Rédacteurs : Johan Nguyen, Claude Pernice

Sommaire

Alzheimer’s Disease

Maladie d'Alzheimer

Articles connexes: - acupuncture expérimentale -

1. Systematic Reviews and Meta-Analysis

1.1. Generic Acupuncture

1.1.1. Wu 2025

Wu J, Teng Y, Xie Y, Xing S, Zhi S. Comparing the efficacy of physical therapy interventions in Alzheimer's disease: a network meta-analysis. Front Aging Neurosci. 2025 Mar 5;17:1541287. https://doi.org/10.3389/fnagi.2025.1541287

Backgroung Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disorder that significantly impairs cognitive function and daily living abilities, representing a major public health challenge. Given the multifactorial nature of AD, effective therapeutic interventions targeting both cognitive and functional decline are critical.
MethodsThis study aimed to conduct a comprehensive comparison of the therapeutic effects of music therapy, acupuncture therapy, game therapy, cognitive training therapy, and exercise therapy on AD patients through a network meta-analysis. Randomized controlled trials (RCTs) published up until 2024 were systematically retrieved from multiple databases. Data were extracted, including the first author, publication year, country, total sample size, mean participant age, type and duration of intervention, and outcome measures such as the Mini-Mental State Examination, Activities of Daily Living, and Alzheimer's Disease Assessment Scale-Cognitive Subscale. Statistical analyses were performed using the RevMan 5.3 and Stata 17 software. The analysis included 52 RCTs with a total of 3,409 participants, offering a strong dataset.
Results The results indicated that game therapy produced statistically significant improvements in mental state and daily living abilities, while acupuncture therapy yielded the most pronounced improvements in cognitive function among AD patients. Notably, the comparative efficacy of these interventions suggests that game therapy may offer short-term benefits, particularly for mental health and functional abilities, whereas acupuncture therapy demonstrated superior long-term cognitive enhancements.
Conclusions In conclusion, tailored physical and cognitive interventions such as game therapy and acupuncture therapy may hold significant potential in optimizing treatment outcomes for AD patients, with implications for both clinical practice and future research.

1.1.2. Guo 2024 (cognitive impairment)

Guo R, Shen X, Ealing J, Zhou J, Lu J, Ning Y. Efficacy and safety of acupuncture for cognitive impairment in Alzheimer's disease: a systematic review and meta-analysis. Front Dement. 2024 Jul 3;3:1380221. https://doi.org/10.3389/frdem.2024.1380221

Objective To systematically evaluate the efficacy of acupuncture in the treatment of cognitive impairment in Alzheimer's disease (AD) by meta-analysis, in order to provide evidence-based evidence for the application of acupuncture therapy in the clinical process of AD.
Methods From the establishment of the database to December 31, 2022, China Biomedical Literature Database (CBM), China National Knowledge Network (CNKI), VIP database, WanFang Database, Pubmed, Embase and Cochrane Library Database were systematically searched. To collect published randomized controlled clinical trials (RCTS) of acupuncture in the treatment of cognitive impairment in AD. The subjects in the intervention group were given acupuncture alone or combined with other treatments the same as the control group; the control group received conventional Western medicine treatment. The main outcome indicators of the study were cognitive function assessment of subjects, including: Simple Mental State Examination Scale (MMSE), Assessment of daily Living Ability Scale (ADL), Alzheimer's Disease Cognitive Function Assessment Scale (ADAS-Cog), TCM syndrome score (SDSD), Montreal Cognitive Test (MoCA), Secondary outcome indicators were the occurrence of adverse reactions. Literature screening, data extraction, and quality evaluation of the included literature were performed independently by two researchers, according to bias risk assessment tools recommended in the Cochrane manual. Data were analyzed by RevMan5.3 software. Dichotomous variables were represented by risk ratio (OR) and 95% CI, and continuity variables were represented by mean difference (MD) and 95% CI. For heterogeneity analysis, when P > 0.1 and I 2 ≤ 50%, fixed effect model was applied. When P ≤ 0.1 and I 2 > 50%, the random effects model is applied.
Results A total of 1,172 eligible subjects were included in 18 RCTS, including 595 in the intervention group and 577 in the control group. The results of meta-analysis are as follows: acupuncture intervention group improved MMSE [MD = 1.67, 95% CI (0.94, 2.41), P < 0.00001], ADL [MD = -1.18, 95% CI (-3.09, 0.72), P = 0.22], ADAS-Cog [MD = 3.31, 95% CI (5.84, 0.78), P = 0.01], SDSD [MD = 2.40, 95% CI (3.53, 1.26), P < 0.0001], MoCA [MD = 4.80, 95% CI (3.74, 5.86), P = 0.04] were better than the control group. No serious adverse reactions related to acupuncture were observed in the intervention group, and the incidence and severity of adverse reactions were lower than those in the control group, with statistical significance [OR = 0.17, 95% CI (0.04, 0.67), P = 0.01].
Conclusion Existing data show that acupuncture therapy has certain advantages in improving cognitive dysfunction and improving self-care ability of patients with Alzheimer's disease. However, due to the small number of RCTS and cases evaluating the efficacy of acupuncture, and the possibility of measurement bias and selectivity bias in included studies, it is still unable to conduct high-intensity demonstration on its effectiveness. Further large-scale, high-quality randomized, double-blind controlled trials are needed to evaluate its efficacy.

