The Effectiveness of Acupuncture Treatment for Patients with Alzheimer’s Disease: A Meta-Analysis of Randomized Controlled Trials
Article information
Abstract
The purpose of this study was to evaluate the effectiveness of acupuncture treatment for the symptoms of Alzheimer’s disease (AD). There were 11 databases searched for randomized controlled trials using acupuncture treatment for AD. The risk-of-bias assessment tool of the Cochrane Library was used to evaluate the quality of each study. Using the Review Manager (RevMan), a meta-analysis was performed using risk ratio, mean difference, 95% confidence interval, and random effect model. There were 32 studies selected, all of which were conducted in China. There were 16 studies where acupuncture was used as the intervention, and 23 studies used Donepezil as the control group. Acupoint GV20 was most frequently selected during the treatment. The Mini Mental State Examination (MMSE) was the most frequently used outcome variable. A period of 12 weeks was the most common treatment duration. As a result of meta-analysis (n = 25), acupuncture improved the MMSE and activities of daily living scores. Electroacupuncture improved the Alzheimer Disease Assessment Scale-Cognitive Subscale, and scalp acupuncture improved the MMSE score for AD. Acupuncture alleviates the symptoms of AD. However, further research is necessary to provide a better level of evidence.
Introduction
Dementia is a syndrome comprehensively referring to the decline in cognitive functions like memory, orientation, daily life problems, insensitivity, depression, anxiety, delusions, hallucinations, and wandering, and behavioral and psychological symptoms of dementia (BPSD). There are various stages of dementia, and Alzheimer disease (AD) is the most common cause (55–70% of all dementia patients) [1]. Other common causes include vascular dementia, Lewy body dementia, and frontotemporal lobar degeneration.
AD is characterized by the progressive damage of cognitive function, and in about 80% of all patients, BPSD appear which may cause deterioration in the patients quality of life and cause suffering for patient and their caregivers [2].
The prevalence rate of dementia in Korea in the population aged 65 years and over has gradually increased from 9.54% in 2015, to 10.29% in 2019, and in particular, the ratio of AD amounts to about 70% of all cases of dementia. In the total elderly population, AD has a high prevalence rate (7%). Medical care benefit costs for dementia amounted to 1.29 trillion won in 2015, and 1.95 trillion won in 2019, which causes a huge social economic burden [3].
At present, there are no treatments for AD just treatments for temporarily alleviating or delaying symptoms e.g. drug therapy like acetylcholinesterase inhibitors (e.g. Donepezil) and glutamate receptor antagonist (e.g. Memantine), and therapies and activities (e.g. cognitive rehabilitation with occupational therapy, cognitive stimulation such as art therapy, music therapy, or exercise therapy, and reminiscence therapy) [4].
Korean medicine treats AD using reminiscence therapy, cognitive function training mixed with Korean medicine treatment (such as acupuncture, moxibustion, and herbal medicine [5]). Various studies have been conducted to verify the effect of Korean medicine treatment on AD. In the published studies of herbal medicine treatment for AD, case reports and the assessments of the effects of oriental medicine have been published [6,7], while in the studies of acupuncture treatment of AD, case reports and studies of acupuncture with magnetic resonance imaging scans have been published [8,9]. In addition, meta-analysis studies of the effect of acupuncture were also reported [10–12]. However, most of the existing meta-analysis studies did not reflect the latest data since they included studies conducted before 2017, and did not reflect the treatment of AD in Korea [10–12]. Thus, the studies conducted in Korea and internationally until June 2020, were included in this literature review to assess the effect of acupuncture on the improvement of symptoms of AD.
Materials and Methods
Search Strategy
Korean databases [National Digital Science Library (NDSL), Korean studies Information Service System (KISS), Research Information Sharing Service (RISS), KoreaMed, Korean Medical dataBASE (KMBASE), and OASIS], and international databases [PubMed, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), China Academic Journal (CAJ), and Scholarly and Academic Information Navigator (CiNii)] were used to retrieve articles before June 15th, 2020.
