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A team from the University of California at Los Angeles believes that turmeric may play a role in slowing down the progression of the neurodegenerative disease.
The finding may help to explain why rates of Alzheimer's are much lower among the elderly in India than in their Western peers.
Previous studies have found that Alzheimer's affects just 1% of people over the age of 65 living in some Indian villages.
Turmeric is found in everything from mild Kormas to the hottest Vindaloos. The crucial chemical is curcumin, a compound found in the spice.
Alzheimer's is linked to the build up of knots in the brain called amyloid plaques.
Turmeric reduced the number of these plaques by a half.
The researchers also found that turmeric had other health benefits.
It aids digestion, helps fight infection and guards against heart attacks.
In the study, middle aged and aged rats were fed a diet rich in curcumin.
All the rats received brain injections of amyloid to mimic progressive Alzheimer's disease.
Not only was there less evidence of plaque build up in the curcumin-fed rats, they also outperformed rats on normal diets when carrying out maze-based memory tests.
Curcumin/tumeric also appeared to reduce Alzheimer's-related inflammation in the brain tissue.
Researcher Dr Sally Frautschy said the compound had potential as a treatment for the prevention of Alzheimer's disease - particularly in tandem with anti-inflammatory drugs such as ibuprofen.
Dr Richard Harvey, director of research at the Alzheimer's Society, said: "Curcumin has both anti-oxidant and anti-inflammatory properties.
"Drugs with similar properties could potentially be used as preventative treatments for Alzheimer's disease."
However, Dr Harvey warned that it could be many years before such drugs were made widely available. Curcumin, the main ingredient of turmeric, inhibits the spread of breast cancer and improves the effectiveness of current remedies. They believe that it could lead to a new way of treating people in the advanced stages of the disease.
The study, published in the Oct. 15 issue of the journal Clinical Cancer Research, reports that the spice appears to shut down a protein active in the spread of breast cancer.
The non-toxic, natural curcumin/tumeric repelled progression of the disease to the lungs and also appeared to reverse a "side-effect" of a commonly prescribed chemotherapy whose prolonged use may actually help to spread the disease.
Curcumin/tumeric breaks down the dose, making the therapy less toxic, but the drug stays just as powerful in fighting cancer.
Researchers studied 60 mice with breast cancer. Among a control group who were not treated, 96 per cent went on to develop visible signs of lung cancer, while treatment with the chemotherapy drug Taxol "modestly reduced" the incidence.
But those given curcumin/tumeric alone or curcumin plus Taxol had far fewer signs of the disease.
"We are excited about the results of the study and the possible implications for taking the findings into the clinic in the next several years," says Bharat Aggarwal, Ph.D., professor of cancer medicine in M. D. Anderson's Department of Experimental Therapeutics. "At this time, advanced breast cancer is a difficult foe to fight with few proven treatments available after surgery, chemotherapy and radiation therapy."
Taxol is currently used as the front-line chemotherapeutic agent in breast cancers, but because the drug frequently induces drug resistance after prolonged use, it is not effective in treating metastatic breast cancer, says Aggarwal.
The researchers studied 60 mice with breast cancer, which were randomly assigned to one of four groups: control group, Taxol only, curcumin only and the combination of Taxol and curcumin/tumeric. After the tumors grew to 10 mm (about the size of a pea), they were surgically removed, and the mice were fed a powdered curcumin/tumeric diet.
Macroscopic lung metastasis, or metastasis that is visible to the naked eye, was seen in 96 percent of the mice in the control group. Treatment using Taxol alone only "modestly reduced" the incidence of metastases, while the group using curcumin alone and curcumin plus Taxol "significantly reduced" both the incidence and numbers of visible lung metastases.
Microscopic metastasis, or metastasis that is visible only when using a microscope, was found in the lungs of 28 percent of mice treated with the combination of curcumin/tumeric and Taxol, and there was no macroscopic disease present. The micrometastases present consisted of only a few cells, suggesting that the combination inhibited the growth of breast cancer tumor cells that were in the lung before the tumors were removed.
In a previous study published in the Aug. 15 issue of the journal Cancer, M. D. Anderson researchers found that when the nuclear factor-kappa B (NF-kB) (a powerful protein known to promote the inflammatory response necessary to cause breast cancer to spread) is shut down, cancer strains are unable to grow and cells are pushed to commit suicide.
