Several mechanisms of action have been proposed which may be relevant to AD, based upon preliminary in vitro and in vivo data. Curcumin has been well-tolerated in clinical trials investigating its use in other diseases. It is generally accepted as safe, however some animal studies have suggested possible toxicities. Periwinkle has historically been used to treat a wide variety of diseases. It was used as a folk remedy for diabetes in Europe for centuries.
In India, juice from the leaves was used to treat wasp stings. In Hawaii, the plant was boiled to make a poultice to stop bleeding.
Ayurvedic Medicine for the Treatment of Dementia: Mechanistic Aspects
In China, it was used as an astringent, diuretic and cough remedy. In Central and South America, it was used as a homemade cold remedy to ease lung congestion and inflammation as well as sore throats. Throughout the Caribbean, an extract from the flowers was used to make a solution to treat eye irritation and infections. Numerous mechanisms of action have been proposed for vinpocetine; it will improve cerebral metabolism, increase glucose and oxygen consumption by the brain, and improve brain resistance to hypoxia.
In the only clinical trial of vinpocetine in AD, 15 patients were treated with increasing doses of vinpocetine 30, 45, and 60 mg per day in a 1-year open-label pilot study. When compared to a matched control group, study participants followed the natural course of disease. There were no significant adverse events reported. A Cochrane meta-analysis of vinpocetine in dementia identified three studies with sufficient data to be analyzed.
All were performed before the 's and enrolled poorly-defined dementia populations. Very few patients were followed for 6 months or more. This analysis suggested a possible benefit on CGI, but insufficient data was available to draw a definitive conclusion and the study populations were very loosely defined.
No serious adverse events have been reported. Gastrointestinal complaints and vertigo have been reported at higher rates than placebo groups, with some suggestions of dose-dependence. Vinpocetine has been reported to have a variety of actions that would hypothetically be beneficial in AD. The only study investigating this agent in a well-defined cohort of AD patients found no benefit. Meta-analysis of older studies of vinpocetine in poorly-defined dementia populations concluded that there is insufficient evidence to support its clinical use at this time.
Phosphatidylserine PS is one of five phospholipids that contribute to the structural matrix of all cell membranes. Endogenous synthesis requires a complex series of reactions and substantial energy expenditure, and most PS is obtained from dietary sources. In the past, supplements were derived from bovine cerebral cortex, which differ in composition from PS obtained from soy. When the bovine cortex origin of this agent became a source of concern in the 's, clinical investigations ceased.
PS accounts for a minor percentage of the membranes, but may be important in determining neuronal membrane surface potential and ionic environment. The functions of PS include cell-cell recognition and communication, and membrane PS expression is implicated in the early phases of apoptosis. All six studies were short; one lasted six months, three lasted three months and two lasted two months. The authors felt this improvement carried over to the subsequent wash-out and treatment phases.
No difference was found on the total CGI scale or on the behavioral scale as a whole. No difference was found on the family-reported behavior scale the third primary outcome measure , or on any of its individual items. No significant differences were found on neuropsychological testing. At the 3 month assessment, they reported a trend for two neuropsychological measures and for a single item of the BDS in favor of BC-PS, only in the subgroup of the most severely affected patients, which reached statistical significance at the 6 month follow-up.
Eight patients receiving BC-PS were in this subgroup. No analysis of the data from the moderately affected group was presented, but the tabular data reported did not demonstrate any meaningful difference between the placebo and BC-PS groups. Twelve, 18, and 24 month follow-up data were never published.
Fifteen participants completed the study, which reported subjective memory improvement and some improvement from baseline to 6 weeks on several neuropsychological tasks. There was no improvement in testing from 6 weeks to 12 weeks, and a practice effect could not be excluded. In the few clinical trials conducted with PS, no significant adverse events were reported. Stomach upset has been reported at higher dosages, and some subjects complained of flatulence related to plant-source PS.
