toxicity of, amyloid protein.79023,79096,79179,80913,81030 Despite these promising results from cell culture and animal studies, early clinical research has shown less promising results. A preliminary clinical study shows that taking the turmeric constituent curcumin, 1 to 4 grams daily for six months, does not significantly change mental state examination scores compared to placebo in patients with Alzheimer's disease.17096 Therefore, at this time there is not enough reliable evidence to recommend turmeric for Alzheimer's disease or dementia.

High Homocysteine Homocysteine is an amino acid that forms in the body during the breakdown of protein. Once formed, homocysteine is further metabolized to methionine. The conversion of homocysteine to methionine requires B vitamins, particularly folate, vitamin B6, and vitamin B12. Without these B vitamins, homocysteine accumulates in the blood. High serum levels of the amino acid homocysteine have been associated with an increased risk for Alzheimer's disease and vascular dementia.93039 Also, many patients with Alzheimer's disease have high levels of serum homocysteine - sometimes twice as high as people without dementia.12288 Some Alzheimer's patients with high levels of homocysteine also seem to show more disease progression on CT scans than patients with lower levels of homocysteine.12289 The B vitamin profile in patients with Alzheimer's also supports this theory. Researchers are finding that patients with the highest serum folate levels (vitamin B9) have the lowest levels of dementia, depression, and institutionalization.12290 Low serum folate is also associated with atrophy of the cerebral cortex in women with Alzheimer's.6234 Additional population research shows that elderly people who have a higher intake of folate from dietary or supplement sources also have a lower risk of developing Alzheimer's disease.13165,15270 Plus a lot of patients with Alzheimer's disease have B12 deficiency, suggesting their bodies are ill-equipped to lower homocysteine.12291,12305 Does taking folic acid or other B vitamins, including niacin (vitamin B3), pyridoxine (vitamin B6), and vitamin B12, help prevent or treat Alzheimer's? So far the bottom-line findings are inconsistent. Some population research shows that higher intake of vitamin B6 or vitamin B12 is not associated with a reduced risk of developing Alzheimer's disease.13165,15270 However, people who consume higher amounts of niacin (17 to 45 mg/day) from food and multivitamin sources seem to have a lower risk of developing Alzheimer's disease compared to people who consume less niacin (14 mg/day).12077 Also, preliminary clinical research shows that taking a combination of vitamin B12, vitamin B6, and folic acid daily for 24 months slows brain atrophy in areas of the brain associated with cognitive decline and Alzheimer's disease in elderly patients, suggesting a potential protective effect.90374 There are also conflicting findings regarding the effects of B vitamins in treating Alzheimer's disease. Some clinical research shows that taking folic acid 1 mg per day for six months improves the response of patients with Alzheimer's disease to treatment with AChEI drugs when compared to placebo.50246 On the other hand, taking vitamin B12 doesn't appear to have consistent positive effects on cognitive test scores in patients with Alzheimer's disease.12305

Hormonal Changes Dehydroepiandrosterone (DHEA) is secreted by the adrenal glands. It affects neurotransmission across cell membranes.12292,12293 Levels of DHEA are known to peak at puberty and then fall with age. Since DHEA is a precursor of the sex steroids, androgen and estrogen levels also fall as people get older.4248 The fact that DHEA levels decline as people get older raises questions as to whether DHEA can help protect against age-related conditions such as dementia. Cell culture studies suggest that DHEA might have a role in stopping the breakdown of amyloid precursor protein.12294 When amyloid precursor protein is cleaved at a particular site, it produces beta-amyloid, the main component of amyloid plaques.12295 Also, there seems to be an association between low levels of DHEA and Alzheimer's disease.12296,12297 However, it's not known if taking a supplement prevents Alzheimer's disease in humans. Taking DHEA supplements doesn't seem to improve symptoms of Alzheimer's.11334 Explain to patients who want to try DHEA that it can have serious side effects. DHEA can have potent steroid effects. There are concerns that taking DHEA long-term or in amounts that can cause higher than normal DHEA levels might increase the risk of prostate cancer, breast cancer, or other hormone-sensitive cancers.2111 DHEA might also cause acne, hair loss, insulin resistance, decreased HDL cholesterol, and hepatic dysfunction.2111 Women who take it can have hirsutism and deepening of the voice, which might not always be reversible. Women are likely to be more sensitive to the side effects of DHEA because they have a fraction of the DHEA that men normally produce. Discourage patients from using DHEA for Alzheimer's disease.