The core search was based on the Medical Subject Headings (MeSH) of the National Library of Medicine. The patient group was only patients with AD and the intervention was only acupuncture. There were no restrictions placed on the publication year, language, or country of study. Titles and abstracts were searched using MeSH terms according to each academic database (Table 1).
Criteria for selection and exclusion
Selection criteria
Patients in studies who were diagnosed with AD based on diagnostic criteria as described in The Diagnostic and Statistical Manual of Mental Disorders (DSM) [2], National Institute of Neurological and Communicative Disorders and Stroke and the AD and Related Disorders Association (NINCDS-ADRDA) [13,14], National Institute of Aging and Alzheimer Association (NIA-AA) [15], or International Classification of Diseases (ICD) [16] were included in this review.
Acupuncture treatment for AD that was part of a clinical study or a randomized controlled trial which verified the effectiveness of the acupuncture treatment (without restrictions placed upon the intervention or the control group).
Exclusion criteria
Studies that were unable to verify the effectiveness of the acupuncture treatment for AD, used human cell culture or animal models, was a literature review, a case report, or an observational study, and a study for which the full text was not accessible.
Measurement tools for the outcome variable
The Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) were used to assess cognitive function. Activities of Daily Living (ADL) was used to assess the activities in daily life. Dementia Neuro-Psychiatric Inventory (NPI) was used to assess BPSD, and the effective rate (the ratio of people who showed treatment effect to the number of subjects in each group) was used to measure the outcome variable [17].
Data extraction
Study selection
One researcher searched for articles based on the inclusion criteria, and another reviewed the results. The title and abstract were checked in the first screening process, and the full text was checked in the second screening. If necessary, the selection of an article was in agreement between the researchers. If the data were incomplete, the authors were contacted using the corresponding author email address on the publication, and if communication was not possible, the study was excluded.
Data extraction
One researcher extracted information from each study and prepared a summary table of demographic information, intervention, treatment duration, outcome variables, and side effects of the 32 included studies. Another researcher reviewed that process.
Risk-of-bias assessment
There were 2 independent researchers who assessed the risk of bias (RoB), using the Revised Cochrane RoB tool for randomized trials. If the assessments by each researcher were different, the RoB was decided by agreement between the 2 researchers.
Meta-analysis method
The therapeutic effect was assessed using 2 or more studies in the Review Manager (RevMan) Version 5.4.0 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Analysis was performed using risk ratio (RR) as a dichotomous variable and mean difference (MD) as a continuous variable. A random-effect model with a 95% confidence interval (CI) was used for the meta-analysis. The heterogeneity between studies was evaluated, using the Chi-square test and Higgin’s I2 statistics (I2), an I2 of more than 50% indicated heterogeneity between the studies. If heterogeneity was confirmed, neither subgroup analysis nor meta-regression was performed.
Publication bias assessment
When there were more than 10 studies with matching intervention and outcome variables, publication bias was assessed using the funnel plot in RevMan.
Results
Search results
There were 2,192 studies initially retrieved from the selected databases. There were 60 articles retrieved from previously published meta-analysis studies resulting in a total of 2,252 studies. Excluding 999 duplicate articles the first screening resulted in 1,253 articles. The full texts were checked in the second screening where the criteria for selection and exclusion were used. There were 32 studies included in this review. The process of selecting the articles is shown in the PRISMA flow chart (Fig. 1), and the summary of study selection is described in Table 2.
Characteristics of the selected studies
Year and country of publication
Of the 32 included studies, 1 was published before 2000; 5, between 2000 and 2010; and 26, after 2010. There was 1 study published in 1999; 1, in 2002; 1, in 2007; 1, in 2008; 1, in 2009; 1, in 2010; 1, in 2013; 10 in 2014; 3, in 2015; 1, in 2016; 2, in 2017; 5, in 2018; 2, in 2019; and 2, in 2020. All studies were conducted in China. There were 3 studies written in English, and 29 studies written in Chinese.
Sample size
There were 2,210 patients across the 32 randomized controlled trials, of which 35 patients dropped out of 4 studies, 2,175 patients remained. The minimum sample size was 30, and the maximum was 141. The number of patients in the intervention group was between 15 and 72, and there were between 14 and 69 in the control group.