1.1.3. Lin 2022

Lin CJ, Yeh ML, Wu SF, Chung YC, Lee JC. Acupuncture-related treatments improve cognitive and physical functions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials. Clin Rehabil. 2022 May;36(5):609-635. https://doi.org/10.1177/02692155221079117

ObjectiveTo determine acupuncture-related treatments' effects and duration on improving cognitive function, physical function, and quality of life in patients with Alzheimer's disease.
Data sources Eight electronic databases were searched for eligible randomized controlled trials from database inception to January 2021, including Medline, PubMed, EBSCO, Embase, Cochrane, Airiti Library, China National Knowledge Infrastructure, and China Journal Full-text Database.
Review methods A systematic review and meta-analysis were conducted on acupuncture types, cognitive function, activity of daily life, muscle strength and quality of life.
ResultsSixty-six studies in total with 4191 participants, the overall risk of bias was classified 60% as low and 24% as high. Acupuncture-related treatments for cognitive function and self-care ability revealed a moderate effect size, with a significant difference in noninvasive and invasive remedies (p < 0.001). Cognitive function showed significant differences in 6, 8, 12, and 24 weeks while self-care ability in the latter two weeks (p < 0.001). Meta-regression analysis showed cognitive function increased by 0.05 points (p = 0.002) and self-care ability decreased by 0.02 points (p = 0.04) after weekly treatment. There was a significant difference in muscle strength (p = 0.0003).
ConclusionAcupuncture-related treatments effectively improved cognitive function with the treatment lasted 6 weeks at least, but self-care ability started showing effects after 12 weeks of treatment. The improvement of muscle strength was also confirmed. Acupuncture-related treatments, particularly noninvasive ones, have few complications and high safety, perhaps providing patients and caregivers diversified choices and clinical care guidelines for reference.

1.1.4. Wang 2021 (Network Meta-Analysis)

Wang XS, Li JJ, Wang YS, Yu CC, He C, Huang ZS, Jiang T, Hao Q, Kong LH. Acupuncture and Related Therapies for the Cognitive Function of Alzheimer's Disease: A Network Meta-Analysis. Iran J Public Health. 2021 Dec;50(12):2411-2426. https://doi.org/10.18502/ijph.v50i12.7924

Background Acupuncture and acupuncture-related therapies are effective for Alzheimer's disease (AD), therefore, we aimed to compare and rank the interventions that mainly focus on acupuncture-related therapies in the treatment of patients with mild to moderate AD.
Methods We used network meta-analysis to evaluate the direct and indirect evidence shown in randomized controlled trials of AD. The data were analyzed using RavMan manager, Stata, and WinBUGS software after two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies.
ResultsWe analyzed a total of 36 eligible studies, including 2712 patients, involving 14 types of acupuncture-related therapies and comprehensive therapies. For Mini-Mental State Examination (MMSE), acupuncture (ACU) combined with cognitive and memory training (Training) was more effective than ACU, ACU+Chinese herb (CH), ACU+Donepezil (DON), CH, DON, DON+Nimodipine (NIM), Music therapy (Music), NIM, Placebo, and Training (P<0.05), while ACU+CH was batter than CH (P<0.05), and ACU+DON+NIM was better than DON+NIM (P<0.05). For Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog), ACU was more effective than DON and placebo (P<0.05). For Activities of Daily Living (ADL), ACU+DON was better than CH, DON, NIM, and Placebo (P<0.05). For the clinical effectiveness rate, ACU, ACU+CH, ACU+CH+DON, ACU+CH+DON+NIM, ACU+DON, CH, NIM were all more effective than DON+NIM (P<0.05), while ACU and ACU+CH were better than DON (P<0.05). The comprehensive ranking results show that ACU+training and ACU have the highest ranking probability.
ConclusionACU+Training and ACU may be the best therapies to improve the cognitive function of patients with mild to moderate AD, while the combination of acupuncture-related therapies and other therapies has a higher overall benefit.

1.1.5. Jiao 2020

Jiao Lan, Ji-fei Miao, Shu-qi Ge, Tie-qu Chai, … Li-ming Lu. Acupuncture for cognitive impairment in vascular dementia, Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis. European Journal of Integrative Medicine. 2020;35. [212068]. doi

Introduction Cognitive impairment is a worldwide health problem. Numerous studies have been conducted to evaluate the effect of acupuncture on cognitive impairment. However, it is still unclear that if acupuncture shows the same efficacy on cognitive impairment caused by different diseases. Therefore, we conducted a systematic review and meta-analysis based on the current evidence to evaluate the efficacy and safety of acupuncture for cognitive impairment in vascular dementia (VD), Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients.
Methods Five databases were searched from their inception to December 2019. Randomized controlled trials (RCTs) involving VD, AD or MCI treated by acupuncture alone or as part of combination therapy were included. The primary outcomes were the Mini-Mental State Examination and the Hierarchic Dementia Scale.
Results Twenty-one RCTs (N = 2253) were quantitatively analyzed. For VD, compared with Western medicine (WM), acupuncture showed better Hierarchic Dementia Scale scores (P < 0.01), and acupuncture plus WM also showed better Hierarchic Dementia Scale scores (P < 0.01). For MCI, acupuncture showed a significant improvement in Mini-Mental State Examination (P < 0.01) and picture recognition test scores compared with WM. For AD, WM resulted in better Hierarchic Dementia Scale scores than acupuncture (P < 0.01). Eight trials reported adverse events, 15 out of 2253 patients had adverse events related to acupuncture treatment, and 25 out of 2253 patients had adverse events related to WM treatment.
Conclusion Acupuncture may be efficacious for improving cognitive function in patients with VD and MCI. However, the evidence is limited, and larger sample size and more rigorous RCTs should be conducted to verify the effectiveness and safety of acupuncture.

