Dementia is a progressive intellectual and functional impairment that affects memory and learning ability, activities of daily living, and quality of life. Dementia is a leading cause of mental and physical disability in the elderly and carries the highest disability weighting of all illnesses. In Australia, there were around 245,400 dementia patients in 2009, and this figure is estimated to reach 1.13 million by 2050 (Access Economics, 2009). The total cost of dementia to the Australian health system was estimated at $6.6 billion in 2002 representing 1% GDP and it may exceed 3% of GDP by 2050 (Access Economics, 2003).
Alzheimer’s disease (AD) is the most common form of dementia accounting for 80%–85% of all dementia cases. The pathogenesis of AD is heterogeneous and may include extracellular amyloid accumulation in the brain, formation of neurofibrillary tangles inside neurons, decreased central nervous system cholinergic function, genetic mutations (e.g., amyloid-precursor-protein gene), allelic variant of apolipoprotein-E (APOE), and lipid abnormalities (Drachman, 2003). Vascular dementia (VaD) that results from cerebrovascular and cardiovascular diseases is a second common dementia accounting for 15%–20% of the dementia population in Western countries (Ogata, 1999). In Asia and some developing countries, the prevalence of VaD is even higher, equaling or exceeding that of AD (Ogata, 1999). Between 1% and 4% of individuals over the age of 65 years old suffer from VaD (Aggarwal and Decarli, 2007), and this figure is doubled with each additional 5–10 years such that in individuals over the age of 85, the prevalence of VaD surpasses AD.
Several classes of pharmaceutical agents are currently used for the management of dementia, especially AD, among which cholinesterase inhibitors and glutamate receptor antagonists are suggested to produce best clinical outcomes (Farlow et al., 2008). However, these improved clinical outcomes are often limited to modest symptomatic relief, meaning that a large proportion of the disease burden lingers. Further, the safety and the long-term therapeutic benefits of these interventions remain uncertain. As such, currently available pharmaceutical appears unsatisfactory for the treatment of dementia.
Complementary and alternative medicine (CAM) has an extensive history of use worldwide, and several interventions have been explored as therapeutic options for the management and prevention of dementia. According to a recent U.S. national survey conducted by the National Centre for Complementary and Alternative Medicine, approximately 38% of U.S. adults aged 18 years and over and approximately 12% of children use some form of CAM (Barnes et al., 2007). The World Health Organization (WHO) estimates that almost 75% of the world’s population has therapeutic experience with herbal remedies (Dubey et al., 2004).
Traditional Chinese medicine (TCM) is an ancient, holistic health care system for promoting health and healing from various diseases and is one of the most popular and fast growing CAM therapies. The use of TCM for treatment of aging-related disorders dates back to 5000 years ago in China where herbal remedies were used to boost memory function and increase longevity. Treatment based on pattern identification is the essence of the theory of TCM. Although in recent years there has been an increase in the number of standardized proprietary herbal medicine products being developed for dementia, treatment based on individual pattern discrimination is still the most common method adopted by TCM practitioners. The common forms of Chinese medicine currently used in the management of dementia include Chinese herbal medicine, acupuncture, moxibustion and cupping, Qigong and Tai Chi exercise, Chinese massage therapy (Tuina), and Chinese nutritional or food therapy.
This post will provide an overview of the scientific evidence for the various Chinese medicine interventions used for the management of dementia focusing, in particular, on the herbal medicine and acupuncture, the two most commonly used modalities of TCM.
Herbal medicines have been used in TCM for thousands of years to boost memory and cognitive functions and to manage behavioral and psychological symptoms asso-ciated with dementia. Some of the most commonly used and studied herbs include Ginkgo biloba, Huperzia serrata, Curcuma longa, Panax ginseng, Panax notogin-seng, Salvia miltiorrhiza, and Melissa officinalis. Green tea (Camellia sinensis) is also considered to be beneficial for cognitive function owing to its antioxidant effects.