Evaluation of results
The duration of treatment in each study was between 20 and 180 days. There were 7 studies which treated patients for 8 weeks; 4, for 4 weeks; and 3, for 3 months. There were 8 which had various treatment periods between 20 and 180 days. As for evaluation indices, the MMSE was used in 27 out of the 32 studies. The effective rate was used in 22 studies. ADL was used in 16 studies; ADAS-cog, in 8 studies; and NPI, in only 1 study [39]. In most studies, the evaluation was performed before and after the treatment, and in 1 study, an intermediate evaluation was performed at Week 6 of the 12-week treatment period [24]. Of all the studies, 3 studies had a follow-up period, which was 12 weeks after the treatment [29,39,46].
Intervention
A total of 16 studies used acupuncture treatment as an intervention. Of those, 9 studies used acupuncture alone. There were 3 studies that used herbal medicine in combination with acupuncture; 3, Western medicine and 1, a placebo [42]. There were There were10 studies that performed electroacupuncture treatment. There were 6 studies that used electroacupuncture alone; 2, herbal medicine in combination with electroacupuncture; and 2, Western medicine. There were 4 studies that used scalp acupuncture, and no electrical stimulation was used in parallel. Of those, 3 studies used Western medicine in combination with scalp acupuncture, and 1 study used scalp acupuncture alone. There was 1 study that used warm needle acupuncture and 1 study that used fire needle acupuncture. Both studies used acupuncture and Western medicine as the intervention.
Control group
As for the number of control groups, 29 studies used 1 control group, and 3 studies used 3 control groups [19,23,36]. There were 29 studies that used Western medicine as the control group. Of those, 23 studies used Donepezil; 3, Nimodipine; 1, Almitrine and Raubasine complex; 1, Huperzine A; and 1, used a placebo. There was a total of 6 studies that used herbal medicine as the control group. The control group for each type of intervention group was as follows. The intervention group that used acupuncture treatment used Nimodipine in 1 case; Donepezil, in 12; Almitrine and Raubasine complex, in 1; Korean medicine, in 3; placebo, in 1 as the control group. The intervention group that used electroacupuncture treatment used Donepezil in 6 cases; Nimodipine, in 2; Huperzine A, in 1; and Korean medicine, in 2 as the control group. The intervention group that used scalp acupuncture treatment used Donepezil in 3 cases and herbal medicine in 1 case as the control group. The intervention group where warm and fire needle acupuncture was used, Donepezil was the control group.
Acupoints
In 32 studies, a total of 73 acupoints were used 218 times. There were 16 scalp acupoints used in 4 studies. There was 1 study that used eye acupuncture in addition to acupuncture, so 4 additional eye acupoints were included [22]. Throughout all studies, GV20 was used the most (in 24 studies). ST36 was also used (in 12 studies); and EX-HN1 (in 10 studies). For acupuncture intervention, GV20, ST36, GB39, LR3, EX-HN3 were mostly used. In 10 studies that used electroacupuncture, GV20 was used the most (in 7 studies). GV14, GV16, GV24 were also used (in 3 studies; Table 3).
Adverse events
Of 32 studies, 5 studies mentioned that adverse events had occurred in the study. Li et al [27] reported that no adverse events occurred in the study. Gu et al [26] reported bleeding and pain in the acupuncture intervention group, there was 1 case of gastrointestinal disorder, and 8 cases of loss of appetite, nausea, diarrhea, and insomnia in the Donepezil control group. Feng et al [46] reported pain in 2 patients who underwent acupuncture treatment and a local hematoma in 1 patient. Zhang et al [47] reported 2 cases of nausea and vomiting in the group using fire needle acupuncture and Donepezil. They also reported 2 cases of diarrhea, 5 cases of nausea, and 1 case of insomnia in the Donepezil monotherapy group. Jia et al [39] reported that a condition not related to AD improved after acupuncture treatment, including 5 cases of insomnia, 4 cases of constipation, 6 cases of benign prostatic hyperplasia, and 2 cases of knee joint disease.