1.1.6. Jin 2020

Jin Hyeon Shin, Hye Jeong Shin, Eui Byeol Kim, Yun Young An, Tae Han Yook, Yoo Min Choi, Beom Yong Song, Jong Uk Kim. The Effectiveness of Acupuncture Treatment for Patients with Alzheimer’s Disease: A Meta-Analysis of Randomized Controlled Trials. J Acupunct Res. 2020;37(4):209-223. [219961]. doi

Purpose The purpose of this study was to evaluate the effectiveness of acupuncture treatment for the symptoms of Alzheimer’s disease (AD).
Methods 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.
Results 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.
Conclusions Acupuncture alleviates the symptoms of AD. However, further research is necessary to provide a better level of evidence.

1.1.7. Lai 2020 (Network Meta-Analysis)

Lai X, Wen H, Li Y, Lu L, Tang C. The Comparative Efficacy of Multiple Interventions for Mild Cognitive Impairment in Alzheimer's Disease: A Bayesian Network Meta-Analysis. Front Aging Neurosci. 2020. [210345]. doi

BackgroundMild cognitive impairment (MCI) is the early phase of Alzheimer's disease (AD). The aim of early intervention for MCI is to decrease the rate of conversion from MCI to AD. However, the efficacy of multiple interventions in MCI, and the optimal methods of delivery, remain controversial. We aimed to compare and rank the treatment methods for MCI in AD, in order to find an optimal intervention for MCI and a way to prevent or delay the occurrence of AD.
Methods Pair-wise and network meta-analysis were conducted to integrate the treatment effectiveness through direct and indirect evidence. Four English databases and three Chinese databases were searched for international registers of eligible published, single or double blind, randomized controlled trials up to September 31st 2019. We included nine comparative interventions: pharmacological therapies which incorporated cholinesterase inhibitors (ChEI), ginkgo, nimodipine, and Chinese medicine; non-pharmacological therapies comprising of acupuncture, music therapy, exercise therapy, and nutrition therapy; and a placebo group. The primary outcome was the Mini-Mental State Examination (MMSE) score. The secondary outcome was the AD Assessment Scale-cognitive subscale (ADAS-cog).
Results Twenty-eight trials were eligible, including 6,863 participants. In the direct meta-analysis, as for the Mini-Mental State Examination scale, the ChEIs (MD: -0.38; 95% CI: -0.74, -0.01), Chinese medicine (MD: -0.31; 95% CI: -0.75, 0.13), exercise therapy (MD: -0.50; 95% CI: -0.65, -0.35), music therapy (MD: -1.71; 95% CI: -4.49, 1.07), were statistically more efficient than placebo. For AD Assessment Scalecognitive subscale outcome, ChEIs (MD: 1.20; 95% CI: 0.73, 1.68), Acupuncture (MD: 1.36; 95% CI: 1.28, 1.44), Chinese medicine (MD: 0.61; 95% CI: 0.49, 0.73) and exercise (MD: 0.61; 95% CI: 0.49, 0.73) were better than placebo. In the network meta-analysis, the MMSE outcome ranked music therapy (59%) as the best and Acupuncture (26%) as second. Nutrition and Ginkgo treatment had the lowest rank among all interventions. For ADAS-cog outcome, acupuncture (52) ranked the best.
ConclusionAmong the nine treatments studied, music therapy appears to be the best treatment for MCI, followed by acupuncture. Our study provides new insights into potential clinical treatments for MCI due to AD, and may aid the development of guidelines for MCI in AD.

1.1.8. Wang 2020

Wang YY, Yu SF, Xue HY, Li Y, Zhao C, Jin YH. Effectiveness and Safety of Acupuncture for the Treatment of Alzheimer's Disease: A Systematic Review and Meta-Analysis. Front Aging Neurosci. 2020. [209248]. doi/

Background The effects of acupuncture on Alzheimer's disease (AD) outcomes remain controversial. The aim of this review was to evaluate the effectiveness and safety of acupuncture for the treatment of AD.
MethodsPubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data were searched to identify relevant randomized controlled trials from inception to January 19, 2019. Data were extracted and evaluated by two authors independently. The data analysis was conducted using R (version 3.6.0) and RStudio (version 1.2.1335) software.
Results Thirty trials involving 2,045 patients were included. Acupuncture plus drug therapy may have been more beneficial for general cognitive function in AD patients than drug therapy alone (short-term treatment: MD, mean difference = 1.94, 95% CI: 1.11, 2.77; p < 0.01; medium-term treatment: MD = 4.41, 95% CI: 1.83, 7.00; p < 0.01). People who received acupuncture plus drug therapy attained higher ADL (Activities of Daily Living) scores than patients who received drug therapy alone for medium-term treatment duration (MD = -2.14; 95% CI: -3.69, -0.59; p < 0.01). However, there is no statistically significant difference in subgroup effect on MMSE (Mini-mental Status Examination) and ADLs (p > 0.05) when comparing acupuncture treatment with drug therapy (such as Donepezil hydrochloride, Nimodipine, or Yizhijiannao), or acupuncture plus drug therapy (such as Donepezil hydrochloride, Dangguishaoyaosan, or Jiannaosan) with drug therapy alone. There was also no significant difference in general cognitive function, ADLs, or incidence of adverse events between acupuncture treatment and drug therapy (p > 0.05).
Conclusions This review indicates that acupuncture plus drug therapy may have a more beneficial effect for AD patients than drug therapy alone on general cognitive function in the short and medium term and on ADLs in the medium term. Acupuncture alone may not have superior effects compared with drug therapy on global cognitive function, ADLs, and incidence of adverse events. Duration of treatment may not modify the effect of acupuncture in comparison with drug therapy. Additional large-scale and high-quality clinical trials are needed.