The mechanism in this curcumin study works the same way. Taxol activated the NF-kB in breast cancer cells, while curcumin stopped this activation by blocking the protein known as "IKK" that switched on the NF-kB, demonstrating how curcumin/tumeric and Taxol work against one another. Taxol produced the inflammatory response, triggering metastasis, and curcumin suppressed it, causing cell death.
Extracted from the roots of the curcuma longa plant otherwise known as Tumeric, curcumin is a member of the ginger family.
While it is not used in conventional medicine, it is widely prescribed in Indian medicine as a potent remedy for liver disorders, rheumatism, diabetic wounds, runny nose, cough and sinusitis.
Traditional Chinese medicine uses curcumin as a treatment for diseases associated with abdominal pain, and it is used in ancient Hindu medicine as a treatment for sprains and swelling.
The study was funded by the United States Department of Defense. Co-authors include Shishir Shishodia, Ph.D.; Yasunari Takada, Ph.D.; Sanjeev Banerjee, Ph.D.; Robert A. Newman, Ph.D.; Carlos Bueso-Ramos, M.D., Ph.D.; and Janet E. Price, Ph.D.
At least a dozen clinical trials on humans are under way in the United States, Israel and England to test the safety and dosages of turmeric's main ingredient, curcumin. It's a hot topic in health journals, too, cited 967 times since 2000 in articles reported on PubMed, the National Library of Medicine's research service.
So far, of the 250 studies conducted worldwide in 2005, Aggarwal has published 6 studies on curcumin.
Low rates among Indians for colorectal, prostate and lung cancers as well as coronary heart disease and Alzheimer's first drew Western researchers to curcumin. While genetics might have explained the low incidences, the rise in rates among Indians whose parents had moved to Western countries suggested a dietary cause. Subsequent lab tests on diseased cells and in mice strengthened claims for curcumin.
It's been demonstrated in animals to protect the liver, inhibit tumors, reduce inflammation and fight some infections.
Curcumin/Tumeric has both antioxidant and anti-inflammatory properties, according to researchers, and may help lower cholesterol.
Microscopic evidence of lung cancer was found in just 28 per cent of mice given both and there were no visible signs of the disease at all.
Dr Mark Matfield, scientific consultant for the St Andrews-based Association for International Cancer Research in Scotland, said: "We have known for some time that curcumin has anti-cancer effects, but this study has really advanced our understanding of exactly how this works. The finding that curcumin can decrease the spread of cancer when it is treated with Taxol is really interesting and potentially very important.
"However, as the authors of this study pointed out, these are only preliminary findings. The crucial next stage is to confirm these findings in patients suffering from lung cancer."
Dr Julie Sharp, senior cancer information officer at Cancer Research UK, said: "A number of laboratory
Studies have suggested that curcumin/Tumeric could be used to treat and even prevent some types of cancer.
But, as yet there is no evidence confirming this in humans. These findings will need to be followed up with clinical trials in humans."
Nevertheless, in presentations to fellow South Asians, Dr Aggarwal has been encouraging the lavish use of turmeric in daily food preparations.
OTHER USES OF TUMERIC
While turmeric has a long history of use by herbalists, most studies to date have been conducted in the laboratory or in animals and it is not clear that these results apply to people. Nevertheless, research suggests that turmeric may be helpful for the following conditions.
(stomach upset, gas, abdominal cramps): The German Commission E (an authoritative body that determined which herbs could be safely prescribed in that country and for which purpose[s]) approved turmeric for a variety of digestive disorders. Curcumin, for example, one of the active ingredients in
Turmeric, induces the flow of bile, which helps break down fats.
In an animal study, extracts of turmeric root reduced secretion of acid from the stomach and protected against injuries such as inflammation along the stomach (gastritis) or intestinal walls and ulcers from certain medications, stress, or alcohol. Further studies are needed to know to what extent these protective effects apply to people as well.
Because of its ability to reduce inflammation, turmeric may help relieve the symptoms of osteoarthritis. A study of people using an Ayurvedic formula of herbs and minerals containing turmeric as well as Withinia somnifera (winter cherry), Boswellia serrata (Boswellia), and zinc significantly reduced pain and disability. While encouraging for the value of this Ayurvedic combination therapy to help with osteoarthritis, it is difficult to know how much of this success is from turmeric alone, one of the other individual herbs, or the combination of herbs working in tandem.
