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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, severe enough to interfere with people's every life and Alzheimer's disease is the most common type of dementia in aging people.
V. Treatments
A. In herbal medicine perspective
1. Ginkgo Biloba(bai Guo)
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from temperate zone to subtropical zone and some parts of north America(592). The herb been used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders and deafness as well as preventing drunkenness, and bedwetting(591).
a. The memory enhancing effects
Capsules containing 60 mg of a standardised extract of
Ginkgo biloba (GK501) and 100 mg of a standardised extract of Panax ginseng (G115) showed significantly to improve an Index of Memory Quality(593), including learning and
memory but not working and long-term memory(596). Its extract, in the logical
memory test and nonsense picture recognition exhibits improvement of 58.62% logical
memory in compared to baseline(594). Comercial extract
Ginkgo biloba EGb 761 enhanced certain neuropsychological/
memory processes of cognitively in older adults, 60 years of age and over(595).
b. Cognitive performance
Administration of single doses (120, 240, 360 mg) of standardised
Ginkgo biloba extract (GBE), according to Northumbria University, showed to improve
cognitive performance, including speed of attention, accuracy of attention, secondary memory, working memory, speed of memory, quality of memory(597). Combination of standardised extracts of
Ginkgo biloba (GK501, Pharmaton SA) and Ginseng (G115, Pharmaton SA) administration showed a 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") in doeses depend-manner(598). On acute
cognitive effects,
Ginkgo biloba extract (GBE) with soy-derived phospholipids, improved secondary memory
performance and significantly increased speed of memory task
performance in comparision to post-dose testing sessions(599).
c. Cognitive impairment
Extracts of the leaves of
Ginkgo biloba showed to improve a range of conditions including memory and concentration problems, confusion, depression, anxiety, dizziness, tinnitus and headache, recognition, regeneration, understanding, and recitation(603), probably thought its action in increasing blood supply by dilating blood vessels, reducing blood viscosity, modification of neurotransmitter systems, and reducing the density of oxygen free radicals(600).
EGb761, acommercuial product of Ginkgo biloba at 240 mg/day, shawed to stabilize or slow decline in cognition, function, behavior, at 22-26 weeks (602).
Accoording to University of Oxford, the use of v ofr treatement of cognitive impairment appeared to be safe with no excess side effects compared with placebo, but with inconsistent results(601).
d. Etc.
References
(591)
http://thedao.com/ginkgo.htm
(592)
http://en.wikipedia.org/wiki/Ginkgo_biloba
(593)
http://www.ncbi.nlm.nih.gov/pubmed/11140327
(594)
http://www.ncbi.nlm.nih.gov/pubmed/22704410
(595)
http://www.ncbi.nlm.nih.gov/pubmed/12404671
(596)
http://www.ncbi.nlm.nih.gov/pubmed/16740301
(597)
http://www.ncbi.nlm.nih.gov/pubmed/17902186
(598)
http://www.ncbi.nlm.nih.gov/pubmed/11842916
(599)
http://www.ncbi.nlm.nih.gov/pubmed/17457961
(600)
http://www.ncbi.nlm.nih.gov/pubmed/19160216
(601)
http://www.ncbi.nlm.nih.gov/pubmed/12519586
(602)
http://www.ncbi.nlm.nih.gov/pubmed/25114079
(603)
http://www.ncbi.nlm.nih.gov/pubmed/24758078
2. Lemon balm
Lemon Balm is a perennial plant in the genus Melissa, belonging to the family Lamiaceae, native to southern Europe and the
Mediterranean region. The herb has been used in traditional medicine to treat nervous complaints(604), lower abdominal disorders(605) and as anti-inflammatory(608), antivirus(606), antibacterial agent(607).
a. Behavioral and psychological symptoms
According to Newcastle University, lemon
balm showed to alleviate behavioral and psychological symptoms in patient with
dementia (BPSD)(609), including anxiety(614). Lozenge, containing lavender oil, extracts from hops,
lemon balm and oat showed to induce a state of relaxation and regeneration for better cope with
psychological and emotional stress(610)(611) and attenuation of mood and anxiety(612). In behavior symttoms, administraion of combined valerian root and
lemon balm extracts, improved
symptoms of poor ability to focus decreased from 75% to 14%, hyperactivity from 61% to 13%, and impulsiveness from 59% to 22% as well as general social
behavior, sleep symptoms in children(613). On laboratory-induced psychological stress, the standardized M. officinalis extract, a significant increase in the speed of mathematical processing, with no reduction in accuracy were observed(617).
b. Cognitive performance and mood
A standardised M. officinalis preparation administered showed significantly in eradicated mood change and cognitive impairment(614), according to joint study lead by Swinburne University. Acute administration of Melissa officinalis (
lemon balm) in highest dose, cognition and mood in in both Secondary Memory and Working Memory factors(615)(616). The effective of the herb, probably through its function in Modulation of mood and
cognitive performance through lowering both nicotinic and muscarinic binding in healthy humans(616). Due to different preparations derived from the same plant species, some researchers suggested that the effectiveness may exhibit different properties depending on the process used for the sample preparation(616).
c. Etc.