1.1.9. Huang 2019

Huang Q, Luo D, Chen L, Liang FX, Chen R. Effectiveness of Acupuncture for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis. Curr Med Sci. 2019;39(3):500-511. [199649].

BackgroundAcupuncture has reportedly improved memory and cognitive impairment in both animal and clinical studies. It may be an effective treatment for Alzheimer's disease (AD).
Objective The purpose of this meta-analysis was to review the effectiveness of acupuncture for the treatment of AD.
MethodsEight databases were searched for articles published up to and including July 2017, and 13 studies fulfilling the inclusion criteria were identified. The main outcomes assessed were clinical efficacy rate, Mini-Mental State Examination score, Ability of Daily Living Scale score, Alzheimer's Disease Assessment Scale-Cognition score, Hasegawa's Dementia Scale (HDS) score, and adverse events. The methodological quality of the articles was assessed using Cochrane's risk of bias. All the studies compared the efficacy of acupuncture with that of medication, and were published in Chinese journals.
ResultsMeta-analysis revealed that acupuncture yielded positive results as determined via all the indexes scored except the HDS (95% CI -0.26 to 0.90, Z=0.35, P=0.73). Only one of the studies reported adverse events associated with acupuncture and medication. The rate of adverse events in the medication group was 13%. In most of the studies assessed in the current meta-analysis, acupuncture alone was better than conventional western medicines for the treatment of AD.

1.1.10. Wang 2019

Wang Yishen, Xu Jia, Fu Qinhui, Pei Jian. [Acupuncture combined with medicine for cognitive functions and life quality of patients with Alzheimer’s disease: a systematic review]. Shanghai Journal of Traditional Chinese Medicine. 2019;1:19-25. [201736].

Objective To systematically evaluate the efficacy and safety of acupuncture combined with medicine for cognitive functions and life quality of the patients with Alzheimer’s Disease ( AD).
Methods The randomized controlled trials ( RCTs) regarding acupuncture combined with medicine for AD published from January 1st of 2008 to August 31th of 2018 were researched in China National Knowledge Infrastructure, VIP medicine information system, Wan Fang database, Chinese Biomedical Database, PubMed, Medline, Springer Link and Cochrane Library. The quality assessment was performed based on the guidance of the Cochrane Reviewers’ Handbook, and Meta-analyses was performed by using Rev Man 5. 3 software.
Results Totally 8 RCTs were included, Involving 472 AD patients. The results of Meta-analyses showed that the treatment group was superior to the control group in improving the mini-mental state examination (MMSE)MD = 0.76,95%CI [0.42,1.10], P<0.000 01), Alzheimer’s disease assessment scale-cognitive section ( ADAS-cog) ( MD =-0.32,95%CI [-0.61,-0.03],P = 0.03), activities of daily living (ADL)( MD =-0.66,95%CI [-1.06,-0.27],P = 0.001).
Conclusion Acupuncture combined with medicine for cognitive functions and life quality of AD patients is effective. However, the included studies were with risk of bias and with clinical heterogeneity. So more RCTs of high quality are needed to further confirm its efficacy and safety.

1.1.11. Zou 2016 ∼

Zou Jingfeng, Xie Ke, Guo Peiyan, Dong Xushuai, Zhao Fei. [Meta-analysis of randomized controlled clinical trial about acupuncture in treating Alzheimer's disease]. Gansu Journal of Traditional Chinese Medicine. 2016;1:80-84. [186969].

Objectives To systematically assess the differences between traditional acupuncture and western medicine in treating alzheimer's disease.
Methods Randomized controlled trials (RCTs) about acupuncture compared with western medicine in treating alzheimer's disease were chosen by searching PubMed, Embase, Cochrane library, CNKI, VIP and Wanfang, the quality of the literature which met the included standard were assessed and meta-analysis was performed by using RevMan 5. 2 software.
Results Eight articles and 349 patients were included. The results of Meta-analysis showed that the difference had no statistical meaning between both groups, while clinical effects of acupuncture in treating alzheimer's disease [OR=1. 15, 95%CI (0. 69, 1. 91)], MMSE scaling [MD=0. 40, 95%CI (-2. 18, 2. 97)], ADL scaling [MD=0. 60, 95%CI (-0. 54, 1. 74)], HDS scaling [MD=-0. 20, 95%CI (-1. 19, 0. 80)] were equivalent to these indexes of western medicine.
Conclusions The advantages of acupuncture in treating alzheimer's disease compared with western medicine are unsure, more large samples and high quality RCTs are needed to further validate the results.

1.1.12. Xu 2015 (combined with western medicine) ☆☆

Xu Xiaotai, Xie Wei. [Meta-analysis on acupuncture combined with western medicine for treatment of Alzheimer’s disease]. World Science and Technology-Modernization of Traditional Chinese Medicine. 2015;4:836-840. [187068].

Objectives This study was aimed to evaluate efficacy of acupuncture combined with western medicine in treatment of Alzheimer’s disease (AD) with meta-analysis of data came from randomized controlled trials (RCTs).
Methods Databases both at home and abroad were comprehensively searched to collect efficacy data of acupuncture combined with western medicine versus western medicine in RCTs. The data was extracted from each study to conduct a meta-analysis with Rev Man 5. 2.
Results The results showed that 10 studies measured up to standard. Seven studies reported effective cases were carried out by meta-analysis. The total RR was 1. 25 [1. 14, 1. 38]. The funnel plot was approximately symmetry. It was suggested that effect of the therapy group was better than the control group (Z = 4. 66, P<0. 01). Four studies reported mini-mental state examination (MMSE) scores were carried out by meta-analysis. The total MD was 2. 87 [0. 64, 5. 10]. The funnel plot was approximately symmetry. It was suggested that the therapy group was better than the control group on AD treatment in cognitive function improvement (Z = 2. 52, P= 0. 01).
Conclusions It was concluded that from current study, acupuncture combined with western medicine in AD treatment was definitely effective. However, it still required further study.

