1 Department of Health and Human Performance, Radford University, Radford, VA, USA
2 School of Teacher Education and Leadership, Radford University, Radford, VA, USA
3 School of Nursing, Radford University, Radford, VA, USA
4 Independent Education Researcher & Program Evaluator, San Diego, CA, USA
5 Vanderbilt University Medical Center, Nashville, TN, USA
The purpose of this systematic review was to ascertain the current state of science regarding the use of turmeric and its pigment curcumin in individuals with Alzheimer’s Disease (AD). A summary of qualitative and quantitative evidence specific to the effect of curcumin on AD is presented in this article. The purpose of the review was to evaluate and summarize findings related to this body of research. Findings indicated a positive correlation between administration of turmeric and improvement AD symptoms; however, long-term benefits need to be researched. Also, experimental research with older adults with mild, moderate, and severe AD should be conducted to determine whether or not turmeric and curcumin improve cognition, depression, and agitation. Specific methodological issues that need to be considered are the dosage and purity of turmeric and curcumin, administration frequency, determination of a suitable placebo, and duration of testing.
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As the aging population grows, dementia is becoming more prevalent, particularly in countries with large middle-class populations [1Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 2013; 9(1): 63-75.e2. [http://dx.doi.org/10.1016/j.jalz.2012.11.007] [PMID: 23305823] ]. Dementia is a neurodegenerative disease characterized by gradual cognitive decline, behavioral changes, memory loss, personality changes, and impaired reasoning. Although dementia can occasionally affect people under the age of 65, it is more common in older adults [2Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (20102050) estimated using the 2010 census. Neurology 2013; 80(19): 1778-83. [http://dx.doi.org/10.1212/WNL.0b013e31828726f5] [PMID: 23390181] ]. In fact, age is one of the most common characteristics of dementia patients, with rates doubling every five years; it is also more common in Western European countries [3Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr Scand 1987; 76(5): 465-79. [http://dx.doi.org/10.1111/j.1600-0447.1987.tb02906.x] [PMID: 3324647] ]. Research has frequently shown that dementia is the leading cause of disability and dependency in older adults [4Sousa RM, Ferri CP, Acosta D, et al. Contribution of chronic diseases to disability in elderly people in countries with low and middle incomes: a 10/66 Dementia Research Group population-based survey. Lancet 2009; 374(9704): 1821-30. [http://dx.doi.org/10.1016/S0140-6736(09)61829-8] [PMID: 19944863] ]. Alzheimer’s Disease (AD)-a type of dementia-is identified as the sixth leading cause of death in the United States [52016 Alzheimer’s Disease Facts and Figures Alzheimer’s Association. Available at: http://www.alz.org/facts/overview.asp. 2016.]. Approximately 35 million older adults in the United States (US) have dementia as the result of AD [2Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (20102050) estimated using the 2010 census. Neurology 2013; 80(19): 1778-83. [http://dx.doi.org/10.1212/WNL.0b013e31828726f5] [PMID: 23390181] ]. The worldwide impact of dementia has put a devastating financial pressure on the global economy. World Alzheimer’s 2015 report has estimated that dementia will cost $1 trillion by 2018 [6Prince MJ. World Alzheimer Report 2015: The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends. Available at: https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf 2015.].
Nearly 7.7 million new cases of dementia are reported annually; in other words, one new case of dementia is identified every four seconds [7Duthey B. Background paper 6.11: Alzheimer disease and other dementias. A Public Health Approach to Innovation 2004; 6: 1-74.]. While the worldwide prevalence of AD was 26.6 million in 2006, it is anticipated that its occurrence will quadruple by 2050 [8Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimers disease. Alzheimers Dement 2007; 3(3): 186-91. [http://dx.doi.org/10.1016/j.jalz.2007.04.381] [PMID: 19595937] ]. The cost of care for individuals with AD is estimated to be $600 billion annually with the United States bearing a share of $236 billion [9Hishikawa N, Takahashi Y, Amakusa Y, et al. Effects of turmeric on Alzheimers disease with behavioral and psychological symptoms of dementia. Ayu 2012; 33(4): 499-504. [http://dx.doi.org/10.4103/0974-8520.110524] [PMID: 23723666] ].
Given the pervasiveness of the problem, safe and effective alternative and complementary therapies have gained attention from the research communities as well as the general public. As a result, a few studies have been conducted to investigate the potential effect of non-traditional therapeutic medicine such as curcumin on AD. Curcumin is a derivative of Curcuma longa and is found in the spice turmeric. In this article, we use the term “turmeric” as a source of curcumin. Turmeric is typically used as a culinary curry powder as well as a coloring agent in food. Although curcumin is less known in Western cultures, traditional Indian doctors have been using this compound as a therapy for several chronic conditions such as asthma, diabetic wound healing, and epilepsy [10Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol 2007; 595: 1-75. [http://dx.doi.org/10.1007/978-0-387-46401-5_1] [PMID: 17569205] ].