Cerebral Insufficiency Impaired blood flow to the brain might play a role in some of the symptoms of Alzheimer's disease. That's why investigators are looking at agents that seem to improve cerebral circulation. As previously discussed, Ginkgo biloba leaf extract might be helpful in Alzheimer's because of its ability to affect the cholinergic system. In addition to this effect, ginkgo leaf extract might also improve cerebral circulation. There is evidence that ginkgo leaf extract decreases blood viscosity2,6,7 and increases microcirculatory flow.5721,6492 As a result, it might help protect the brain against ischemia. However, as summarized above, most research suggests that taking ginkgo extract does not prevent or slow the progression of Alzheimer's disease or other types of dementia. However, taking ginkgo extract might improve cognitive function in dementia patients. Interestingly, many studies involving ginkgo have been excluded from meta-analyses of treatments for Alzheimer's. That's because a lot of the early ginkgo investigations involved patients diagnosed with "cerebral insufficiency," not "Alzheimer's disease." Cerebral insufficiency is an older term that refers to any decline in mental function believed to result from decreased cerebral blood flow in older people. Nevertheless, most of the early studies that looked at cerebral insufficiency found that using ginkgo is beneficial.12299 Unfortunately, many of these early studies were poor quality and the findings might not be reliable. It is also important to keep in mind that ginkgo's potentially beneficial effect of increasing circulation can also have a downside. Ginkgo inhibits platelet aggregation and might increase the risk of bleeding if combined with other antiplatelet or anticoagulant drugs such as aspirin or warfarin.6048,9760 Practice Pearl Numerous case reports have documented serious bleeding events in patients taking ginkgo.244,578,579,8581,13002,13135,13179,13194,14456,87868 While some population and clinical research suggests that ginkgo has no effect on international normalized ratio (INR) in healthy people or those with a stable INR,11905,12881,15176,87727,87889 an analysis of a large medical record database suggests that gingko increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin.91326 Ginkgo may need to be taken for at least two to three weeks to have a significant effect on platelet aggregation.14811 Patients taking ginkgo along with anticoagulant or antiplatelet drugs should be monitored to ensure that the combination does not significantly alter their prothrombin time (PT) and INR results. Vinpocetine is another agent that might be helpful in increasing cerebral blood flow. It is a synthetic derivative of apovincamine, a compound derived from the lesser periwinkle plant, Vinca minor.1786,1793 Vinpocetine is a potent vasodilator that acts directly on vascular smooth muscle.43,12300 It can also lower blood viscosity and might decrease platelet aggregation.43,1801 In addition to these effects on circulation, vinpocetine appears to have cholinergic activity and seems to be able to protect neurons against oxidative stress.1784 Practice Pearl The synthesis of vinpocetine requires considerable laboratory manipulation. As a result, some researchers question whether vinpocetine can be considered a dietary supplement according to the Dietary Supplement Health and Education Act (DSHEA) definition. In fact, on September 7, 2016 the U.S. Food and Drug Administration (FDA) announced a tentative ruling that vinpocetine is not a dietary supplement under DSHEA. However, the ruling is not yet final.92936 Vinpocetine looks promising. There is some evidence that vinpocetine can modestly improve cognitive impairment due to vascular disease, Alzheimer's disease, and other kinds of dementias. However, most studies have lasted four months or less.1784,1787,1789,82121,82151,82152,82153,82154,82179,82180,82182,82183 Also, many of the studies were published prior to 1990 and used a variety of terms and criteria for cognitive decline and dementia.10221,10827 Therefore, it's too soon to recommend it for most patients. However, if a patient decides to try it, make sure they use an appropriate dose of 5 to 10 mg three times daily. Practice Pearl Keep in mind that vinpocetine might increase the risk of bruising and bleeding in patients who take it with other antiplatelet or anticoagulant drugs.1801,10829

The Bottom Line Several natural medicines look promising for Alzheimer's disease. Some patients might benefit by taking ginkgo extract, huperzine A, phosphatidylserine, vitamin E, acetyl-L-carnitine, or vinpocetine. What products are your patients taking? Start a discussion on Colleagues Interact. For most of these products, there are still important unanswered questions about long-term benefits and long-term safety. Also so far, none of these, except vitamin E, has been shown to be as effective as conventional treatments for treating Alzheimer's disease. Don't recommend the other products. However, keep in mind that many patients with Alzheimer's and their caregivers are desperate for a treatment that helps. These patients are likely to try natural medicines even in the absence of solid evidence. For these patients, help them use these products safely. Advise patients not to use cholinergic natural medicines (e.g., huperzine A) in combination with conventional AChEI drugs. Also, tell patients not to take gingko or vinpocetine if they also take aspirin, warfarin, or other antiplatelet or anticoagulant drugs. Acetyl-L-carnitine, ginkgo leaf, huperzine A, phosphatidylserine, and vinpocetine show some evidence of reducing symptoms of Alzheimer's disease, while vitamin E shows some evidence of slowing its progression. Have any of your patients mentioned taking these supplements? Do they know the risks and/or potential drug interactions that may occur with some of these supplements? Print a Natural Medicines recommendation chart as a reference for your practice site. Recommendation Chart for Natural Medicines Used for Alzheimer's Disease Likely Safe  Possibly Safe  Insufficient Evidence  Possibly Unsafe  Likely Unsafe  Unsafe  Effective  Likely Effective  Possibly Effective  -Acetyl-L-carnitine -Ginkgo leaf -Vitamin E -Huperzine A -Phosphatidylserine -Vinpocetine Insufficient Evidence  -Caprylic acid -Coconut oil -Evening primrose oil -Fish oil -Folic acid -MCTs -Niacin -Turmeric -Vitamin B12 -Alpha-GPC -Cat's claw -DHEA -Gamma-linolenic acid -Gotu kola -Homotaurine -Phosphatidylcholine -Butea superba -Evodia Possibly Ineffective  -Beta-carotene -Choline -Pyridoxine -Vitamin C Likely Ineffective  -Lecithin -DMAE Ineffective