1.1.13. Zhou 2015 ☆☆

Zhou J, Peng W, Xu M, Li W, Liu Z. The Effectiveness and Safety of Acupuncture for Patients with Alzheimer Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Medicine (Baltimore). 2015;94(22). [183449].

Objectives The use of acupuncture for treating Alzheimer disease (AD) has been increasing in frequency over recent years. As more studies are conducted on the use of acupuncture for treating AD, it is necessary to re-assess the effectiveness and safety of this practice. The objective of this study was to assess the effectiveness and safety of acupuncture for treating AD.
Methods Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, Embase, PsycINFO, Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC) and China National Knowledge Infrastructure (CNKI) were searched from their inception to June 2014. Randomized controlled trials (RCTs) with AD treated by acupuncture or by acupuncture combined with 1 kind of drugs were included. Two authors extracted data independently. The continuous data were expressed as mean differences (MD) with 95% confidence intervals (Cis). Weighted MD (WMD) was used instead of standardized MD (SMD) when the same scales were used. Adverse reactions related to acupuncture were also investigated.
Results Ten randomized controlled trials with a total of 585 participants were included in the meta-analysis. The combined results of 6 trials showed that acupuncture was better than drugs at improving scores on the Mini Mental State Examination (MMSE) scale (MD 1.05, 95% CI 0.16-1.93). Evidence from the pooled results of 3 trials showed that acupuncture plus donepezil was more effective than donepezil alone at improving the MMSE scale score (MD 2.37, 95% CI 1.53-3.21). Out of 141 clinical trials, 2 trials reported the incidence of adverse reactions related to acupuncture. Seven out of 3416 patients had adverse reactions related to acupuncture during or after treatment; the reactions were described as tolerable and not severe
Conclusions Acupuncture may be more effective than drugs and may enhance the effect of drugs for treating AD in terms of improving cognitive function. Acupuncture may also be more effective than drugs at improving AD patients' ability to carry out their daily lives. Moreover, acupuncture is safe for treating people with AD

1.1.14. Cao 2014 Ø

Cao Fei, Pan Xiao-Ling, Li Xuan-Chao, Chen Bao, Jin Yuan, Huang Peng. [Systematic review and meta-analysis on acupuncture for Alzheimer disease in chinese population]. Acta Academiae Medicinae Jiangxi. 2014;9:59-61, 6. [186901].

Objectives To assess the therapeutic effect of acupuncture on Alzheimer disease (AD)in Chinese population, and to provide more reliable information for the treatment of AD.
Methods The literature published from January 1979 to December 2013 on the acupuncture for treatment of Alzheimer disease in Chinese population was collected, and the effects of acupuncture on mini-mental state examination (MMSE) and activity of daily living (ADL) were assessed. The meta-analysis was conducted by using RevMan5. 0.
Results A total of 5 randomized controlled trials were identified and all controls were oral medications. In the aspect of cognitive function, the weighted mean difference (WMD)was -0. 61 (- 1. 34, 0. 13). In the aspect of ADL, the WMD was -0. 48 (-0. 72, 0. 76).
Conclusions Compared with oral medications, the acupuncture can not improve the MMSE and ADL scores in patients with AD. Furthermore, the quality of literature is poor. Therefore, more observations are needed to verify the effect of acupuncture on AD.

1.1.15. Lee 2009

Lee MS, Shin BC, Ernst E. Acupuncture for Alzheimer's disease: a systematic review. Int J Clin Pract. 2009;63(6):874-9. [153322].

BackgroundAcupuncture is often used as a treatment for dementia and is claimed to be effective in improving intelligence.
Aims The objective of this review is to assess the clinical evidence for or against acupuncture as a treatment for Alzheimer's disease (AD).
methodsWe searched the literature using 17 databases from their inception to August 2008, without language restrictions. We included all randomised clinical trials (RCTs) of needle acupuncture to treat human patients suffering from AD. Methodological quality was assessed using the Jadad score.
ResultsThree RCTs met all inclusion criteria. Two RCTs assessed the effectiveness of acupuncture on cognitive function compared with drug therapy. Their results suggested no significant effect in favour of acupuncture [n = 72, weight mean difference (WMDs), -0.55; 95% confidence intervals (CIs) -1.31 to 0.21, p = 0.15, heterogeneity: tau(2) = 0, chi(2) = 0.048, p = 0.49, I(2) = 0%]. Two RCTs tested acupuncture for activities of daily living (ADL). One RCT reported favourable effects of drug therapy compared with acupuncture for ADL, while the other failed to so. The meta-analysis of these data showed significant effects of drug therapy compared with acupuncture (n = 72, WMD, -1.29; 95% CIs: -1.77 to -0.80, p < 0.001, heterogeneity: tau(2) = 0, chi(2) = 0.17, p = 0.68, I(2) = 0%).
Conclusion Even though the number of studies is small, the existing evidence does not demonstrate the effectiveness of acupuncture for AD.

