Welcome from Dr. Bredesen

Updated: Nov 13, 2020

With our current knowledge, virtually no one needs to get Alzheimer’s disease—combining prevention, identification of risk factors and drivers of this process, and early reversal of cognitive decline, we can now make Alzheimer’s the rare disease that it should be.  I recognize fully that this claim contradicts the “party line” that “there is nothing that will prevent, delay, or reverse Alzheimer’s disease,” but it is what we have now shown in hundreds of patients, and published in peer-reviewed medical and scientific journals.

We have now trained 1500 physicians in 10 different countries and all over the US, but the vast majority of doctors do not understand or know how to practice this new approach.  As you may already be aware, medicine is exceedingly slow to change—whereas Silicon Valley is about disruption, which has led to new technologies such as smart phones and search engines, medicine is about tradition and permission.  A painful example is scurvy, which claimed thousands of lives as doctors rediscovered and then rejected the effective treatment for centuries.  I hope that this will not be the case for Alzheimer’s, and we can all contribute to positive change by sharing information on social networks, asking our physicians to be aware of new techniques and approaches, and sharing results of ongoing clinical trials.     

1.  A 21st Century Approach to Medicine

Medicine is undergoing a radical transformation. Twentieth-century medicine, characterized by a one-size-fits-all, monotherapeutic approach, has been largely unsuccessful in treating chronic illnesses. It makes a diagnosis of what—Alzheimer’s or cardiovascular disease or hypertension, etc.—without understanding why. The high rate of failure of Alzheimer’s drug trials—greater than 99%—highlights the weaknesses of this approach and the need for a more complete understanding of the fundamental drivers—i.e., the root causes—of the disease.

Twenty-first century medicine combines systems medicine, large data sets, and computer-based algorithms to close the complexity gap—the gap between the remarkable complexity of the human organism and the lack of complexity in standard medical evaluations—and determine accurate subtypes of chronic illnesses such as Alzheimer’s, along with optimal, personalized, multi-modal therapeutic programs.  This approach led to the first reports of the reversal of cognitive decline in Alzheimer’s disease in 2014 and 2016 (Bredesen, Aging 2014; Bredesen et al., Aging 2016).  There are now over 2000 patients using the protocol described in these initial reports, with success that has not been described previously.  Just as so many of us take for granted that we should know our cholesterol level, it is equally important that we know critical mediators of cognitive decline, such as fasting insulin, C-reactive protein, mycotoxin load, microbiome status, and others included in a “cognoscopy”—a screening test for the prevention of cognitive decline.  These tests and the basis for their role in cognitive decline, along with the therapeutic approach, are described in the book, The End of Alzheimer’s (Random House, 2017), a New York Times Bestseller. 

2. The Failure of Medicine for Dementia (and Most Chronic Illnesses)

After billions of dollars and over 400 clinical trials, there is still no truly effective drug for Alzheimer’s disease.  In fact, things are so bad that most people have come to accept without question the standard line that “there is nothing that prevents, reverses, or delays cognitive decline in Alzheimer’s disease.”  For an innovative society that takes moonshots for granted and readily embraces Silicon Valley’s disruptive advances like Twitter and Uber, the utter failure in Alzheimer’s disease has been accepted with uncharacteristic passivity.   

The reasons for such abject failure reach deep into the workings of medicine itself, and reveal a fundamental schism in its practice: 20th-century medicine, which unfortunately is still the standard of care when it comes to dementia and other chronic illnesses, has failed because it is basically about what—diagnosis followed by prescription.  In contrast, 21st-century medicine is about why—determining the root cause and contributors to each patient’s illness (or, preferably, risk for illness).  When it comes to complex chronic illnesses—from lupus to inflammatory bowel disease to rheumatoid arthritis to Alzheimer’s disease and more—20th-century medicine has little to offer.  In contrast, 21st-century medicine—whether practiced as P4 medicine, integrative medicine, functional medicine, or precision medicine—has achieved unprecedented success in the treatment of these illnesses, but has not become the standard of care.

