MD, PhD, FMedSci, FSB, FRCP, FRCPEd

One could define alternative medicine by the fact that it is used almost exclusively for conditions for which conventional medicine does not have an effective and reasonably safe cure. Once such a treatment has been found, few patients would look for an alternative.

Alzheimer’s disease (AD) is certainly one such condition. Despite intensive research, we are still far from being able to cure it. It is thus not really surprising that AD patients and their carers are bombarded with the promotion of all sorts of alternative treatments. They must feel bewildered by the choice and all too often they fall victim to irresponsible quacks.

Acupuncture is certainly an alternative therapy that is frequently claimed to help AD patients. One of the first websites that I came across, for instance, stated boldly: acupuncture improves memory and prevents degradation of brain tissue.

But is there good evidence to support such claims? To answer this question, we need a systematic review of the trial data. Fortunately, such a paper has just been published.

The objective of this review was to assess the effectiveness and safety of acupuncture for treating AD. Eight electronic databases were searched from their inception to June 2014. Randomized clinical trials (RCTs) with AD treated by acupuncture or by acupuncture combined with drugs were included. Two authors extracted data independently.

Ten RCTs with a total of 585 participants were included in a 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. 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. Only 2 trials reported the incidence of adverse reactions related to acupuncture. Seven patients had adverse reactions related to acupuncture during or after treatment; the reactions were described as tolerable and not severe.

The Chinese authors of this review concluded that 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.

Anyone reading this and having a friend or family member who is affected by AD will think that acupuncture is the solution and warmly recommend trying this highly promising option. I would, however, caution to remain realistic. Like so very many systematic reviews of acupuncture or other forms of TCM that are currently flooding the medical literature, this assessment of the evidence has to be taken with more than just a pinch of salt:

  • As far as I can see, there is no biological plausibility or mechanism for the assumption that acupuncture can do anything for AD patients.
  • The abstract fails to mention that the trials were of poor methodological quality and that such studies tend to generate false-positive findings.
  • The trials had small sample sizes.
  • They were mostly not blinded.
  • They were mostly conducted in China, and we know that almost 100% of all acupuncture studies from that country draw positive conclusions.
  • Only two trials reported about adverse effects which is, in my view, a sign of violation of research ethics.

As I already mentioned, we are currently being flooded with such dangerously misleading reviews of Chinese primary studies which are of such dubious quality that one could do probably nothing better than to ignore them completely.

Isn’t that a bit harsh? Perhaps, but I am seriously worried that such papers cause real harm:

  • They might motivate some to try acupuncture and give up conventional treatments which can be helpful symptomatically.
  • They might prompt some families to spend sizable amounts of money for no real benefit.
  • They might initiate further research into this area, thus drawing money away from research into much more promising avenues.

IT IS HIGH TIME THAT RESEARCHERS START THINKING CRITICALLY, PEER-REVIEWERS DO THEIR JOB PROPERLY, AND JOURNAL EDITORS STOP PUBLISHING SUCH MISLEADING ARTICLES.

14 Responses to Acupuncture for Alzheimer’s?

  • One has to approach this sort of literature with the understanding that it has not been undertaken for the purpose of furthering science but to promote alternative medicine. Relatively few health care providers have the time, interest or skill to critically read the literature. As a result supporting research for “integrative ” medicine just has to be there. For “experts” in the field such as David Katz from Yale it is all that is needed to claim that they are not abandoning patients when there are limited options for diseases such as AD. It never occurs to them that offering false hope actually victimizes their patients. The poor studies probably let them sleep well at night.

  • How do you know Alzheimers isn’t caused by an imbalance between Yin and Yang, eh? EH? You scientists and your reductionist insistence on empirically verifiable fact. I am certain my morgellons was cured by unicorn tears, and nobody will persuade me otherwise.

  • “IT IS HIGH TIME THAT RESEARCHERS START THINKING CRITICALLY, PEER-REVIEWERS DO THEIR JOB PROPERLY, AND JOURNAL EDITORS STOP PUBLISHING SUCH MISLEADING ARTICLES.”
     
    Yes indeed; to put it mildly. I was astonished to find this review was published in the journal Medicine, which is a long-standing, reasonable quality journal with an impact factor ~4.5. And I was further amazed to find that Medicine invites submissions on CAM. I have a growing fear that journal editors are doing their job with minimum possible input. Nowadays they receive an honorarium, even for editing barrel-bottom journals, but they also come under pressures to keep the pages full. If there is no editorial board member specializing in the subject of a submitted article, one method for selecting referees is often to look down the paper’s list of references and invite reviewers from among the citations. It’s not only altmed that picks up inappropriate or biased reviewers this way. And the editors seldom have time to read all the papers accepted themselves: the whole peer-review process occurs very much at arm’s length, nowadays.
     
    You have worded your critique of the paper with a light touch. Among the 10 trials analysed, four were of the A+B vs. B type, whose worthlessness you have drawn to our attention several times before. Concealment of treatment allocation was “unclear” in 9 of 10 studies, blinding of outcome assessors was “unclear” in 7 of 10, and process of randomization was “unclear” in 5 of 10. This summary of the 10 included studies alone should have alerted any halfway competent referee to reject the paper.
     
    This publication does a great disservice to the whole concept of the systematic review; it diminishes the journal’s reputation.