Gingko biloba
Ginkgo biloba leaf extract (ginkgo) is one of the most studied herbs. The principal active components in ginkgo are flavonol glycosides (e.g., quercetin and kaempferol) and terpenoids (e.g., ginkgolide and bilobalide). Various preclinical studies demonstrate that gingko’s neuroprotective effects derive from its ability to decrease oxygen radical discharge and pro-inflammatory functions of macrophages (antioxidant and anti-inflammatory), reduce corticosteroid production (anxiolytic), increase glucose uptake and utilization and ATP production, improve blood flow by increasing red blood cell deformability, decrease red cell aggregation, induce nitric oxide production, and inhibit platelet-activating factor receptors (Chan et al., 2007). In healthy young adults, ginkgo has been shown to improve speed of processing, working memory, executive function, and cognitive function (Kennedy et al., 2007). In clinical trials with dementia patients, however, the effectiveness of ginkgo for enhancing mem-ory and cognitive function remains controversial. Several early controlled clinical studies demonstrated various levels of improvement in memory loss, concentration, anxiety, and other symptoms associated with dementia (Howes and Houghton, 2003). For example, a randomized, double-blind, placebo-controlled trial of 216 partici-pants with AD or VaD showed significant improvement in the attention and memory function in the EGb761 (a standard ginkgo preparation)-treated group after 24 weeks treatment (Kanowski et al., 1996). However, the use of self-assessment question-naires in some of these early studies raises concerns regarding the validity of the results (Howes and Houghton, 2003). Several more recent clinical trials with greater participant numbers and longer intervention periods reported no difference between ginkgo and placebo (Schneider, 2008). As a result, a recently updated Cochrane sys-tematic review on the use of ginkgo for dementia concluded that the existing evi-dence is inconsistent and, therefore, unconvincing (Birks and Evans, 2009).
Possible Mechanismsof ActionPolyphenols (e.g., epigallocatechin)
Huperzia serrata
Huperzine A (HupA) is an alkaloid derived from the club moss, Huperzia serrata. It has been used to treat dementia in China and is sold over the counter as a dietary supplement in the United States for memory loss and mental impairment. Besides HupA’s well-known anticholinesterase property, it has been suggested to exert other pharmacological effects including antioxidant, anti-beta-amyloid peptide fragmentation, inhibition of oxygen–glucose deprivation, and NMDA receptor antagonism (Howes and Houghton, 2003). To date, the clinical trials of HupA have been mainly conducted and published in China. A meta-analysis of HupA for the treatment of AD identified 11 studies (one open-label study, two centre reports, and eight controlled clinical trials) among which four trials involving 474 patients (235 in the HupA treatment group and 239 in the control group) were included in the final analysis (Wang et al., 2009). The results demonstrated that HupA (300–500 µg/day) significantly improved cognitive function (as assessed by the mini-mental state examination [MMSE] and activities of daily living [ADLs]). A recent Cochrane systematic review conducted in China, which included six clinical trials with a total of 454 patients, also suggested that HupA may improve general cognitive function, global clinical status, behavioral disturbance, and functional performance with minimal side effects in AD patients (Li et al., 2009). A similar Cochrane review investigated HupA for VaD, but only identified one small study involving 14 participants in which HupA proved no better than placebo (Hao et al., 2009). However, as noted in these reviews, the lack of quality data, small sample sizes of individual clinical trials, and short intervention periods limit firm conclusions about HupA’s clinical efficacy and highlight the need for rigorous randomized controlled trials with large sample sizes.