Two trials of BC-PS in AD and one larger trial of BC-PS in poorly defined dementia patients failed to show convincing evidence of cognitive improvement and were too short to evaluate any neuroprotective effect. No longer-term studies of PS in AD patients are currently underway. No adverse events were reported in the clinical trials to date. Concerns regarding the safety of BC-PS relate directly to the cattle from which it the agent is derived. Numerous alternative medicines are touted as being beneficial for Alzheimer's disease. While the basic science underlying many of these agents provides interesting hypothetical effects, to date these have not been manifest in well-designed clinical trials, with the possible exception of huperzine A, which is currently under investigation.
The modest improvements reported in some older studies of these agents these have not been replicated in recent more rigorously designed trials that enrolled well-characterized AD populations. None of these agents provides clearly documented meaningful improvement or modulation of the natural course of AD in the trials conducted to date. This is an important point, as many patients may expect such a response based upon the advertisements for these agents.
In general, they appear to be safe, with few significant adverse events occurring during clinical trials and only rare case reports of adverse events temporally associated with their use. The available evidence for the eight agents discussed in this review does not clearly recommend any of them as being efficacious. Nonetheless, they continue to be widely used.
The use of alternative medicines is an exercise in shared medical decision-making, with the ultimate decision resting with the patient and their family. While there is clearly insufficient evidence to recommend any of these agents at this time, it is not clear whether clinicians should actively discourage their use. It is our hope that this review provides sufficient detail to inform discussions between clinicians and their patients regarding use of these substances.
National Center for Biotechnology Information , U. Author manuscript; available in PMC Aug Kelley , MD and David S. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Neurologist. See other articles in PMC that cite the published article. Abstract Background Alternative medicine has an extensive worldwide history and is commonly used by older patients. Review Summary This paper discusses the available clinical trial evidence regarding eight agents commonly used by people having Alzheimer's disease.
Conclusion While many of these compounds have been associated with interesting basic science, none has shown clear clinical benefit to date. Alzheimer's disease, alternative medicine, ginkgo biloba, huperzine A, piracetam. Ginkgo biloba — The Bottom Line Overall, there is weak evidence that GbE may provide modest cognitive benefit in some patients with Alzheimer's disease.
Acetyl-L-carnitine — The Bottom Line Two large, well-designed studies in patients with probable AD that employed current diagnostic definitions and outcome measures found no benefit for ALC. Lecithin Lecithin, a choline-containing phospholipid, is the major dietary source of choline and has been shown to increase serum choline levels. Huperzine A Huperzine A HupA is an extract of Huperzia serrata Chinese club moss, Lycopodium serrata, Qian Ceng Ta, Shuangyiping , a hardy plant which grows in a variety of temperate habitats, preferring semi-to-full shade, and sandy, well-drained soil.
Huperzine A — The Bottom Line The limited available data, including human and animal studies conducted in China, suggest that HupA may compare favorably in symptomatic efficacy to the cholinesterase inhibitors currently in use. Piracetam Piracetam is a derivative of GABA which was first marketed for the treatment of vertigo and events associated with ageing in Piracetam — The Bottom Line In summary, piracetam was developed in and has been marketed for a variety of indications.
Curcumin Curcuma longa is a member of the ginger family indigenous to South and Southeast Asia, where it is grown commercially. Curcumin — The Bottom Line Although the use of curcumin as a treatment for AD is currently under investigation, no clinical trial data is currently available. Periwinkle —Vinca minor Vinpocetine Periwinkle has historically been used to treat a wide variety of diseases. Phosphatidylserine Phosphatidylserine PS is one of five phospholipids that contribute to the structural matrix of all cell membranes.
Wright J, Morgenthaler J. Don't let your doctor give you horse urine! The roots of ancient medicine: Use of alternative therapies in older outpatients in the United States and Japan: Complementary and alternative medicine use among elderly persons: Ethnic minority use of complementary and alternative medicine CAM: Altern Ther Health Med. Courses involving complementary and alternative medicine at US medical schools. Mayo Clinic Staff Complementary and alternative medicine: Evaluate claims of treatment success [ MayoClinic.
