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Summary

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Background:  Acupuncture 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).

Methods:  We 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.

Results:  Three 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: τ2 = 0, χ2 = 0.048, p = 0.49, I2 = 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: τ2 = 0, χ2 = 0.17, p = 0.68, I2 = 0%).

Conclusion:  Even though the number of studies is small, the existing evidence does not demonstrate the effectiveness of acupuncture for AD.


Review Criteria

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

We included all randomised clinical trials of needle acupuncture to treat human patients suffering from AD using 20 databases from their inception to August 2008, without language restrictions.

Message for the Clinic

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Acupuncture is one of the most popular types of complementary medicine. It is often used as a treatment for dementia and is claimed to be effective in improving intelligence. Even though the number of studies is small, the existing evidence does not demonstrate the effectiveness of acupuncture for Alzheimer’s disease.

Introduction

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Alzheimer’s disease (AD) is the most common cause of dementia in older people and accounts for 60–80% of cases (1). Patients often use complementary medicine (CM) hoping that such treatments might produce improvements in quality of life and delay cognitive decline (2–4). One survey reported that 55% of responders had tried at least one form of CM for improving memory and 20% had tried three or more such therapies (5). Acupuncture is one of the most popular types of CM. It is often used as a treatment for dementia and is claimed to be effective in improving intelligence (6). Considering these facts, it is pertinent to investigate the effectiveness of acupuncture for treating AD. Currently, no systematic review of this subject is available. The objective of this systematic review was to summarise and critically assess the evidence from randomised clinical trials (RCTs) for or against the effectiveness of acupuncture in treating AD.

Materials and methods

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Data sources

The following electronic databases were searched from inception up to August 2008: Medline, AMED, British Nursing Index, CINAHL, EMBASE, PsycInfo, The Cochrane Library 2008 (Issue 3), six Korean Medical Databases (Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, Korea Med and Korean National Assembly Library), four Chinese Medical Databases (China Academic Journal, Century Journal Project, China Doctor/Master Dissertation Full Text DB and China Proceedings Conference Full Text DB) and three Japanese Medical Databases. The search terms were used ‘acupuncture AND Alzheimer’. We also manually searched our departmental files and relevant journals [(Focus on Alternative and Complementary Therapies) and Forschende Komplementärmedizin und Klassische Naturheilkunde (Research in Complementary and Classical Natural Medicine) up to August 2008]. The references in all located articles were searched manually for further relevant articles. Dissertations and abstracts were included.

Study selection

All articles were included that reported an RCT in which human patients with AD were treated with needle acupuncture with or without electrical stimulation. Trials were included if they employed acupuncture as the sole treatment or as an adjunct to other treatments. Trials comparing two different forms of acupuncture and those in which no clinical data or insufficient data for comparison were reported were excluded. No language restrictions were imposed.

Data extraction and quality assessment

Hard copies of all included articles were obtained and read in full. All articles were read by two independent reviewers (MSL, BCS), and data from the articles were validated and extracted according to predefined criteria.

Allocation concealment was assessed using the Cochrane classification (7). For assessing methodological quality, we used a modification of the Jadad scale (8). Points were awarded as follows: study described as randomised, one point; appropriate randomisation method, one point; inappropriate randomisation method, deduct one point; patient blinded to intervention (i.e. control procedure was indistinguishable from real acupuncture), one point; evaluator blinded to intervention, one point; description of withdrawals and dropouts, one point. The maximum points available were five. Patient blinding was assumed where the control intervention was indistinguishable from acupuncture, even if the word ‘blinding’ did not occur in the report. Points for evaluator blinding were only given if specified in the text. Discrepancies were resolved through discussions between the two reviewers (MSL, BCS) and if needed, by seeking the opinion of a third reviewer (EE).

The quality of acupuncture (9) was assessed by one reviewer (BCS), certified traditional medical doctor, with 14 years of acupuncture experience. He answered the question, ‘How would you treat the patients included in the study?’ using five categories, including ‘exactly or almost exactly the same way’, ‘similarly’, ‘differently’, ‘completely differently’ or ‘could not assess’ (because of insufficient information on acupuncture or on the patient). The degree of confidence that acupuncture was applied in an appropriate manner was assessed on the 100-mm visual analogue scale (with 0% = complete absence of evidence that the acupuncture was appropriate, and 100% = total certainty that the acupuncture was appropriate).

