Review ArticleThe Effectiveness and Safety of Manual Acupuncture Therapy inPatients with Poststroke Cognitive Impairment: A Meta-analysis

Wei Liu , Chang Rao , Yuzheng Du , Lili Zhang , and Jipeng Yang

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China

Correspondence should be addressed to Yuzheng Du; drduyuzheng@163.com

Wei Liu and Chang Rao contributed equally to this work.

Received 19 June 2020; Revised 7 October 2020; Accepted 28 October 2020; Published 25 November 2020

Academic Editor: Zhen Zheng

Copyright © 2020 Wei Liu et al. This is an open access article distributed under the Creative Commons Attribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background. Poststroke cognitive impairment (PSCI) is a common cause of disability among patients with stroke. Meanwhile,acupuncture has increasingly been used to improve motor and cognitive function for stroke patients. The aim of the presentstudy was to summarize and evaluate the evidence on the effectiveness of acupuncture in treating PSCI. Methods. Eightdatabases (PubMed, The Cochrane Library, CNKI, WanFang Data, VIP, CBM, Medline, Embase databases) were searchedfrom January 2010 to January 2020. Meta-analyses were conducted for the eligible randomized controlled trials (RCTs).Assessments were performed using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA),Barthel Index (BI), or modified Barthel Index (MBI). Results. A total of 657 relevant RCTs were identified, and 22 RCTswith 1856 patients were eventually included. Meta-analysis showed that acupuncture appeared to be effective forimproving cognitive function as assessed by MMSE (mean difference ðMDÞ = 1:73, 95% confidence interval (CI) (1.39,2.06), P < 0:00001) and MoCA (MD= 2:32, 95% CI (1.92, 2.73), P < 0:00001). Furthermore, it also suggested thatacupuncture could improve the activities of daily life (ADL) for PSCI patients as assessed by BI or MBI (SMD = 0:97,95% CI (0.57, 1.38), P < 0:00001). Conclusions. Compared with nonacupuncture group, acupuncture group showed bettereffects in improving the scores of MMSE, MoCA, BI, and MBI. This meta-analysis provided positive evidence thatacupuncture may be effective in improving cognitive function and activities of daily life for PSCI patients. Meanwhile,long retention time of acupuncture may improve cognitive function and activities of daily life, and twist technique maybe an important factor that could influence cognitive function. However, further studies using large samples and arigorous study design are needed to confirm the role of acupuncture in the treatment of PSCI.

1. Introduction

Stroke ranks only second to ischemic heart disease as theleading cause of death and the third leading cause ofdisability-adjusted life-years (DALYs) lost worldwide [1]. InChina, with over 2 million new cases annually, stroke has aclose relationship with the highest DALYs lost of any disease[2]. Cognitive decline is a major cause of disability in strokesurvivors [3]. It is estimated that 11.8 million patients whohave had a stroke, 9.5 million of whom have had cognitiveimpairments after their stroke [4].

Poststroke cognitive impairment (PSCI) contains twodifferent degrees of cognitive impairment, including post-stroke cognitive impairment with no dementia (PSCIND)and poststroke dementia (PSD) [5]. In the study [6] whichenrolled 620 patients in 12 hospitals with ischemic stroke,of the 506 patients who were followed-up at 3 months afterstroke, 353 patients (69.8%) suffered cognitive impairmentas measured by the Korean Vascular Cognitive ImpairmentHarmonization Standards neuropsychological protocol (K-VCIHS-NP). In America, the study on 212 subjects fromthe Framingham Study suggested that 19.3% of cases

HindawiNeural PlasticityVolume 2020, Article ID 8890521, 15 pageshttps://doi.org/10.1155/2020/8890521

https://orcid.org/0000-0001-7974-849Xhttps://orcid.org/0000-0003-0798-1756https://orcid.org/0000-0002-4536-2756https://orcid.org/0000-0003-0935-4991https://orcid.org/0000-0002-5033-6165https://creativecommons.org/licenses/by/4.0/https://creativecommons.org/licenses/by/4.0/https://doi.org/10.1155/2020/8890521

developed into dementia in 10 years after stroke [7]. PSCI isstrongly related to a higher risk of mortality [8], poor func-tional outcome [9], and poor quality of life [10]. Identifyingpatients at risk of cognitive impairment is, therefore, impor-tant as well as targeting interventions to this group.

Unfortunately, treatment of PSCI has not been standard-ized [11]. So far, there are many drugs to improve cognitive,including acetylcholinesterase inhibitors, memantine [12],and nicergoline [13]. But because of the unclear efficacyand side effect, until now, there is a none drug that has beenapproved by the Food and Drug Administration (FDA) totreat vascular cognitive impairment [14].

In recent years, the spectrum of diseases suitable for acu-puncture abroad has been significantly broader, like nervoussystem, muscular tissue, skeletal system, connective tissue,mental and behavioral disorders, digestive system, and respi-ratory system [15]. The World Health Organization has alsorecommended acupuncture as an alternative and comple-mentary strategy for stroke treatment and improvement[16]. In the treatment of apoplexy sequelae, acupuncture ismainly used to treat dyspraxia [17], enhance life quality[18], improve cognition [19], and deal with depression andanxiety [20]. Animal experiments [21] showed that acupunc-ture could improve cognitive function by stimulating cholin-ergic enzyme activity and regulating brain-derivedneurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) expression in the rats’ brain; Caiet al. [22] demonstrated that electroacupuncture can improvecognitive impairment in Alzheimer’s disease mice by inhibit-ing synaptic degeneration and neuroinflammation.

After searching the database, we found that there werefew systematic reviews or meta-analysis focused on the effec-tiveness of acupuncture in treating PSCI recently, althoughthe number of papers related to this area has an upward trendin the last five years. For instance, the latest meta-analyses onacupuncture treating PSCI were published in 2014 [23] and2016 [24]. But due to the limitation of sample size and thequality of trials included in the former one, the effectivenessof acupuncture in treating PSCI has not been fully deter-mined. Meanwhile, the later one which also lacked qualityrandomized controlled trials (RCTs) was merely focused onthe effectiveness of scalp acupuncture. Therefore, the pur-pose of this study is to evaluate the clinical efficacy of acu-puncture in the treatment of PSCI by meta-analysis andprovide evidence for its rational clinical application.