Curcuma longa
The perennial herb Curcuma longa (turmeric) has been applied in therapeutic prepara-tions for centuries in different parts of the world, and is a well-documented treatment for various disease conditions including asthma, bronchial hyperactivity and respiratory allergy, liver disorders, anorexia, rheumatism, diabetic wounds, runny nose, cough, and sinusitis, as well as for neurodegenerative disorders (Goel et al., 2008). Turmeric contains three structurally closely related chemical components—curcumin, deme-thoxycurcumin, and bisdemethoxycurcumin, which together are commonly referred to as “curcumin” or “curcuminoids” (Goel et al., 2008). Commercially available “curcumin” extracts are often claimed to contain either 70% or 95% curcuminoids.
Data from various animal and/or in vitro studies suggest that curcuminoids possess antioxidant, anti-inflammatory, and cholesterol-lowering properties, all of which are key processes involved in pathogenesis of AD (Ringman et al., 2005). It has also been suggested that curcuminoids directly bind small beta-amyloid species to block aggregation and fibril formation, supporting the rationale for curcuminoids to be used therapeutically for AD (Yang et al., 2005). However, evidence from rigorous clinical trials to support this therapeutic claim is still generally lacking. In a large, population-based study, the relationship between consumption of curry (often contains turmeric) and cognitive function was investigated in 1010 elderly non-demented Asians (Singaporeans). The data demonstrated that consumption of curry containing turmeric was associated with significantly better cognitive performance measured by MMSE than those who “never or rarely” consumed curry containing turmeric (Ng et al., 2006). A randomized, double-blind, placebo-controlled trial was recently undertaken in 34 AD patients in Hong Kong to evaluate curcumin’s effect on AD. Six months treatment of one or four grams of curcumin did not significantly change the MMSE scores or other pathological parameters, although a trend toward increase in serum A040 emerged, which may represent an increase in disaggregation of Ap deposits by curcumin treatment. This study was one of the earliest attempts to evaluate the clinical effectiveness of curcumin for AD, in which several factors including small sample size, relatively short invention period, and lack of cognitive decline in the placebo group significantly limited the generalization of the findings. Several larger-scale clinical trials are currently underway or soon to be completed, and their results will no doubt help determine the therapeutic value of curcumin for the treatment and prevention of age-related dementia.
Panax ginseng
Panax ginseng (ginseng) root has been used for the management of AD in many Asian countries. Most of the cognition-enhancing effects of ginseng have been studied in animals and healthy individuals. The relevant principal bioactive components of ginseng are ginsenosides, which have been suggested to have antioxidant, anti-inflammatory, and anti-apoptotic effects (Radad et al., 2006). A recent in vitro study also demonstrated that ginsenoside Rg3 promotes beta-amyloid peptide degradation via enhancing gene expression (Yang et al., 2009).
Data from human studies suggest that ginseng modestly improves thinking and secondary and working memory in healthy volunteers (Kennedy et al., 2003; Reay et al., 2006). Two recent small, open-label trials demonstrated the potential therapeutic benefits of ginseng for AD (Heo et al., 2008; Lee et al., 2008). In the former study, 12 week treatment of low-dose (4.5 g/day; n = 15) and high-dose (9 g/day; n = 15) Korean ginseng showed significant effects on Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) and clinical dementia rating (CDR) when compared with those in the control group (n = 31) (Heo et al., 2008). In the latter study, in which 87 AD patients (n = 58 in the ginseng group; n = 39 in the control group) were involved, 12 weeks’ treatment with ginseng powder (4.5 g/day) produced significant improvements in ADAS-cog and MMSE scores (Lee et al., 2008). Ginseng has also demonstrated clinical benefits when combined with ginkgo in improving cognitive function in humans (Wesnes et al., 2000; Kennedy et al., 2001). Large-scale, long-term studies using standardized extracts are now required to confirm the clinical efficacy of ginseng therapy in AD.