Early studies suggest that turmeric may prove helpful in preventing the build up of atherosclerosis (blockage of arteries that can eventually cause a heart attack or stroke) in one of two ways. First, in animal studies an extract of turmeric lowered cholesterol levels and inhibited the oxidation of LDL ("bad") cholesterol. Oxidized LDL deposits in the walls of blood vessels and contributes to the formation of atherosclerotic plaque. Turmeric may also prevent platelet build up along the walls of an injured blood vessel. Platelets collecting at the site of a damaged blood vessel cause blood clots to form and blockage of the artery as well. Studies of the use of turmeric to prevent or treat heart disease in people would be interesting in terms of determining if these mechanisms discovered in animals apply to people at risk for this condition.
There has been a substantial amount of research on turmeric's anti-cancer potential.
Evidence from laboratory and animal studies suggests that Tumeric has potential in the treatment of various forms of cancer, including prostate, breast, skin, and colon.
Human studies will be necessary before it is known to what extent these results may apply to people.
Roundworms and Intestinal worms
Laboratory studies suggest that curcuminoids, the active components of turmeric, may reduce the destructive activity of parasites or roundworms.
Liver Disease Animal studies provide evidence that turmeric can protect the liver from a number of damaging substances such as carbon tetrachloride and acetominophen (also called paracetamol, this medication, used commonly for headache and pain, can cause liver damage if taken in large quantities or in someone who drinks alcohol regularly.) Turmeric accomplishes this, in part, by helping to clear such toxins from the body and by protecting the liver from damage.
Turmeric's volatile oil functions as an external antibiotic, preventing bacterial infection in wounds.
In animal studies, turmeric applied to wounds hastens the healing process.
A mixture of the volatile oils of turmeric, citronella, and hairy basil, with the addition of vanillin (an extract of vanilla bean that is generally used for flavoring or perfumes), may be an alternative to D.E.E.T., one of the most common chemical repellents commercially available.
One study of 32 people with uveitis (inflammation of the uvea, the middle layer of the eye between the sclera [white outer coat of the eye] and the retina [the back of the eye]) suggests that curcumin may prove to be as effective as corticosteroids, the type of medication generally prescribed for this eye disorder. The uvea contains many of the blood vessels that nourish the eye. Inflammation of this area, therefore, can affect the cornea, the retina, the sclera, and other important parts of the eye. More research is needed to best understand whether curcumin may help treat this eye inflammation.
LATEST RESEARCH IN INDIA
In tandem with Aggarwal's findings, scientists at the Bose Institute (Kokata) are also reporting that the true therapeutic benefit of the use of natural products, especially acceptable dietary components such as curcumin, has opened new horizons in cancer prevention and treatment.
In their report 'Amelioration of immune cell number depletion and potentiation of depressed detoxification system of tumor-bearing mice by curcumin,' S.Pal and colleagues from the Bose Institute say,
"The ability of curcumin to regress tumor as well as to protect the host from tumor-induced immunosuppression and toxicity strongly supports the candidacy of Tumeric as a potential agent for the dietary therapy of cancer.
Turmeric—A Natural Powerhouse
Turmeric Protects Your Brain Cells Double-barreled curry spice is an antioxidant and an anti-inflammatory
By Will Block
One thing leads to another." That old saying usually comes up in the context of sexual shenanigans, when things just spiral out of control—sometimes with a happy ending, sometimes not. But there are other arenas as well—our health, for example—where things can get out of control unless we take prudent measures to keep a lid on them.
Are you in the mood for a slightly spicy prudent-measures article? (Sorry, no sex included.)
Being committed to a long, healthy, happy life means, among other things, being cognizant of a stark fact to which most people seem oblivious: the human brain is as susceptible to disease as any other organ of the body, and it needs to be protected and maintained in the same way the rest of the body is: through good nutrition (including judiciously chosen dietary supplements) and regular exercise (mental gymnastics). Doing this will most likely prevent one thing from leading to another, namely, aging leading to mild cognitive impairment leading to dementia leading to a tragic and premature death. (Keep that sequence in mind.)
Aging Is Inevitable
Like politicians lying, aging is inevitable. Also inevitable, it seems, is some degree of benign memory loss (commonly called age-related memory loss), owing to the wear and tear on the brain of just having lived for a long time. All that thinking and loving and wondering and worrying, etc., take their toll, albeit to very different degrees: some people seem blessed with brains that remain quick, strong, and agile well into old age, just as some oldsters remain remarkably physically fit (often the two go hand-in-hand, probably not coincidentally).
