|LETTER TO EDITOR
|Year : 2013 | Volume
| Issue : 4 | Page : 398-400
Dietary approach for cognitive and behavioral problems in dementia
Prasan R Bhandari
Department of Pharmacology, S.D.M. College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India
|Date of Web Publication||15-Oct-2013|
Prasan R Bhandari
Department of Pharmacology, S.D.M. College of Medical Sciences and Hospital, Sattur, Dharwad - 580 009, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bhandari PR. Dietary approach for cognitive and behavioral problems in dementia. Int J Nutr Pharmacol Neurol Dis 2013;3:398-400
Plants have been a valuable source of drugs and their phytochemicals have also provided templates to develop synthetic drugs (e.g., rivastigmine, based on the chemical structure of physostigmine from Physostigma venenosum). Although scientific evidence for efficacy and safety has been explored, more research is needed, particularly to identify active phytochemicals to produce standardized herbal products. Naturally-occurring agents in the diet have great potential, thus proving Hippocrates, who proclaimed 25 centuries ago, "Let food be thy medicine and medicine be thy food."
Presently, the only approved treatment options for Alzheimer's disease (AD) are the four cholinesterase inhibitors (tacrine, rivastigmine, donepezil and galantamine) and a partial N-Methyl-D-aspartate receptor antagonist (memantine). Unfortunately, these agents fail to totally cure the disease. This makes it mandatory to search and develop a novel class of targets that would over a due course lead to effective drugs for the treatment of AD. This is significant and timely information for investigators in this field as existing management options in the field are insufficient in number and demonstrated unsatisfactory results.
Non-pharmacologic interventions are recommended as the most appropriate initial strategy for managing problematic behaviors. It is, therefore, not unusual in clinical practice to encounter patients and caregivers inquiring about dietary recommendations for lowering the risk of dementia. Medical foods as a class of intervention alternatives are not well-known to most clinicians but are a growing area.  In lieu of the above, it could be stated that plants provide a wealth of bioactive compounds, which exert a substantial approach for the treatment of neurological disorders such as AD. It would be worthy to mention certain plants of Indian origin, which have validated to possess favorable properties for managing dementia/AD.
Growing body of evidence states that the dietary consumption of antioxidants such as vitamin E, ascorbate, carotenoids and plant phenols, either through supplementation or the intake of different foods, may decrease the risk of some neurodegenerative diseases. Although their precise mechanism(s) of action are still largely unknown, the neuroprotective effects of these plant-derived phytochemicals are presumed to be mediated mostly due to their antioxidant and anti-inflammatory actions. 
Several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD have been effectively restricted by "aged garlic extract" and one of its active ingredients, S-allyl-L-cysteine.  It is suggested that apoptotic parameters like DNA fragmentation, expression of Bcl2 and p53 are protected by the administration of garlic extract. In addition, garlic could prevent free radicals associated deterioration of cognitive functions and neurobehavioral activities.  Furthermore, findings also suggest that consumption of garlic may lead to inhibition of Aβ aggregation in the human brain. 
It has been demonstrated that the anti-amyloidogenic effect of crocin, a carotenoid from the stigma of the saffron (Crocus sativus) flower, could probably be exerted not only by the inhibition of Aβ amyloid formation, but also by the disruption of amyloid aggregates.  Systemic administration of safranal (active metabolite of saffron), effectively and dose-dependently decreased the Quinolinic acid-induced lipid peroxidation and oxidative DNA damage. Safranal also prevented the decrease of hippocampal thiol redox and antioxidant status produced by Quinolinic acid.  Saffron extract also demonstrated a moderate acetylcholinesterase (AChE) inhibitory activity (up to 30%).  Saffron was found to be as effective as donepezil in the treatment of mild-to-moderate AD after 22 weeks in a double-blind study of parallel groups of patients (n = 54). 
Although, there are no proven ways to delay onset or slow progression of AD, studies suggest that diet can affect the risk. Polyphenols have been shown to be neuroprotective in different model systems. Pomegranates contain very high levels of antioxidant polyphenolic substances as compared to other fruits and vegetables. Supporting the statement it was demonstrated that mice treated with pomegranate juice had significantly less (approximately 50%) accumulation of soluble Aβ 42 and amyloid deposition in the hippocampus as compared to control mice.  However further studies to validate and determine the mechanism of these effects, as well as whether substances in pomegranate juice may be useful in AD, should be considered.
The fresh leaves of Murraya koenigii (curry leaf) are often added to various dishes in Asian countries due to the delicious taste and flavor that they impart. These leaves have also been proven to have health benefits. It has been demonstrated that extracts of M. koenigii reversed the amnesia induced by scopolamine and diazepam. Interestingly, the brain cholinesterase activity was also reduced significantly by total alkaloidal extract of M. koenigii leaves.  This study indicates M. koenigii to be a useful remedy in the management of AD and dementia.
Daucus carota extract (carrot) reversed the amnesia induced by scopolamine and diazepam. D. carota extract also reduced significantly the brain AChE activity.  Therefore, D. carota extract may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.