Panax notoginseng
Panax notoginseng (San Qi) is commonly used in Chinese medicine to treat atherosclerosis, hypertension, various thrombosis, external injury, and pain. In addition, San Qi has been suggested to provide therapeutic benefits for dementia. In NG108- 15 cells senile dementia model induced by amyloid beta-peptide (AP), San Qi significantly increased the survival rate, differentiation, and growth rate of NG108-15 cells, suggesting that the herb can minimize the neural toxic effects of Ap (Liu et al., 2004). San Qi has also been shown to enhance learning and memory ability as well as to increase ACh content in hippocampus in Ap and ibotenic acid-induced dementia models in rats (Guo et al., 2004; Sun et al., 2007). Saponins (e.g., ginsenoside Rb1, Rd, Re, notoginsenoside R1, R2, R3, etc.) are the key bioactive components responsible for the neuroprotective effects of San Qi (Chen and Chen, 2004).
Salvia miltiorrhiza
Salvia miltiorrhiza (Dan Shen) is one of most popular Chinese herbs and has been used for the management of various diseases, especially cardiovascular diseases such as coronary artery disease, ischemic strokes, and cerebral thrombosis. Animal studies demonstrated that Dan Shen extracts produced neuroprotective effects and reversed learning and memory deficits in AD animal models (mice and rats) induced by beta-amyloid peptide treatment (Zhang et al., 2001; Liu and Li, 2007). In VaD models in rats, Dan Shen extracts have also markedly increased the content of ACh and 5-HT and decreased AChE activities in the brain tissue (Yuan et al., 2002).
In addition, it is reported that Dan Shen decreased the number of apoptosis of cranial nerve cells (Huang, 2002). The mechanisms of action underpinning these effects have been suggested to attribute to antioxidant, anti-inflammation, anti-cholinesterase, and CNS-sedatives effects, all of which are relevant to AD (Chen and Chen, 2004). Tanshinone has been suggested to be the key biomarker (He et al., 2009).
Crocus sativus
Crocus sativus (Xi Hong Hua) is commonly used in TCM as an antidepressant, antispasmodic, and anticatarrhal. Data from in vivo and in vitro studies demonstrated that Xi Hong Hua possesses neuroprotective properties. Xi Hong Hua extract has shown to improve learning and memory function in ethanol-induced memory impairment in mice and to ameliorate cerebral ischemia–induced oxidative dam-age in rat hippocampus (Abe and Saito, 2000; Hosseinzadeh and Sadeghnia, 2005). Crocitin, the principal constituent of Xi Hong Hua, which has a strong antioxidant, is suggested to be largely responsible for saffron’s protective effect on the central nervous system (Abe and Saito, 2000).
Camellia sinensis
Data from animal and epidemiological studies suggested that drinking green tea (Camellia sinensis) may help to protect the brain against the aging process. There is evidence that suggests a probable inverse correlation between tea consumption and the incidence of AD and other neurodegenerative diseases (e.g., Parkinson’s disease) (Sharangi, 2009). The chief bioactive components of tea are polyphenols, caffeine, and amino acids. Polyphenols are responsible for tea’s well-known antioxidant properties (Sharangi, 2009). In particular, its main catechin polyphenol constituent, epigallocat-echin gallate (EGCG), has been shown to exert neuroprotective/neurorescue activities in a wide array of cellular and animal models of neurological disorders (Mandel et al., 2008). In a human cross-sectional study assessing the effect of green tea on cognitive functions in elderly Japanese participants, it was reported that green tea consumption of two or more cups (100 mL per cup) per day reduced the prevalence of cognitive function impairments in the participant cohort (Kuriyama et al., 2006). More recently, Nurk and his colleagues (2009) examined the relationship between intake of three flavonoid-rich foods (chocolate, wine and tea) in the elderly participants aged between 70 and 74 years. The results showed that the consumption of these foods (especially tea) is associated with enhanced cognitive function in a dose-dependent manner (Nurk et al., 2009).