Dementia Is Not
What is not inevitable (in most cases), however, is dementia, of which the Big Two are Alzheimer’s disease and vascular dementia. The latter is easy to prevent: maintain good cardiovascular—and thus cerebrovascular—health through diet and exercise (and, of course, no smoking). Do that, and you will probably have no atherosclerosis, no heart attack, no stroke, and no vascular dementia, and you will have a leg up on preventing Alzheimer’s disease as well. (In real life, these two forms of dementia are often commingled, and it can be difficult to make an accurate diagnosis except at autopsy.)
Vascular dementia is primarily due to well-understood “plumbing” problems in the circulatory system. Alzheimer’s is a more complex disease, the origins of which, although still largely a mystery, are related to oxidative stress and inflammatory processes in neurons (brain cells). In a convoluted web of causes and effects, these two biochemical phenomena are related to two hallmark features of the Alzheimer’s-ravaged brain: senile plaques and neurofibrillary tangles, and they lead to the ultimate hallmark: the death of neurons in certain regions of the brain, notably those governing memory and other cognitive functions.
But Mild Cognitive Impairment Usually Leads to Dementia
In the discussion above, did you notice how we skipped from aging to dementia, with a brief digression on age-related memory loss? What happened to mild cognitive impairment, which was one of the links in that one-thing-leads-to-another chain? Let’s backtrack.
Unlike age-related memory loss, which is considered to be normal and no significant threat to brain health, mild cognitive impairment (MCI) is a recognized disease state. In its most common form, its primary characteristic is memory loss (more severe than normal, but still “mild”), with other cognitive functions usually being impaired to a less significant degree.1 It is a major threat to brain health, because it usually (but not always) leads to Alzheimer’s disease: over a 6-year period, about 80% of MCI patients will progress (degenerate is a better term) to Alzheimer’s.*
-------------------------------------------------------------------------------- *Not all cases of MCI fit the profile just described. There are variations on the theme, and other forms of MCI, in which cognitive functions other than memory are more significantly affected, tend to lead more to other forms of dementia (such as vascular dementia or Lewy body dementia) than to Alzheimer’s. (For more on MCI, see “Galantamine May Help with Mild Cognitive Impairment” and “Galantamine May Help Block the Road to Alzheimer’s” in the February 2003 and September 2003 issues, respectively.)
-------------------------------------------------------------------------------- Because MCI is a much less severe condition than Alzheimer’s, however—it’s a transitional phase between normalcy and dementia—it has received nowhere near as much attention from the scientific community as Alzheimer’s has. That, however, is changing, with the growing awareness that anything that could prevent MCI from occurring would therefore probably also prevent Alzheimer’s. Seen from a different perspective, anything that’s potent enough to help alleviate Alzheimer’s (galantamine, e.g.) could probably alleviate—and better yet, prevent—its precursor, MCI. That premise remains to be proved through clinical trials, but it’s a reasonable one that few would disagree with.
Turmeric (Curcuma longa) Turmeric—“The Spice of Life” Meanwhile, more research is being focused on the possible benefits of nutritional supplements that can impact either of the two above-mentioned chemical processes that are implicated in cognitive decline: oxidation and inflammation of brain neurons. Of special interest are nutrients that can impact both of these processes, because intervention strategies for Alzheimer’s disease (and MCI) may require targeting both oxidation and inflammation.2
Among the nutrients that may fill this bill, the most notable is a member of the ginger family: turmeric (Curcuma longa), the Indian spice that gives some mustards their bright yellow color. Turmeric is better known as one of the principal ingredients (along with cumin, coriander, and other spices) of curry powder, a staple throughout much of India and Southeast Asia, where since ancient times it has been called “the spice of life.”
Is it a coincidence that elderly residents of rural India, who eat large amounts of curry, appear to have the lowest incidence of Alzheimer’s in the world?
3 No one knows for sure. A mere correlation proves nothing (think of the countless other factors, besides curry consumption, that differentiate rural Indians from urban Americans, say—what effect might those factors have?). Nonetheless, the correlation is intriguing to scientists, who believe that certain compounds found in the rhizomes (rootstalks) of the turmeric plant may indeed be responsible for conferring some degree of protection against Alzheimer’s.