  • The mechanism for acupuncture’s putative effects in AD treatment has been reviewed over here by Zeng et al. of the Neurodegenerative Disease Research Group of King’s College London, who claim that acupuncture decreases the amount of amyloidic proteins in the hippocampus.

    • @A1candidate
      I was unable to access the full review chapter whose abstract you link to, but took a look at the peer-reviewed literature by searching Medline for articles with keywords ‘alzheimer’ and ‘acupuncture’. There were 57 hits. I am not a neuroscientist and know very little about Alzheimer’s disease. I looked at the abstracts of the first 15 most recent papers that dealt with animal models among the first 40 search hits. Seven involved rats, eight involved mice. Ignoring the many differences in the detail of the models (aged rats vs. transgenic mice vs. chemically induced pseudo-Alzheimer’s; electro-acupuncture vs. laser vs. manual stimulation; different acupuncture points stimulated) all the studies involved some measurement of hippocampal structure and/or function. Acupuncture variously reduced Abeta protein levels, downregulated p53 protein expression, improved neuron mitochondrial structure, suppressed mitochondrial alcohol dehydrogenase and cytochrome oxidase, reduced neuronal loss, increased superoxide dismutase and catalase, raised p-P38 MAP kinase protein and interleukin-1beta mRNA, increased triose phosphate isolmerase, increased muscarinic cholerinergic receptor density and decreased glial fibrillary acidic protein. Nie et al. (Chinese Journal of Integrated Traditional & Western Medicine 2014, 34(8):991-6) measured upregulation of 39 hippocampal transmembrane signal proteins in acupuncture-stimulated mice.
       
      I repeat, I am not in any way knowledgeable about neurobiology, but how this spew of findings can be summarized by Zeng et al.’s abstract to “[acupuncture] enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Aβ proteins in the hippocampus and relevant brain regions” I’m unclear. Perhaps the conclusion is based on the few papers I didn’t peek at.
       
      A good review article or book chapter can be invaluable to researchers in a field, comprehensibly summarizing world literature, highlighting disagreements between experimental findings, pulling together results from disparate studies to provide new insights, and so on. Unfortunately, there are very many examples of poor reviews. The format allows for cherry picking and other types of bias, and authors are free to emphasize their own points of view at the expense of possibly better ones. This is why the concept of the systematic review, where literature is analysed according to predetermined criteria, has emerged as a superior approach for analysis of data in very specific areas: so far it’s been applied almost only to clinical trials.
       
      In my own laboratory, I have frequently insisted on double-blind approaches to experimentation. When an investigator knows which test tube or animal is experimental and which control, there is a risk of data bias, even among honestly intentioned researchers. The animal/Alzheimer experiments strike me as particularly vulnerable to bias when done unblinded. Thank you for drawing my attention to this somewhat curious area of research.

      • i know A1candidate from Wikipedia. He has an unfortunate tendency to overestimate the significance of tentative findings. For example, he created an article in purinergic signalling which stated that it is the mechanism by which acupuncture works. That got toned down, obviously.

        It is all sounding a bit like homeopathy. It’s water memory. No, that lasts less than a picosecond. It’s silicates. No, that’s just sloppy experimentation, all solutions in glass vessels contain silicates. It’s nano bubbles. No, that has no evidence of bioavailability and in any case contradicts the claim that dilution increases potency.

        The one possibility the true believers won’t accept is the one that Occam’s Razor suggests is most likely.

        • And let’s not forget the wonders of the primo vascular system that explains acupuncture. That also has an irony-free entry in Wikipedia. I wonder if that can also be found in rats and mice: after all, I’ve learned this morning that rats and mice also have acupuncture points.

      • The sole abstract look fishy to me.

        “In Alzheimer’s animal models, acupuncture stimulation at acupoints enhances cholinergic neurotransmission, trophic factor releasing, reduces apoptotic and oxidative damages, improves synaptic plasticity and decreases the levels of Aβ proteins in the hippocampus and relevant brain regions.”

        A-beta is a peptide, not a protein, so even the wording is wrong.
        It would be nice to remember that A-beta is more a marker of Alzheimer than a symptom, that’s normally aged people can have A-beta, that anti-A-beta immunotherapy haven’t showed big improvement for patient yet (even when clearing A-beta from brain)…

        I can’t see the complete article too, but i don’t know how you can assess all the parameter described in the abstract because they are very invasives, this just look like generalization of bad mouses/rat studies with no or little critical analysis.

        And I REALLY hope that acunpuncture doesn’t down-regulate p53 protein or this method should be stopped right now because it could be a cancer-inducing practice (p53 is a very well known tumor suppressor, disabled in many form of cancer) ! I’m always amazed by the contradiction in alter-medicine “it’s very safe with no secondary effect” -> well you admit that it can play with a central protein implicated it nearly all the cell process, so i doubt that… Or maybe this is just a pile of crap !

  • As to peer review – if study done by pseudoscientists is published in a journal where the reviewers are pseudoscientists would it not still count as peer reviewed? Actual scientists not trained in nonsense would not actually be peers. These days one has to question the Journal as well as the study. This takes time which many critical thinkers just do not have enough of. In the end these poor studies are designed just to be present not to actually be read.

    @Guy Let us know your source for unicorn tears – I’ll just have to give them a try. I read about them somewhere.

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