HERBAL FORMULATION AND SYNERGISTIc EFFEcTS
Combination therapy underpins the philosophy of Chinese herbal medicine, where patients are generally treated with multi-herbal formulations. There is preliminary evidence that complex chemical mixtures enhance therapeutic efficacy by facilitating synergistic action and/or ameliorating/preventing potential side effects (Kroll and Cordes, 2006; Wagner and Ulrich-Merzenich, 2009). Synergistic effects can occur in many ways, including for example, where constituents from herbal extracts interact with one another to improve their solubility and hence the bioavailability (Wagner and Ulrich-Merzenich, 2009). Furthermore, constituents of complex herbal extracts can affect different targets, which make them ideal therapies for disorders such as dementia, which have multifactorial/multisystem pathophysiological components (Kroll and Cordes, 2006). For example, clinical studies in healthy volunteers have found that the cognitive effects of a ginkgo–ginseng combination are significantly greater than those of either extract delivered alone, suggesting the possibilities of synergistic interactions between the extracts (Kennedy et al., 2001; Scholey and Kennedy, 2002).
Over hundreds of years of TCM clinical practice, numerous complex herbal formulations have been used for managing dementia-like symptoms. For example, Guipi decoction is a multi-herbs herbal formulation (Atractylodes macrocephala, Astragalus henryi, Arillus longan, Semen zizyphi spinosae, Radix ginseng, Radix aucklandiae, Radix glycyrrhizae, Radix Angelicae sinensis, and Radix polygalae), which was first used back in 1253 in China. Data from animal studies suggest that Guipi decoction can significantly improve learning and memory function in AD animal models in mice and rats (Hou and Xu, 2006; Qian et al., 2006; Zou et al., 2006). In the following section, research on a three-herb, standardized herbal formulation, WNK (which the authors have been partially involved) will be discussed to provide an example of the development of new herbal medicine formulations. Using modern chemistry, pharmacognosy, and pharmacology techniques, WNK’s chemical and pharmacological profiles were clearly defined. The data from these experiments demonstrate significant improvements in learning and memory functions, pathogenic biochemical parameters in blood and brain tissue, and antioxidant capacity in various experimental dementia models.
In an in vivo study, WNK (11, 22, and 44 mg/kg/day over 15 days) was administered to dysmnesia models in mice induced by scopolamine, reserpine, chlorderazin, sodium nitrite, and alcohol, respectively. Compared with the control, the middle- and high-dose treatment of WNK markedly decreased the error numbers and prolonged the latencies of dysmnesia in all active groups in step-through or step-down tests (Xu et al., 2007). In a chronic cerebral hypoperfusion model induced by bilateral common carotid artery ligation in rats, 8 weeks treatment of WNK (i.g.) significantly shortened the persistent time of finding the platform in Morris Water Maze (Xu et al., 2008). Activity of cholinesterase was also significantly decreased while the ACh level was markedly increased in the brain tissue. In addition, the activity of superoxide dismutase (SOD) was significantly enhanced. The effects of WNK on ACh were also investigated in an amyloid 0-protein-induced dementia model in rats (Liu et al., 2004). After 30 days treatment of WNK (15.5 and 31.0 mg/kg/day, i.g.), ACh levels in the brain tissue increased significantly by 18.56% and 19.97%, respectively, when com-pared with the model group. Similarly, in a PDAPPv7171 transgenic dementia model in mice, WNK treatment at 31 and 62 mg/kg/day i.g. over 12 weeks significantly increased ACh in both treatment groups, while serotonin (5-HT) levels in the brain tis-sue decreased significantly in the high-dose WNK group only (Cong et al., 2007). The effects of crocin alone (one of the principal active components of WNK) on ischemia/ reperfusion (I/R) injury were investigated using a global or bilateral common carotid artery occlusion (BCCAO) model in mice (Zheng et al., 2006). Transient global cerebral ischemia (20 min) followed by 24 h of reperfusion significantly increases the production of nitric oxide (NO) and malondialdehyde (MDA) in cortical microvascular homogenates and decreases the activities of superoxide dismutase (SOD) and glutathione peroxide (GSH-px). Pretreatment with crocin at 20 mg/kg, on the other hand, resulted in a significant decrease in MDA content and a significant elevation in total antioxidant capacity (increased SOD and GSH-px activities).
