Tuesday 29 October 2013

Dementia Treatments -In Herbal Medicine Perspective

I. Dementia
About 5-8% of all people over the age of 65 have some form of dementia, and this number doubles every five years above that age. Dementia is the loss of mental ability that is severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people. American typical diet contains high amount of saturated and trans fat, artificial ingredients with less fruits and vegetable which can lead to dementia and other kind of diseases.


II. Treatments
A. In herbal medicine perspective
1. Ginkgo Biloba
a. The memory enhancing effects
In the study to investigate The effects of capsules containing 60 mg of a standardised extract of Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) on various aspects of cognitive function were assessed in healthy middle-aged volunteers, showed that the Ginkgo/ginseng combination was found significantly to improve an Index of Memory Quality, supporting a previous finding with the compound. This effect represented an average improvement of 7.5% and reflected improvements to a number of different aspects of memory, including working and long-term memory. This enhancement to memory was seen throughout the 12-week dosing period and also after a 2-week washout(1)

b. Cognitive performance 
In the study to investigate whether acute administration of a combination of standardised extracts of Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) had any consistent effect on mood and aspects of cognitive performance ("quality of memory", "secondary memory", "working memory", "speed of memory", "quality of attention" and "speed of attention") conducted by indicated that  Following a baseline cognitive assessment, further test sessions took place 1, 2.5,4 and 6 h after the day's treatment. The most striking result was a dose-dependent improvement in performance on the "quality of memory" factor for the highest dose. Further analysis revealed that this effect was differentially targeted at the secondary memory rather than the working memory component. There was also a dose dependent decrement in performance of the "speed of attention" factor for both the 320 and 640 mg doses(2).

c. Cognitive impairment
Scientists at the University of Oxford, in the conclusion of the study of Ginkgo biloba for cognitive impairment and dementia showed that Ginkgo biloba appears to be safe in use with no excess side effects compared with placebo. Many of the early trials used unsatisfactory methods, were small, and we cannot exclude publication bias. Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. However, the three more modern trials show inconsistent results. Our view is that there is need for a large trial using modern methodology and permitting an intention-to-treat analysis to provide robust estimates of the size and mechanism of any treatment effects(3).

d. Etc.




2.  Lemon balm
a. Behavioral and psychological symptoms
Dr. Perry E and Howes MJ. at the Newcastle University, showed that Behavioral and psychological symptoms of dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can be alleviated by some plant species (e.g., lemon balm and lavender alleviate agitation in people with dementia; St John's wort treats depression in the normal population)(4).

b. Cognitive performance and mood 
Other study indicated that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer's disease. The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation(5).


c. Etc. 

3. Lavender
a. Spatial performance
Scientists at the Shaheed Beheshti University of Medical Sciences in the study to  to evaluate the effects of aqueous extract of lavender (Lavandula angustifolia) on spatial performance of AD rats, found that in the first stage of experiment, the latency to locate the hidden platform in AD group was significantly higher than that in control group. However, in the second stage of experiment, control and AD rats that received distilled water (vehicle) showed similar performance, indicating that the maze navigation itself could improve the spatial learning of AD animals. Besides, in the second stage of experiment, control and AD rats that received lavender extract administration at different doses (50, 100, and 200 mg/ kg) spent less time locating the platform (except for the AD rats with 50 mg/kg extract treatment), as compared with their counterparts with vehicle treatment, respectively. In addition, lavender extract significantly improved the performance of control and AD rats in the probe test, only at the dose of 200 mg/kg, as compared with their counterparts with vehicle treatment(6).



b. Behavioural symptoms 
Some researchers at the Aged Mental Health Research Unit, Monash University, suggested that the use of lavender oil is effective in reducing challenging behaviours in individuals with dementia, it will potentially provide a safer intervention rather than reliance on pharmacology alone. The study's findings will translate easily to other countries and cultures(7).

c. Cognitive function, emotion, and aggressive behavior 
"A Lavender aromatherapy hand massage program is effective on emotions and aggressive behavior of elderly with dementia of the Alzheimer's type", Dr. Lee SY. at the Department of Nursing, Kongju National University suggested(8)



d. Etc.



4. Huperzine A, a chemical made from the plant Huperzia serrata have been studied for its effect on patient of dementia.
a. Dr. and the scientists at the suggested that Huperzine a, a potential therapeutic agent for Alzheimer's disease, inhibits acetylcholinesterase in primary cultures derived from forebrain, hippocampus, cortex and cerebellum of embryonic rat brain. Glutamate induces cell death in cultures from all these brain regions. and concluded that  Huperzine A could be a potent neuroprotective agent not only where cholinergic neurons are impaired, but also under conditions in which glutamatergic functions are compromised(9).

b. Activation of Wnt/β-catenin signaling pathway
In the study to search for new mechanisms by which HupA could activate Wnt signaling and reduce amyloidosis in AD brain, researchers at the China Medical University, in the study of "Huperzine A activates Wnt/β-catenin signaling and enhances the nonamyloidogenic pathway in an Alzheimer transgenic mouse model", suggested that HupA inhibited GSK3α/β activity, and enhanced the β-catenin level in the transgenic mouse brain and in SH-SY5Y cells overexpressing Swedish mutation APP, suggesting that the neuroprotective effect of HupA is not related simply to its AChE inhibition and antioxidation, but also involves other mechanisms, including targeting of the Wnt/β-catenin signaling pathway in AD brain(10).


c. Mild to moderate vascular dementia (VaD)
In the investigation of the efficacy and safety of Huperzine A in treatment of mild to moderate vascular dementia (VaD), researchers at Third Military Medical University indicated that after 12 weeks of treatment, the MMSE, CDR, and ADL scores significantly improved in the Huperzine A group (P < 0.01 for all comparisons), whereas the placebo group did not show any such improvement (P > 0.05 for all comparisons). No serious adverse events were recorded during the treatment.
http://www.ncbi.nlm.nih.gov/pubmed/21833673

d. Etc.