2. Methods

2.1. Search Methods for Identification of Studies.We searchedCNKI, WanFang Data, VIP, CBM, PubMed, Medline,Embase, and The Cochrane Library to collect randomizedcontrolled trials of acupuncture in the treatment of PSCIpublished in both Chinese and English. The retrieval timewas from January 2010 to January 2020. Searching termsincluded stroke, cerebral infarction, encephalorrhagia, cogni-tive impairment and so on. For example, the searching strat-egy we used on Pubmed is ((((cognitive[Title/Abstract]) ORCognition[Title/Abstract])) AND (((((((stroke[Title/Ab-stract]) OR cerebral infarction[Title/Abstract]) OR apoplex-

y[Title/Abstract]) OR hematencephalon[Title/Abstract])OR encephalorrhagia[Title/Abstract]) OR cerebral hemor-rhage[Title/Abstract]) OR infarct of brain[Title/Abstract]))AND acupuncture[Title/Abstract].

2.2. Inclusion/exclusion Criteria. Relevant clinical trials wereincluded if the following criteria were met: (1) they were ran-domized controlled trials (RCTs); (2) they included patientsdiagnosed with poststroke cognitive impairment; (3) theyuse cognitive function as an outcome measure; (4) the differ-ence of interventions between experimental and controlgroups is whether they use acupuncture or not. To be moreprecise, the intervention of experimental group is acupunc-ture therapy plus another therapy or standard treatment;the intervention of control group is standard treatment orthe therapy which also be used in the experimental groupexcept acupuncture therapy. If trials which met above criteriacontained more than two groups, the group receiving acu-puncture was chosen as the experimental group, and thenonacupuncture treatment group was chosen as the controlgroup.

Trials were excluded if they met any of the following cri-teria: (1) acupuncture were used in the control group; (2) nei-ther the Mini-Mental State Examination (MMSE) nor theMontreal Cognitive Assessment (MoCA) was used as cogni-tive function evaluation scale; (3) specific type of acupunc-ture treatment was used in the experimental group, such aselectroacupuncture and laser needles for acupuncture.

2.3. Data Extraction. Two reviewers (L.W. and R.C.) inde-pendently extracted the general information of the includedtrials and reached consensus on all items. Extracted dataincluded authors, year of publication, sample size, source ofdiagnosis, interventions, main outcomes, and informationabout acupuncture treatment (including course, frequency,and retention time).

Measures of the outcome evaluation that were reportedin the included studies were Mini-Mental State Examination(MMSE), Montreal Cognitive Assessment (MoCA), BarthelIndex (BI), or modified Barthel Index (MBI). MMSE whichcontains domains of orientation, memory, attention, lan-guage, and visuospatial ability is the most common usedscreening scale [25, 26]. MoCA, which is also a cognitivescreening and tracking tool, is more useful for the mild stagesof the cognitive impairment [27]. It is composed of severalcognitive domains such as memory, executive function,attention, language, abstraction, naming, delayed recalls,and orientation [28]. BI is one of the most widely used out-come measures to assess functioning for the patients whohave neurological disorders [29, 30]. It consists of 10 others’rated questions which are for the purpose of evaluating theability of daily life [31].

2.4. Quality Assessment. The methodological quality and therisk of bias of the included studies were evaluated by the riskof bias 2.0 (ROB 2.0) tool. One author assessed the risk of biasof included studies by using ROB 2.0, and the other authorconfirmed the judgment. The following items were catego-rized as having high, low, or unclear risk of bias:

2 Neural Plasticity

randomization process, deviations from intended interven-tions, missing outcome data, measurement of the outcome,and selection of the reported result and overall.

2.5. Statistical Analysis. The Review Manager software (ver-sion 5.3 Cochrane Collaboration, Oxford, United Kingdom)was used to perform most of the statistical analysis. Themean difference (MD) which was used as the effect analysisstatistics for continuous data was calculated with a 95% con-fidence interval (CI).

The I2 statistic was used to analyze the heterogeneitybetween the data of included trials. If the figure of I2 wasabove 50%, which means significant heterogeneity, sensitivityanalysis would be performed to analysis the source of hetero-geneity. Random-effects model was applied to calculate thestudy results with significant heterogeneity, while a fixedeffect model is used if the statistical heterogeneity was inap-parent. Publication bias was detected using a funnel plot.

3. Results

3.1. Study Description. Our search identified 657 articles afterremoving duplicates. Among them, 22 RCTs met our inclusioncriteria and were included in this study (Figure 1). The articlesincluded in the analysis are summarized in Table 1. There are2 in English [32, 33] and 20 articles in Chinese [34–53].

3.2. Study Quality. The risk of bias assessment of the includedRCTs is illustrated in Figure 2. With regard to randomizationprocess, 4 studies had a low ROB, and 18 studies had anunclear ROB. With regard to deviations from intended inter-

ventions, all RCTs had a low ROB. With regard to missingoutcome data, 16 studies had a low ROB, and 6 studies hada high ROB. With regard to measurement of the outcome,2 studies had a low ROB, and 20 studies had an unclearROB. With regard to selection of the reported result, 1 studyhad a low ROB, and 21 studies had an unclear ROB.

3.3. Descriptions of Acupuncture Treatment. The acupunc-ture interventions of the included trials varied across the 22trials. The majority of the studies [32, 35–39, 42–45] usedacupuncture with medicine, such as cholinesterase inhibitoror lipid-lowering medication, as the intervention of theexperiment group. Eight studies [34, 41, 46–48, 50–52] usedacupuncture with cognitive training; two studies [33, 53]used acupuncture alone; two studies [42, 49] used acupunc-ture with rehabilitation training.