A pilot randomized, double-blind, placebo-controlled clinical trial of WNK for VaD in humans demonstrated some promising results (Liu et al., 2007). Sixty-two patients (32 in active group, 30 in placebo group) with probable or possible VaD according to the National Institute for Neurologic Disease and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDS-AIREN) criteria were recruited. Patients received 16 weeks treatment of either active or identical placebo after randomization. At completion of treatment, the mean scores of the primary efficacy parameter (ADAS-cog) reduced from 24.5 to 20.3 (mean reduction, 4.18 ± 0.75) in patients receiving WNK and from 18.98 to 17.81 (mean reduction, 1.18 ± 0.58) in patients receiving the placebo. While the minor differences in baseline ADAS-cog scores were not significantly different, the improve-ment of ADAS-cog scores following WNK treatment was significantly greater than that of the placebo group. WNK also significantly reduced the degree of impairment in quality of life caused by VaD as evidenced by the significant improvement in SF36 scores. Out of eight domains, significant improvements were observed in “role emo-tion,” “mental health,” “role physical,” and “social functioning” in patients receiving WNK while significant trends toward improvement were also noted in two other domains (“physical functioning” and “bodily pain”). Importantly, the results for ADAS-cog are consistent with the finding from a single photon emission computed tomography (SPECT) sub-study of 18 patients (n = 7 WNK; n = 11 placebo) within this trial. The SPECT scan results showed that when compared to the placebo, WNK treatment appeared to increase blood flow in the inferior frontal and anterior tempo-ral lobes, an effect which was more marked in the left hemisphere. These regions are known to be associated with cognitive, memory, auditory, and speech functions. No serious adverse events were reported within this trial.
Acupuncture is one of the main modalities of TCM and has gained popularity over the past decade in the Western world. In TCM, acupuncture is viewed as complex intervention comprising diagnosis, needling, lifestyle advice, therapeutic alliance, and adjunctive treatments such as moxibustion, cupping, and sometimes even Chinese herbs. Acupuncture is practiced widely by not only TCM practitioners but also medical doctors and other allied health practitioners including physiotherapists, chiropractors, nurses, and osteopaths; however, the latter groups tend to focus on the needling component. Acupuncture needling normally involves inserting fine needles into specific points on the body surface (acupoints) to promote circulation of qi and blood through the meridian channel systems and to restore the balance of yin and yang and, in doing so, to treat illness and promote health. Acupuncture has been used to treat various diseases including, pain, musculoskeletal injuries, and depression. There is also some evidence to suggest that acupuncture might provide therapeutic benefits in the management of dementia and associated symptoms (e.g., agitated and aggressive behaviors).
Acupuncture treatment has been found to improve cognitive and memory function in patients with dementia (especially VaD). In a study by Zhao et al. (2009), 90 VaD patients were randomized to receive electro-acupuncture, nimodipine, or electro-acupuncture plus nimodipine for 6 weeks. Significant improvements in MMSE scores were reported in all three groups compared with baseline. A similar finding was reported in a study that evaluated the effects of long-term retention of scalp needle on MMSE, Hastgawa dementia scale (HDS), activity of daily living (ADL), and latency and amplitude of event-related potential P300 of EEG in VaD patients (Chu et al., 2008). Here, 65 patients were randomly allocated to acupuncture (n = 33) and almitrine bismesylate (duxil). The total effective rates (compared to baseline) of MMSE, HDS, ADL, and the latency of P300 were significantly greater in the acupuncture group than those in the medication group. The results suggest that the scalp acupunc-ture treatment can improve cognitive function and activity of daily living in VaD. In another study by Lin et al. (2009), the combination of acupressure (a special acupunc-ture technique in which pressure is applied to acupoints, rather than needle insertion) and Montessori-based activities was found to be effective in relieving agitated and aggressive behaviors in 133 institutionalized residents with dementia in Taiwan.