RoB assessment
Random sequence generation
In 2 studies, the RoB was high because patients were assigned to a group according to the sequence of visits and treatments in random allocation [22,28]. Nine studies were judged to have an unclear RoB since they did not mention the method of random allocation. In the remaining 21 studies, the RoB was low because patients were randomly allocated using the tables of random numbers or drawing lots.
Allocation concealment
In 4 studies, the allocation sequence was concealed, using a sealed envelope [39,46,48,49]. The other 28 studies did not mention allocation concealment.
Blinding of the study to participants and personnel
Although all 32 studies did not mention blinding, it was judged that the blinding of the study to participants and personnel was not performed due to the nature of the intervention since all studies compared acupuncture treatment with herbal medicine or Western medicine. Thus, the RoB in all studies was judged to be high.
Blinding of outcome assessment
The RoB in only 2 studies was judged to be low due to blinding of the study to the assessor [39,46], the remaining 30 studies were judged to be unclear because it was not mentioned.
Incomplete outcome data
The RoB of 1 study was judged as unclear because the total number of patients or the number of dropouts was not mentioned in the outcome variables [24]. The RoB of the remaining 31 studies was judged to be low because the occurrence of dropouts or the inclusion of statistics of the dropouts was mentioned, or the study was completed without dropouts.
Selective reporting
RoB for selective reporting were unclear in all 32 studies.
Effectiveness evaluation
Of 32 studies, 7 studies were excluded because they did not use the same intervention and outcome variables. Therefore, a total of 25 studies were used for meta-analysis.
Acupuncture versus Donepezil
In 7 studies, acupuncture treatment intervention groups had statistically significantly improved the MMSE scores in AD patients compared with Donepezil [MD = 1.57, 95% CI (0.29, 2.86), I2 = 88%, Z = 2.40, p = 0.02]. Acupuncture significantly improved ADL scores in 5 studies [MD = −2.22, 95% CI (−2.81, −1.62), I2 = 0%, Z = 7.29, p < 0.00001] and the effective rate in 6 studies [RR = 1.42, 95% CI (1.20, 1.67), I2 = 17%, Z = 4.12, p < 0.0001]. In 2 studies which compared the acupuncture treatment intervention group with Donepezil, acupuncture treatment did not show a significant improvement in ADAS-cog scores [MD = −1.49, 95% CI (−4.64, 1.65), I2 = 0%, Z = 0.93, p = 0.35]. For BPSD, there was 1 study that compared acupuncture with Donepezil, but it did not show any statistically significant differences [MD = −0.36, 95% CI (−1.46, 0.74), Z = 0.64, p = 0.52; Fig. 4].
Acupuncture plus Donepezil versus Donepezil
In 3 studies that compared acupuncture and Donepezil combined treatment intervention group with Donepezil monotherapy, acupuncture significantly improved the ADL scores [MD = −3.12, 95% CI (−4.56, −1.69), I2 = 61%, Z = 4.25, p < 0.0001]. There were no statistically significant differences in 3 studies that compared the acupuncture and Donepezil combined treatment intervention group with the Donepezil monotherapy using the MMSE score [MD = −0.04, 95% CI (−2.88, 2.79), I2 = 97%, Z = 0.03, p = 0.98]. For ADAS-cog score [MD = −1.57, 95% CI (−4.37, 1.24), I2 = 79%, Z = 1.10, p = 0.27] and effective rate [RR = 1.72, 95% CI (0.75, 3.97), I2 = 72%, Z = 1.27, p = 0.20], and when the acupuncture and Donepezil combined treatment intervention group was compared with Donepezil monotherapy, it did not show statistically significant differences (Fig. 5).
Acupuncture versus herbal medicine
There were 2 studies that compared acupuncture with herbal medicine which did not show statistically significant differences in effective rate [RR = 1.01, 95% CI (0.81, 1.28), I2 = 0%, Z = 0.12, p = 0.90; Fig. 6A].