In terms of acupoint selecting, single area acupuncturepoints were used in five studies [39, 40, 45, 49, 50], includingthe eye, ear, and scalp acupuncture. Special acupuncturetherapy, Jin three-needle therapy, and tri-jiao therapy werealso used in three studies [46, 47, 53]. Apart from that, a totalof 33 acupoints were selected in other 14 studies. Acupointsused for cognitive impairment in most trials were DU 20(Bai Hui) and DU24 (Shen Ting) (Figure 3).

3.4. Effects of Acupuncture Treatment According to MMSEAssessment Scales. A total of 17 studies reported MMSEscores, including 1389 patients. Heterogeneity test resultsshowed high heterogeneity between groups (I2 = 95%, P <0:00001). Sensitivity analysis was done by using the leave-one-out approach; five studies [40, 46, 48, 51, 53] were found

Records identified throughdatabase serching

(n = 657)

Additional records identifiedthrough other sources

(n = 0)

Records a�er duplictesremove

(n = 401)

Records screened(n = 401)

Full-text articles assessed foreligibility(n = 91)

Full-text articles excluded, withreasons(n = 69)

Studies included inquantitative synthesis

(meta-analysis)(n = 22)

Records excluded(n = 310)

Figure 1: Flow diagram of the systematic review.

3Neural Plasticity

Table1:Summaryof

rand

omized

controlledtrialsof

acup

unctureforPSC

I.

Autho

r(year)

Sample

size

Participants

Source

ofdiagno

stic

Intervention

grou

pregimen

Con

trol

grou

pregimen

Mainou

tcom

esAcupu

ncture

course

Acupu

ncture

frequency

Acupu

ncture

retentiontime

Average

age

(years)[i]

Sex

(male/female)

Wang2016

[32]

79a 65:2±

7:1

a 26/14

Stroke:C

Tor

MRI

Acupu

ncture

Nim

odipine

1.MoC

A12

weeks

5times

per

week

30min

b60:6±6:7

b26/13

CI:MoC

ANim

odipine

Jiang2016

[33]

101

a 61:58

±9:71

a 25/27

Stroke:clin

ical

diagno

sis

Acupu

ncture

Con

ventional

treatm

ent

1.MMSE

12weeks

5times

per

week

30min

b60:53±

9:19

b24/25

CI:MMSE

Con

ventional

treatm

ent

2.MoC

A

3.FIM

Wang2018

[34]

115

a 52:37

±8:43

a 30/25

Stroke:C

Tor

MRI

Acupu

ncture

Con

ventional

treatm

ent

1.MMSE

3mon

ths

Daily

Scalp

acup

uncture:6h

b52:72±

9:65

b28/22

CI:MoC

A,C

DR

Con

ventional

treatm

ent

Cognitive

training

2.TCD

Bod

yacup

uncture:0.5h

Cognitive

training

3.NO

4.TG,H

DL-C,

LDL-C,T

C

Bao

2012

[35]

60a 63±

6a 19/11

Stroke:C

Tor

MRI

Acupu

ncture

Don

epezil

1.MMSE

2mon

ths

6times

per

week

50min

b64

±6

b21/9

CI:MMSE

Don

epezil

2.MESS

3.Barthel

Zhang

2017

[36]

84a 63:28

±10:68

a 27/15

Stroke:C

Tor

MRI

Acupu

ncture

Atorvastatin

1.MMSE

4weeks

5times

per

week

20min

b63:07±

10:59

b28/14

CI:complainof

mem

oryloss

Atorvastatin

2.WBV,H

BV

LBV

WangQ

2019

[37]

118

a 68:88

±3:64

a 36/23

Stroke:C

Tor

MRI

Acupu

ncture

Atorvastatin

1.MMSE

30days

Daily

30min

b67:71±

3:02

b32/27

CI:complainof

mem

oryloss

Atorvastatin

2.WBV,H

BV

LBV,F

IB

3.SA

S

Yang2015

[38]

72a 65:89

±3:276

a 25/11

Stroke:C

Tor

MRI

Acupu

ncture

Nim

odipine

1.MoC

A3mon

ths

6times

per

week

30min

b65:97±

3:308

b21/15

CI:MoC

ANim

odipine

Du2017

[39]

60a 64:60

±2:84

a 16/14

Stroke:C

Tor

MRI

Acupu

ncture

Don

epezil

1.MMSE

6weeks

7times

per

week

30min

b64:43±

3:27

b14/16

CI:MMSE

,CDR

Don

epezil

2.Barthel

3.Hcy

110

a 59:47

±8:62

a 36/19

Stroke:C

Tor

MRI

Eye

acup

uncture

1.MMSE

4weeks

Daily

5min

4 Neural Plasticity

Table1:Con

tinu

ed.

Autho

r(year)

Sample

size

Participants

Source

ofdiagno

stic

Intervention

grou

pregimen

Con

trol

grou

pregimen

Mainou

tcom

esAcupu

ncture

course

Acupu

ncture

frequency

Acupu

ncture

retentiontime

Average

age

(years)[i]

Sex

(male/female)

Teng2018

[40]

Standard

treatm

ent

b58:65±

8:17

b35/20

CI:MMSE

and

LOTCA

Standard

treatm

ent

Cognitive

training

2.LO

TCA

Cognitive

training

Qiu

2018

[41]

60a 54:18

±4:137

a 17/11

Stroke:M

RI

Acupu

ncture

Standard

treatm

ent

1.MoC

A1mon

th5times

per

week

30min

b54:93±

3:443

b19/10

CI:MoC

A,N

CSE

Standard

treatm

ent

Rehabilitation

2.EEGsignal

Rehabilitation

Li2019

[42]

80a 66:9±

5:9

a 18/22

Stroke:C

Tor

MRI

Acupu

ncture

Standard

treatm

ent

1.MoC

A6weeks

5times

per

week

30min

b67:4±6:1

b22/18

CI:MoC

A,M

MSE

Don

epezil

Don

epezil

2.MMSE

Standard

treatm

ent

3.Barthel

Ding2019

[43]