The biochemical mechanism involved may be the same as that through which these compounds help to confer some protection against the dangers of spoiled meat (which is one reason, along with masking the bad flavor, why curry is used so extensively in regions where refrigeration is not available). That mechanism is antioxidation, the chemical neutralization of destructive free radicals, which are widely believed to play a major role in the pathogenesis of Alzheimer’s disease, as well in many other age-related conditions—including MCI.4
Amyloid-beta—Killer of Neurons
The antioxidant/anti-inflammatory compounds in turmeric are a group of polyphenols called curcuminoids, named for the best known among them, curcumin. In a recent laboratory study at the University of Illinois, researchers tested nine curcuminoids isolated from turmeric root for their ability to protect cultured rat cells from damage caused by amyloid-beta (also called beta-amyloid); this small protein molecule is the principal constituent, along with some polysaccharides, of the senile plaques found in the brains of Alzheimer’s victims.5
From the brain’s point of view, amyloid-beta is a disaster: it is believed to be formed in part through oxidative damage caused by free radicals, and it causes further free radical production, causing further oxidative damage, etc. In fact, amyloid-beta is neurotoxic—it kills neurons. In addition, it plays a role in the formation of neurofibrillary tangles, its evil, neurotoxic twin in the pathology of Alzheimer’s. All this death and destruction occurs primarily in cholinergic neurons (those for which acetylcholine is the neurotransmitter) in certain regions of the brain, notably the hippocampus, which govern vital aspects of memory and other cognitive functions.
Curcumin—An Amyloid-beta Killer?
Thus, one of the principal aims of Alzheimer’s research is to find agents that can inhibit or prevent the formation of amyloid-beta, and a growing body of evidence points to curcumin as a prime candidate in this regard.2,6 In the Illinois study, it turned out that five of the nine curcuminoids (including curcumin) were strongly protective against amyloid-beta neurotoxicity in the rat cells; one other was weakly protective, and three were inactive.*
-------------------------------------------------------------------------------- *Oddly, the cells chosen for this study were not cholinergic but adrenergic (those for which adrenaline or noradrenaline is the neurotransmitter), taken from a benign tumor called a pheochromocytoma. The reason for this was not explained. In any event, laboratory studies such as this are encouraging but do not reveal whether similar results would be seen in living rats, let alone in living humans, which is obviously the ultimate objective.
-------------------------------------------------------------------------------- UCLA Researchers Mess with Mice, Stifle Alzheimer’s
In another study, researchers at the University of California, Los Angeles, conducted a variety of biochemical tests of the action of curcumin in mice that had been genetically engineered (“transgenic” mice) to be highly susceptible to human-type Alzheimer’s disease.6* They found evidence of potent antioxidant and anti-inflammatory activities of curcumin that enable it to interfere with the pathogenesis of Alzheimer’s through multiple biochemical mechanisms. An important consequence of these activities in the mouse brains was the strong suppression of amyloid-beta formation.
-------------------------------------------------------------------------------- *This research was discussed in more detail in the article “Turmeric May Help Prevent Alzheimer’s and Parkinson’s Diseases” (February 2002 issue), which also outlined various other health benefits attributed to turmeric.
-------------------------------------------------------------------------------- The UCLA researchers’ observations tended to confirm and amplify the conclusions reached in many prior studies. One such conclusion was that curcumin is safe even at very high dosages (its use by countless humans throughout their lives argues for its long-term safety as well). In that regard, curcumin is different from ibuprofen and many other nonsteroidal anti-inflammatory drugs (NSAIDs), which are effective in reducing the risk for Alzheimer’s disease but which pose a serious danger for long-term human use because of their tendency to produce gastrointestinal damage, including ulcers.7 (Curcumin is itself an NSAID and is widely used in the treatment of arthritis as well as other inflammatory disorders.)
UCLA Researchers Ratchet up to Rats, with Similar Results
In a study with rats, the same research group at UCLA placed various groups of middle-aged and elderly rats on diets containing curcumin or ibuprofen, or no supplement, for 2 months.2 They then used surgical methods to infuse soluble amyloid-beta directly into specific areas of the rats’ brains in order to create a simulated Alzheimer’s-like state of neurodegeneration (remember that amyloid-beta causes oxidative and inflammatory damage and kills neurons). The objective was to determine the extent to which curcumin and ibuprofen could protect the rats’ brains and their cognitive function from this biochemical assault (the control rats were infused with a neutral solution containing no amyloid-beta).
