Curcumin has been used extensively in Ayurveda (Indian system of medicine) for centuries as an agent to relieve pain and inflammation in the skin and muscles. Curcumin, the active ingredient of the spice turmeric, has proven to have anticancer properties and holds a high place in Ayurvedic medicine as a “cleanser of the body.” Today, science is finding a growing list of diseases and conditions that can be healed by the active ingredient in turmeric.1
Recent clinical studies reported from a number of credible institutions, such as the University of California, Los Angeles, and UCLA, Riverside medical schools and the Human BioMolecular Research Institute, have revealed that curcumin alone and in combination with vitamin D3
may help stimulate the immune system to clear the beta-amyloid plaques considered to be the main cause of Alzheimer’s disease (AD).2
AD is a progressive neurodegenerative disease. Although it is not known what starts the disease process, it is established that damage to the brain begins as early as 10 to 20 years before any problems are evident. More than 5 million Americans are believed to have AD, and by 2050, as the U.S. population ages, this number could increase to 15 million. AD is also becoming more common worldwide, with an estimated 26 million people affected. This global figure is projected to grow to more than 106 million by 2050. The emotional and financial costs of this disease alone are very significant.2
In this article, we will briefly revisit the causes, signs, symptoms, and treatments of AD with a focus on the alternative new findings about the effect of curcumin in prevention and treatment. These new findings were first reported in the Journal of Alzheimer’s Disease in July 2009.2
This disease is named after its discoverer, Alois Alzheimer. In 1906, Dr. Alzheimer found unusual changes in the brain tissue of one of his patients who had died of a mental illness. This patient had memory loss, language problems, and unpredictable behavior. After she died, he found many abnormal clumps made of a toxic protein (known now as amyloid plaques) and tangled bundles of fibers (known now as neurofibrillary tangles) in her brain. Plaques and tangles in the brain are two of the main features of AD. The third is the loss of connections between nerve cells (neurons) in the brain.3
AD is the most common form of dementia (aging loss of memory), and is an irreversible, progressive brain disease that slowly steals the minds of its victims, destroying memory and thinking skills and, eventually, the ability to carry out the simplest tasks. It has been reported that there are two types of patients with AD: patients with type 1 AD (early onset, before age 60 years) and patients with type 2 AD (late onset, after age 60). In most people with AD, symptoms first appear after age 60.3
Signs and Symptoms
Memory problems are one of the first signs of AD. In comparison, some people have more memory problems than others of their age. This is called amnestic mild cognitive impairment (MCI). Although the symptoms are not as severe as those in people with AD, those with MCI are likely to develop the disease.
Other changes may also signal the very early stages of AD. Examples are problems with the sense of smell and cognitive problems. These findings may offer tools that could help detect AD early, track the course of the disease, and monitor response to treatments. AD is characterized by several stages and progresses from mild to severe forms. By the final stage, plaques and tangles have spread throughout the brain, and the brain tissue has shrunk significantly. People with severe AD cannot communicate and are completely dependent on others for their care. Towards the end, patients with AD may rest in bed most of the time as the body starts to shut down.1,3
The neuropathologic process consists of neuronal loss and atrophy, principally in the temporoparietal and frontal cortex, with an inflammatory response to the deposition of amyloid plaques and the abnormal clustering of protein fragments and neurofibillary tangles. This damaging process spreads to a nearby structure, called the hippocampus, which is essential in forming memories.1
Several factors have been claimed to cause this disease, and they include genetic, environmental, and lifestyle factors. Because people differ in their genetic make-up and lifestyle, the importance of these factors for preventing or delaying AD differs from person to person. The plaques can now be visualized by imaging the brains of living individuals. Findings from these studies will help clinicians understand the underlying causes of the disease. Also, in people with AD there is an increased presence of monocytes/macrophages in the cerebral vessel wall and of reactive or activated microglial cells in the adjacent parenchyma. The main protein component of amyloid in AD is the 39-42 amino acid (beta-amyloid peptide).3
One of the puzzles of AD is why it largely strikes older adults. Research on how the brain changes normally with age is shedding light on this question. For example, scientists are learning how age-related changes in the brain may harm neurons and contribute to Alzheimer’s damage. These age-related changes include atrophy (shrinking) of certain parts of the brain, inflammation, and the production of very damaging and unstable molecules called free radicals due to oxidative stress and cell respiration.4
It has been reported that a minority of people develop AD in their 30s, 40s, and 50s (type 1). Many of these people have a mutation, or permanent change, in one of three genes that they inherited from a parent. We know that these gene mutations cause AD in these early-onset familial cases. Not all early-onset cases are caused by such mutations.5
Most people with AD have late-onset Alzheimer’s, which usually develops after age 60 years (type 2). Many studies have linked a gene called APOE to late-onset Alzheimer’s. This gene has several forms, and one of them, APOE e4, increases a person’s risk of getting the disease. About 40% of all people who develop late-onset AD carry this gene. However, carrying the APOE e4 form of the gene does not necessarily mean that a person will develop AD, and people carrying no APOE e4 forms can also develop the disease. There are reports by experts in the field that additional genes may influence the development of late-onset AD in some way.1,4
One of the most controversial theories concerns aluminum, which became a suspect in AD when researchers found traces of this metal in the brains of patients with AD. Many studies since then have either not been able to confirm this finding or have had questionable results. Aluminum does turn up in higher amounts than normal in some autopsy studies of patients with AD, but not in all.6
Aluminum is found in small amounts in numerous household products and in many foods. As a result, there have been fears that aluminum consumed in the diet or absorbed from other sources could be a factor in AD. Too much zinc and certain toxins in food are believed to cause neurologic damage and have been linked to early dementia.7
Early diagnosis by CT and MRI is beneficial for several reasons. Getting an early diagnosis and starting treatment in the early stages of the disease can help preserve function for months to years, even though the underlying disease process cannot be changed. Having an early diagnosis also helps families plan for the future, make living arrangements, take care of financial and legal matters, and develop support networks. In addition, an early diagnosis can provide greater opportunities for people to get involved in clinical trials. In a clinical trial, scientists test drugs or treatments to see which are most effective and for whom they work best.