Observational studies on turmeric and one of its essential components, curcumin, on AD have shown that there is a significant correlation between turmeric consumption and incidence of AD. Turmeric has been used in India for over 5,000 years, which may potentially explain why both rural and urban populations have some of the lowest prevalence rates of AD in the world today [11Chandra V, Pandav R, Dodge HH, et al. Incidence of Alzheimers disease in a rural community in India: the Indo-US study. Neurology 2001; 57(6): 985-9. [http://dx.doi.org/10.1212/WNL.57.6.985] [PMID: 11571321] ]. Turmeric is a powerful antioxidant that is thought to reduce inflammation of neural tissue associated with AD. Studies indicate that curcuminoids, which are composed of a mixture of curcumin, demethoxy-curcumin, and bisdemethoxy-curcumin, may counteract symptoms of AD by blocking the formation of pathological beta-amyloid plaques [12Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimers disease: An overview. Ann Indian Acad Neurol 2008; 11(1): 13-9. [http://dx.doi.org/10.4103/0972-2327.40220] [PMID: 19966973] ], by enhancing their clearance in AD patients [13Zhang L, Fiala M, Cashman J, et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimers disease patients. J Alzheimers Dis 2006; 10(1): 1-7. [PMID: 16988474] ], or by reducing inflammation of neural tissue [13Zhang L, Fiala M, Cashman J, et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimers disease patients. J Alzheimers Dis 2006; 10(1): 1-7. [PMID: 16988474] ], and which when combined with vitamin D3, further enhances the neuro-restorative process [14Masoumi A, Goldenson B, Ghirmai S, et al. 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimers disease patients. J Alzheimers Dis 2009; 17(3): 703-17. [PMID: 19433889] ]. Additionally, curcumin appears to increase dopamine, norepinephrine, and serotonin in the brain in animal models [15Lopresti AL, Maes M, Maker GL, Hood SD, Drummond PD. Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study. J Affect Disord 2014; 167: 368-75. [http://dx.doi.org/10.1016/j.jad.2014.06.001] [PMID: 25046624] , 16Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 2014; 48: 102-11. [http://dx.doi.org/10.1016/j.pnpbp.2013.09.017] [PMID: 24104186] ]. Studies report the role of curcumin in reducing the symptoms of depression in the general population [17Lopresti AL, Maes M, Maker GL, Hood SD, Drummond PD. Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study. J Affect Disord 2014; 167: 368-75. [http://dx.doi.org/10.1016/j.jad.2014.06.001] [PMID: 25046624] -19Yu J-J, Pei L-B, Zhang Y, Wen Z-Y, Yang J-L. Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 2015; 35(4): 406-10. [PMID: 26066335] ]. Studies also suggest that turmeric may have a beneficial effect on cognition, depression, and agitation in older adults with AD [9Hishikawa N, Takahashi Y, Amakusa Y, et al. Effects of turmeric on Alzheimers disease with behavioral and psychological symptoms of dementia. Ayu 2012; 33(4): 499-504. [http://dx.doi.org/10.4103/0974-8520.110524] [PMID: 23723666] , 20Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol 2006; 164(9): 898-906. [http://dx.doi.org/10.1093/aje/kwj267] [PMID: 16870699] , 21Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimers disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther 2012; 4(5): 43. [http://dx.doi.org/10.1186/alzrt146] [PMID: 23107780] ].
Improved understanding of how turmeric interacts biologically and influences clinical outcomes of AD should assist in determining purity and dosage levels for such a common ingredient being added to a patient’s diet. Even at high doses, turmeric is safe in humans; however, this spice may cause gallbladder contraction and is not advised for individuals with biliary problems [22Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008; 28(1): 110-3. [http://dx.doi.org/10.1097/jcp.0b013e318160862c] [PMID: 18204357] ]. The purpose of this systematic literature review was two-fold: a) to summarize and synthesize existing research on the effects of turmeric on cognition, depression, and agitation in older adults with AD; and b) to determine existing gaps in the literature to identify best practices about the use of turmeric in individuals with AD.
The purpose of this systematic review was to summarize and synthesize the existing literature on curcumin and AD to identify gaps in the knowledge base. A methodical search was performed in the following databases: AgeLine, Alt Health Watch, CINAHL, Heath Source: Nursing/Academic Edition, Psychology and Behavioral Sciences Collection. The following keywords were used: turmeric AND dementia, turmeric AND Alzheimer’s, curry AND dementia, curry AND Alzheimer’s, curcumin AND dementia, and curcumin AND Alzheimer’s. Ninety-four articles focusing on dementia and AD were reviewed; however, only a few focused on the effect of curcumin or turmeric on behavioral symptoms in humans.
Table 1 Search process used.
The inclusion criteria consisted of all articles that implemented an appropriate and accurate research design (including quantitative, qualitative, or mixed methods designs), that examined any part of a turmeric and/or curcumin intervention, conducted a study on humans, were primary sources, and were written in English. All secondary sources, such as literature reviews and book chapters, were not included. Additionally, all non-peer reviewed articles, such as conference proceedings and dissertations, did not meet the criteria. Finally, all studies investigating biomarkers and physiological parameters were excluded.
