The first proven plan to reverse Alzheimer’s Disease.
In The End of Alzheimer’s Dr Dale Bredesen offers real hope to anyone looking to prevent and even reverse Alzheimer’s Disease and the cognitive decline of dementia.
Dr Bredesen reveals the 36 affecting metabolic factors and outlines a proven programme to rebalance them, which patients can follow with the help of a healthcare professional. There are also general lifestyle and dietary changes al readers can adopt to improve cognitive health.
∙ Rewrites the science of Alzheimer’s Disease
∙ Step-by-step advice to follow with your doctor
∙ The first major breakthrough to stop Alzheimer’s in its tracks
Dale Bredesen, MD, is internationally recognized as an expert in the mechanisms of neurodegenerative diseases, such as Alzheimer’s disease. He is Professor of Neurology at the University of California, Los Angeles.
“The End of Alzheimer’s is a monumental work. Dr. Bredesen completely re-contextualizes this devastating condition away from a mysterious and unsolvable process to one that is both preventable and, yes, reversible.”
—DAVID PERLMUTTER, MD, AUTHOR OF THE #1 New York Times BESTSELLERS Grain Brain AND Brain Maker
“The End of Alzheimer’s is a masterful, authoritative, and ultimately hopeful patient guide that will help you prevent and reverse Alzheimer’s disease, whether you have the ApoE4 gene or not. My patients fear Alzheimer’s more than any other diagnosis. This is the book to transmute fear into action.”
—SARA GOTTFRIED, MD, AUTHOR OF THE New York Times BESTSELLER Younger
“Dr. Dale Bredesen is a world-class neuroscientist-neurologist who through his innovative and exacting research has discovered a safe and effective approach to the prevention and treatment of Alzheimer’s disease that will revolutionize the way we think about the disease.”
—JEFFREY BLAND, PHD, FOUNDER OF THE INSTITUTE FOR FUNCTIONAL MEDICINE, THE CLEVELAND CLINIC
“Dr. Bredesen has provided enormous hope for the heretofore intractable clinical problem of Alzheimer’s. Bredesen’s early studies suggest that this approach can halt and in many cases reverse early Alzheimer’s.”
—LEROY HOOD, MD, PHD, AWARDED THE NATIONAL MEDAL OF SCIENCE, PRESENTED BY PRESIDENT BARACK OBAMA IN 2011, AND FOUNDER OF THE INSTITUTE FOR SYSTEMS BIOLOGY
“Every citizen and medical professional interested in the brain and its health should read this seminal book. It should provide much of the basis for a true revolution in brain health medicine.”
—MICHAEL MERZENICH, PHD, WINNER OF THE 2016 KAVLI PRIZE IN NEUROSCIENCE
“A must-read for anyone wondering what can be done for this dread disease, whether for themselves, a loved one, or a patient.”
—NATHAN PRICE, PHD, PROFESSOR AND ASSOCIATE DIRECTOR OF THE INSTITUTE FOR SYSTEMS BIOLOGY
“Having spent several years implementing many of Dr. Bredesen’s insights in my patients, I can assure you that following his advice can save yourself, your loved ones, and your friends from suffering from this preventable and reversible curse.”
—STEVEN GUNDRY, MD, MEDICAL DIRECTOR OF THE INTERNATIONAL HEART AND LUNG INSTITUTE AND AUTHOR OF THE New York Times BESTSELLER The Plant Paradox
“This book represents a major turning point in our approach to Alzheimer’s disease. For the first time ever, patients and families affected by Alzheimer’s—as well as those at high risk for this devastating disease—truly have a reason to be hopeful.”
—CHRIS KRESSER, MS, LAC, AUTHOR OF THE New York Times BESTSELLER The Paleo Cure
“The End of Alzheimer’s offers a new beginning in medicine. Dr. Bredesen translates the knowledge of science to the wisdom that helps to heal our people … and provide a vision for the end of Alzheimer’s.”
—PATRICK HANAWAY, MD, FOUNDING MEDICAL DIRECTOR AND DIRECTOR OF RESEARCH, THE CENTER FOR FUNCTIONAL MEDICINE, THE CLEVELAND CLINIC
“An experimental program that some patients say has literally reversed their symptoms and allowed them to live a normal life.”