Acupuncture plus herbal medicine versus herbal medicine
There was no significant difference in the comparison of acupuncture and herbal combined treatment intervention group with herbal treatment alone in the effective rate [RR = 1.14, 95% CI (0.93, 1.39), I2 = 0%, Z = 1.29, p = 0.20; Fig. 6B].
Electroacupuncture versus Western medicine
There were no statistically significant differences in the 4 studies that compared electroacupuncture intervention treatment with Donepezil using the MMSE score [MD = 1.35, 95% CI (−0.01, 2.72), I2 = 55%, Z = 1.94, p = 0.05]. Electroacupuncture did not show statistically significant differences compared to Nimodipine in ADL scores [MD = 2.53, 95% CI (−1.70, 6.77), I2 = 91%, Z = 1.17, p = 0.24]. In the comparison between electroacupuncture and Nimodipine [RR = 0.76, 95% CI (0.53, 1.08), I2 = 0%, Z = 1.52, p = 0.13] and the comparison between electroacupuncture and Donepezil [RR = 1.17, 95% CI (0.98, 1.39), I2 = 0%, Z = 1.78, p = 0.08], there were no significant differences (Fig. 7A).

Meta-analyses of (A) electroacupuncture versus western medicine and (B) meta-analyses of electroacupuncture plus Donepezil versus Donepezil.
MMSE, mini-mental state examination; AT, manual acupuncture; ADL, activities of daily living; ADAS-cog, the Alzheimer’s disease assessment scale-cognitive subscale.
Electroacupuncture plus Donepezil versus Donepezil
In ADAS-cog score, 2 studies that compared the improvement between the electroacupuncture and Donepezil combined treatment intervention group, with the Donepezil group, the electroacupuncture group showed a significant improvement [MD = −3.36, 95% CI (−5.18, −1.54), I2 = 0%, Z = 3.62, p = 0.0003; Fig. 7B].
Electroacupuncture plus herbal medicine versus herbal medicine
In a comparison of electroacupuncture and herbal medicine combined treatment intervention and herbal medicine monotherapy, the improvement of electroacupuncture on the effective rate showed a statistically significant difference [RR = 1.35, 95% CI (1.09, 1.68), I2 = 0%, Z = 2.75, p = 0.006]. There were no statistically significant differences in 2 studies that compared the electroacupuncture and herbal medicine combined treatment intervention group, with the herbal medicine monotherapy group using the MMSE score [MD = 5.16, 95% CI (−0.62, 10.94), I2 = 96%, Z=1.75, p = 0.08] and the ADL scores [MD = −5.80, 95% CI (−13.42, 1.82), I2 = 90%, Z = 1.49, p = 0.14; Fig. 8].
Scalp acupuncture plus Donepezil versus Donepezil
In 3 studies that compared the scalp acupuncture and Donepezil combined treatment intervention group with the Donepezil monotherapy group, the effect of acupuncture on the improvement of the MMSE score was statistically significant [MD = 1.81, 95% CI (0.13, 3.49), I2 = 0%, Z = 2.11, p = 0.03]. There were no statistically significant differences between the comparison of scalp acupuncture and Donepezil combined treatment intervention group, with Donepezil alone using the ADL score [MD = −2.02, 95% CI (−4.72, 0.67), I2 = 66%, Z = 1.47, p = 0.14; Fig. 9].
Warm acupuncture plus Donepezil versus Donepezil
In 1 study, the warm acupuncture and Donepezil combined treatment intervention group was compared with Donepezil alone, and warm acupuncture improved the MMSE score [MD = 2.03, 95% CI (0.08, 3.98), Z = 2.04, p = 0.04] and effective rate [RR = 1.37, 95% CI (1.01, 1.86), Z = 2.01, p = 0.04] [45].
Fire acupuncture plus Donepezil versus Donepezil
In 1 study that compared fire acupuncture and Donepezil combined intervention treatment with Donepezil monotherapy, fire acupuncture improved the MMSE score [MD = 5.09, 95% CI (4.12, 6.06), Z = 10.32, p < 0.00001], the ADL score [MD = −2.93, 95% CI (−4.45, −1.41), Z = 3.78, p = 0.0002], and the effective rate [RR = 1.31, 95% CI (1.01, 1.70), Z = 2.05, p = 0.04] [47].
