The Rise of Pseudomedicine for Dementia and Brain Health

It is all very well to criticise 'alternative' therapies for Alzheimer's disease except you should also include in your analysis that there are no effective therapies for AD. Not one of the 4 drugs available to AD clinicians has any significant benefit in AD. In spite of this taxpayers fund the pharmaceutical industry to the tune of billions of dollars for drugs that do not work. In the UK , NICE, does not recommend any drugs for AD and yet they are prescribed both to give the hapless AD consultant an option (who wants to tell someone with AD that there is no hope) and to support the pharmaceutical industry.

I agree that it is wrong to give false hope through alternative remedies but it is equally wrong to push drugs that do not work to people diagnosed with AD.

Hellmuth, Rabinovici, and Miller should be congratulated for this timely and thoughtful viewpoint. One more action that the community of dementia scientists should consider is being less shy about the efficacy of currently available drugs. They state that Alzheimer's disease "lacks effective approaches for prevention or a cure". True, it cannot be cured, but it can be treated.

We should not be ashamed to speak out that there are 4 drugs which have shown effectiveness in about 20 different well designed, serious, and reliable clinical trials; that their use is endorsed, among others, by the World Health Organization; that despite often difficult to appreciate in the individual patient, overall, treated patients have better cognitive performance and better outcomes than non-treated patients; and finally that the notion that they are not effective is simply not true. Indeed, the impact on patients’ quality of life is limited, but it is not zero. Patients should be educated that the decision of some payer to withdraw reimbursement is not based on scientific evidence, but it is a political interpretation of scientific evidence - a totally different story.

If we want patients to believe in science rather than pseudoscience, we should be the first believers.

If Professor Frisoni is going to suggest that 'science' supports the efficacy of any of the 4 available drugs for AD then he should provide the evidence.

For example, the recent Cochrane review of one such drug found no significant efficacy and also that all data available were from drug company-funded trials (1).

The travesty of AD is that drug companies make huge amounts of profit out of drugs that give little or no hope to anyone with a diagnosis of AD. Under those conditions, what are the incentives to actually discover drugs that might have some efficacy, no matter how limited?

References

1. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001191.pub4/media/CDSR/CD001191/CD001191.pdf

I am reading this article as that of questioning professional integrity rather than that of defending evidence-based medicine. The argument that we should only practice only with class I and II recommendations would be severely misleading as it would presuppose that practice guidelines are complete in their knowledge base. However, clinicians involved in ambulatory care have typically have many patients who have persistent symptoms and remain refractory despite standard medical care. Many such cases also involve patients with symptoms only and no ongoing clinical trials, or worse, trial centers which are too inconveniently located. In such instances I see no reason why not to offer treatments for which there are no data. Medicine as a science and through history has always been an "n of 1" trial. If a treatment does not work then try something else next time. Historically medicine has always been practical. Find what works first; do the science later.

Regarding the cost issue particularly here in the USA under health care reform, we now have an entire generation which the system has "left behind" due to the prohibitive cost of health care and the impact of high deductible plans. The chronically ill will be the ones incurring the cost of the premium and much if not all of the cost of care on an annual basis. Cancer notwithstanding, many in the public are questioning the value (or price) of orthodox medical care. The consequence of the current system is that the public is asked to "shop" for higher value (lower price with equivalent or higher quality). The public is then left to choose and a small but significant portion are choosing naturopathy and lay-midwifery. (No disrespect is intended towards those professionals) However a healthcare system designed around public health has now created a generational conflict -- the elderly with government insurance and the young with private insurance -- as well as an professional identity conflict -- an orthodox system that requires self-verification of its value to the public. As we all need to work within our respective health care systems, I find no need to place the interests of the system before the needs of the patient.

Dr William Osler said many years ago: "One of the first duty of the physician is to educate the masses not to take medicine." And although medicine and pharmacology have come a long way, his admonition is still an important one. Presumably the "medicines" available in his time were mostly ineffective and/or harmful. But we still have numerous agents promoted to treat or cure your painful, or even fatal, condition.