—MARIA SHRIVER, APPEARING ON THE Today SHOW
“The End of Alzheimer’s, for the first time, synthesizes the latest science into a practical plan that can reverse Alzheimer’s and dramatically improve brain health and function. If you have a brain, read this book.”
—MARK HYMAN, MD, DIRECTOR OF THE CENTER FOR FUNCTIONAL MEDICINE, THE CLEVELAND CLINIC, AND AUTHOR OF THE #1 New York Times BESTSELLER Eat Fat, Get Thin
“The End of Alzheimer’s is a phenomenal book. Dr. Dale Bredesen’s research is some of the most exciting work that I have seen in years and tackles the most important health issue of our time. This helps us understand this complex and devastating condition but is also the roadmap to prevent it in the first place. It is a must-read book. By tackling arguably the most important disease of our age, Dr. Dale Bredesen is actually changing the way we look at all chronic disease. This is a masterpiece.”
—RANGAN CHATTERJEE, MBCHB, BSC (HONS), MRCP, MRCGP
This book is dedicated to my wife,
Dr. Aida Lasheen Bredesen—a superb and caring physician who introduced me to the world of functional and integrative medicine, and who has taught me more than anyone about this critical field—and to our two beloved daughters, Tara and Tess.
The Alzheimer’s Solution
You never change things by fighting the existing reality. To change something, build a new model that makes the existing model obsolete.
—R. BUCKMINSTER FULLER
IT IS IMPOSSIBLE to escape the drumbeat of grim news about Alzheimer’s disease: that it is incurable and largely untreatable, that there is no reliable way to prevent it, and that the disease has for decades beaten the world’s best neuroscientists. Despite the billions and billions of dollars spent by government agencies, pharmaceutical companies, and biotechnology wizards to invent and test drugs for Alzheimer’s, 99.6 percent of what we have come up with have been abysmal failures, not even making it out of the testing phase. And if you think there is hope in the 0.4 percent of discoveries that have reached the market—after all, we need only one Alzheimer’s drug if it’s effective, right?—think again. As the Alzheimer’s Association puts it in a bleak reality check, “A genuinely new Alzheimer’s drug has not been approved since 2003, and the currently approved Alzheimer’s medications are ineffective in stopping or slowing the course of the disease.” Although the four available Alzheimer’s drugs “may help lessen symptoms, such as memory loss and confusion,” they do so only “for a limited time.”
Maybe you’re racking your memory to recall when you last read about the Food and Drug Administration approving a new Alzheimer’s drug. Don’t worry if you can’t: of 244 experimental Alzheimer’s drugs tested from 2000 to 2010, exactly one—memantine—was approved, in 2003. And as I’ll explain below, its effects are modest at best.
As I said, grim. No wonder a diagnosis of Alzheimer’s disease is the last thing anyone wants to hear. One man whose wife was in the midst of the long goodbye of Alzheimer’s shook his head, bereft, and said, “We are told repeatedly that drugs are being developed that will slow the decline—but why would anyone do that? I can tell you, living with this every day—that is the last thing you would want.”
Alzheimer’s disease has become part of the zeitgeist. In news articles and blogs and podcasts, on the radio and television and in films both documentary and fictional, we read and hear story after story about Alzheimer’s disease. Sadly, all end tragically. We fear Alzheimer’s as we fear no other disease. There are at least two reasons for that.
First, it is the only one—let me repeat that: the only one—of the nation’s ten most common causes of death for which there is no effective treatment. And by “effective,” I am setting the bar pretty low. If we had a drug or other intervention that made people with Alzheimer’s disease even a little better, never mind curing the disease, I’d sing its praises to the rooftops. So would everyone who has a loved one with Alzheimer’s, everyone at risk for Alzheimer’s, and of course everyone who has already developed Alzheimer’s. But no such drug exists. We don’t even have a treatment to keep people with subjective cognitive impairment or mild cognitive impairment (two conditions that often precede Alzheimer’s disease) from going on to develop full-blown Alzheimer’s.