Over the past few decades, research into Alzheimer’s disease has revealed novel features of Alzheimer’s disease: findings of insulin resistance, microbiome alterations, chronic inflammation, metabolic syndrome, vascular permeability, hormone deficiency, hypovitaminosis D, chronic infections by the yeast Candida, oral bacteria P. gingivalis, Herpes viruses, and others, the salutary effects of beta-amyloid against pathogens, all indicate that Alzheimer’s disease is a systemic disorder that goes far beyond the now-outdated concept of Alzheimer’s as a disease caused by amyloid and tau.

These findings have critical implications for medical practice, continuing medical education, and patient outcomes.  If physicians purporting to offer treatment for patients with cognitive decline fail to evaluate and treat insulin resistance, then they may be providing suboptimal care; if they fail to evaluate and treat systemic inflammation, they may be providing suboptimal care; if they fail to evaluate and treat gastrointestinal hyperpermeability, they may be providing suboptimal care; if they fail to evaluate and treat Alzheimer-associated pathogens, they may be providing suboptimal care; if they fail to evaluate and treat mycotoxin exposure, they may be providing suboptimal care; if they fail to evaluate and treat chemotoxin exposure, they may be providing suboptimal care; if they fail to evaluate and treat sleep apnea and other causes of oxygen desaturation, they may be providing suboptimal care; if they fail to evaluate and treat microbiome abnormalities, they may be providing suboptimal care; if they fail to evaluate and treat hormonal deficiency, they may be providing suboptimal care; if they fail to evaluate and treat nutritional deficiencies, they may be providing suboptimal care; if they fail to evaluate and treat vascular disease, they may be providing suboptimal care; if they fail to evaluate and treat methylation defects, they may be providing suboptimal care.  Furthermore, since the vast majority of neurologists lack experience in treating these contributors, it is important for neurologists to partner with integrative physicians or others trained to treat these conditions. 

Thus from the patient’s perspective, it is a simple equation: I can go to an accepted center and receive standard care, in which case I am 100% certain I will not improve; or I can go to a clinic demonstrating anecdotal improvements, in which case I may improve.

The attempts to develop an effective therapeutic for Alzheimer’s disease have been decidedly inside-the-box, and a very tiny box, at that: limiting trials to monotherapeutics instead of programs, monophasic instead of multiphasic, uniform instead of personalized, univariable instead of multivariable, and mechanism-blind instead of targeted, has constrained the exploration of potential therapeutic space to a small, and demonstrably ineffective, domain.  Should we not, therefore, welcome novel, and even unconventional approaches, at least until such time as we have a modestly effective, disease-modifying therapy?

Such novel approaches are typically criticized by the medical establishment, and history is replete with misplaced criticisms of novel approaches—from Semmelweis to Lister to Paracelsus to Lind—but there are few areas more in need of novel approaches than in the treatment of neurodegenerative diseases.  It has been a remarkably short time since such advances as microbiome effects on neurodegeneration, prions, the antimicrobial effect of beta-amyloid, and neural stem cells were either unknown or viewed with skepticism.  How many such surprises will it take to bring about the open-mindedness that may well be needed for the development of an effective treatment for Alzheimer’s and other forms of neurodegeneration?

The Nobel laureate Richard Feynman stated, “For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled.”  There are few fields in which public relations, politics, and finance have played a greater role than in Alzheimer’s disease.  Let us therefore insert reality—it is time for disruption, time for new directions, and time to make direct comparisons of reported anecdotal successes with the current standard of care. 

Drugs have had a profound and positive impact on our health; that is without question, and many alive today would not be alive without the support of pharmaceutical agents.  However, optimal treatment for complex chronic illnesses is likely to require a combination of pharmaceuticals and personalized programs targeting the underlying drivers of the process.  Indeed, this comprehensive approach is what has had the greatest success in cardiovascular disease. 