1.2. Special Acupuncture Techniques

1.2.1. Comparison of acupuncture techniques

1.2.1.1. Yin 2023 (Network Meta-Analysis)

Yin W, Chen Y, Xu A, Tang Y, Zeng Q, Wang X, Li Z. Acupuncture May Be a Potential Complementary Therapy for Alzheimer's Disease: A Network Meta-Analysis. Evid Based Complement Alternat Med. 2022 Nov 23;2022:6970751. https://doi.org/10.1155/2022/6970751

With Alzheimer's disease (AD) becoming a worldwide problem, traditional Chinese medicine (TCM), especially acupuncture, stands out as a complementary therapy because of its feature-“treatment based on syndrome differentiation”. This systematic review and network meta-analysis (NMA) confirms the complement effect of acupuncture and explores the best combination of therapy for AD based on the total effect and activity of daily living scale (ADL). We searched relevant randomized controlled trials (RCTs) that applied acupuncture for treating AD. 58 studies with 4334 patients were included in accordance with PRISMA guidelines. The results showed that for the total effect, the order of probability for the effect: acupuncture + western medicine > acupuncture + herbal medicine > acupuncture > acupuncture + western medicine + herbal medicine. For the ADL score, the order of probability for the effect: acupuncture + western medicine > acupuncture > acupuncture + western medicine + herbal medicine > acupuncture + herbal medicine. The combination of acupuncture and medicine has a better clinical effect than acupuncture only in a way. Acupuncture + western medicine has an obvious and exact improvement in the curative effect from both total effect and ADL score, but further higher quality studies, which can detail the classification of these interventions, are still needed to verify it.
1.2.1.2. Yin 2022 (Network Meta-Analysis)

Yin Z, Li X, Wang L, Sun M, Zhao L, Liang F. The Comparative Efficacy of Multiple Acupuncture for Alzheimer's Disease: A Bayesian Network Meta-Analysis. Evid Based Complement Alternat Med. 2022 May 17;2022:3288948. https://doi.org/10.1155/2022/3288948

Background Alzheimer's disease (AD) is a progressive neurodegenerative disease. Numerous cases have illustrated that the acupuncture method could improve AD patients' cognitive function and daily living ability. However, the optimal acupuncture treatments remain controversial. Therefore, we aimed to conduct a systematic review to compare the efficacy of multiple acupuncture therapies for AD and identify the optimal acupuncture intervention for delaying AD progression.
Methods To select potentially concerned randomized controlled trials (RCTs), we searched four English databases, four Chinese databases, and additional sources from 1 May 2021. Two independent reviewers conducted study screening, data extraction, and methodological quality assessment. The primary outcome was global cognitive function improvement. Pairwise and Bayesian network meta-analyses were performed using STATA v15.0 and ADDIS v1.16.8. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to assess the quality of evidence.
Results This study included 34 RCTs with 2,071 participants. Regarding global cognitive function improvement, the pairwise meta-analysis confirmed that electronic acupuncture (EA) plus conventional medicine (CM) and manual acupuncture (MA) plus CM were statistically significantly different from CM, and EA plus CM was ranked as the best combination in the network meta-analysis. In terms of response rate, MA outperformed CM statistically significantly; warm acupuncture (WA) was ranked as the best in the network meta-analysis. Regarding activity of daily living improvement, EA plus CM, MA plus CM, and fire acupuncture plus CM, MA, and scalp acupuncture were statistically significantly different from CM, and EA plus CM was ranked as the best combination in the network meta-analysis. However, the evidences were ranked as low to critically low.
Conclusions Acupuncture, as a monotherapy or an adjuvant therapy, may have a beneficial effect on efficacy for AD. EA plus CM may be the optimal acupuncture therapy for AD and should be administered to AD patients. It may aid and support patient, operative, and societal decision-making. Due to the dearth of high-quality evidence, additional high-quality studies should be conducted to ensure these findings in the future. This study is registered with PROSPERO (CRD42021252305).

1.2.2. Combined with Traditional Chinese Medicine

1.2.2.1. Wang 2023 (combined with tonifying kidney decoction)

Wang XC, Chu CL, Lu K, Chen X, Jin XQ, Quan SJ. The role of tonifying kidney decoction and acupuncture in the treatment of Alzheimer's disease: A network meta-analysis. Medicine (Baltimore). 2022 Nov 18;101(46):e31243. https://doi.org/10.1097/MD.0000000000031243.

Importance As one of the chronic neurological degenerative diseases with the highest incidence of amnesia and dementia, Alzheimer's disease (AD) carried out the clinical treatment based on the 2 traditional Chinese medicine (TCM) of Chinese herbal compound and acupuncture (AP). With the vigorous development of TCM, doctors are facing the problem of choosing TCM or western medicine in clinical work. Hence there is an urge to make pairwise comparisons among these interventions to provide evidence for clinical practice.
Objective The used efficacy of the 2 TCM methods and combined with donepeziline were compared to compile the best treatment through network meta-analysis.
MethodsPatients diagnosed with AD were included in the randomized clinical trial, who were treated with tonifying kidney decoction (TKD) or AP combined with donepezil hydrochloride (DH) as an intervention measure, while the control group was treated with DH. The total effective rate was the primary outcome, and mini-mental state examination (MMSE) score and activities of daily living (ADCS-ADL) scores were the secondary indicators.
ResultsEventually 30 studies reporting 2236 patients underwent TKD or AP combined with DH were enrolled. In terms of total efficiency, compared with TKD and DH, TKD + DH was significantly preferable. In addition, TKD were classified into 2 categories, namely tonifying kidney with reducing phlegm formulas (TKRP) and tonifying kidney with filling lean marrow (TKFLM). Regarding to MMSE score of TKD, of the 3 interventions, only TKRP + DH (standard mean difference [SMD] = 4.84, 95% confidence interval [CI]: 0.86-8.82) and TKFLM + DH (SMD = 3.93, 95% CI: 1.06-6.80) had significant efficacy over TKFLM (SMD = 4.25, 95%CI: -2.58 to 11.08). Although no difference between TKRP and other groups, its effectiveness was higher than TKFLM + DH and TKFLM (surface under the cumulative ranking curve (SUCRA) = 61.5%). For the ADL score, compared with TKFLM + DH and DH, TKRP + DH had more effective (SUCRA = 70.2%). Regarding to the total effective rates, AP + DH was more statistically better than AP, and AP was statistically better than DH.
ConclusionTKD or AP in combination with DH are significantly superior in treating AD.
1.2.2.2. Jiao 2020