110

a 66:9±

11:1

a 39/19

Stroke:stand

ard[

ii]

Acupu

ncture

Com

poun

dmusk

injection

1.GCS

3weeks

5times

per

week

30min

b65:9±11:5

b29/26

CI:standard

[iii]

Com

poun

dmusk

injection

2.MoC

A

3.Barthel

4.Assessm

entof

scores

forTCM

5.Hem

atom

avolume

Nie2019

[44]

63——

a 16/14

Stroke:C

Tor

MRI

Acupu

ncture

Butyphthalid

e1.MoC

A40

days

Daily

30min

b18/12

CI:MoC

A,M

MSE

Butyphthalid

eStandard

treatm

ent

2.MMSE

Standard

treatm

ent

3.ADL

4.Ngb

Bai2012

[45]

60a 60±

6a 16/14

Stroke:C

Tor

MRI

Acupu

ncture

Piracetam

1.MMSE

4weeks

5times

per

week

6h

b60

±6

b18/12

CI:CCSE

Piracetam

2.Plasm

acortisol

5Neural Plasticity

Table1:Con

tinu

ed.

Autho

r(year)

Sample

size

Participants

Source

ofdiagno

stic

Intervention

grou

pregimen

Con

trol

grou

pregimen

Mainou

tcom

esAcupu

ncture

course

Acupu

ncture

frequency

Acupu

ncture

retentiontime

Average

age

(years)[i]

Sex

(male/female)

Zeng2018

[46]

80——

a 22/18

Stroke:imaging

Acupu

ncture

Standard

treatm

ent

1.MMSE

4weeks

6times

per

week

30min

b24/16

CI:MMSE

Standard

treatm

ent

Cognitive

training

2.Barthel

Cognitive

training

Zhang

2019

[47]

70a 59:95

±8:71

a 20/15

Stroke:stand

ard[

ii]

Acupu

ncture

Com

puteraided

treatm

ent

1.MMSE

8weeks

6times

per

week

30min

b61:12±

9:62

b19/16

CI:MMSE

Com

puteraided

treatm

ent

Standard

treatm

ent

2.Barthel

Standard

treatm

ent

Rehabilitation

Rehabilitation

WangZ

2019

[48]

208

a 62±

7a 62/42

Stroke:C

Tor

MRI

Acupu

ncture

Cognitive

training

1.Hcy

30days

5times

per

week

30min

b62

±7

b61/43

CI:MMSE

Cognitive

training

2.hs-C

RP

3.CPI

4.VILIP-1

5.BDNF

6.GFA

P

7.MMSE

8.ADL

Mao

2019

[49]

78a 57:3±

15:6

a 18/21

Stroke:C

Tor

MRI

Acupu

ncture

Standard

treatm

ent

1.MoC

A6weeks

5times

per

week

6h

b58:2±16:2

b19/20

CI:MoC

AStandard

treatm

ent

Rehabilitation

2.Barthel

Rehabilitation

Liu2016

[50]

63a 68:07

±2:82

a 16/14

Stroke:C

Tor

MRI

Eye

acup

uncture

Standard

treatm

ent

1.MMSE

4weeks

7times

per

week

30~4

0min

b67:83±

3:35

b18/12

CI:standard

[iv]

Standard

treatm

ent

Cognitive

training

2.Barthel

Cognitive

training

6 Neural Plasticity

Table1:Con

tinu

ed.

Autho

r(year)

Sample

size

Participants

Source

ofdiagno

stic

Intervention

grou

pregimen

Con

trol

grou

pregimen

Mainou

tcom

esAcupu

ncture

course

Acupu

ncture

frequency

Acupu

ncture

retentiontime

Average

age

(years)[i]

Sex

(male/female)

Song

2017

[51]

62a 56:37

±1:27

a 24/7

Stroke:C

Tor

MRI

Acupu

ncture

Standard

treatm

ent

1.MMSE

12weeks

5times

per

week

30min

b58:19±

1:24

b19/12

CI:MMSE

Standard

treatm

ent

Cognitive

training

2.miR-124,m

iR-132,m

iR-134,m

iR-138

expression

levels

Cognitive

training

Zhang

2018

[52]

63a 59:03

±6:066

a 14/16

Stroke:M

RI

Acupu

ncture

Standard

treatm

ent

1.MMSE

4weeks

6times

per

week

30min

b58:17±

6:539

b13/17

CI:MoC

AStandard

treatm

ent

Cognitive

training

2.MoC

A

Cognitive

training

3.Barthel

Li2012

[53]

60a 67:31

±10:98

——

Stroke:C

Tor

MRI

Acupu

ncture

Standard

treatm

ent

1.MMSE

3weeks

6times

per

week

30min

b66:24±

12:53

CI:MMSE

Standard

treatm

ent

2.ADL

[i]aExperim

entalgrou

p;bcontrolgrou

p.[ii]Key

pointsfordiagno

sisof

variou

scerebrovasculardiseases.[

iii]NationalInstituteof

NeurologicalDisorders

andStroke-C

anadianstroke

networkvascular

cognitive

impairmentharm

onizationstandards.

[iv]Spectrum

ofdiseasein

vascular

cognitiveim

pairment.

7Neural Plasticity

which could vary the direction of the combined estimates.Three [40, 48, 51] of them were removed for incorrect usingof MMSE. The score of MMSE should be related to educationlevel when detecting cognitive impairment [54], but thesestudies used same scoring criteria for people with differenteducational levels in the inclusion criteria which could causethat patients without cognitive impairment, but low educa-

tional level were included in the studies. In addition, anothertwo [46, 53] of them that we removed could significantly varythe direction of the combined estimates (test for subgroupdifferences: chi2 = 187:08, df = 1 (P < 0:00001), I2 = 99:5%)(Figure 4). After studying the full articles carefully, we foundthat the difference between these two and other article is thatthey both used Jin 3-needle technique which has a uniquetwist technique. This indicated that the source of heterogene-ity might be related to the frequency and duration of twisttechnique. It also illustrated that twist technique may influ-ence the effect of improving cognitive function, as the studiesused Jin 3-needle technique (MD= 11:82, 95% CI (10.41,13.23), P < 0:00001, I2 = 0%) had better outcomes than thestudies did not (MD= 1:73, 95% CI (1.39, 2.06), P <0:00001, I2 = 50%). However, further research is still neededdue to the small number of included studies using Jin 3-needle technique.