Research into AD has developed to a point where scientists can look beyond treating symptoms to address the underlying disease process. In ongoing clinical trials, scientists are looking at many possible interventions, such as cardiovascular and diabetes treatments, antioxidants, immunization therapy, cognitive training, and physical activity.3
Alzheimer’s is a complex disease, and no single “magic bullet” is likely to prevent or cure it. That is why current treatments focus on several different aspects, including helping people maintain mental function and managing behavioral symptoms in order to slow, delay, or prevent the disease.
Current Drug Therapy
Four medications are approved by the FDA to treat Alzheimer’s. Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) are used to treat mild-to-moderate AD (donepezil can be used for severe AD as well). These drugs act to stop the breakdown of acetylcholine by delaying formation of the enzyme acetylcholinesterase. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the central nervous system to improve cognitive deficits.
The fourth drug, or memantine (Namenda), is an N-methyl-D-aspartate receptor antagonist used to treat moderate-to-severe AD. This drug works by regulating neurotransmitters (the chemicals that transmit messages between neurons). They may help maintain thinking, memory, and speaking skills, and assist with certain behavioral problems. However, all these drugs do not change the underlying disease process and may help only for a few months to a few years. They also have their own side effects and drug interactions.8
Curcumin structurally belongs to the curcuminoids, a group of polyphenolic compounds with strong antioxidant properties. The botanical name for the turmeric plant is Curcuma longa, from the family Zingiberaceae, the ginger family. Turmeric is a sterile plant and does not produce any seeds. The plant grows from 3 to 5 feet in height and has dull yellow flowers. The underground rhizomes or roots of the plant are used for medicinal and food preparation. The rhizomes are boiled and then dried and ground to make the distinctive bright yellow spice turmeric.1,9
The early research findings, which appeared in the July 2009 issue of the Journal of Alzheimer’s Disease, may lead to new approaches in preventing and treating AD with curcumin. It is reported that natural or synthetic curcumin alone or with vitamin D3 will boost the immune system to protect the brain against beta-amyloid. The mechanism of this process is reported to be through the activation of certain immune genes, such as MGAT III and TLR-3. Bisdemethoxycurcumin has been found to have a role in this mechanism.10
Naturally occurring curcumin is not readily absorbed, and it has a tendency to break down in the gastrointestinal system before it can be utilized. Absorption appears to be better with food and other spices such as black pepper. Cosupplementation with 20 mg of piperine (extracted from black pepper) significantly increases the bioavailability of curcumin by 2,000%.3,9 The synthetic curcuminoids have been found more stable and effective than the natural products. After absorption, curcumin is readily conjugated in the intestine and liver to form curcumin glucuronides.
