| ObjectiveAlthough there are currently increasing clinical studies on the treatment of Alzheimer’s disease(AD) by combining traditional Chinese medicine (TCM) and Western medicine, the number of articles that have been systematically reviewed is insufficient for comparing the treatment of AD through a combination of Chinese and Western medicine, just Western medicine, and just TCM, as well as an insufficient number of articles that comprehensively and systematically study and consolidate the TCM treatment of AD. This study collected literature on randomized control studies published at home and abroad on AD treatment through a combination of Yiqibushenhuoxue prescription and Donepezil while aiming to compare the effectiveness and safety of AD treatment with an evidence-based medicine method, thus exploring TCM treatment through a combination of TCM and Western medicine as well as providing a clinical basis for AD treatment.Materials and Methods1. The efficacy and safety of AD treatment was evaluated using Chinese medicine of Yiqibushenhuoxue prescription combined with Donepezil. A systematic and comprehensive search strategy was developed, and was used to search literature included in the Chinese Biomedical Literature Database (CBM), the Chinese National Knowledge Infrastructure (CNKI), Wanfang database, the VIP database, the PubMed database, the EMBASE database, and the Cochrane Library by combining a manual search and other search methods. In addition, the searches spanned from the date the database was first created to September 2014. Inclusion criteria and exclusion criteria were determined according to the contents of objectives in different types of publications, and quality assessments were taken on these publications. General information, study design types, basic information about patients, basic information about intervening measures, and follow-up visit and outcome indicators were extracted. Review Manager 5.2 (software) was used to take a meta-analysis on data with the same indicators, and a sensitivity analysis was performed to check the stability of the meta-analysis. Clinical efficacy and safety of AD treatment were analyzed to compare the combination of Chinese medicine of Yiqibushenhuoxue prescription combined with Donepezil against just Donepezil. A subgroup analysis was performed on the group treated with the combination of Chinese medicine of Yiqibushenhuoxue prescription and Donepezil according to the treatment duration (less than six (6) months and over six (6) months).The measurement index, which cannot be quantitatively synthesized, and the incidence rate of very low events were qualitatively evaluated.2. For the rules of syndrome and treatment in TCM of AD, a combination of TCM and Western medicine was explored. Inclusion and exclusion criteria were determined, and were used to select randomized control studies on the combination of TCM and Western medicine for AD treatment. The therapeutic measures for patients in treatment groups included a combination of TCM and Western medicine or a combination of TCM, acupuncture, and Western medicine. Such literature on non-randomized control studies, repeated reports, vascular dementia, and other kinds of dementia were excluded. The databases for the searches are the same as abovementioned, and the searches spanned from the date the database was first created to September 2014. The title name, author, journal title, year of publication, and those described in the text (including Chinese medicine pathology, Chinese medicine therapy, and each applied herbal medicine) all needed to be extracted as well as unified and regulated. After processing uniformly, such data was inputted in Microsoft Office Excel 2003. A frequency analysis was taken on Chinese medicine pathology, Chinese medicine therapy, and each applied herbal medicine in order to collate the relevant data about AD. Descriptive statistics was taken, and frequency and percentage were considered as statistical methods.ResultsA comparison was made between the Chinese patent medicine Yiqibushenhuoxue combined with donepezil treatment group and the donepezil control group. Here,761 patients were included in nine (9) studies (380 cases in the treatment group and 381 cases in the control group), with a minimum sample size of 40 cases and maximum of 160 cases. The duration of treatment was three (3) months at least and 12 months at most. Four(4)studies were