Finally, after sensitivity analysis, a total of 12 studies wereincluded for evaluating the effect of acupuncture treatmentaccording to MMSE. The fixed effect model was used foranalysis on the basis of heterogeneity test (I2 = 50%). Theresults of meta-analysis showed that the MMSE score of theacupuncture treatment group was higher than that of thecontrol group (MD= 1:73, 95% CI (1.39, 2.06), P < 0:00001).According to subgroup analysis based on treatment duration,meta-analysis results showed that MMSE score of the acu-puncture treatment group was higher than that of the treat-ment group in ≤7-week subgroup (MD= 1:63, 95% CI (1.28,1.99), P < 0:00001, I2 = 60%). MMSE score in the >7-weeksubgroup was higher than that in the treatment group(MD= 2:36, 95% CI (1.43, 3.29), P < 0:00001, I2 = 0%)(Figure 5). It illustrated that the duration of acupuncture treat-ment was also a factor that could influence heterogeneity buthave few effect on the outcomes. We also conducted subgroupanalysis based on retention time and frequency of acupunc-ture, but those did not have much influence on heterogeneityor outcomes.

3.5. Effects of Acupuncture Treatment According to MoCAAssessment Scales. There are nine [32, 33, 38, 41–44, 49, 52]trials that used MoCA to compare the cognitive functionbetween acupuncture group and nonacupuncture group. Ahigh statistical heterogeneity was observed (I2 = 84% > 50%).

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Du 2017

Liu 2016

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Figure 2: Risk of bias assessment for included studies.

DU20

DU24

Figure 3: DU 20 (Bai Hui) and DU24 (Shen Ting).

8 Neural Plasticity

After using sensitivity analysis of studies, we found one article[49] that had relatively large impact on statistical heterogene-ity. What distinguishes it from other studies is the retention

time of acupuncture, so we conducted subgroup analysis basedon retention time (Figure 6). It shows that the score of MoCAin the acupuncture group was observed to be higher than that

Study or subgroup

2.3.1 without Jin.Bai (2012)Bao (2012)Du (2017)Jiang (2016)Li (2019)Liu (2016)Nie (2019)Wang Q (2019)Wang (2018)Zhang (2017)Zhang (2018)Zhang (2019)

Experimental

mean SD SD

s 3-needle technique24.57

26.928.07

21.125.6118.3327.7726.8427.3226.8321.8723.49

4.716

1.364.832.643.882.342.193.542.34

3.54.42

Total Total

30 303030

30

30 303059

30

30 3030

305240 40

595542 42

28

Mean

21.5323.5

26.9719.8824.0416.4324.0925.1224.5725.3121.7720.92

Control

2.995.7

1.224.132.373.192.621.673.351.743.776.05

49

50

Weight

2.6 %1.2 %

24.3 %3.4 %8.6 %3.2 %6.6 %

21.0 %6.0 %

13.4 %3.1 %1.4 %

3.04 [1.04, 5.04]3.40 [0.44, 6.36]1.10 [0 45, 1.75]

1.22 [–0.53, 2.97]1.57 [0.47, 2.67]1.90 [0.10, 3.70]3.68 [2.42, 4.94]1.72 [1.02, 2.42]2.75 [1.43, 4 07]1.52 [0.64, 2.40]

0.10 [–1.74, 1.94]2.57 [–0.14, 5.28]

1.73 [1.39, 2.06]94.8%450456Subtotal (95% CI)Heterogeneity: chi2 = 22.03, df =11 (P = 0.02); I2 = 50% Test for overall effect: Z = 10.21 (P < 0.0001)

2.3.2 with Jin’ s 3-needle techniqueLi (2012)Zeng (2018)Subtotal (95% CI)Heterogeneity: chi2 = 0.03, df = 1 (P = 0.86); I2 = 0%Test for overall effect: Z = 16.45 (P < 0.00001)

26.8769.6

1.8611.23

203454

15.0158.2

2.799.45

203454

4.8%0.4%5.2%

100.0%

11.86 [10.39, 13.33]11.40 [6.47, 16.33]

11.82 [10.41, 13.23]

Mean difference

lV, fixed, 95%Cl

Total (95% Cl) 510 504 2.25 [1.93, 2.58]Heterogeneity: chi2 = 209.14, df = 13 (P < 0.00001); I2 = 94%Test for overall effect: Z = 13.17 (P < 0.00001)Test for subgroup differences: chi2 = 187.08, df = 1 (P < 0.00001); I2 = 99.5%

–10 –5Favours (experimental) Favours (control)

0 5 10

Mean differenceIV, fixed, 95% Cl

Figure 4: The forest plots of MMSE (subgroup: with or without Jin 3-needle technique).

