Hasegawa's Dementia Scale
One RCT using the Revised Hasegawa's Dementia Scale (HDS-R),20 and another one using the HDS18 were pooled together. The SMD was 0.09 (95% CI −0.28 to 0.46) using the fixed model, and there was no statistically significant difference in HDS score increase when comparing acupuncture with Western medicine (Figure 4).
Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog)
The MD was −5.14 (95% CI −8.75 to −1.53) in 1 RCT.17 There was a statistically significant difference between electroacupuncture and donepezil for reducing the ADAS-cog score (Figure 5).
Four RCTs were pooled together.17,20,21 (Ke YM, MD, unpublished data, June 2014) The MD was −2.80 (95% CI −4.57 to −1.02) using the fixed model, and there was a statistically significant difference between the effects of acupuncture and western medicine (Figure 6).
Functional Activities Questionnaire (FAQ)
The MD was −1.41 (95% CI −4.87 to 2.05) in 1 RCT.20 There was no statistically significant difference between acupuncture and nimodipine in improving the FAQ score (Figure 7).
Acupuncture Plus Donepezil Versus the Same Donepezil Alone
Three RCTs were pooled together.22–24 The MD was 2.37 (95% CI 1.53–3.21) using the fixed model, and there was a statistically significant difference between acupuncture plus donepezil and donepezil alone in improving the MMSE score (Figure 8).
The MD was −0.90 (95% CI −4.00 to 2.20) for 1 RCT.24 There was no statistically significant difference between acupuncture plus donepezil and donepezil alone in reducing the ADAS-cog score (Figure 9).
Montreal Cognitive Assessment (MoCA)
The MD was 2.00 (95% CI −0.89 to 4.89) for 1 RCT.22 There was no statistically significant difference between acupuncture plus donepezil and donepezil alone in increasing the MoCA score (Figure 10).
Two RCTs were pooled together.22,23 The MD was −2.64 (95% CI −4.95 to −0.32) using the fixed model. There was a statistically significant difference between acupuncture plus donepezil and donepezil alone in reducing the ADL score (Figure 11).
Acupuncture Versus No Treatment
The MD of 1 RCT25 was 3.74 (95% CI 1.34–6.14). There was a statistically significant difference between acupuncture and no treatment in increasing the MMSE score (Figure 12).
The MD for 1 RCT25 was −8.82 (95% CI −19.83 to 2.19) using the fixed model. There was no statistically significant difference between acupuncture and no treatment in reducing the ADL score (Figure 13).
There were 141 clinical studies with a total of 3416 AD patients treated by acupuncture or by acupuncture combined with other therapy. None of these studies reported any severe adverse events related to acupuncture. However, 2 trials ineligible for included in meta-analysis reported the incidence of adverse reactions related to acupuncture.28,29 One trial (experimental group treated by acupuncture, n = 15) reported 1 case of hemorrhage of local skin, 1 case of fatigue, 2 cases of feeling faint during acupuncture, and 2 cases of drowsy and sleepy feelings after acupuncture.27 The incidence of adverse reactions in this trial was 40%, and the percentage of patient compliance was 87.3%. The other trial that reported an adverse reaction was an observational study about AD treated by acupuncture (n = 103) that reported 1 case of dizziness and nausea during the treatment, giving an incidence of 0.97%.28 None of the remaining clinical trials reported any adverse reactions related to acupuncture.
AD is a chronic and progressive disease.29 There is currently no effective cure for this serious disorder,30 and adverse events have been reported to be correlated with pharmacological interventions.31 Acupuncture has shown effectiveness in improving cognitive function, and is progressively being used in more clinical practices.10 Ten RCTs were included in this meta-analysis, with a total of 585 participants that had their outcome measured using the MMSE scale.
One RCT concluded that acupuncture was better than no treatment in improving the MMSE score.25 However, meta-analysis was not possible for only a single RCT. Moreover, this single-centre trial was not designed to assess the patients at follow-up, and the sample size was too small to provide powerful evidence. Therefore, evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough.
The combined results of 6 RCTs showed that acupuncture was superior to drugs in improving the MMSE score, and acupuncture plus donepezil was better than donepezil alone in improving the MMSE score (Ke YM, MD, unpublished data, June 2014).17–21 However, there was too little information in these 10 RCTs regarding the processes of randomization and allocation concealment, which may have led to a high risk of selection bias. Additionally, only two17,25 out of the 10 RCTs blinded the statisticians, which may have led to considerable risk of bias. Inadequate information about missing data may also have potential attrition bias. One RCT was an unpublished thesis for a master's degree (Ke YM, MD, unpublished data, June 2014) and all of the included RCTs were conducted in China and published in Chinese, which may have led to publication bias. Moreover, none of the RCTs were designed to assess patients’ condition by follow-up for a period of time after treatment. So overall there was an inadequate number of high quality RCTs to provide powerful evidence.
