Today, you cannot read a newspaper or listen to the radio without learning that there has been a significant, sensational, momentous, unprecedented, etc. breakthrough in the treatment of Alzheimer’s disease. The reason for all this excitement (or is it hype?) is this study just out in the NEJM:


The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer’s disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer’s disease.


We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab (10 mg per kilogram of body weight every 2 weeks) or placebo. The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points were the change in amyloid burden on PET, the score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14; range, 0 to 90; higher scores indicate greater impairment), the Alzheimer’s Disease Composite Score (ADCOMS; range, 0 to 1.97; higher scores indicate greater impairment), and the score on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL; range, 0 to 53; lower scores indicate greater impairment).


A total of 1795 participants were enrolled, with 898 assigned to receive lecanemab and 897 to receive placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001). In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo (difference, −59.1 centiloids; 95% CI, −62.6 to −55.6). Other mean differences between the two groups in the change from baseline favoring lecanemab were as follows: for the ADAS-cog14 score, −1.44 (95% CI, −2.27 to −0.61; P<0.001); for the ADCOMS, −0.050 (95% CI, −0.074 to −0.027; P<0.001); and for the ADCS-MCI-ADL score, 2.0 (95% CI, 1.2 to 2.8; P<0.001). Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with edema or effusions in 12.6%.


Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease. (Funded by Eisai and Biogen; Clarity AD number, NCT03887455. opens in new tab.)

It’s a good study, and I (like everyone else) hope that it will mean tangible progress in the management of that devastating disease. Most media outlets are announcing the news with the claim that it is the FIRST TIME that any treatment has been shown to delay the cognitive decline of Alzheimer’s disease patients.Image result for ginkgo biloba

But is this true?

I think not!

There have been several studies showing that the herbal remedy GINKGO BILOBA slows the Alzheimer-related decline. Here is the latest systematic review of the subject:

Background: Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer’s disease. The objective of this review is to explore the effectiveness and safety of Ginkgo biloba in treating mild cognitive impairment and Alzheimer’s disease.

Methods: Electronic search was conducted from PubMed, Cochrane Library, and four major Chinese databases from their inception up to 1(st) December, 2014 for randomized clinical trials on Ginkgo biloba in treating mild cognitive impairment or Alzheimer’s disease. Meta-analyses were performed by RevMan 5.2 software.

Results: 21 trials with 2608 patients met the inclusion criteria. The general methodological quality of included trials was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores at 24 weeks for patients with Alzheimer’s disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and Activity of Daily Living (ADL) scores at 24 weeks for Alzheimer’s disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional medicine in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild.

Conclusion: Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer’s disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of ginkgo biloba in treating mild cognitive impairment and Alzheimer’s disease.

I know, the science is not nearly as good as that of the NEJM trial. I also know that the trial data for ginkgo biloba are not uniformly positive. And I know that, after several studies showed good results, later trials tended not to confirm them.

But this is what very often happens in clinical research: studies are initially promising, only to be disappointing as more studies emerge. I sincerely hope that this will not happen with the new drug ‘Lecanemab’ and that today’s excitement will not turn out to be hype.

9 Responses to A significant breakthrough in the treatment of Alzheimer’s disease

  • Dr Bredesen, founder of the Buck Institute gerontology center, has written a book, The End of Alzheimer’s: the First Program to Prevent and Reverse Cognitive Decline, in which he gives many cured cases. According to him there isnt a single factor causing decline; he gives about 40 of which any one patient might need to address 5 or so. Some of the factors are genetic, inflammation, hormonal, toxic exposure, insulin resistance, microbiome, nutritional, etc.. And so there isnt any single magic bullet that will cure all cases of Alzheimers.

    • Has he published paper on these claimed “cured” cases in reputable, peer reviewed scientific journals? I’ll bet not.

    • @stan
      I think we should be very wary of any doctors or practitioners making claims about ‘many cured cases’ for diseases that are considered incurable up until now – all the more if these people sell books about their purported discovery. At the very least, it is wise to look for independent information about those claims. And alas, it seems that this Dr. Dale Bredesden got a bit carried away with his ideas, letting his desire for fame prevail over good science:

      It also isn’t really helpful to fire off a list of wildly diverging possible causes and contributing factors. The more sensible thing to do is simply admit that we don’t know the cause yet. Maybe there is a single cause after all, but we haven’t spotted it yet. Or maybe there is a multi-step cause, each step of which is innocuous in and of itself – a bit like cancer, which often requires an accumulation of multiple specific DNA mutations before things get out of control. There are lots of speculative causal mechanisms, and I think it’s best to leave it to scientists to slowly work away at evaluating them. But it almost never happens that one doctor/scientist comes up with an effective cure or ‘protocol’ out of the blue.

  • stan says:

    The End of Alzheimer’s: the First Program to Prevent and Reverse Cognitive Decline, in which he gives many cured cases.

    Can we trust The End of Alzheimer’s?

    In terms of study design, the three scientific papers first-authored by Bredesen (in 2014, 2016, and 2018) are all clinical case series that describe the outcome of participants who have adopted his intervention. Case series are inherently a descriptive type of research that offer limited evidence and are problematic when used to demonstrate the effectiveness of a medical therapy. Case series cannot accurately evaluate the effect of a new treatment because they are not designed to test hypotheses. Instead, clinical trials with control groups and randomisation are suited to determine the efficacy of a new therapeutic intervention. Despite the certainty inferred by the book’s subtitle, there is no published study that tests or proves the hypothesis that the Bredesen protocol can prevent and reverse cognitive decline. His study design, combined with the particular intervention described, also presents the substantial potential for a placebo effect. Placebos can have greater effect sizes in patient improvement when the intervention is novel, complex, expensive, has high-status branding, and there is an expectation of benefit from either the participant or provider. Another consideration with the study design is that case series are highly vulnerable to selection bias from included or excluded participants.

    When carefully examined,multiple red flags appear in the scientific studies supporting the Bredesen protocol. To date, the evidence does not support its claim to prevent and reverse cognitive decline. Hope is important in the face of incurable diseases and intuitive interventions can be compelling. However, unsupported interventions are not medically, ethically, or financially benign, particularly when other parties might stand to gain.

    In the same article, several concerns were raised regarding the three studies the book was based on:
    Summary of concerns in three scientific articles evaluating the Bredesen protocol

  • The NEJM study is interesting. But it’s no breakthrough. The New York Time article (Nov. 30) was properly restrained and noted the serious side effects seen in a few patients. And the Times quoted Dr. Madhav Yhambisetty, a researcher at the National Institute on Aging as follows: “From the perspective of a physician caring for Alzheimer’s patients, the difference between iecanemab and placebo is well below what is considered to be a clinically meaningful treatment effect.”

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