Study or subgroup2.1.1 MMSE (≤ 7 weeks)Bai (2012)Du (2017)Li (2019)Liu (2016)Nie (2019)Wang Q (2019)Zhang (2017)Zhang (2018)Subtotal (95% CI)Heterogeneity: chi2 = 17.53, df = 7 (P = 0.01); I2 = 60%Test for overall effect: Z = 9.04 (P < 0.00001)

2.1.2 MMSE (>7 weeks)

ExperimentalMean MeanSD SD

24.5728.0725.6118.3327.7726.8426.8321.87

4.711.362.643.882.342.192.34

3.5

Total Total

30 3030

3030

3030

3040 40

59 5942 4230 30

Control

21.5326.9724.0416.4324.0925.1225.3121.77

2.991.222.373.192.621.671.743.77

WeightMean differenceIV, fixed, 95% CI

2.8 %25.7 %

9.1 %3.4 %6.9 %

22.2 %14.1 %

3.2 %291 291 87.4 %

3.04 [1 .04, 5.04]1.10 [0.45, 1.75]

1.57 [0. 47, 2.67]

3.68 [2.42, 4.94]1 .90 [0. 10, 3.70]

1 .72 [1.02, 2.42]1 .52 [0.64, 2.40]

0.10 [–1.74, 1.94]1.63 [1.28,199]

26.9 6 30 23.5 5.7 30 1.3% 3.40 [0.44, 6.36]21.1 4.83 52 19.88 4.13 49 3.6% 1.22 [–0.53, 2.97]

27.32 3.54 55 24.57 3.35 50 6.3% 2.75 [1.43, 4.07]23.49 4.42 28 20.92 6.05 30 1.6% 2.67 [–0.14, 5.28]

165 159 12.6% 2.36 [1.43, 3.29]

Bao (2012)Jiang (2016)Wang (2018)Zhang (2019)Subtotal (95% CI)Heterogeneity: chi2 = 2.46, df = 3 (P = 0.48); I2 = 0%Test for overall effect: Z = 4.96 (P < 0.00001)

Total (95% CI) 456 450 100.0% 1.73[1.39, 2.06] Heterogeneity: chi2 = 22.03, df = 11 (P = 0.02); I2 = 50%Test for overall effect: Z = 10.21 (P < 0.00001)Test for subgroup differences: chi2 = 2.03, df = 1 (P = 0.15), I2 = 50.8%

–4 –2 0 2 4Favours [experimental] Favours [Control]

Mean differenceIV, fixed, 95%Cl

Figure 5: The forest plots of MMSE (subgroup: course ≤ 7weeks or course > 7weeks).

9Neural Plasticity

in the nonacupuncture group (MD= 2:32, 95% CI (1.92,2.73), P < 0:00001); the difference is statistically significant. Italso illustrated that retention timemay also influence the effectof improving MoCA score, as the study with retention time of6h (MD= 6:32, 95% CI (4.81, 7.83), P < 0:00001) had betteroutcomes than the studies with retention time of 0.5h(MD= 2:15, 95% CI (1.39, 2.91), P < 0:00001, I2 = 64%).However, further research is still needed due to the smallnumber of included studies with long retention time.

3.6. Effects of Acupuncture Treatment According to Activitiesof Daily Living. There are nine [35, 42–44, 46, 47, 49, 50,52] trials that used Barthel Index or modified Barthel Indexto compare ADL between acupuncture group and nonacu-puncture group. The other two trials [48, 53] also mentionedthey evaluated ADL but did not specified what kind of scalethey used; therefore, we did not include them in this analysis.A high statistical heterogeneity was observed(I2 = 83% > 50%). Therefore, random-effects model analysis

420–2–4Favours [experimental] Favours [control]

ExperimentalMean SD Total SD Total Weight

3.11 [1.19, 5.03]1.27 [–1.34, 3.88]2.22 [1.15, 3.29]3.48 [2.37, 4.59]0.91 [0.03, 1.78]

1.00 [–0 .77, 2.77]3.48 [1 .93, 5.03]1.74 [0 .93, 2.55]2.15 [1 .39, 2.91]89.0%

13.1%10.9%10.2%12.9%12.3%12.4%7.6%9.7%5555

524030284036301.6

Mao (2019)Subtotal (95% CI)

Heterogeneity: not applicableTest for overall affect: Z = 8.20 (P < 0.00001)

Test for overall affect: Z = 4.84 (P < 0.00001)Test for subgroup differences: chi2 = 23.34, df = 1 (P < 0.00001), I2 = 95.7%

Total (95% CI)

Footnotes(1) 23.20

Heterogeneity: tau2 = 2.07; chi2 = 48.71, df = 8 (P < 0.00001); I2 = 84%

27.08 3.62 39 20.76 3.17 3939

11.0%11.0%

100.0%

6.32 [4.81, 7.83]6.32 [4.81, 7.83]

2.62 [1.56, 3.68]

39

350 347

3.843.3

1.7531.892.716.744.5720.58

17.9622.6926.6816.4624.5

26.8321.47Zhang (2018)

Subtotal (95% CI)Heterogeneity: tau2 = 0.71; chi2 = 19.70, df = 7 (P = 0.006); I2 = 64% Test for overall effect: Z = 5.52 (P < 0.00001)

Yang (2015)Wang (2016)Qiu (2018)Nie (2019) (1)Li (2019)Jiang (2016)Ding (2019)

2.2.1 acupuncture retention time is 0.5 hour

2.2.1 acupuncture retention time is 6 hour

311

49403029393630

3081.619.73

23.3523.5

15.55223.2

20.4716.6917.47

2.784.6

1.6172.452.146.665.65

MeanStudy or subgroupControl Mean difference

IV, random, 95% CIMean difference

IV, random, 95% CI

Figure 6: The forest plots of MoCA.

420–2–4Favours [experimental] Favours [control]

ExperimentalMean SD Total SD Total YearWeight

Mao (2019)Subtotal (95% CI)

Heterogeneity: not applicableTest for overall affect: Z = 8.32 (P < 0.00001)

Test for Overall affect: Z = 4.70 (P < 0.00001)Test for subgroup differences: chi2 = 28.26, df = 1 (P < 0.00001), I2 = 96.5%

Total (95% CI)Heterogeneity: tau2 = 0.32; chi2 = 46.46, df = 8 (P < 0.00001); I2 = 83%

316 319 100.0% 0.97 [0.57, 1.38]

2.58 [1.97, 3.19]2.58 [1.97, 3.19]

0.79 [0.53, 1.05]

201910.4%10.4%39

89.6%280277Ding 2019Nie 2019Zhang 2019Li 2019Zeng 2018Zhang 2018Liu 2016Bao 2012 51.2