5. Bacopa
a. Increases Cerebral Blood Flow 
In the study to test Bacopa monnieri's chronic and acute effects on CBF compared with Ginkgo biloba and donepezil, Dr. Kamkaew N, and the research team at the Naresuan University, showed that G. biloba (60 mg/kg) also increased CBF (by 29% to 3019 ± 208 PU, p < 0.05, nine rats). No clear effect was obtained with donepezil (1 mg/kg). Chronic administration of the preparations had no effect on blood pressure. In contrast, intravenous acute infusion of these herbals (20-60 mg/kg) had marked dose-dependent hypotensive actions (diastolic ~31 mmHg lower with 40 mg/kg of either extract), which correspondingly reduced CBF by ~15%.  Increased CBF with B. monnieri may account for its reported procognitive effect, and its further exploration as an alternative nootropic drug is worthwhile(11).


b. Ethnobotanical treatment
Scientists at the Jodrell Laboratory in the study of Ethnobotanical treatment strategies against Alzheimer's disease, suggested that Since two of the currently licensed drugs for AD are based on natural products (galantamine and rivastigmine), it is not surprising that many plants are now being investigated as a potential source of new therapies for AD. This review discusses those plants that have ethnobotanical uses suggestive of alleviation of AD pathology and associated symptoms, for cognitive and for behavioural and psychological symptoms of dementia (BPSD). An emphasis is placed on those plants that have shown some promising effects in clinical studies with dementia patients (e.g. Crocus sativus, Ginkgo biloba, Salvia species), but other plants and their phytochemicals showing relevant mechanistic effects for AD (e.g. Bacopa monnieri, Centella asiatica, Ptychopetalum olacoides) are also discussed(12).



c. Cognitive performance, anxiety, and depression 
In the study to evaluate effects of Bacopa monnieri whole plant standardized dry extract on cognitive function and affect and its safety and tolerability in healthy elderly study participants, Dr. Calabrese C, and the research team at National College of Natural Medicine, indicated that Controlling for baseline cognitive deficit using the Blessed Orientation-Memory-Concentration test, Bacopa participants had enhanced AVLT delayed word recall memory scores relative to placebo. Stroop results were similarly significant, with the Bacopa group improving and the placebo group unchanged. CESD-10 depression scores, combined state plus trait anxiety scores, and heart rate decreased over time for the Bacopa group but increased for the placebo group. No effects were found on the DAT, WAIS digit task, mood, or blood pressure. The dose was well tolerated with few adverse events (Bacopa n = 9, placebo n = 10), primarily stomach upset(13).

d. Etc. 


6. Other potential herbs
Dr. Howes MJ and Dr. Perry E. at the Jodrell Laboratory, Kew, Richmond, in the study to investigate The role of phytochemicals in the treatment and prevention of dementia suggested that Other phytochemicals discussed include cannabinoids (e.g. cannabidiol) from Cannabis sativa, which are emerging as potential therapeutic agents for BPSD, and resveratrol (occurs in various plants) and curcumin (from turmeric [Curcuma longa]), which have been investigated for their pharmacological activities relevant to dementia and their potential effects on delaying dementia progression. The review also discusses plant extracts, and their known constituents, that have shown relevant mechanistic effects for dementia and promising clinical data, but require more evidence for their clinical efficacy and safety. Such plants include Ginkgo biloba, which has been extensively studied in numerous clinical trials, with most outcomes showing positive effects on cognitive functions in dementia patients; however, more reliable and consistent clinical data are needed to confirm efficacy. Other plants and their extracts that have produced promising clinical data in dementia patients, with respect to cognition, include saffron (Crocus sativus), ginseng (Panax species), sage (Salvia species) and lemon balm (Melissa officinalis), although more extensive and reliable clinical data are required. Other plants that are used in traditional practices of medicine have been suggested to improve cognitive functions (e.g. Polygala tenuifolia) or have been associated with alleviation of BPSD (e.g. the traditional prescription yokukansan); such remedies are often prescribed as complex mixtures of different plants, which complicates interpretation of pharmacological and clinical data and introduces additional challenges for quality control(14).

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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/11140327
(2) http://www.ncbi.nlm.nih.gov/pubmed/11842916
(3) http://www.ncbi.nlm.nih.gov/pubmed/12519586
(4) http://www.ncbi.nlm.nih.gov/pubmed/22070157
(5) http://www.ncbi.nlm.nih.gov/pubmed/12888775
(6) http://www.ncbi.nlm.nih.gov/pubmed/21441971
(7) http://www.ncbi.nlm.nih.gov/pubmed/20649945
(8)  http://www.ncbi.nlm.nih.gov/pubmed/15860944
(9) http://www.ncbi.nlm.nih.gov/pubmed/9141073
(10) http://www.ncbi.nlm.nih.gov/pubmed/21289607
(11) http://www.ncbi.nlm.nih.gov/pubmed/22447676 
(12) http://www.ncbi.nlm.nih.gov/pubmed/22329652
(13) http://www.ncbi.nlm.nih.gov/pubmed/18611150
(14) http://www.ncbi.nlm.nih.gov/pubmed/21639405

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