Our search resulted in 300 articles. After reading all articles abstracts, we identified 94 relevant abstracts with words and phrases related to our search criteria. We read each article to determine whether it met our inclusion criteria. Furthermore, we generated an Excel database and created a classification criterion for all relevant studies based on the following characteristics: (a) purpose, (b) research goal and objectives, (c) human versus animal, (d) research design, and (e) methodology. We conducted a critical assessment of the 94 articles. Four articles were found to meet all the inclusion criteria described above (Table 1). Each article was read carefully to identify themes and codes for summary analysis.
The four research articles were analyzed through a series of categories and themes, the organization and selection of which was guided by the research question. Several main themes among these research studies were identified. First, the four studies utilized a valid and reliable mental status tool, the Mini-Mental State Examination (MMSE), to systematically assess the participants’ mental status. Second, the range of dementia selected for these four studies varied from mild to moderate range. Third, a various methodological approach was chosen, for example, two studies followed an experimental design, one was an observational study, and one was a case study. The observational study with large sample size (n > 1,000) indicated a positive correlation between curcumin consumption and score on MMSE, while the experimental study with considerably smaller sample size than the observational study did not suggest any relationship between curcumin and score on MMSE. A summary of each research article that satisfied the criteria is provided in Table 2 below and includes authors, purpose, design, sample, instruments used, findings, dosage, and the form of curcumin administration.
Table 2 Summary of research evaluating turmeric in older adults with dementia or AD.
Our analysis identified several gaps in the existing literature that could potentially hinder researchers’ ability to predict or explain the effect of curcumin on AD. Although existing literature on the effect of curcumin on animals has demonstrated neurobiological potential, the scarcity of research on human subjects makes it challenging to predict any effect on human behavior. Although some of the studies included in this literature review indicated positive results for the use of turmeric, the findings of these four studies were not conclusive. Also, there were additional concerns related to the generalizability of the studies and their inconclusive results. Some of these concerns include their small size, duration, and curcumin dosage. Three of these four studies had small sample sizes (n = 3 (a case study); n = 36 and n = 34). Most of the studies were conducted for less than six months. One of these three studies was essentially clinically testing a specific product, Curcumin C3 Complex®, which could indicate an insufficient mixture of curcumin and other unproven ingredients in the dosage. The study that utilized a large sample size (greater than 1,000 human subjects) was a correlational study that compared human subjects from three groups who self-reported their curry consumption under the three following categories: never or rarely, occasionally, and often or very often. These subjects had no medical diagnosis of AD nor were the human subjects medically diagnosed as being potentially at-risk for AD. All the subjects were over the age of 59. Mediating variables of known socio-demographic factors, health factors, and other behavioral correlates were considered in the analyses. Using scores from the Mini-Mental State Examination (MMSE), the researchers reported evidence of better cognitive performance in elderly Asians who did not have dementia and consumed greater amounts of curry.
Significant evidence is thus not yet apparent for the role of curcumin in benefitting individuals with AD. The findings of this literature review demonstrate the need for an experimental study with a large sample size over an extended period of time. Additionally, there is a need to identify the most suited form of consumption and the dosage needed for effective results. Given the lack of significant evidence, it is likely that turmeric and curcumin are not being used as a therapeutic intervention for individuals with mild or moderate AD.
This analysis of research articles using human subjects diagnosed with dementia or AD examined the effect of turmeric on cognition, depression, and agitation. Although two of the four studies suggested a correlation between curcumin administration and behavioral symptoms of AD, the long-term effects of curcumin need to be studied. Further research, including experimental designs with human subjects, should be conducted with older adults diagnosed with mild dementia or diagnosed with a potential for AD to determine whether or not curcumin results in improved cognition, reduced depression, and/or diminished episodes of agitation. Specific design issues that need to be considered are the dosage and purity levels of turmeric and/or curcumin as well as the administration frequency rate, the amount of time needed to determine if effects are present, and a suitable placebo that could be used.
CONFLICT OF INTEREST
The authors confirm that this article content has no conflict of interest.
Sousa RM, Ferri CP, Acosta D, et al. Contribution of chronic diseases to disability in elderly people in countries with low and middle incomes: a 10/66 Dementia Research Group population-based survey. Lancet 2009; 374(9704): 1821-30. [http://dx.doi.org/10.1016/S0140-6736(09)61829-8] [PMID: 19944863]
Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 2014; 48: 102-11. [http://dx.doi.org/10.1016/j.pnpbp.2013.09.017] [PMID: 24104186]
Sanmukhani J, Satodia V, Trivedi J, et al. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res 2014; 28(4): 579-85. [http://dx.doi.org/10.1002/ptr.5025] [PMID: 23832433]
Yu J-J, Pei L-B, Zhang Y, Wen Z-Y, Yang J-L. Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 2015; 35(4): 406-10. [PMID: 26066335]
Ringman JM, Frautschy SA, Teng E, et al. Oral curcumin for Alzheimers disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther 2012; 4(5): 43. [http://dx.doi.org/10.1186/alzrt146] [PMID: 23107780]