performed before 2011 and five(5)studies after 2011. Patients in the treatment group received the treatment of the Chinese patent medicine Yiqibushenhuoxue in combination with donepezil, and patients in the control group received donepezil treatment. The outcome indicators in each study were different, of which, three (3) studies reported the efficacy, nine (9) studies reported the mini-mental state examination (MMSE) score, nine (9) studies reported the activities of daily living (ADL) score, three (3)studies reported the ADAS-Cog score, two (2) studies reported the Hasegawa dementia scale (HDS) score, two (2) studies reported the clinical dementia rating (CDR) score, one (1) study reported the global deterioration scale (GDS) score, and eight (8) studies reported adverse reactions. Meta-analysis showed that the pooled RR= 1.26 [1.10,1.45]of the efficacy; the pooled MD= 2.78 [2.41,3.14]of the MMSE score; the pooled MD=-4.89 [-7.17,-2.62]of the ADL score; the pooled MD=-2.99 [-5.18,-0.81]of the ADAS-Cog score, and the pooled RR= 0.85 [0.52,1.40]of adverse reactions. The funnel plots were basically symmetrical. Through the sensitivity analysis there were not any change in the overall results.For outcome indicators reported in one (1) to two (2) studies, there was statistically significant difference between the treatment group and the control group after treatment. Patients were divided into subgroups according to the treatment duration (less than six (6) months and over six (6) months). Seven(7)studies with the treatment duration of more than six (6) months reported MMSE score, with the pooled MD= 2.50 [1.81,3.20] and the test for overall effect Z = 7.07, P<0.05. Two(2)studies with the treatment duration within six (6) months reported the MMSE score, with the pooled MD=2.15[0.27,4.02] and the test for overall effect Z= 2.24, P<0.05. The funnel plots in the two (2) subgroups were basically symmetrical. Although the pooled MD in the subgroup with the duration of treatment of over six (6) months was greater than that within six (6) months, the test of the difference between the two (2) subgroups showed P= 0.72> 0.05, indicating there was no significant difference between the two (2) subgroups.A comparison was made between the treatment group of Yiqibushenhuoxue decoction combined with donepezil and the donepezil control group. Here,492 patients were included in six (6) studies from China (246 cases in the treatment group and 246 cases in the control group), with a minimum sample size of 60 cases and maximum of 112 cases. The duration of treatment was one (1) month at least and six (6) months at most. Four (4) studies were performed before 2011 and two(2)studies after 2011. Patients in the treatment group received the treatment of the Yiqibushenhuoxue decoction combined with donepezil, and patients in the control group received donepezil treatment. The outcome indicators in each study were different, of which, five(5) studies reported the efficacy, five (5) studies reported the mini-mental state examination (MMSE) score, two (2) studies reported the activities of daily living (ADL) score, one(1)study reported the Montreal cognitive scale (MoCA) score, one(1) study reported the behavioral pathology rating scale of the Alzheimer’s disease (BEHAVE-AD) score, and two (2) studies reported adverse reactions. Meta-analysis showed that the pooled RR= 1.29 [1.06,1.58]of efficacy and the funnel plot was substantially symmetrical; the pooled MD= 1.56 [0.41,2.71]of the MMSE score and the funnel plot was asymmetrical, suggesting a bias. Through the sensitivity analysis there were not any change in the overall results. There was no significant difference in adverse reactions between the two groups. Other outcome indicators that were reported in only one (1) to two (2) studies showed significant difference between the treatment group and the control group after treatment. Patients were divided into subgroups according to the treatment duration (less than six (6) months and over six (6) months). There was one (1) report for the duration of treatment of more than or equal to six (6) months and five (5) reports for the duration of treatment less than six (6) months. One (1) study with the treatment duration over six (6) months reported the MMSE score, with the MD value of 1.24,95% CI [-0.36,2.84]. Four (4) studies with the treatment duration within six (6) months reported the MMSE score, with