Data synthesis

The mean change of cognitive function (Mini Metal Status Examination; MMSE) and activities of daily living (ADL) compared with baseline was used to assess the differences between the intervention groups and the control groups. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated using the Cochrane Collaboration’s software [Review Manager (RevMan) Version 5.0 for Windows, Copenhagen, Denmark: The Nordic Cochrane Centre] for continuous data. The variance of the change was imputed using a correlation factor of 0.4 as suggested by the Cochrane Collaboration. The τ2 test, χ2 test and the Higgins I2 test were used to assess heterogeneity.

Results

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Study description

The searches identified 40 potentially relevant studies, of which three met our inclusion criteria (Figure 1). The key data from all included RCTs are summarised in Table 1 (10–12). Among the excluded studies, two RCTs (13,14) were excluded because it was not possible to extract data for acupuncture alone, and one RCT had insufficient data for comparing the effectiveness (15). All trials originated from China. One of the included trials adopted a two-arm parallel group design (12), one had a three-arm parallel group design (11) and one employed a four-arm parallel group design (10).

image

Figure 1.  Flow chart of trial selection process. AD, Alzheimer’s disease; AT, acupuncture; RCT, randomised clinical trial

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Table 1.   Summary of randomised clinical trials with parallel design of acupuncture for Alzheimer’s disease
ReferencesSample size Degree of AD Quality score* Gender (M/F) Validity of acupuncture†Intervention (regimen)Control intervention (regimen)Main outcome measuresMain results Acupuncture points used De-qi Adverse effects (I:C)
  1. *Quality score: Jadad score [randomisation + randomisation method (+inappropriate randomisation method − 1 point) + drop out or withdraw + assessor blind + patients’ blind, maximum 5]. †Validity of acupuncture was expressed as [quality of acupuncture, degree of confidence]: quality of acupuncture: 0, could not assess; 1, completely differently; 2, differently; 3, similarly; 4, exactly or almost exactly the same way; degree of confidence: degree of confidence that acupuncture was applied in an appropriate manner100 mm visual scale (with 0% = complete absence of evidence that the acupuncture was appropriate and 100% = total certainty that the acupuncture was appropriate). ‡This group was not considered in this review because this intervention has no evidence of their effectiveness for AD. EA, electronic acupuncture; HDS, Hasegawa Dementia Scale; ADL, activities of daily living; BPRS, Brief Psychiatric Rating Scale; MMSE, Mini Mental State Examination; ns, not significant; ES, effect size; N/A, not applicable; n.r., not report; AD, Alzheimer’s disease.