The results showed that curcumin, but not ibuprofen, provided strong protection from oxidative damage. On the other hand, the two agents provided equivalent protection from inflammatory damage (not surprisingly, considering that they’re both NSAIDs). Curcumin dramatically reduced the actual numbers of senile plaques in the rats’ brains—by 80% with a low dosage but by only 45% with a much higher dosage (the data for ibuprofen were not given). In a water-maze test of the rats’ spatial memory, the curcumin-fed rats fared much better than the no-supplement amyloid-beta-damaged rats, performing as well as the amyloid-beta-free control rats. (For some reason, the ibuprofen-fed rats were not given this test.)<
The researchers concluded by saying,
Curcumin has a long history of safe use and is well tolerated in humans with limited or no side effects reported at effective anti-inflammatory and antioxidant doses. The data reported here argue that curcumin or another combined antioxidant/NSAID may prove useful for Alzheimer’s disease prevention or treatment.
It’s Turmeric Time!
In that context, another antioxidant that has received much attention in the scientific literature recently is vitamin E (see the sidebar). As potent an antioxidant as vitamin E unquestionably is, however, it appears that curcumin is several times more potent still, which makes it all the more attractive as a potential preventive and therapeutic agent for Alzheimer’s and other neurodegenerative disorders.8
Your Brain Needs Vitamin E—and C
Vitamin E has a well-earned reputation as a powerful antioxidant that plays an important role in heart health. Less well known, however, is its role in preserving brain health (not that these two aspects of health are separate—in fact, there is much common ground there). By combating oxidative stress in your brain—which churns out more free radicals than any other part of your body, owing to its disproportionately high rate of energy consumption—vitamin E helps to stave off the tendency toward cognitive decline.
The results of different studies on this subject have not been entirely consistent, however. An epidemiological study by researchers in Chicago showed that older people with the highest levels of vitamin E intake were at substantially lower risk for cognitive decline than those with the lowest levels.1 The authors drew the startling conclusion that the effects on cognitive decline from being at the highest level of daily intake of vitamin E (whether from food plus supplements or from food alone) were equivalent to a corresponding decline in age of 8 to 9 years—a handsome payoff from taking your vitamins!
More recently, a team of researchers studied the elderly residents of Cache County, Utah, who are known for their extraordinary longevity.2 It turned out that the risk for developing Alzheimer’s disease was dramatically lower than the norm among those who took substantial daily supplemental amounts of both vitamin E and vitamin C (which is also an antioxidant). No such effect was seen, however, among those who took one vitamin or the other, but not both, and there was only a modest effect among those who took a conventional multivitamin formulation without additional supplementation with E or C.
Contrary to several other studies demonstrating vitamin E’s antioxidant benefits for cognitive function when taken alone, the Cache County study suggested that vitamin E was effective (for that population, anyway) only in conjunction with vitamin C—which everyone should be taking in substantial quantities anyway, so it’s almost a moot point. So take all your vitamins! (For more on this subject, see “Antioxidant Vitamin Combo Cuts Alzheimer’s Risk” in the March 2004 issue.)
Morris MC et al. Vitamin E and cognitive decline in older persons. Arch Neurol 2002;59:1125-32. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JCS, for the Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements. Arch Neurol 2004;61:82-8.
Isn’t that nice? Just think—it could have been something awful, like cod liver oil. Instead, it’s a delightful spice that most people love to eat. If you’re not one of those people, however, and if, in any case, you don’t care to eat turmeric every day, the best way to assure yourself of its uninterrupted benefits is via supplementation. And for that, you’ve come to the right place.
References Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985-92. Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Ab-induced cognitive deficits and neuropathology. Neurobiol Aging 2001;22:993-1005. Ganguli M, Chandra V, Kamboh MI, Johnston JM, Dodge HH, Thelma BK, Juyal RC, Pandav R, Belle SH, DeKosky ST. Apolipoprotein E polymorphism and Alzheimer disease: the Indo-US Cross-National Dementia Study. Arch Neurol 2000;57:824-30. Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, Catani M, Cecchetti R, Senin U, Mecocci P. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 2003;24:915-9. Park S-Y, Kim DSHL. Discovery of natural products from Curcuma longa that protect cells from amyloid-beta insult: a drug discovery effort against Alzheimer’s disease. J Nat Prod 2002 Sep;65(9):1227-31. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001;21:8370-7. in ’t Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MMB, Stricker BHC. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 2001;345:1515-21. Zhao BL, Li XJ, Ho RG, Cheng SJ, Xin WJ. Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys 1989;14:175-85
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