Incredibly, given the astounding progress in other areas of medicine over the last twenty years—think cancer or HIV/AIDS or cystic fibrosis or cardiovascular disease—as I write this in 2017 not only is there no cure for Alzheimer’s disease, there is not even anything that reliably prevents or slows Alzheimer’s disease. You know how critics make fun of TV afternoon specials and Lifetime movies about angelic children or saintly mothers and fathers who bravely battled cancer and, with the aid of the latest miracle drug, are restored to perfect health before the final credits roll? Schmaltzy, sure. We in the Alzheimer’s field would happily settle for schmaltzy if it were even remotely plausible to depict a happy ending to this disease.
The second reason Alzheimer’s disease inspires such dread is because it’s not “only” fatal. Lots of diseases are fatal. As the old joke has it, life is fatal. Alzheimer’s is worse than fatal. For years and sometimes decades before it opens the door to the grim reaper, Alzheimer’s disease robs its victims of their very humanity and terrorizes their families. Their memories, their capacity for thought, their ability to live full and independent lives—all gone, in a grim and unrelenting descent into a mental abyss where they no longer know their loved ones, their past, the world, or themselves.
The linguistics professor who is the heartbreaking protagonist of the 2014 movie Still Alice carries a DNA mutation that causes Alzheimer’s disease to develop by middle age, discovered in 1995. You’ve probably read about the great strides that cancer biologists have made by discovering genes associated with tumors and crafting drugs based on them. With Alzheimer’s disease? That 1995 discovery has not led to the development of a single Alzheimer’s drug.
This awful disease stands out for one additional reason. The last fifty years have brought triumph after triumph in molecular biology and neuroscience. Biologists have untangled the immensely complex pathways that lead to cancer and have figured out how to block many of them. We have mapped out the chemical and electrical processes in the brain that underlie thoughts and feelings, developing effective, if imperfect, drugs for depression and schizophrenia, for anxiety and bipolar disorder. Sure, there’s a lot left to be learned, and a lot of improvement needed for the compounds in our pharmacopoeias. But in virtually every other disease there is a strong sense that research is on the right track, that the basics are understood, that although nature will keep throwing curve balls at us, she has revealed to us the fundamental rules of the game. Not so with Alzheimer’s.
In this disease, it’s as if nature handed us a rule book written in disappearing ink and edited by evil gremlins who rewrite entire sections when our backs are turned. What I mean is this: seemingly rock-solid evidence from lab rodents suggested that Alzheimer’s disease is caused by the accumulation in the brain of sticky synapse-destroying plaques made of a piece of a protein called amyloid-beta. Those lab studies indicated that amyloid-beta is formed in the brain by a series of steps, and that either intervening in those steps or destroying amyloid-betafn1 plaques would be an effective way to treat and even prevent Alzheimer’s disease. Since the 1980s most neurobiologists have treated this basic idea, called the amyloid hypothesis, as dogma. It has won its developers multimillion-dollar prizes, countless accolades, and prestigious academic positions. It has had a huge influence on which Alzheimer’s papers get published in top medical journals (hint: preference goes to those that toe the amyloid line) and what studies get funded by the U.S. National Institutes of Health, the nation’s chief source of support for biomedical research (ditto).
But here’s the thing: when drug companies tested compounds that are based on any piece of the amyloid hypothesis, the results have ranged from frustrating to bewildering. In clinical trials, human brains did not respond to these compounds the way the rule book said they should. It would be one thing if the compounds failed to do what they were designed to do. That wasn’t what happened. In many cases the compounds (usually, antibodies that bind to amyloid in an attempt to remove it) did a great job at removing amyloid plaques. Or if the compound was designed to block the enzyme needed to produce amyloid, it did a great job at that. The experimental compounds did precisely what their inventors intended, following the amyloid rule book, but patients either got no better or, incredibly, got worse. What keeps emerging from these clinical trials (which, by the way, often cost upward of $50 million each) is exactly the opposite of what all the test-tube research based on the amyloid hypothesis and all the mouse models of the amyloid hypothesis and all the theories of the amyloid hypothesis predicted. Targeting amyloid was supposed to be the golden ticket to curing Alzheimer’s. It wasn’t.
It’s as if our space rockets exploded on the launchpad every single time.
Something is enormously wrong here.
Just as tragic as the blinkered adherence to the amyloid hypothesis is mainstream medicine’s assumption that Alzheimer’s is a single disease. As such, it is typically treated with donepezil (Aricept) and/or memantine (Namenda). I know I said that there is currently no treatment for Alzheimer’s disease, so let me explain.