In a perfect world—a world in which the health of the many patients with cognitive decline or risk for cognitive decline would be put first—there would be open dialogue and cooperative strategizing.  As Francis Crick said, “Avoid the temptation to work so hard that there is no time left for serious thinking.”  If we are to develop truly effective treatments for neurodegenerative diseases, we will have to do some serious thinking.  We all share the same goal—to discover effective treatments for the many patients suffering neurodegenerative diseases.  The ultimate arbiter will be patient outcome, and to date, standard of care medicine has shown only failure.  Therefore, let us cast a net that is wide enough to identify effective treatments for most or all neurodegenerative diseases, and let us not pretend that we have the judgment to predict which approaches will turn out to be most effective.  

3. Disruption of the Current Approach

Alzheimer’s disease impacts the lives of nearly everyone in one way or another.  It is a rising, family-destroying, trillion-dollar global healthcare problem, one that will bankrupt Medicare in the next two decades.  All of the standard approaches have failed to date: pharmaceutical companies have poured billions of dollars into development and clinical trials for drugs without success, driving some, such as Pfizer, completely out of the field; leading Alzheimer’s experts and centers have nothing to offer, and are unable even to determine why each patient developed Alzheimer’s; the National Institutes of Health have produced no research that has eased the suffering of the 5.4 million Americans with Alzheimer’s or the 45 million currently living Americans destined to develop Alzheimer’s.

When it comes to effective therapeutics, the field of neurodegenerative diseases—from Alzheimer’s to Lou Gehrig’s to Parkinson’s—is the area of greatest biomedical failure.  Why is this?  It is because medicine has not moved out of the 20th century.  The great success of 20th century medicine was to combine public health policy and antibiotics to prevent or control many infectious diseases.  Healthcare has applied this same simplistic approach—assume a single cause, find a single drug, use it for all cases—to the complex chronic illnesses, such as Alzheimer’s, without success.

We are the first group to show that the cognitive decline of Alzheimer’s disease and its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment) can be reversed, and improvement sustained—this work was published in a peer-reviewed journal in 2014 and 2016 (Bredesen, Aging 2014; Bredesen et al., Aging 2016), detailed in the book, The End of Alzheimer’s (Random House, 2017), and forms the basis of an ongoing clinical trial.  This unprecedented success, which has continued in over 2000 patients currently on the protocol we developed, was the result of 30 years of neuroscience research, which showed that the prevailing view of Alzheimer’s treatment is completely backward:

• The prevailing view is that Alzheimer’s disease is a single disease of unknown cause and no effective treatment.  Our work showed that this is incorrect: there are 4 subtypes of Alzheimer’s disease (Bredesen, Aging 2015; Bredesen, Aging 2016), over 30 different contributors, and successful treatment can be achieved with programmatics—personalized programs that target the many contributors—not with a monotherapy that ignores the actual root cause of the disease.
• The prevailing view is that Alzheimer’s disease is caused by amyloid, and billions of dollars have been spent in removing amyloid, without success.  Our research, and that of others, has shown that this is incorrect: the amyloid is actually a protective response to four different insults, each of which can be identified and addressed.  Thus the goal of treatment is not to remove the amyloid, but rather to determine what insults have caused its formation, and address those.
• The prevailing view is that Alzheimer’s disease evaluation can be performed with a few blood tests and MRI, neither of which shows what actually caused the problem.  Our research has shown that this is incorrect: we use much larger data sets that identify why each person developed cognitive decline, show that most people have 10-25 different contributors, and show that each person is different, making personalized therapy critical.  We have developed a computer-based algorithm that identifies each contributor, subtypes each patient, and generates an optimal personalized program.

Thirty years ago, my laboratory team and I began research to determine whether we could understand the fundamental nature of neurodegeneration, in hopes of translating our results to develop the first effective treatment for cognitive decline.  It took us quite a while, but in 2014, we reported the first reversals of cognitive decline in patients with Alzheimer’s disease and pre-Alzheimer’s (mild cognitive impairment, MCI).  Since then, hundreds of patients have shown documented, sustained improvement, and we are currently in the midst of the first clinical trial of the protocol we developed, which is called ReCODE for reversal of cognitive decline.  We have an opportunity, for the first time, to reduce the global burden of dementia.