Jiao Li. [Systematic Review of Acupuncture Combined with Traditional Chinese Medicine in Treatment of Alzheimer's Disease ]. Journal of Hubei Minzu University (Medical Edition). 2020. [212897].

ObjectiveThe aim of the study is to comprehensively evaluate the clinical efficacy of acupuncture combined with Traditional Chinese Medicine in the treatment of a Alzheimer disease.
Methods We performed online searches of the CNKI, Wanfang, VIP, PubMed, web of Science (SCI), Medline until July 2019 to find randomized controlled trials about acupuncture combined with Traditional Chinese Medicine in the treatment of Alzheimer disease. Two reviewers independently screened and extracted data according to inclusion and exclusion criteria. Review Manager5. 3 was used to perform the meta-analysis.
Results Totally 12 RCTs involving 737 patients were included eventually. The results of Meta-analysis showed that compared with Western medicine, acupuncture combined with Traditional Chinese Medicine had better efficacy in improving effective rate [RR=1. 29, 95%CI (1. 16, 1. 44)] and MMSE score [WMD=1. 87, 95%CI (0. 76, 2. 98)] (P<0. 01).
Conclusion Current RCTs clinical evidence indicated that acupuncture combined with Traditional Chinese Medicine was better than Western medicine in the treatment of Alzheimer disease, and there was no serious adverse reaction. Due to the small sample size and the generally low quality of included studies, this conclusion still needs support from large sample, multi-center, high-quality randomized controlled research.
1.2.2.3. Zhou 2017

Zhou S, Dong L, He Y, Xiao H. Acupuncture plus Herbal Medicine for Alzheimer's Disease: A Systematic Review and Meta-Analysis Am J Chin Med. 2017;45(7):1327-1344. [52387].

Background Alzheimer's disease (AD) is associated with the unprecedented aging tendency in our world population and has become a significant health issue. The use of Traditional Chinese Medicine to treat AD has been increasing in recent years.
Objective The objective of this meta-analysis is to evaluate the effectiveness of combining acupuncture with herbal medicine to treat AD.
MethodsRandomized controlled trials (RCTs) of acupuncture plus herbals versus treatment with western drugs for AD were retrieved from 11 databases. The data were extracted by two authors; dichotomous data were expressed as odds ratio (Ors) and 95% confidence intervals (Cis), while continuous data were calculated by mean differences (MDs) with 95% Cis.
Results Although the combined analysis of the score of Activity of Daily Life (ADL) scale MD was [Formula: see text]3.59 (95% CI [Formula: see text]7.18-0.01, [Formula: see text]), which indicates there was no statistically significant difference between the two treatments at reducing the ADL scale score, the pooled results of 12 trials indicated that acupuncture plus Chinese herbal medicine was better than western drugs at improving the effectiveness rate (OR 2.24, 95% CI 1.40-3.56), the combined evidence of 11 articles showed that acupuncture plus Chinese herbal medicine was more effective than western drugs at improving the scores for the Mini Mental State Examination (MMSE) scale (2.10, 95% CI 0.69-3.51, [Formula: see text]) and the traditional Chinese medicine symptom (MD 5.07, 95% CI 3.90-6.25, [Formula: see text]).
ConclusionsFrom the current research results, acupuncture plus herbal medicine may have advantages over western drugs for treating AD. Nevertheless, well-designed RCTs with a larger sample size are required in the future.
1.2.2.4. Zou 2016 ☆

Zou Jingfeng, Guo Peiyan, Xie Ke, Dong Xushuai, Zhao Fei. [Meta-analysis of the effectiveness of acupuncture treatment combined with traditional chinese medicine treatment of Alzheimer disease]. China Journal of Chinese Medicine. 2016;1:138-143. [186905].

目的: 比较针刺联合中药与单用中药治疗阿尔茨海默病的疗效差异. 方法: 通过检索PubMed、Embase、CNKI等中外论文数据库, 筛选出针药对照单用中药治疗阿尔茨海默病的随机临床对照试验. 对符合标准的文献评价质量, 并应用RevMan Manager 5. 2软件进行Meta分析. 结果: 纳入共包括335例患者的6篇文献. Meta分析结果显示, 针药结合、单用中药治疗阿尔茨海默病后的有效率分别为76. 96％和65. 28％, 合并效应量的比值比OR=1. 89, (95％ CI=1. 11, 3. 21), P=0. 02 ＜0. 05, 提示差异有统计学意义;针药与单用中药治疗阿尔茨海默病后的MMSE、ADL量表评分的分析结果分别为MD=1. 55, (95％CI=0. 98, 2. 12), P＜0. 000 01、WMD=0. 36, (95％ CI=0. 14, 0. 59), P=0. 002, 以上结果P均＜0. 05, 提示治疗前后量表评分改变上针药与单用中药的疗效比较, 差异有统计学意义. 结论: 针药结合比单用中药治疗阿尔茨海默病更具优势, 但仍需更多大样本高质量的随机临床对照试验进一步验证.