Li et al. (10)104 Mild to moderate 1 (1 + 0 + 0 + 0 + 0) 60/44 (3, 80%)EA (continuous wave, 2–4 Hz, 30 min, once daily for 6 days after 1 day rest, for 8 weeks, n = 37)(A) Nimodipine (20–40 mg × 3/day for 8 weeks, n = 14) (B) Herbs (for 8 weeks, n = 18) (C) EA + herbs (for 8 weeks, n = 35)‡(1) MMSE (2) ADL (3) HDS (4) Responders rate(1) Intergroup: EA vs. (A): ns (ES = 0.31); EA vs. (B): ns (ES = 0.29); Within group: EA: p < 0.01 (ES = 1.14); (A): p < 0.01 (ES = 1.61); (B): p < 0.05 (ES = 0.79) (2) Intergroup: EA vs. (A): p < 0.01 (ES = 1.20); EA vs. (B): ns (ES = 0.07); Within group: EA: p < 0.01 (ES = 2.04); (A): ns (ES = 3.38); (B): ns (ES = 0.35) (3) Intergroup: EA vs. (A): p < 0.01 (ES = 1.38); EA vs.(B): p < 0.01 (ES = 0.82); Within group: EA: p < 0.01 (ES = 0.62); (A): p < 0.01 (ES = 1.58); (B): p < 0.05 (ES = 0.68) (4) Intergroup: EA vs. (A): ns (51%, 64%); EA vs. (B): ns (51%, 56%); Within group: N/AGV20, Sishenchong (EX), GB20, BL23 (major points) Considered n.r.
Dong et al. (11)32 n.r. 1 (1 + 0 + 0 + 0 + 0) 20/12 (4, 90%)EA [(continuous wave, 180 Hz for 15 min, plus longitudinal wave, total 40 min, once daily, 5 times weekly for 1 month – 1 session), total 3 sessions, n = 11](A) Hupperzine [(100 μg × 2/ day for 1 month – 1 session), total 3 sessions, n = 10] (B) Psychological consultation (for 3 months, n = 11)(1) MMSE (2) ADL(1) Intergroup: EA vs. (A): ns (ES = 0.47); EA vs. (B): p < 0.01 (ES = 1.22); Within group: EA: ns (ES = 0.53); (A): p < 0.01 (ES = 1.59); (B): ns (ES = 0.22) (2) Intergroup: EA vs. (A): ns (ES = 0.10); EA vs. (B): p < 0.01 (ES = 1.52); Within group: EA: ns (ES = 0.28); (A): ns (ES = 0.53); (B): ns (ES = 0.04)(A) GV20, GV14, BL23, HT7, PC6, SP6 (B) Sishenchong (EX), GB20, KI3, ST36, ST40, LR3 (A) and (B), alternately Stimulation: lifting and thrusting + twirling Considered n.r.
Ou et al. (12)30 Mild to moderate 1 (1 + 0 + 0 + 0 + 0) 19/11 (2, 50%)EA (continuous wave, 2–4 Hz, 30 min, once daily for 6 days after 1 day rest, for 8 weeks, n = 16), plus perphenazine (4–30 mg/day for 8 weeks)Perphenazine (8–40 mg/day for 8 weeks, n = 14)(1) BPRS (2) Responders rate(1) Intergroup: ns (ES = 0.32); Within group: AT: p < 0.01 (ES = 2.28); Con: p < 0.01 (ES = 1.93) (2) Intergroup: ns (81% vs. 79%); Within group: N/AGV20, Yintang (EX), GV14 Considered Extrepyramidal side effects (4 : 7)

Study quality and acupuncture validity

The methodological quality of the trials was poor. None of included RCTs reported methods of randomisation, details of allocation concealment, described patient or assessor blinding. Sufficient details of drop-outs and withdrawals were described in none.

Regarding our assessment of the quality of the acupuncture treatments, the authors would have treated the patients differently in one trial (12), similarly in another trial (10), and exactly or almost exactly the same way in another trial (11). The degree of confidence that acupuncture was applied appropriately ranged from 50% to 90%.

Outcomes

Cognitive function (MMSE)

Two RCTs compared electro-acupuncture (EA) with conventional drug therapy (10,11). Both suggested no significant improvement compared with drug therapy. The meta-analysis of these data showed no significant effect (n = 72, WMD, −0.55; 95% CI: −1.31 to 0.21, p = 0.15, heterogeneity: τ2 = 0, χ2 = 0.048, p = 0.49, I2 = 0%) (Figure 2A). zOne RCT compared EA with drug therapy on the Hasegawa Dementia Scale (HDS) and reported favourable effects of drug therapy (12).

image

Figure 2.  Forest plot of acupuncture for Alzheimer’s disease on (A) cognitive function with mini mental status examination (MMSE) and (B) activity of daily living (ADL) compared with drug therapy. AT: acupuncture

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One RCT (10) tested effectiveness of EA compared with a herbal mixture and failed to show favourable effects of EA on MMSE and HDS, while one RCT (11) compared EA with psychological consultation and reported favourable effects of EA on MMSE.

Activities of daily living

Two RCTs tested EA for ADL (10,11). One RCT (10) reported favourable effects of acupuncture compared with drug therapy for ADL, while the other (11) failed to so. The meta-analysis of these data showed a significant effect of drug therapy compared with acupuncture (n = 72, WMD, −1.29; 95% CI −1.77 to −0.80, p < 0.001, heterogeneity: τ2 = 0, χ2 = 0.17, p = 0.68, I2 = 0%) (Figure 2B).

One RCT (11) compared EA with psychological consultation and reported favourable effects of EA, while one RCT (10) tested effectiveness of EA compared with a herbal mixture and failed to show favourable effects of EA.