The lowdown on Ginkgo biloba. Smith JV, Luo Y. Studies on molecular mechanisms of Ginkgo biloba extract. Ahlemeyer B, Krieglstein J. Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci. Ginkgo biloba extract Egb inhibits beta-amyloid production by lowering free cholesterol levels. Protection by EGb against beta-amyloid-induced neurotoxicity: Free Radic Biol Med. Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb and ginkgolides in transgenic Caenorhabditis elegans.
A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. Age-related differences in global-local processing: J Geriatr Psychiatry Neurol. Size of the treatment effect on cognition of cholinesterase inhibition in Alzheimer's disease. J Neurol Neurosurg Psychiatry. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type. Napryeyenko O, Borzenko I. Ginkgo biloba special extract in dementia with neuropsychiatric features.
A randomised, placebo-controlled, double-blind clinical trial.
Alzheimer’s & Dementia: Symptoms, Causes & How it relate to Autism
A 5-year double-blind randomized trial of the efficacy of EGb for prevention of Alzheimer disease in patients over 70 with a memory complaint. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann N Y Acad Sci. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Paclitaxel and Cisplatin-induced neurotoxicity: A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy.
Acetyl-L-carnitine in Alzheimer disease: Alzheimer Dis Assoc Disord. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease.
A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Hudson S, Tabet N. Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. Higgins JP, Flicker L. Lecithin for dementia and cognitive impairment.
PATENTED HOMEOPATHIC CURE FOR ALZHEIMER’s?
Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Wang R, Tang XC. Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease.
Huperzine-A in capsules and tablets for treating patients with Alzheimer disease. Ayurveda dates back to the period of the Indus Valley civilization about B. These include the Rigveda, Yajurveda, Samaveda, and Atharvaveda, which were composed between the 12th and 7th century B. Ayurvedic medicine includes descriptions of over signs and symptoms of various diseases and herbs and 6, formulations to treat them. A direct reference to dementia in Ayurvedic literature has not been mentioned.
However, the symptoms of forgetfulness and memory loss have been described [ 10 ]. Ayurvedic medicine mentions and explains the use of several herbs and their qualities for the treatment of nervous system disorders, including memory loss typically seen in older adults, but only recently have mechanistic studies been carried out, to determine the effects of these herbs on CNS disorders such as AD [ 11 ]. In recent years, there is renewed interest in the use of phytochemicals for the treatment of dementia, since pharmacological treatment of dementia using drugs haloperidol, risperidone, aripiprazole, olanzapine, cholinesterase inhibitors, memantine, and benzodiazepines is often inadequate and has many side effects [ 12 — 18 ].
Homeopathic Remedy & Treatment for Alzheimer's & Dementia Disease
The purpose of this review is to outline signal transduction processes and molecular mechanisms of some Ayurvedic medicinal plants used for the treatment of dementia. It is hoped that this description can be further explored with modern scientific validation approaches, to reveal new therapeutic leads and jump-start more studies on the use of Ayurvedic medicine for prevention and treatment of dementia.
The use of complementary medicines, such as plant extracts, in dementia therapy varies according to different cultural traditions. Ayurvedic medicinal herbs modulate the neuro-endocrine-immune systems and are also rich sources of antioxidants and anti-inflammatory compounds [ 19 , 20 ]. They are claimed to enhance memory and rejuvenate cognitive functions [ 21 — 23 ]. Several Ayurvedic medicines have been exploited for the treatment and management of acute and chronic neurological diseases.
These formulations induce specific effects on brain functions, such as increase in blood flow and maintenance of memory [ 11 ]. Ashwagandha Withania somnifera , fam. Solanaceae , or Indian Ginseng, is a common herb used in Ayurvedic medicine as an adaptogen or antistress agent. Ashwagandha root contains a large variety of compounds including 12 alkaloids, 40 withanolides, and several sitoindosides and flavonoids [ 24 — 26 ]. Withaferin A WL-A and withanolide A are two constituents which show similar pharmacokinetic profiles, except that the oral bioavailability for WL-A is 1.