Nevertheless, amongst the included 10 RCTs, a group of 5 RCTs17,21–24 (Ke YM, MD, unpublished data, June 2014) used donepezil and 1 trial used nimodipine;20 these 2 drugs are both strongly recommended by the British Association for Psychopharmacology for treating dementia.32 Although the drugs used in the remaining RCTs (amitrine and rubasine,18 hydroergotoxine,19 and piracetam21) have not been proven in evidence-based studies, they have been shown to improve cognitive function.30 Furthermore, memory impairment is the core symptom of AD,32 and memory is 1 part of cognitive function. The MMSE scale is the most commonly used measurement for assessing cognitive function,33 and the improved score compared with baseline was 3.72, which is the mean MCID.26 The MMSE score of 5 RCTs out of the included 10 RCTs compared with the baseline score was improved by more than 3.72 points,20–23 (Ke YM, MD, unpublished data, June 2014) which means the treatment of AD with acupuncture was clinically meaningful with respect to improving cognitive function.34 In general, the results of the meta-analysis were meaningful for clinical practice, and indicate that acupuncture may be better than drugs and may enhance the effect of donepezil in terms of improving the cognitive function of AD patients.
The symptoms of AD are also reflected in other ways besides impairment of cognitive function.29 One RCT showed that acupuncture did not reduce the ADL score,25 but meta-analysis is impossible for only 1 RCT; therefore the evidence on the effectiveness of acupuncture in improving the ability of AD patients to carry out daily life was insufficient. The combined results from 4 RCTs found that acupuncture was superior to drugs (donepezil,17 [Ke YM, MD, unpublished data, June 2014] nimodipine,20 and piracetam21) in reducing the ADL score; however, due to the lack of high quality studies, the power of the evidence is limited. Therefore we can only conclude that acupuncture may be more effective than drugs for improving the ability of AD patients to carry out daily living. Furthermore, assessment of improvement in the condition of AD patients as measured by other scales such as MoCA, HDS, ADAS-cog, and FAQ was limited by small sample sizes and an inadequate number of RCTs. This also meant that the evidence was insufficient to show the effectiveness of acupuncture to enhance the effect of drugs for treating AD.
It is difficult to conduct a meta-analysis due to the variety of symptoms and the low number of adverse reactions reported, so a description of adverse reactions was conducted. One hundred forty-one clinical studies with a total of 3416 AD patients treated by acupuncture or by acupuncture combined with another therapy were screened to assess the safety of acupuncture for treating AD. Adverse reactions related to acupuncture occurred in only 7 cases, in which the reactions were described as tolerable and not severe; none of the other studies mentioned any adverse reactions related to acupuncture. Therefore acupuncture is safe for treating patients with AD.
There are some limitations of our systematic review. We attempted to minimize publication bias by searching the databases of conference literatures and theses, and hand-searching the journals that were not included in the electronic databases; however, there were difficulties in obtaining all of the unpublished data, and only Chinese and English databases were searched. Reporting biases could not be detected by funnel plot due to lack of adequate RCTs. Moreover, all of the included RCTs only made the clinical diagnosis, but did not report the atrophy volume of the hippocampus of patients. In addition, none of the included RCTs assessed the condition of patients by follow-up after treatment. Finally, the included RCTs were all conducted in China, so more studies are needed to make the conclusions more applicable to other areas.
There are 2 other existing systematic reviews of acupuncture treatment of AD patients; 1 reviewed 3 trials and was published in 2009,35 and the other reviewed 8 trials and was published in 2012.36 These 2 reviews only included studies that compared acupuncture with drugs, and the effectiveness of acupuncture for enhancing the effect of drugs was not explored. The 2 previous reviews found no difference between acupuncture and drugs for improving the MMSE score or reducing the ADL score. Furthermore, the safety aspect of acupuncture was not mentioned in these 2 reviews. Our systematic review included more trials as it had different inclusion criteria for interventions.
In conclusion, the results of the meta-analysis indicate that acupuncture may be more effective than drugs, and may also enhance the effect of donepezil in improving the cognitive function of patients with AD. Acupuncture might also be more effective than drugs in improving the ability of daily living of patients with AD. Moreover, acupuncture is safe for treating patients with AD. For future research, the process of randomization and allocation concealment must be rigorously controlled and described, and more detailed methodologies need to be reported. There also needs to be more information provided in future studies about the diagnosis of AD, supported by the degree of atrophy of hippocampal volume as measured by MRI. A detailed description should be given of the data integrity and the methods used to deal with missing data. Well-designed trials with larger sample sizes are needed to provide reliable evidence on the effectiveness of acupuncture for treating AD.
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