64.8353.2

21.7368.6158.4778.3168.45 15.25

3.989.619.621.953.94

16.1611.5 30 44.6

54.6747.8

18.8464.0456.4774.6752.35 15.6

9.614.78

9.032.793.8

16.1310.3

3030

3055

344028

30 11.1% 0.60 [0.08, 1.11]0.62 [0.10, 1.14]1.38 [0.81, 1.94]1.18 [0.67, 1.70]0.49 [0.04, 0.93]

0.21 [–0.31, 0.72]0.82 [0.29, 1.35]1.04 [0.64, 1.44] 2019

2019201920192018201820162012

11.1%

11.1%

11.1%11.0%12.0%

11.6%

10.7%3030

3055

354030

393939

6.125.6274.08 58.76

Subtotal (95% CI)Heterogeneity: tau2 = 0.08; chi2 = 15.52, df = 7 (P = 0.03); I2 = 55% Test for overall effect: Z = 5.90 (P < 0.00001)

3.1.1 acupuncture retention time is 0.5 hour

3.1.2 acupuncture retention time is 6 hour

MeanStudy or subgroupControl Std. mean difference Std. mean difference

IV, random, 95% CI IV, random, 95% CI

Figure 7: The forest plots of activities of daily life.

10 Neural Plasticity

was chosen to conduct meta-analysis. After using sensitivityanalysis of studies, we found one article [49] that had rela-tively large impact on statistical heterogeneity. What distin-guishes it from other studies was the retention time ofacupuncture, so we conducted subgroup analysis based onretention time (Figure 7). Therefore, we divided the 9 articlesinto 2 groups according to the acupuncture retention time. Itshows that the score in the acupuncture group was observedto be higher than that in the nonacupuncture group(SMD = 0:97, 95% CI (0.57, 1.38), P < 0:000 01); the differ-ence is statistically significant. It also showed that longer acu-puncture retention time may lead to better result in activitiesof daily life (0.5 hours: SMD = 0:79, 95% CI (0.53, 1.05),P < 0:000 01; 6 hours subgroup: SMD = 2:58, 95% CI(1.97, 3.19), P < 0:000 01).

3.7. Safety. Safety of acupuncture therapy was reported innine [32, 33, 37, 39, 42–44, 48, 50] of the included articles.Six [32, 33, 37, 39, 43, 48] of the articles reported no adverseevents related to acupuncture therapy happened during thetrials. One article [50] reported one case of adverse eventbut did not mention the reason. One article [42] reportedone case of subcutaneous hematoma in the experiment groupand three cases of fainting in the control group. Another arti-cle [44] reported one case of fainting during acupuncture andtwo cases of subcutaneous hematoma.

3.8. Publication Bias. We used STATA V.15.1 to evaluatepublication bias. For MMSE, publication bias was assessedusing Begg’s test (Figures 8 and 9) and Egger’s test(Figures 10 and 11), which did not show significant publica-tion bias in the included studies. For MoCA and Barthel, thepublication bias could not be assessed as less than ten articleswere included.

4. Discussion

After searching PubMed, the Cochrane Library, CNKI, Wan-Fang Data, VIP, CBM, Medline, and Embase databases, 657relevant RCTs were found in this meta-analysis, and 22 RCTswith 1856 patients were eventually included. According tothis study, more evidence was provided to prove that acu-puncture treatment is beneficial to PSCI patients in termsof cognitive function and ability of daily life. PSCI, whichhas high prevalence rate, is a result of mixed damage mecha-nisms [55]. Jeremy’s study [56] suggested that ongoing ische-mic vascular processes were the main mechanism which alsoemphasized the importance of management for vascular riskfactor. Apart from that, there is no established therapy forprevention for PSCI so far. Hence, it is of vital importancefor us to explore an effective and highly compliant treatmentfor PSCI patients.

There were a few relevant meta-analyses about acupunc-ture treatment for cognitive impairment. Liu et al. [57]searched RCTs that used acupuncture in the treatment ofPSCI before February 2012 and included 21 RCTs with a totalof 1421 patients. Due to the high risk of bias and lack of uni-fied scale for evaluating cognitive function of the includedstudies, it is hard to reach reliable conclusions on the effectof acupuncture. Furthermore, it did not focus on analyzingthe effects of acupuncture alone but on the combined treat-ment with acupuncture, which made it difficult to objectivelyevaluate the effect of acupuncture treatment for PSCI. Kimet al. [58] searched the RCTs on mild cognitive impairment(MCI) patients from October 2007 to August 2017 and

1.50

–2

0

2

4

6

Begg’s funnel plot with pseudo 95% confidence limits

WM

D

s.e. of: WMD1.5

Figure 8: Begg’s funnel plot.

Begg’s test

adj. Kendall’s score (P–Q) = 16Std. dev. of score = 14.58

Number of studies = 12z = 1.10

Pr > |z| = 0.273z = 1.03 (continuity corrected)

Pr > |z| = 0.304 (continuity corrected)

Figure 9: Begg’s test.

11Neural Plasticity

compared the effect of electroacupuncture (EA) to westernmedication. Their study, which included 5 RCTs with 257patients, showed that EA had a higher score on MMSE andMoCA than western medications. But the weak methodolog-ical quality of the studies and small sample size may affect thereliability of the results.