These components produce antistress, antioxidant, and immunomodulatory effects in acute models of experimental stress [ 28 — 30 ]. According to Ayurvedic medicine, Ashwagandha constituents provide a number of healthful effects such as youthful state of physical and mental health and increase in happiness. It is not only given to children as tonics but is consumed by the middle-aged and elderly to increase longevity [ 31 , 32 ].
It is suggested that WL-A activates the translocation of Nrf2 to the nucleus, where the transcription factor upregulates the expression of neuroprotective proteins, such as heme oxygenase-1 [ 34 , 35 ]. Treatment of human neuroblastoma SK-N-SH cells with methanolic extracts of Ashwagandha root results in dendrite extension, neurite outgrowth, and synapse formation [ 36 , 37 ]. WL-A also attenuates the expression of semaphorin 3A to facilitate neural regeneration. The beneficial effects of Ashwagandha root constituents in neurodegenerative diseases may be due to their neurite promoting, antioxidant, anti-inflammatory, antiapoptotic, and anxiolytic activities, as well as their ability to improve mitochondrial dysfunction and restore energy levels and increase levels of antioxidant defenses such as reduced glutathione [ 38 ] Figure 3.
Based on the above information, it is proposed that WL-A is an important candidate for the treatment of dementia and neurodegenerative diseases, since it is able to repair damaged neuronal networks [ 33 , 38 ]. Ashwagandha is a safe herb [ 39 , 40 ], although a few people experience diarrhea or nausea after consuming the root. It should not be taken with barbiturate-type sedatives, since the herb can increase the effectiveness of these drugs. Ashwagandha can cross the blood-brain barrier and lower inflammation in the brain.
The half-lives of Ashwagandha in the circulation and the brain are not known. Large multicenter clinical trials of Ashwagandha in patients with dementia have not been performed. It is derived from the rhizome of Curcuma longa , which belongs to the family Zingiberaceae. It has antioxidant, anti-inflammatory, and cancer chemopreventive properties [ 42 ]. Curcumin reduces oxidative damage and improves cognitive functions related to the aging process. It induces antioxidant effects by modulating the Nrf2-keap1 pathway and reduces genomic instability events [ 43 ].
Nrf2 is primarily present in the cytoplasm, where it is bound with the Kelch-like ECH-associated protein 1 Keap1. Interaction of curcumin with Keap 1 releases Nrf2, which migrates into the nucleus and binds as a heterodimer to antioxidant responsive elements in DNA, to initiate target gene expression.
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Nrf2-regulated genes include antioxidant enzymes, molecular chaperones, DNA repair enzymes, and anti-inflammatory response proteins [ 44 ] Figure 4. These proteins promote the reduction in ROS generation while increasing the ability of the cell to repair any subsequent damage [ 44 , 45 ]. Curcumin attenuates neuroinflammation through the inhibition of phospholipase A 2 PLA 2 and cyclooxygenase COX-2 enzymes associated with the metabolism of neural membrane phospholipids to prostaglandins Figure 4.
The absorption rate and bioavailability of curcumin can be increased by consuming it with black pepper Piper nigrum. Studies have indicated that piperine, an active ingredient in black pepper, increases the bioavailability and bioefficacy of curcumin by inhibiting its glucuronidation [ 49 ]. Interestingly, consumption of piperine and curcumin has been found to protect against chronic unpredictable stress-induced cognitive impairment and oxidative damage in mice [ 50 , 51 ].
The half-lives of curcumin in the circulation and the brain are not known. Large multicenter clinical trials of curcumin in patients with dementia have not been performed, although a number of small studies have been conducted in healthy individuals. Bacopa monnieri belongs to the family Scrophulariaceae and is found throughout the Indian subcontinent in wet, damp, and marshy areas [ 54 ]. It has many branches with small oblong leaves and purple flowers. This plant is not only used for the treatment of a number of nervous system disorders such as insomnia, anxiety, and epilepsy, but also used for enhancing memory and the intellect [ 55 ].