Publication bias assessment
Publication bias could not be assessed due to an insufficient number of studies included by intervention and outcome variables.
Discussion
AD accounts for the largest cause of dementia in sufferers, causing a decline in the quality of life for patients (and caregivers) due to the deterioration of cognitive function, decrease of daily living activity, and various BPSD. In addition, with an aging population the prevalence rate of AD will increase, and it is expected that there will be an enormous social and economic expense in the long-term [1].
Acupuncture is the easiest and most accessible treatment for patients in the clinical setting. Li et al. conducted acupuncture in an AD rat model and reported that hippocampal nerve cell loss decreased, and action performance ability increased [50]. Using functional magnetic resonance imaging Zheng et al. reported that acupuncture activated the sections in the brain that related to cognitive function in patients with AD [9]. Similarly, other studies mentioned the potential of acupuncture in the improvement of AD [8,10–12].
AD is diagnosed using as clinical symptoms, cytopathological examination, and radiological findings, and typically, diagnosis is based on The DSM 5, ICD-10 and NINCDS-ADRDA [17]. Some studies grouped AD with senile dementia however, AD is a cause of senile dementia just as vascular cognitive impairment causes dementia making AD difficult to identify. Diagnostic criteria for AD may also be country dependent [51,52]. Thus, this review selected studies where patients were diagnosed with AD based on the diagnostic criteria used most often internationally (e.g. DSM, NINCDS-ADRDA, and ICD-10) and NIA-AA diagnostic criteria which was developed relatively recently [15].
In this review studies using acupuncture, electroacupuncture, fire acupuncture, and warm acupuncture were included, and pharmacopuncture and thread-embedding were excluded. Scalp acupuncture to stimulate the brain was separately classified from acupuncture stimulating the meridian point. Electroacupuncture is applied in parallel with acupuncture to increase the intensity of needle stimulation and add continuous and periodic stimulation. Since the stimulation of electroacupuncture has a different pattern or strength to activate the brain compared with acupuncture [53], it was separately classified, due to the possibility that it may affect the improvement of symptoms of AD.
Western medicine and herbal medicine were used as control groups in the studies included in this review, most studies used Western medicine, in particular Donepezil which is used to improve cognitive function. Donepezil is an acetylcholinesterase inhibitor, inhibiting the breakdown of the neurotransmitter acetylcholine to increase the level and duration of a signal to improve nerve cell communication and cognitive function [4]. Almitrine-Raubasine is a combination drug used for hypomnesia due to senile brain dysfunction, and in 2008 Liu used it in the control group (not currently licensed in South Korea) [54]. Nimodipine is a calcium channel blocker and a potent cerebral vasodilator, mainly used for the treatment of ischemic neuropathy. In the past, it was used to treat AD, but recently, research on the improvement of cerebral blood flow in vascular dementia has been conducted. Of the literature included in this study, 2 studies used Nimodipine in the control group. Maybe nimodipine would be more appropriate for patients with vascular dementia rather than AD [55,56]. Huperzine A is a plant extract that has been reported to have a significant effect on the improvement of cognitive functions of patients with AD and vascular dementia, and as a cholinesterase inhibitor it improves the level of neurotransmitter available. One study reported that in an animal model, Huperzine A had a stronger effect on the suppression of cholinesterase than Donepezil [57], and a meta-analysis study was reported that the MMSE and ADL scores of patients with AD significantly improved [58]. In this review Huperzine A was used as in the control group and was used less frequently than Donepezil [40]. Thus, it is assumed that its use in the clinical setting is low, and it is necessary that further clinical studies are conducted [58].
There were 6 studies that used herbal medicine in the control group, and 6 different prescriptions were used. Angelicae Gigantis Radix was prescribed 3 times, and Salviae Miltiorrhizae Radix, Poria Sclerotium, and Cnidii Rhizoma were used 2 times. Typically, medicine that controls the blood are used [59]. It was difficult to find the relevance between the prescriptions used in each study. However, Korean medicine treatment has the merit that it considers the patient’s symptoms and conditions so, as long as prescriptions are written according to the Pattern Identification within AD in the future, this will support a higher level of evidence.