The motivation to take these substances cannot be overestimated. Most people lack the training to understand the necessary, rigorous testing - and resources - which go into vetting a drug and proving its efficacy and tolerability.

In 1962 my mother was diagnosed with lung cancer. I was 14 at the time. An older brother of mine was in pharmacy school and learned of a novel and "promising" drug called krebiozen. Our whole family was hopeful, even elated, that there was something that could possibly help her, even cure the cancer and save her life. Our family doctor was doubtful, and of course he was right to be.

One treatment touted for brain health is Prevagen which is widely advertised. I researched this a few years ago and learned that the FTC had filed a lawsuit against the manufacturer because of false and/or unsubstantiated claims of efficacy. But the advertising continues. I can certainly imagine that the legal costs of fighting the lawsuit pale in comparison to the profits from sales of the product. However, I cannot understand how the manufacturer, which apparently hasn't come up with convincing evidence of efficacy, can continue to hawk this "extract from jellyfish." I realize that this is a legal question, not a medical one, but can the authors explain this to me?

Osler also said: "The desire to take medicine is perhaps the greatest feature which distinguishes man from animals." This may be the greatest obstacle to getting rid of useless pills and potions, and at the same time the biggest advantage for their purveyors.

This article fails to see the big picture on brain health and, worse, calls into question important emerging research on non-pharmacologic approaches to brain health. In the face of a global crisis with dementia that has seen no novel drugs for more than a decade, framing the conversation as pseudo-science is troubling. Certainly, It is dangerous to corner our ability to improve and maintain brain health with supplements. No single supplement is a cure, but combined with other actions, research is emerging suggesting that they may be an important part of a protocol to support brain and overall health. We should promote that research, not discourage or disparage it. Think of the brain like we now do the heart. Our understanding of heart health changed the way we live to improve and maintain cardiovascular health.

In 2017, The Lancet International Commission on Dementia Prevention, Intervention and Care found that one third of dementias may be preventable through certain lifestyle factors [1]. The FINGER study was the first to show long-term cognitive benefits of diet, exercise, cognitive training, and other factors [2]. New NIH-funded research shows that intensive lowering of blood pressure may reduce mild cognitive impairment, a known risk factor for dementia [3].

The fact is that supplements will never be the whole story. It’s misleading to talk about brain health and supplements exclusively. Supplements deserve more research and scrutiny as we focus on efforts to improve brain health, but are just one part of the equation.

Understanding cognitive health throughout the life span, along with earlier detection and diagnosis of Alzheimer’s is urgently needed to improve our understanding of the disease and to allow us to take proactive steps for brain health that could potentially delay symptoms, reduce risk and even prevent disease. A balanced and healthy diet, exercise, sleep, and in some cases, dietary supplements, are pillars that all are proven to support a healthy brain. As our understanding of the connections between brain health and Alzheimer’s becomes clearer, we must advocate for best practices, credible information, and use our collective thinking to empower more Americans with informed information that enables living a longer, healthier life.

Consumers deserve to know that taking care of the brain in the same way that we do the heart can have cognitive benefits.

UsAgainstAlzheimer’s is a patient-centric advocacy organization committed to accelerating treatments and cures for Alzheimer’s. We believe it is time to make brain health part of overall health on our path to stop Alzheimer’s.

References

[1] https://www.prnewswire.com/news-releases/the-lancet-commission-one-third-of-dementia-may-be-preventable-300488834.html

[2] http://alzheimersprevention.org/downloadables/FINGER-study-report-by-ARPF.pdf

[3] The SPRINT MIND Investigators for the SPRINT Research Group. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial ;Published online January 28, 2019. doi:10.1001/jama.2018.2144

Hellmuth et al raise important considerations regarding the proliferation of unsubstantiated therapies for Alzheimer's disease. However, anyone caring for Alzheimer's patients over a period of years has repeatedly experienced the lack of longlasting benefit of the medications approved for AD. For the patients, their families, and their healthcare providers, that's a failure. In the vacuum left by the inability of well-intended researchers to find a cure, or even a truly effective treatment for AD, it is no wonder that both contrarians and opportunists arise to fill the void.