Automatic translation
Objectives to compare the Alzheimer's disease treated by acupuncture combined with traditional Chinese medicine and traditional Chinese medicine efficacy.
Methods Search PubMed, Embase, CNKI database and foreign papers, filter out acupuncture controlled randomized controlled clinical trials of traditional Chinese medicine for treatment of Alzheimer's disease alone. To meet the standard of quality of literature evaluation, and using RevMan Manager 5. 2 software Meta analysis.
Results included in total including 335 cases 6 references. Meta analysis shows that acupuncture and using traditional Chinese medicine for treatment of Alzheimer's disease, the effective rate was 76. 96% and 65. 28%, the combined effect of the ratio of OR=1. 89, (95% CI=1. 11, 3. 21), P=0. 02 <0. 05, indicating there was a statistically significant difference; acupuncture and using traditional Chinese medicine in the treatment of Alzheimer's disease after the MMSE, ADL scale scores results for MD=1. 55, (95%CI=0. 98, 2. 12), P<0. 000 01、WMD=0. 36, (95% CI=0. 14, 0. 59), P=0. 002, results above all <0. 05, scores on the changes before and after treatment of acupuncture and medicine with comparison of the curative effect of traditional Chinese medicine alone, there was a statistically significant difference.
Conclusions acupuncture has an advantage over using traditional Chinese medicine in the treatment of Alzheimer's disease, but still needs more large scale high quality randomized controlled trials for further verification.

1.2.3. Warm needle

1.2.3.1. Chen 2022

Chen X, Liu F, Lin N, Lin Q, Lyu Z, Xiu H, Nie P. Warming needle moxibustion for Alzheimer's disease: A systematic review of randomized controlled trials. Geriatr Nurs. 2022 Jan-Feb;43:219-226. https://doi.org/10.1016/j.gerinurse.2021

Objective To systematically research the impact of warming needle moxibustion (WNM) for Alzheimer's Disease (AD).
MethodsFour Chinese databases and six English databases were systematically searched. Randomized controlled trials (RCTs) involving the use of WNM to intervene in AD patients were included. Data were extracted from the included studies and methodological quality was evaluated according to the Cochrane Handbook for Systematic Reviews of Intervention 5.1.0. Meta-analysis was performed using RevMan 5.4 software.
Results8 RCTs comprising 524 patients were included. Most studies had no significant bias. The study showed that WNM was more effective in the treatment of AD than acupuncture or pharmacotherapy. The findings were as follows: MMSE (MD = 1.01, 95%CI: 0.13, 1.90, P = 0.03) and CDR (MD = -0.73, 95%CI: -0.84, -0.61, P < 0.00001) for global cognitive function, ADL (MD = -1.84, 95%CI: -2.47, -1.22, P < 0.00001) for activities of daily living, Syndrome Differentiation Scale of Dementia (SDSD) (MD = -2.67, 95%CI: -3.62, -1.72, P < 0.00001), and the total effective rate of patients (OR = 3.20, 95%CI: 1.90 to 5.38, P < 0.0001). The differences in all indicators were statistically significant.
Conclusion WNM might have a significant effect on improving cognitive function and daily living ability, reducing the symptoms of AD, and increase the total effective rate. WNM is an effective non-pharmacological therapy for patients with AD.

2. Overviews of systematic reviews

2.1. Ke 2024

Ke C, Shan S, Yu J, Wei X, Pan J, Zhang W. Acupuncture for patients with Alzheimer's disease: An evidence map of randomized controlled trials, systematic reviews, and meta-analysis. J Alzheimers Dis. 2024 Dec;102(4):924-942. https://doi.org/10.1177/13872877241295400

Backgound Acupuncture is an effective complementary treatment for Alzheimer's disease (AD). This review aims to summarize the available evidence provided by randomized controlled trials (RCTs) and systematic reviews (SRs) or meta-analyses (MAs) on the effect of acupuncture on AD.
Objective To systematically summarize and combine clinical research evidence on AD distribution.
Methods We conducted a comprehensive search of various databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese BioMedical Literature Database (CBM) and Chonqing VIP (CQVIP), from their inception to September 2023. Relevant literature about acupuncture for AD was included, and the characteristics of the evidence map were presented through charts and textual analyses.
Results In total, 117 RCTs and 17 SRs or MAs were included. The results were divided into three categories: basic characteristics of the included literature, clinical characteristics and quality assessment of the included RCTs, and clinical characteristics and quality assessment of the included SRs and MAs.
Conclusions Acupuncture as a therapeutic measure for AD has some advantages in improving cognition and quality of life; thus, it is imperative to conduct multi-center, large-scale RCTs to enhance the evidence supporting the use of acupuncture in AD. This is the first evidence map exploring acupuncture treatment for AD, providing insights into the current clinical research landscape on acupuncture treatment for AD. Furthermore, the findings of this study highlight research gaps in this field and serve as a valuable reference for guiding the planning and selection of topics for future research.

3. Clinical Practice Guidelines

3.1. National Institute for Health and Care Excellence (NICE, UK) 2018 Ø

Dementia: assessment, management and support for people living with dementia and their carers (NG97). Evidence-based recommendations on diagnosing and managing dementia (including Alzheimer’s disease) . London (UK): National Institute for Health and Care Excellence (NICE). 2018;:43P. [174901]. Annexes realtives à l'acupuncture [174901-b].

1.4 Interventions to promote cognition, independence and wellbeing. 1.4.5 Do not offer acupuncture to treat dementia.