Since vitamin D and curcumin work differently with the immune system, curcumin or a combination of the two—depending on the individual patient—may be more effective. No dosage of vitamin D or curcumin can be recommended at this point. Larger vitamin D and curcumin studies with more patients are under way to determine a dosage for both.11
Mode of Action
Curcumin is a promising agent since it attacks AD from many different angles. It has been reported that curcumin may boost the immune system to clear the beta-amyloid protein from the brain. It has antiproliferative actions on microglia (brain glial cells). The chronic activation of microglia secretes cytokines and some reactive substances that exacerbate beta-amyloid pathology.11 Curcumin has been reported to have a potent inhibitory effect on proinflammatory cytokines, and it may work on AD through these various anti-inflammatory effects.1
Curcuminoids are proven to have strong antioxidant action, demonstrated by inhibition of the formation and propagation of free radicals. They decrease the low-density lipoprotein oxidation and the free radicals that cause the deterioration of neurons, not only in AD but also in other neurondegenerative disorders such as Huntington’s and Parkinson’s diseases. Curcumin increases the level of glutathione, which is an important endogenous antioxidant and essential cofactor for antioxidant enzymes that protect the mitochondria against oxygenfree radicals.11
The lipophilic nature of curcumin allows it to cross the blood-brain barrier. At high concentrations, curcumin binds to beta-amyloid protein and blocks its self-assembly. Researchers have discovered that curcuminoids enhanced the surface binding of beta-amyloid to macrophages and that vitamin D3 strongly stimulated the uptake and absorption of beta-amyloid by macrophages in a majority of patients.12
Finally, by interacting with heavy metals such as cadmium and lead, curcumin prevents neurotoxicity caused by these metals.
The chronic use of curcumin can cause liver toxicity. For this reason, turmeric products should probably be avoided by individuals with liver disease, heavy drinkers, and those who take prescription medications that are metabolized by the liver. Curcumin was found to be pharmacologically safe in human clinical trials with doses up to 10 g/day. A phase 1 human trial with 25 subjects using up to 8,000 mg of curcumin per day for 3 months found no toxicity from curcumin.4
The Role of Diet and Exercise
A nutritious diet, physical activity, social engagement, and mentally stimulating pursuits can all help people stay healthy. Mounting evidence suggests that physical activity may have benefits beyond a healthy heart and body weight. Through the past several years, population studies have suggested that exercise that raises the heart rate for at least 30 minutes several times a week can lower the risk of AD. Physical activity appears to inhibit Alzheimer’s-like brain changes in mice, slowing the development of a key feature of the disease.12
About 30 years ago, our knowledge of AD was very limited. Since then, scientists have made many important advances. Research supported by the National Institutes of Health, the Alzheimer’s Disease Foundation, and other organizations has expanded our knowledge of brain chemistry and function in healthy older people. Medical science has identified ways we might lessen normal age-related declines in mental function and has deepened our understanding of AD. As a continuing international effort, researchers are now working together to discover the genetic, biological, and environmental factors that ultimately result in AD worldwide. This effort is bringing us closer to preventing, slowing down, and ultimately curing this devastating disease.
These new results will open the door for further research and development in finding better drugs based on curcumin for treating AD. New reports also support some of the above-mentioned properties of curcumin in AD; however, large-scale human studies are required to determine the prophylactic and therapeutic effects of curcumin. 9 Other brain boosters such as resveratrol (an antioxidant) and ginkgo biloba and their effects on dementia are also under investigation.13
1. Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer’s disease. Ann Indian Acad Neurol. 2008;11(1):13-19.
2. Fiala M, Mahanian M, Rosenthal M, et al. Could vitamin D3 and curcumin help improve amyloid beta clearance in Alzheimer’s patient? J Alzheimers Dis. 2009;17(3):457-467.
3. Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement. 2009;5(3):234-274.
4. Garcia-Alloza M, Borrelli LA, Rozkalne A, et al. Curcumin labels amyloid pathology in vivo, disrupts existing plaques and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem.
5. Environmental factors in Alzheimer’s disease. The Cleveland Clinic Foundation. www.nbrc.ac.in/faculty/ranjit/Giri-JNChem-Curcumin.pdf.pdf. Accessed May 13, 2011.
6. Giri RK, Rajagopal V, Kalra VK. Curcumin, the active ingredient constituent of tumeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor. J Neurochem. 2004;91:1199-1210. http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2004.02800.x/full. Accessed April 11, 2011.
7. Bala K, Tripathy BC, Sharma D. Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology. 2006;7:81-89.
8. Farlow MR, Cummings JL. Effective pharmacologic management of Alzheimer’s disease. Am J Med. 2007;120(5):388-397.
9. Ringman JM, Frautschy SA, Cole GM, et al. A potential role of the curry spice curcumin in Alzheimer’s disease. Curr Alzheimer Res. 2005;2:131-136.
10. Fiala M, Liu PT, Aracela-Espinosa J, et al. Proc Natl Acad Sci. 2007;104(31):12849-12854.
11. Hamaguchi T, Ono K, Yamada M. Review:
Curcumin and Alzheimer’s disease. CNS Neurosci Ther. 2010;16(5):285-297.
12. Zhang L, Fiala M, Cashman J, et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer’s disease patients. J Alzheimers Dis. 2006;
13. Buschert V, Bodke AL, Hampel H. Alzheimer disease: cognitive intervention: physical exercise. www.medscape.org/viewarticle/726725_4. Accessed April 22, 2011.
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