This review assessed outcome variables from studies that used the MMSE, ADL, and ADAS-cog scores, NPI, and the effective rate of treatment. Many studies used functional magnetic resonance imaging scans and cytopathological examination as outcome variables [35,42,60]. Although it would not be realistic to presume that these tests could be run as the outcome variable in the typical Korean medicine clinical setting. Analysis of the selected literature showed that the MMSE, the screening inspection of dementia, and the assessment of cognitive function was adopted as an outcome variable in most of the selected studies. In addition, the ADL score to assess daily living function, and the effective rate of treatment were adopted in more than half of the studies. However, the frequency of use of the ADAS-cog, another scale to assess cognitive function (8 studies) and the NPI to assess BPSD (1 study) was low. The ADAS-cog comprehensively assesses cognitive function however, it takes a relatively long time (30 minutes) to perform. The MMSE can be conducted in a relatively short time (10 minutes) [17]. So, the ADAS-cog may have a lower priority compared with the MMSE when it is used in the clinical setting. The NPI was utilized in only 1 study, possibly because herbal medicine treatment is the mainstream treating of the BPSD in the clinical setting [61,62]. As a result of an analysis of the outcome variables used, acupuncture focused on the improvements in cognitive function and daily living activity. The effects of acupuncture on the improvement of the BPSD, it is necessary to conduct further study (e.g. A comparison between Western medicine and oriental medicine).
In a comparison between the acupuncture intervention group and the Western medicine control group, there was a statistically significant difference in the MMSE, ADL scores, and effective rates. In a comparison between the acupuncture and Western medicine combined treatment intervention group, there was a statistically significant improvement in the ADL score compared with the Western medicine control group. In a comparison between the electroacupuncture and Western medicine combined treatment intervention group and the Western medicine control group, there was a significant improvement in ADAS-cog score in the combined treatment intervention group. In a comparison between the electroacupuncture and herbal medicine combined treatment intervention group and the herbal medicine control group, the effective rate was statistically significantly higher in the combined treatment intervention group. In a comparison between the scalp acupuncture and Western medicine combined treatment intervention group and the Western medicine control group, there was a statistically significant improvement in the MMSE score in the combined treatment intervention group. In the other comparisons, there were no statistically significant results. To sum up these results, acupuncture treatment improved cognitive function and ability to perform ADL in patients with AD. In some analysis in this literature review, there was no statistically significant difference, this is probably because there was an insufficient number of patients by the intervention and outcome variable, and because there was strong heterogeneity between the studies utilized in the meta-analysis.
This literature review investigated the effects of acupuncture on the symptoms of AD at a higher level of evidence however, this study had some limitations. Firstly, there was not sufficient assessment of the acupuncture for the BPSD of AD. Secondly, all studies included in this review were conducted in China where the treatment method or result may differ depending on the differences in the medical environment and socio-cultural environment so generalizations cannot be made. Thirdly, most of the selected studies had high or unclear RoB. Fourthly, there was a small number of studies and patients included in the meta-analysis (due to strong heterogeneity between the studies). Fifthly, there were insufficient studies that had follow up consultations to determine the long-term effects of acupuncture. However, taking into consideration that the herbal medicine is used in the treatment of the BPSD in AD, additional studies to verify the effect of acupuncture can be combined with herbal medicine. In addition, it would be beneficial to perform randomized controlled trials or long-term observation studies in Korea designed to deliver a higher level of evidence.
Conclusion
Meta-analysis suggests that acupuncture treatment improved cognitive function and improved daily living for patients with AD. However, there was heterogeneity and a high RoB in the studies reviewed. Further research is required to provide a better level of evidence.
Acknowledgments
This work was supported by a National Research Foundation of Korea grant which was funded by the Korean government (no.: 2016R1C1B2016274).
Notes
Conflicts of Interest
The authors have no conflicts of interest to declare.