Nonetheless, I could not help but be struck by the irony of the long list of pharmaceutical companies in the COI disclosures from whom the authors have received remuneration. The pharmaceutical industry has its own long and sullied history of promoting medications on the basis of misleading statistics (such as relative risk reduction rather than absolute risk reduction and number needed to treat), at oftentimes astronomical cost per patient actually meaningfully benefited. Their methods do not engender trust, and the supplement ads for one heavily advertised supplement that I see often are no more offensive than the marketing tactics of pharmaceutical companies.

There is fault on both sides of the argument, and in the end, it is the patients and their families who lose. Simultaneous with the search for pharmaceuticals that will make a meaningful impact on AD, there needs to be equally rigorous research into the impact of a multifactorial lifestyle and nutritional approach to AD prevention. It's not all about drugs, and from the standpoint of truly impactful therapy, at this point at least, one could argue that it's not at all about drugs.

The authors are correct to criticize "interventions promoted by licensed medical professionals that target unsubstantiated etiologies of neurodegenerative disease (eg, metal toxicity; mold exposure; infectious causes, such as Lyme disease)." These intervention do not fill a void but are exploitative and harmful. Physicians who care about this problem can help victimized patients complain to the appropriate state licensing board.

Stephen Barrett, MD

Hellmuth, Rabinovici, and Miller shared their Viewpoint that many remedies are marketed to dementia patients and families without scientific evidence of efficacy; the FDA Commisioner recently voiced similar concerns (1).

However, I think the Viewpoint lacks three important considerations:

1) not mentioning any published work on OTC preparations,
2) not mentioning the daunting tasks of doing academic research in this arena, and
3) not more fully addressing the needs of these patients, driven to those remedies given the current lack of disease-modifying agents, and numerous reports of failed trials.

It is curious that the authors cite papers highlighting the problems of vitamin E, a widely available OTC. Why did they not cite positive research on vitamin E and dementia, published in JAMA?

Dysken published a study of over 600 patients that showed a positive effect of high dose vitamin E. (2) Evans and co-authors in an accompanying editorial (3) point out some issues in this double-blind placebo-controlled randomized controlled trial, but also praised the general trial design and execution.

DeKosky and Schnieder (4) discuss the daunting task of analyzing prevention data, including clever “piggyback” studies of large cohorts, in their editorial about one such publication. A reader would conclude that it may be unrealistic to expect any breakthroughs soon.

So, despite the enormous efforts of clever and brilliant investigators, and the formidable tasks in doing the research (including the discouraging history of failure), where does that leave a patient or family?

The Viewpoint suggests that patients and families need a better understanding of what doesn’t work. In cancer care, some advocate a “palliative care” approach right from the time of diagnosis, perhaps refining a focus on quality of life, expectations, and symptom management. While there are cognitive therapies and other non-drug options for dementia patients, with varying levels of evidence and efficacy, should all patients with cognitive decline be offered palliative care at diagnosis, given the harsh reality that nothing really works to “cure” or modify these diseases ?

References:

1.https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm631065.htm.

2.Dysken MW, Sano M, Asthana S, et al. Effect of vitamin E ... doi:10.1001/jama.2013.282834

3.Evans DA, Morris MC, Rajan KB. Vitamin E, Memantine.... JAMA. 2014;311(1):29–30. doi:10.1001/jama.2013.282835

4.DeKosky ST, Schneider LS. Preventing Dementia: Many Issues and Not Enough Time. JAMA Neurol. 2017;74(5):508–510. doi:10.1001/jamaneurol.2017.0045
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