In a positron emission tomography (PET) study, Huang et al. (2005) investigated whether acupuncture improved cerebral glucose metabolism in 10 patients with VaD. Half of the patients received acupuncture at LI15, SJ5, LI4, SP10, ST36, SP6, and LR3 (standard hemiplegia needling) whereas the other half received acupuncture at these same points plus DU20, DU26, and HT7 (VaD specific needling). The acupuncture was administered every weekday for four weeks, i.e., 20 sessions. Compared with baseline, standard hemiplegia needling increased glucose metabolism in the lentiform nucleus of the affected hemisphere and the temporal lobe of the non-affected hemisphere. The addition of VaD-specific needling increased glucose metabolism in the frontal lobes and thalami bilaterally as well as in the temporal lobe and the lentiform nucleus of the non-affected hemisphere, which is consistent with the results of a study using the same cohort of participants that showed a significant increase in blood circulation in response to acupuncture to the respective areas of the brain (Huang et al., 2006).
Despite the encouraging results from the aforementioned clinical trials, there are significant methodological limitations to most of these studies. Perhaps most importantly, these studies did not include placebo comparators, making it difficult to determine if the observed effects of acupuncture reflect its efficacy or some other processes, such as the placebo effect. Further, most of the studies had relatively small sample sizes. Weina et al. (2007) recently conducted a Cochrane review of acupunc-ture for VaD. The authors identified 95 relevant studies of which improvement was reported in up to 71%–90% of the treatment group. However, none of these trials met their inclusion criteria due to inadequate methodology. Of the 95 trials, only 17 were randomized controlled trial and these were limited due to combining interventions or providing pharmaceutical treatment to the control groups. This led to a conclu-sion that the effectiveness of acupuncture for VaD is uncertain and that high-quality randomized placebo-controlled trials of acupuncture are needed.
There has been substantial research into acupuncture needling on animals, most of which has been published in the Chinese literature. These studies attempt to determine mechanistic actions of acupuncture and are generally consistent with findings from clinical trials in terms of the potential cognition enhancing effects of acupuncture. For example, in VaD rats, animals given acupuncture needling performed better in subsequent tasks in a Morris water maze when compared with those in the control groups (Lai et al., 2000; Wang, 2002; Meng et al., 2009). The following mechanistic pathways have been postulated based on the existing animal studies.
Effects on neurotransmitter: Acupuncture is reported to reduce the activity of cholinesterase and hence slow down the ACh metabolism in the brain of VaD mice (Tian et al., 2002). An increase in expression of ChAT mRNA and ChAT protein– positive cells in the hippocampus of VaD rats was observed after acupuncture treatment, implying enhanced cholinergic neuron function (Ma and Tang, 2009). Acupuncture is also found to be able to reverse the dementia-induced reduction of 5-HT, dopamine, and noradrenalin in cortex, hippocampus, and hypothalamus (Lai et al., 1999). Electro-acupuncture can also increase the level of arginine vasopressin, an important neuropeptide closely related to memory and learning (Mo et al., 2002).
Effects on oxygen free radicals: Electro-acupuncture has been shown to increase the activity of superoxide dismutase (SOD) and decrease malondialdehyde (MDA), suggesting that the intervention promotes free-radical scavenging abilities and hence minimizes the tissue damage caused by the free radicals (Lai et al., 2000; Zhao et al., 2000).
Effects on vasoactive substances: Electro-acupuncture treatment was associated with an increase in nitric oxide (NO) content in hippocampus in VaD rats. This change correlated well with the improvement of learning and memory observed in the same animals (Lai and Yu, 2001). Acupuncture is also shown to increase 6-keto-PGF1 in plasma and this may be, at least partially, responsible for the beneficial antiplatelet aggregation and vasodilation effects of acupuncture in VaD (Tian et al., 2002).