Responder rates

Two RCTs compared EA alone (10) or EA plus drug therapy (11), with drug therapy in terms of responder rates. In both cases, the results failed to show significant effects in favour of acupuncture.

Discussion

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Few RCTs have tested the effects of acupuncture for AD. None of the existing trials is methodologically rigorous. Collectively, the results fail to show superiority of acupuncture alone or as an adjunct to drug therapy over conventional drug therapy. According to these findings, cognitive function and ADL do not improve with acupuncture. However, the number of trials and the total sample size are too small to draw firm conclusions.

Of the three RCTs, none reported randomisation methods, and none made any attempt at either subject or assessor blinding. Concealment of treatment allocation was not reported in any of the studies. Trials with inadequate blinding and inadequate allocation concealment are likely to show exaggerated treatment effects and thus limit the reliability of the study results (16). None of the RCTs reported checks on the success of blinding. Unblinding is, therefore, a possibility with potential for overestimation of treatment effects (16,17). All of the included RCTs have failed to report details of ethical approval. All of these RCTs had small sample sizes. According to our meta-analysis, the effectiveness of acupuncture on cognitive function and ADL is less than that of drug therapy. Comparing acupuncture plus drug therapy with drugs only failed to generate favourable effects on a psychiatric rating scale and on the responder rates.

One RCT excluded (15) because of its small sample size, tested the effectiveness of acupuncture (n = 4) on agitation of AD compared with placebo acupuncture (n = 2) and supportive counselling (n = 3), and claimed improvement of agitation in the acupuncture group. However, this trial had a small sample size and no enough information about the data to confirm this conclusion. There are no controlled clinical trials but only one uncontrolled trial published as an abstract. The results of this trial implied that acupuncture improves cognitive function measured with MMSE compared with preintervention in eight patients with mild or moderate AD after 1 month of treatment (18). One excluded uncontrolled clinical trial (19) involving 10 AD patients and one dementia patient reported a significant improvement in depression and anxiety scores after at least 22 acupuncture sessions. Unfortunately, such data are highly susceptible to bias, and hence they provide little useful information on the specific effects of acupuncture, as a therapeutic intervention for symptoms of AD.

Future RCTs of acupuncture for treating AD should adhere to accepted standards of trial methodology. In particular, trials should have sufficiently large samples, ideally based on formal power calculations which, in turn, should be based on data from appropriate pilot studies. They should also include appropriate intervention duration with sufficient frequency, describe all aspects of their methodology in full detail to ensure reproducibility, use validated primary outcome measures and employ adequate statistical tests. These should evaluate functional benefit and quality of life and should also report the number of participants who withdraw from the intervention in each arm and their reason for doing so. Even if future research proves acupuncture to be therapeutically valuable, one would require further evidence on whether it has significant advantages over non-penetration sham acupuncture needles in the same acupoints, with assessor blinding and allocation concealment to minimise the bias.

Our review has a number of important limitations. Although strong efforts were made to retrieve all RCTs on the subject, we cannot absolutely be certain that we succeeded. Moreover, selective publishing and reporting are other major causes for bias, which have to be considered. It is conceivable that several negative RCTs remained unpublished and thus distorted the overall picture (20–22). Further limitations include the paucity and the often suboptimal methodological quality of the primary data. In total, these facts limit the conclusiveness of this systematic review considerably. Even though the number of studies is small, the existing evidence does not demonstrate the effectiveness of acupuncture for AD.

Acknowledgement

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

The authors specially thank Kate Boddy in Peninsula Medical School, Universities of Exeter & Plymouth, Exeter, UK for editing this manuscript.

Author contributions

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References

Myeong Soo Lee designed the review, performed searches, appraised and selected trials, extracted data, contacted authors for additional data, carried out analysis and interpretation of the data and drafted this report. Byung-Cheul Shin performed Chinese literature searches, appraised and selected trials, extracted data, assisted interpretation of the data. Edzard Ernst reviewed and critiqued on the review protocol and this report, assisted in designing of the review.

References

  1. Top of page
  2. Summary
  3. Review Criteria
  4. Message for the Clinic
  5. Introduction
  6. Materials and methods
  7. Results
  8. Discussion
  9. Acknowledgement
  10. Funding
  11. Author contributions
  12. References
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