References
(604)
http://www.ncbi.nlm.nih.gov/pubmed/21076869
(605)
http://www.ncbi.nlm.nih.gov/pubmed/19023806
(606)
http://www.ncbi.nlm.nih.gov/pubmed/18693101
(607)
http://www.ncbi.nlm.nih.gov/pubmed/24283351
(608)
http://www.ncbi.nlm.nih.gov/pubmed/22567036
(609)
http://www.ncbi.nlm.nih.gov/pubmed/22070157
(610)
http://www.ncbi.nlm.nih.gov/pubmed/15546807
(611)
http://www.ncbi.nlm.nih.gov/pubmed/15272110
(612)
http://www.ncbi.nlm.nih.gov/pubmed/16444660
(613)
http://www.ncbi.nlm.nih.gov/pubmed/24837472
(614)
http://www.ncbi.nlm.nih.gov/pubmed/25360512
(615)
http://www.ncbi.nlm.nih.gov/pubmed/12062586
(616)
http://www.ncbi.nlm.nih.gov/pubmed/12888775
(617)
http://www.ncbi.nlm.nih.gov/pubmed/15272110
3. Lavender
Lavender is a flower plant of the genus Lavandula, belonging to the family Lamiaceae, native to Asia. The herb has been used in traditional medicine as antimicrobial, anti-inflammatory and mood alleviating(618), and burns and insect bites effects(623), as well as depression, stress and mild anxiety(621) probably through its phytochemicals(constituents (-)-linalool, (+)-α-pinene and (+)-limonene ) in modulation of the immune and neuroendocrine system by interfering with metabolism of tryptophan(618).
a. Spatial performance
Lavender extract (LE, in AD animal model showed effectively in improvement of
spatial performance, through atentuation of Aβ production in histopathology of hippocampus(619) which involved in memory forming, organizing, and storing. Its aqueous extract of
lavender (
Lavandula angustifolia), also significantly improved the
performance of control and reverse
spatial learning amd memory deficits(621) in AD rats(620). Inhaled
lavender oil, oxidative stress induced rat, exhibited neuroprotective effects through its potent antioxidant and antiapoptotic activities(622).
b. Behavioural symptoms
Lavender aromatherapy, according to Kongju National University, is effective on emotions and aggressive behavior of elderly with dementia of the Alzheimer's type(624)and reduced disruptive behaviour in people with dementia(625). In agitated behaviour in severe dementia, 2%
lavender oil aromatherapy stream administered on the ward for a two hour period, showed a modest effects in compared with placebo(626). The effectiveness of the herb in reduced behaviours in individuals with
dementia potentially provide a safer intervention rather than reliance on pharmacology alone. The study's findings will translate easily to other countries and cultures(627).
c. Cognitive performance and Mood disorders
Aromatherapy applied to 28 elderly people with dementia, 17 of whom had Alzheimer's disease (AD), showed significant improvement in personal orientation related to
cognitive function on both the Gottfries, Brane, Steen scale (GBSS-J)and Touch Panel-type Dementia Assessment Scale (TDAS), according to Tottori University(628) and emotions and aggressive behavior of elderly with dementia, according to Kongju National University(629). In emotional parameters, lavender essential oil also significantly enhance mood responses, including anxiety(631)(633) and depression(632)(634) probably through its relaxing effect(630).
d. Etc.