Investigations reveal that the Withania somnifera (ashwagandha) fruit afforded lipid peroxidation inhibitory with anamides that are more potent than the commercial antioxidants. With anamides A (WA) and with anamides C (WC) protect the rat neuronal cells, from β-amyloid induced cell damage. Molecular modeling studies showed that WA and WC uniquely bind to the active motif of β-amyloid (25-35) and suggest that withanamides have the ability to prevent the fibril formation. It has been demonstrated that the remarkable therapeutic effect of W. somnifera is mediated through up-regulation of liver low-density lipoprotein receptor-related protein. This indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in AD models. , Further understanding of the mechanism of action and in vivo efficacy of these withanamides may facilitate its development as a prophylaxis.
As per Joshi and Parle Desmodium gangeticum (Shalaparni) appears to be a promising candidate for improving memory and it would be worthwhile to explore the potential of this plant in the management of dementia and AD. 
Some other common dietary ingredients that have a beneficial effect in the treatment of AD and its associated symptoms are: Bacopa monnieri (brahmi)/Centella asiatica (ekpanni), Curcuma longa (haldi) and Piper methysticum (pepper).  In addition, Essa et al., have reviewed the neuroprotective properties of blueberry, strawberry tree, grape seed, papaya, apple, green tea, coffee, walnut, curcumin, cinnamon, ginger, amla and coriander leaf. 
Monosodium glutamate (ajinomoto) is the sodium salt of an amino acid, glutamic acid. It is frequently used as a food additive. It has been observed that glutamate in high doses produces neuroendocrine abnormalities, neurodegeneration, neurotoxicity and oxidative damage. Hence, it would be prudent to restrict the usage of such agents in patients of AD. 
Since most of the above mentioned plants are consumed regularly in the diet, their incorporation could be practicable even in many distant and rural areas of resource-constrained countries. These therapeutic opportunities can diminish treatment gap particularly to the disadvantaged and deprived patients living in rural inaccessible areas of developing countries with lowest imaginable affordability. Considering the strong clinical need consideration of such options as herbal medicines, research imports should be directed at creating a continuing authoritative database on herbal medicine for dementia. Additional epidemiological and follow-up studies of promising phytopharmaceuticals or related nutraceuticals for disease prevention are necessary.
| References|| |
|1.||Sadowsky CH, Galvin JE. Guidelines for the management of cognitive and behavioral problems in dementia. J Am Board Fam Med 2012;25:350-66. |
|2.||Guest JA, Grant RS. Effects of dietary derived antioxidants on the central nervous system. Int J Nutr Pharmacol Neurol Dis 2012;2:185-97. |
|3.||Ray B, Chauhan NB, Lahiri DK. The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD). Curr Med Chem 2011;18:3306-13. |
|4.||Javed H, Khan MM, Khan A, Vaibhav K, Ahmad A, Khuwaja G, et al. S-allyl cysteine attenuates oxidative stress associated cognitive impairment and neurodegeneration in mouse model of streptozotocin-induced experimental dementia of Alzheimer's type. Brain Res 2011;1389:133-42. |
|5.||Gupta VB, Indi SS, Rao KS. Garlic extract exhibits antiamyloidogenic activity on amyloid-beta fibrillogenesis: Relevance to Alzheimer's disease. Phytother Res 2009;23:111-5. |
|6.||Ghahghaei A, Bathaie SZ, Kheirkhah H, Bahraminejad E. The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro. Cell Mol Biol Lett 2013;18:328-39. |
|7.||Sadeghnia HR, Kamkar M, Assadpour E, Boroushaki MT, Ghorbani A. Protective effect of safranal, a constituent of Crocus sativus, on quinolinic acid-induced oxidative damage in rat hippocampus. Iran J Basic Med Sci 2013;16:73-82. |
|8.||Geromichalos GD, Lamari FN, Papandreou MA, Trafalis DT, Margarity M, Papageorgiou A, et al. Saffron as a source of novel acetylcholinesterase inhibitors: Molecular docking and in vitro enzymatic studies. J Agric Food Chem 2012;60:6131-8. |
|9.||Akhondzadeh S, Shafiee Sabet M, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology (Berl) 2010;207:637-43. |
|10.||Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, et al. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease. Neurobiol Dis 2006;24:506-15. |
|11.||Mani V, Ramasamy K, Ahmad A, Parle M, Shah SA, Majeed AB. Protective effects of total alkaloidal extract from Murraya koenigii leaves on experimentally induced dementia. Food Chem Toxicol 2012;50:1036-44. |
|12.||Vasudevan M, Parle M. Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions. Biol Pharm Bull 2006;29:1154-61. |
|13.||Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, et al. Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci U S A 2012;109:3510-5. |
|14.||Jayaprakasam B, Padmanabhan K, Nair MG. Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer's disease. Phytother Res 2010;24:859-63. |
|15.||Joshi H, Parle M. Antiamnesic effects of Desmodium gangeticum in mice. Yakugaku Zasshi 2006;126:795-804. |
|16.||Singhal AK, Naithani V, Bangar OP. Medicinal plants with a potential to treat Alzheimer and associated symptoms. Int J Nutr Pharmacol Neurol Dis 2012;2:84-91. |
|17.||Essa MM, Vijayan RK, Castellano-Gonzalez G, Memon MA, Braidy N, Guillemin GJ. Neuroprotective effect of natural products against Alzheimer's disease. Neurochem Res 2012;37:1829-42. |
|18.||Kumaravel P, Subash S, Seethalakshmi KS, Murugan N, Yuvarajan R, Subramanian P. Monosodium glutamate modulates the circadian rhythms of biochemical variables and behavioral activity in rats under constant light. Int J Nutr Pharmacol Neurol Dis 2012;2:251-7. |