the pooled MD=1.62[0.25,2.99] and the funnel plots were basically symmetrical. Although the pooled MD in the subgroup with the duration of treatment over six (6) months was less than that within six (6) months, the test of difference between the two subgroups showed P= 0.72> 0.05, indicating there was no significant difference between the two(2)subgroups.A systematice review was made between the treatment of Yiqibushenhuoxue prescription and acupuncture combined with donepezil as well as the treatment of donepezil. Here,329 patients were included in five (5) studies from China (166 cases in the treatment group and 163 cases in the control group), with a minimum sample size of 38 cases and maximum of 86 cases. The duration of treatment was 28 days at least and six (6) months at most. Two(2)studies were performed before 2011 and three(3)studies after 2011. Patients in the treatment group received the treatment of acupuncture combined with donepezil in two(2)studies, and the treatment of Yiqibushenhuoxue decoction and acupuncture combined with donepezil in two studies, and the treatment of the Chinese patent medicine Yiqibushenhuoxue and acupuncture combined with donepezil in one (1) study. Patients in the control group received donepezil treatment. The outcome indicators in each study were different, of which, one(1)study reported the efficacy, five (5) studies reported the mini-mental state examination (MMSE) score, three (3) studies reported the activities of daily living (ADL) score, one(1)study reported the ADAS-Cog score, one(1)study reported the clinical dementia scale (CDR) score, one(1)study reported the Montreal cognitive scale (MoCA) score, one (1)study reported the tumor necrosis factor a, one(1)study reported the amyloid β,and one (1)study reported adverse reactions. Since similar intervening measures were taken in one (1) to two (2) studies, meta-analysis was not performed. Studies showed that there was significant difference between the treatment group and control group (P<0.05). In one(1)study, two(2)cases had nausea, loss of appetite, abdominal discomfort, and other adverse reactions, which were relieved after symptomatic treatment.For the rules of syndrome and treatment in TCM of AD, a combination of TCM and Western medicine was explored. There were 47 publications included, which were randomized control studies related to the combination of TCM and Western medicine, or the combination of TCM, acupuncture, and Western medicine.Approximately 12 types of pathogenesis were acquired after specifying and adjusting the TCM pathogenesis. The top 5 types of pathogenesis were deficiency of the kidney (37 times and accounts for 78.72%), blood stasis (25 times,53.19%), turbid phlegm (22 times,46.81%), deficiency of qi (11 times,23.40%) and deficiency of spleen (9 times,19.15%), indicating the main pathogenesis of AD were the deficiency of the kidneys, the spleen, and vital energy, and the main pathogenic factors are blood stasis and turbid phlegm. After combining the abovementioned TCM therapy, there were 13 kinds of therapeutic methods, and the top 5 therapies were tonifying kidneys (41 times,87.23%), promoting blood circulation to remove blood stasis (29 times, 61.70%), reducing phlegm for resuscitation (24 times,51.06%), tonifying vital energy (20 times,42.55%), and calming the mind and nerves (10 times,21.28%).From the 47 incorporated literatures, there were 146 kinds of herbal medicines, and the total applied frequency was 726. These 146 kinds of herbal medicines can be divided into 18 types. The most frequently used one was the drug for tonifying deficiencies (which was used 296 times and had 41 kinds), followed by the drug for promoting blood circulation to remove blood stasis (which was used 111 times and had 13 kinds). The other frequently used drugs were tranquilizers (which was used 47 times and had 10 kinds), heat-clearing drugs (which was used 44 times and had 14 kinds), resuscitation drugs (which was used 34 times and had 4 kinds), damp-clearing drugs (which was used 33 times and had 5 kinds), and drugs for relieving exterior syndromes (which was used 32 times and had 9 kinds). For the drug frequency, the top 5 drugs for tonifying deficiencies were the prepared rhizome of rehmannia (which was used 31 times and accounts for 65.96%), Astragalus membranaceus (which was used 23 times and accounts for 48.94%), licorice (which was used 21 times and accounts for 