References
(618)
http://www.ncbi.nlm.nih.gov/pubmed/25515049
(619)
http://www.ncbi.nlm.nih.gov/pubmed/25561935
(620)
http://www.ncbi.nlm.nih.gov/pubmed/21441971
(621)
http://www.ncbi.nlm.nih.gov/pubmed/22402245
(622)
http://www.ncbi.nlm.nih.gov/pubmed/23351960
(623)
http://www.ncbi.nlm.nih.gov/pubmed/?term=lavender+burns+and+insect+bites+effects
(624)
http://www.ncbi.nlm.nih.gov/pubmed/15860944
(625)
http://www.ncbi.nlm.nih.gov/pubmed/23837414
(626)
http://www.ncbi.nlm.nih.gov/pubmed/11994882
(627)
http://www.ncbi.nlm.nih.gov/pubmed/20649945
(628)
http://www.ncbi.nlm.nih.gov/pubmed/20377818
(629)
http://www.ncbi.nlm.nih.gov/pubmed/15860944
(630)
http://www.ncbi.nlm.nih.gov/pubmed/22612017
(631)
http://www.ncbi.nlm.nih.gov/pubmed/19968674
(632)
http://www.ncbi.nlm.nih.gov/pubmed/24559818
(633)
http://www.ncbi.nlm.nih.gov/pubmed/19258850
(634)
http://www.ncbi.nlm.nih.gov/pubmed/16520572
4. Huperzine A
Huperzine A, a chemical made from the plant Huperzia serrata have been studied for its effect on patient of dementia with conflict results
1. Cognitive effects
In induced Alzheimer's
disease animal study, Huperzine A showed a significant effect in inhibited acetylcholinesterase, derived from forebrain, hippocampus, cortex and cerebellum(635), through neuron protective effects and enhanced glutamatergic functions(635). In mild to moderate vascular
dementia (VaD) patients, The medicine also improved the cognitive function with serious adverse events(636). But according to University of California,, in a phase II trial of
huperzine A, regardless to doses,
huperzine A did not demonstrate cognitive effect in patients with mild to moderate AD(637). According to Beijing University of Chinese Medicinealthough
Huperzine A showed a beneficial effects on improvement of cognitive function, daily living activity in global clinical assessment in participants with Alzheimer's disease, the findings should be interpreted with caution due to the poor methodological quality of the included trials(638).
b. Inhibitiobn of amyloid plaque burden and oligomeric β-amyloid (Aβ)
Huperzine A, showed to reduce in Aβ levels and Aβ burden in AD brain, through activation of
Wnt signaling(regulate cell-to-cell interactions) and targeting of the Wnt/β-catenin signaling pathway in various components in contribution to disease, (639), modulation of amyloidogenic and nonamyloidogenic pathways(640), reduction of iron in the brain(641) via a multi-target mechanism(642).
c. Mild to moderate vascular dementia (VaD) and Alzheimer's disease
In patients with
mild to
moderate vascular dementia (
VaD), Huperzine A significantly improve the cognitive function in mini-mental state examination (MMSE), clinical
dementia rating (CDR), and activities of daily living (ADL) scores(643)(644).
In patients with Alzheimer's disease (AD), Huperzine A also showed improvement in memory function and cognitive enhancement at a dose of 0.4 mg using MMSE, MQ, ADAS-COG, and ADL tests(645); against organophosphate (OP) intoxication and reduction of glutamate-induced cell death(646). According to Georgetown University Hospital, the antioxidant and neuroprotective properties of Huperzine A suggest that it may be useful as a disease-modifying treatment for Alzheimer's disease (AD)(647).
Due to data supporting its use are limited by weak study design, theMassachusetts College of Pharmacy and Health Sciences-Worcester/Manchester suggested that randomized, placebo-controlled trials are necessary to establish the role of
huperzine A in the treatment of AD(648).
d. Etc.
References
(635)
http://www.ncbi.nlm.nih.gov/pubmed/9141073
(636)
http://www.ncbi.nlm.nih.gov/pubmed/21833673
(637)
http://www.ncbi.nlm.nih.gov/pubmed/21502597
(638)
http://www.ncbi.nlm.nih.gov/pubmed/24086396
(639)
http://www.ncbi.nlm.nih.gov/pubmed/?term=Huperzine+A+Wnt%2F%CE%B2-catenin+signaling+pathway
(640)
http://www.ncbi.nlm.nih.gov/pubmed/22002568
(641)
http://www.ncbi.nlm.nih.gov/pubmed/24332448
(642)
http://www.ncbi.nlm.nih.gov/pubmed/15956816
(643)
http://www.ncbi.nlm.nih.gov/pubmed/?term=Huperzine+A+and+Mild+to+moderate+vascular+dementia+(VaD)
(644)
http://www.ncbi.nlm.nih.gov/pubmed/24639880
(645)
http://www.ncbi.nlm.nih.gov/pubmed/21766442
(646)
http://www.ncbi.nlm.nih.gov/pubmed/12895686
(647)
http://www.ncbi.nlm.nih.gov/pubmed/18230054
(648)
http://www.ncbi.nlm.nih.gov/pubmed/19240260
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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