In Ayurvedic medicine, Bacopa monnieri is used as a memory enhancing, anti-inflammatory, analgesic, antipyretic, sedative, and antiepileptic agent, which acts as a nootropic repairing damaged neurons and improving brain function. Bacosides inhibit lipoxygenase activity and scavenge free radicals. They protect neural cells of the prefrontal cortex, hippocampus, and striatum against cytotoxicity and DNA damage implicated in AD.
Bacosides increase glutathione peroxidase, chelate iron [ 58 , 59 ], and enhance nitric oxide-mediated cerebral vasodilation, leading to improvements in total memory score [ 59 ]. This leads to an increase in protein and RNA turnover in certain brain regions such as the hippocampus [ 57 ]. Furthermore, the combination of bacosides A and B not only induces antistress effects [ 61 ], but also protects the brain against smoking-induced membrane damage [ 62 ] and D -galactosamine-induced liver injury [ 63 ].
While there are no studies that prove that Bacopa monnieri causes side effects, it has been observed that excessive intake of Bacopa monnieri may lead to stomach upset, diarrhea, and nausea. The intake and use of Bacopa monnieri should be avoided by pregnant and breastfeeding women. The half-lives of bacosides in the circulation and the brain are not known. A number of clinical trials have been carried out in human subjects on the use of Bacopa monnieri for improving cognition.
Bacopa monnieri treatment for 3 months decreases the rate of forgetting of newly acquired information in human subjects between 40 and 65 years of age [ 55 ]. The roots and rhizomes of Acorus calamus are used in Ayurvedic medicine on a regular basis for the treatment of insomnia, melancholia, neurosis, loss of memory, and remittent fevers.
Convolvulus pluricaulis has been shown to improve learning and memory in rodents [ 68 ]. Saussurea lappa has been reported to produce anti-inflammatory activity [ 69 ]. Old clarified butter or old ghee is described in Ayurveda as a memory enhancer, anticonvulsant, and anti-inflammatory agent [ 70 , 71 ]. This formulation is used for the treatment of a number of neurological disorders such as anxiety and dementia [ 72 ]. Finally, old clarified butter is especially good for healing the mind [ 77 ]. Shankhpushpi Convolvulus pluricaulis is a common plant in India. It belongs to the family Convolvulaceae.
The whole plant of Shankhpushpi is used in various formulae as a nervine tonic for improvement of memory and cognitive function [ 78 , 79 ]. Shankhpushpi is recommended for nervous system disorders, such as stress, anxiety, mental fatigue, and insomnia [ 79 — 81 ]. The major bioactive components of Convolvulus pluricaulis are glycosides, flavonoids, coumarins, anthocyanins, and alkaloids. Sitosterol glycoside, octacosanol tetracosane, hydroxycinnamic acid, and glucose have also been isolated from the plant [ 83 ].
These metabolites contribute to its nootropic and memory enhancing properties, along with its other pharmacological activities [ 79 , 82 , 84 ]. Ethanolic extracts of Shankhpushpi improve learning and memory and induce antioxidant effects in rats [ 68 ]. Furthermore, ethanolic extracts of the whole Shankhpushpi plant, when administered to cholesterol-fed gerbils, induce reduction in serum levels of cholesterol, LDL cholesterol, triglycerides, and phospholipids [ 79 ]. The administration of ethanolic extracts of Shankhpushpi increases acetylcholine content in fields CA1 and CA3 of the hippocampus in a dose-dependent manner [ 85 , 86 ].
This is accompanied by a significant increase in the number of dendritic intersections, branch points, and dendritic processes arising from the cell bodies of neurons, in comparison with age-matched saline controls.
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Results suggest that ethanolic extracts of Shankhpushpi enhance memory by increasing neurite outgrowth [ 86 , 87 ]. Gotu kola Centella asiatica is another herb that is known as Brahmi besides Bacopa monnieri.