44.68%), Chinese yam (which was used 20 times and accounts for 42.55%), and ginseng (which was used 19 times and accounts for 40.43%). The top 5 drugs for promoting blood circulation to remove blood stasis were Ligusticum wallichii (which was used 26 times and accounts for 55.32%), Salvia miltiorrhiza (which was used 21 times and accounts for 44.68%), safflower (which was used 11 times and accounts for 23.40%), peach seed (which was used 11 times and accounts for 23.40%), Radix curcumae (which was used 10 times and accounts for 21.28%), and ginkgo leaf (which was used 10 times and accounts for 21.28%). The top 5 tranquillizers were Polygala tenuifolia (which was used 21 times and accounts for 44.68%), spina date seed (which was used 6 times and accounts for 12.77%), Poria cocos (which was used 6 times and accounts for 12.77%), Semen platycladi (which was used 4 times and accounts for 8.51%), cinnabar (which was used 3 times and accounts for 6.38%) and lucid ganoderma (which was used 3 times and accounts for 6.38%). The top 5 heat-clearing drugs were golden cypress (which was used 11 times and accounts for 23.40%), Coptis chinensis (which was used 6 times and accounts for 12.77%), rhizome of rehmannia (which was used 5 times and accounts for 10.64%), jasmine (which was used 4 times and accounts for 8.51%), Radix scrophulariae (which was used 2 times, and accounts for 4.26%). The total frequencies of the top 20 herbal medicines for AD treatment using the combination of TCM and Western medicine was 360, accounting for 50% of all herbal medicines. These top 20 herbal medicines are the main ones for treating AD, including prepared rhizome of rehmannia, Rhizome acori graminei, Ligusticum wallichii, Astragalus membranaceus, Poria cocos, Polygala tenuifolia, dogwood, Salvia miltiorrhiza, licorice, Chinese yam, ginseng, medlar, Polygonum multiflorum, Angelica sinensis, Herba epimedii, Fructus alpiniae oxyphyllae, Radix paeoniae alba, golden cypress, safflower, and peach seed.ConclusionFor the treatment of AD with the Chinese patent medicine Yiqibushenhuoxue combined with donepezil, as compared with donepezil, the treatment group could achieve a better and improved efficacy as well as dementia scale than those in the control group, with significant difference between them. Patients in the two (2) groups had mild adverse reactions, showing no statistical significance between them.For the treatment of AD with the Yiqibushenhuoxue decoction combined with donepezil, as compared with donepezil, the treatment group could achieve a better and improved efficacy as well as dementia scale than those in the control group, with significant difference between them. Patients in the two (2) groups had mild adverse reactions, showing no statistical significance between them.Compared with the donepezil treatment group, the treatment of Yiqibushenhuoxue prescription and acupuncture combined with donepezil could achieve a better and improved efficacy as well as dementia scale than those in the control group, with significant difference between them. Adverse reactions were mild, which could be relieved after symptomatic treatment.For the rules of syndrome and treatment in TCM of AD, a combination of TCM and Western medicine was explored. The main pathogenesis of TCM treatment of AD is the deficiency of the kidneys, the spleen and vital energy, and the main pathogenic factors are blood stasis and turbid phlegm. Treatment strategies of TCM for AD are to strengthen the kidneys, promote blood circulation to remove blood stasis, reduce phlegm for resuscitation, nourish the vitality, and calm the mind and nerves. From the incorporated literatures,146 kinds of herbal medicines were applied and the total applied frequency was 726. The herbal medicines of the top 5 frequencies were drugs for tonifying deficiencies, drugs promoting blood circulation to remove blood stasis, tranquilizers, heat-clearing drugs, and resuscitation drugs. The 20 kinds of herbs frequently used for treatment of AD were as follows:prepared rhizome of rehmannia, Rhizome acori graminei, Ligusticum wallichii, Astragalus membranaceus, Poria cocos, Polygala tenuifolia, dogwood, Salvia miltiorrhiza, licorice, Chinese yam, ginseng, medlar, Polygonum multiflorum, Angelica sinensis, Herba epimedii, Fructus alpiniae oxyphyllae, Radix paeoniae alba, golden cypress, safflower, and peach seed. |
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