This present review offered several significant perspec-tives. Firstly, a common deficiency of previous RCTs andreviews is the lack of attention to ADL. There were only 9RCTs that we included used BI or MBI to evaluate ADL onPSCI patients. ADL is one of the most important measuresto evaluate how serve PSCI is and an essential measure to dis-tinguish PSCIND and PSD [12]. Moreover, PSD has a signif-icant higher fatality rate than PSCIND [55]. Therefore, westrongly recommend future studies to focus on the abilityof daily life for PSCI patients and explore if acupuncturehas the benefit of preventing PSCIND progressing to PSDwhenever possible. Secondly, it may cause false increase inpatients’ test results by using the same version of scale toevaluate cognitive function before and after the treatment.In order to ensure accuracy of MoCA test, we completedMoCA’s official standardized training and certification pro-gram online. We learned from the official website (https://www.mocatest.org/training-certification/) that the delaybetween administration should be sufficient to decrease therisk of a possible learning effect when administering theMoCA to the same subject; the alternative/equivalent ver-sions of the MoCA should be used to decreased possiblelearning effects when the MoCA is administered, respec-tively. Therefore, we suggest using different versions ofMoCA, such as 7.1, 7.2, or 7.3 versions at different stages of

assessment. Thirdly, more attention should be paid to thestandardized use of the scale. For instance, in this review,three articles were found incorrect using of MMSE. Thewrong use of the scale may lead to serious errors in screeningand evaluation of patients. Furthermore, most of theincluded RCTs have unclear bias of randomization process,measurement of the outcome, and selection of the reportedresults, which have a significant impact on the evaluation ofthe results. It is true that the nature of the acupuncture madeit difficult for investigators to blind participants and almostimpossible to blind the therapists; all the RCTs we includedlikewise did not blind the participants or therapists. How-ever, we should attach more importance to the blinding onoutcome assessors, especially the scale evaluators whosejudgement may have a large influence on the outcome. Wealso advise that all the RCTs which study the effect of acu-puncture should have a protocol with complete informationprior to the start of trials. The protocol should providedetailed information according to the CONSORT statementand STRICTA recommendations in order to minimize theperformance and assessment bias of RCTs.

This review also had certain limitations. Firstly, althoughwe searched the trials written in Chinese or English, all thetrials included were conducted in China. This is related tothe less application of using acupuncture treatment on PSCIin countries other than China, and it may limit the universal-ity of the results. Moreover, our study mainly focused on theeffect of acupuncture alone but neglected the synergisticeffect between acupuncture and other effective treatment,such as medication or cognitive training. In addition, thisstudy did not consider the possible placebo effect of

0

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effe

ct2

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Egger’s publication bias plot

1 2 3Precision

Figure 10: Egger’s publication bias plot.

Egger’s test

Std_Eff Coef. Std. err. t P > |t|2.00 0.073 –.1205776 2.240555

3.279164–.75476190.193

(95% conf. interval)

1.391.059989 .5298442

.90522321.262201Slope

Bias

Figure 11: Egger’s test.

12 Neural Plasticity

https://www.mocatest.org/training-certification/https://www.mocatest.org/training-certification/

acupuncture as no sham/placebo-controlled trials wereincluded. Furthermore, significant heterogeneities wereobserved in our study. Experimental design, various acupointselecting, and therapist skill difference can contribute to thehigh heterogeneity. Problems about which acupoints aremost effective for PSCI and how long the treatment shouldlast need to be resolved in future studies.

5. Conclusions

Compared with the nonacupuncture group, the acupunc-ture group showed better effects in improving the scoresof MMSE, MoCA, BI, and MBI. This meta-analysis pro-vided positive evidence that acupuncture may be effectivein improving cognitive function and activities of daily lifefor PSCI patients. Meanwhile, long retention time of acu-puncture may improve cognitive function and activities ofdaily life, and twist technique may be an important factorthat could influence cognitive function. However, furtherstudies using large samples and a rigorous study designare needed to confirm the role of acupuncture in the treat-ment of PSCI.

Abbreviations

DALYs: Disability-adjusted life-yearsPSCI: Poststroke cognitive impairmentPSCIND: Poststroke cognitive impairment with no

dementiaPSD: Poststroke dementiaK-VCIHS-NP: Korean Vascular Cognitive Impairment

Harmonization Standards neuropsychologi-cal protocol

RCTs: Randomized controlled trialsFDA: The Food and Drug AdministrationBDNF: Brain-derived neurotrophic factorCREB: cAMP-response element-binding proteinCNKI: China National Knowledge InfrastructureCBM: China Biology Medicine discVIP: China Science and Technology Journal

DatabaseRCT: Randomized controlled trialMMSE: Mini-Mental State ExaminationMoCA: Montreal Cognitive AssessmentBI: Barthel IndexMBI: Modified Barthel IndexMD: Mean differenceCI: Confidence intervalROB 2.0: Risk of bias 2.0CI: Confidence interval.

Data Availability

The datasets generated during and analysed during the cur-rent study are available from the corresponding author onreasonable request.

Conflicts of Interest

The authors declare that there is no conflict of interestregarding the publication of this article.

Authors’ Contributions

Wei Liu and Chang Rao developed the study concept anddesign, performed the data acquisition and analysis, anddrafted the manuscript. Jipeng Yang and Lili Zhang modifiedthe manuscript. Yuzheng Du read, modified, and approvedthe final manuscript for submission.

Acknowledgments

This study was financially supported by the Tianjin Scienceand Technology Project (NO. 18PTLCSY00060).

Supplementary Materials

Supplemental Files: PRISMA Checklist (the 27 checklistitems pertain to the content of a systematic review andmeta-analysis, which include the title, abstract, methods,results, discussion, and funding). (Supplementary Materials)

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15Neural Plasticity

The Effectiveness and Safety of Manual Acupuncture Therapy in Patients with Poststroke Cognitive Impairment: A Meta-analysis1. Introduction2. Methods2.1. Search Methods for Identification of Studies2.2. Inclusion/exclusion Criteria2.3. Data Extraction2.4. Quality Assessment2.5. Statistical Analysis

3. Results3.1. Study Description3.2. Study Quality3.3. Descriptions of Acupuncture Treatment3.4. Effects of Acupuncture Treatment According to MMSE Assessment Scales3.5. Effects of Acupuncture Treatment According to MoCA Assessment Scales3.6. Effects of Acupuncture Treatment According to Activities of Daily Living3.7. Safety3.8. Publication Bias

4. Discussion5. ConclusionsAbbreviationsData AvailabilityConflicts of InterestAuthors’ ContributionsAcknowledgmentsSupplementary Materials