Anti-apoptotic effects: Bcl-2 is an important anti-apoptotic gene. Ear acupuncture has shown to significantly increase expression of the anti-apoptotic Bcl-2 protein in CA1 region of hippocampus. The result suggests that acupuncture can provide protective effects to hippocampal neurons against apoptosis in VaD, and hence con-tribute to the improvement of learning and memory function (Zhang et al., 2001).
Other mechanisms: It is reported that electro-acupuncture increased the number and density of the neurons in CA1 area of hippocampal gyrus in VaD model in mice (Zhao et al., 2001). A study investigating the effect of electro-acupuncture on the cerebral circulation revealed that the treatment at Du20, Du14, and St36 increased the regional cerebral blood flow in the parietal lobe and hippocampus in VaD rats (He, 2002). Ear acupuncture has also shown to cause increased expression of c-fos mRNA and protein-positive cell in CA1 area of the hippocampus in VaD rat model (Zhang et al., 2001).
While these animal studies are suggestive of potential anti-dementia effects of acupuncture needling, it is unclear if and how these findings might generalize to humans and this needs to be investigated empirically.
Other Chinese medicine modalities that have been used in clinical practice to treat dementias and/or alleviate associated symptoms include (but are not limited to): Qigong exercise, Tai Chi, Tuina, nutritional or food therapies. The direct scientific evidence to support the use of these interventions for dementia is currently lacking, although there is some preliminary evidence regarding Qigong and Tai Chi, which is described in the following.
Qigong is an ancient and widely practiced Chinese meditation exercise combining meditation, controlled breathing, and gentle physical movements aimed at directing mental attention to specific area of the body (Posadzki et al., 2010). Qigong has been suggested to be able to control the vital energy (qi) of the body and consequently to improve spiritual, physical, and mental health (Jones, 2001). Medical Qigong can be divided into two parts: internal and external. The former is developed by individual practice of Qigong exercise. The latter refers to experienced Qigong practitioners emitting qi to a patient for the purpose of healing/curing diseases (Sancier, 1996).
Preliminary evidence suggests that Qigong practice can help to relieve stress and anxiety. For example, a clinical trial involving 24 generally healthy male participants found that Qigong significantly improved anxiety, alertness, depression, fatigue, and tension (Jung et al., 2006). It has also been reported that Qigong could normalize, stabilize, and sustain positive and pleasant emotional states of human mind and as a result improve the well-being and quality of life in humans (Posadzki et al., 2010). In a randomized controlled trial by Lee et al. (2005), heart-rate variability (HRV) was compared in 40 subjects receiving external Qigong or placebo. Here, Qigong significantly reduced heart rate and increased HRV, suggesting that the treatment stabilizes the sympathovagal function when compared with the placebo (Lee et al., 2005). EEG topographic mapping also revealed some unique EEG pat-terns in response to Qigong practice, which were clearly different from that of resting status with eyes closed (Zhang, 1988). The alpha activity occurred predominantly in the anterior half of brain during Qigong state. There were also significant increased alpha1 component and decreased alpha2 component, suggesting significant slowing of alpha peak frequency.
The mechanisms of action underpinning the observed physiological/psychological effects of Qigong are not clear. However, acute Qigong training has been associated with a significant increase in the levels of human endogenous opioids peptides (e.g., beta-endorphin) and a decrease in stress-related hormones including adrenocortico-trophic hormone (ACTH), cortisol, and dehydroepiandrosterone-sulfate (DHEA-S) (Ryu et al., 1996; Jones, 2001). These indicate that Qigong, when used as a stress coping method, can affect hormonal regulation to maintain neurological homeostasis.
Combined with evidence that Qigong can increase local cerebral blood flow (Cahn and Polich, 2006), this suggests that this type of exercise may have the potential to improve dementia symptoms or delay its onset.
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