Aricept is what’s called a cholinesterase inhibitorfn2: it keeps a particular enzyme (cholinesterase) from destroying acetylcholine, a type of brain chemical called a neurotransmitter. Neurotransmitters carry signals from one neuron to another, which is how we think, remember, feel, and move, and so is important for memory and overall brain function. The rationale is simple: in Alzheimer’s disease, there is a reduction in acetylcholine. Therefore, if you block the enzyme (cholinesterase) that breaks down acetylcholine, more will remain in your synapses. Then, even as Alzheimer’s is ravaging the brain, the synapses might remain functional a little while longer.
To a modest extent, this rationale does work, but there are important caveats. First, blocking the breakdown of acetylcholine does not affect the cause or progression of Alzheimer’s disease. The disease therefore still progresses. Second, the brain often responds to inhibition of cholinesterase as you might expect: by making more cholinesterase. That obviously limits the drugs’ efficacy (and can become a real problem if the drug is stopped suddenly). Third, like all drugs, cholinesterase inhibitors have side effects; they include diarrhea, nausea and vomiting, headache, joint pain, drowsiness, loss of appetite, and bradycardia (slowed heart rate).
As for memantine, it too acts on brain chemicals and molecules that have little to do with fundamental Alzheimer’s pathophysiology, but, like Aricept, might reduce (or even delay) the symptoms of the disease, at least for a time. It is typically used later in the disease, but may be used in combination with a cholinesterase inhibitor. Memantine inhibits the transmission of brain signals from one neuron to the next via the neurotransmitter glutamate. Inhibiting that transmission reduces what’s called glutamate’s excitotoxic effect, meaning the toxic effect associated with neuronal activation. Unfortunately, memantine may also inhibit the very neurotransmission critical to memory formation, and so may initially impair cognitive function.
Most important, neither cholinesterase inhibitors nor memantine gets at the underlying causes of Alzheimer’s or stops the disease from worsening—and they certainly do not cure it.
All of that is bad enough, but there is a more fundamental problem. Alzheimer’s is not a single disease. Sure, the symptoms might make it look like it is, but as I explain in chapter 6, we discovered that there are three main subtypes of Alzheimer’s. Our research on the different biochemical profiles of people with Alzheimer’s has made it clear that these three readily distinguishable subtypes are each driven by different biochemical processes. Each one requires a different treatment. Treating them all the same way is as naive as treating every infection with the same antibiotic.
It’s bad enough that Alzheimer’s disease has, for more than thirty years, defeated the greatest minds in neuroscience and medicine. (I’m not counting the seventy-plus years between when the disease was named and when the amyloid hypothesis emerged; much less research was done on Alzheimer’s disease in those decades.) Anyone who pays attention can see that we’re using the wrong approach. In particular, the idea of identifying the cause of the amyloid production, removing that, and then removing the amyloid, has not been tested.
If you have a high risk of developing Alzheimer’s because of the genes you carry, if you have already developed it, or if you have a loved one who has, you therefore have every right to be very upset about this situation.
No wonder we have come to fear Alzheimer’s disease as omnipotent. As hopeless. As impervious to any and all treatments.
Until now.
Let me say this as clearly as I can: Alzheimer’s disease can be prevented, and in many cases its associated cognitive decline can be reversed. For that is precisely what my colleagues and I have shown in peer-reviewed studies in leading medical journals—studies that, for the first time, describe exactly this remarkable result in patients. Yes, I know it flouts decades of conventional wisdom to claim that cognitive decline can be reversed, that there are hundreds of patients who have done just that, and that there are steps we can all take now to prevent the cognitive decline that experts have long believed to be unavoidable and irreversible. These are bold claims deserving of healthy skepticism. I expect you to exercise that skepticism as you read about the three decades of research in my lab, which culminated in the first reversals of cognitive decline in early Alzheimer’s disease and its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment). I expect you to exercise that skepticism as you read the stories of these patients, patients who climbed out of the abyss of cognitive decline. I expect you to exercise that skepticism as you read about the personalized therapeutic programs we developed to enable everyone to prevent cognitive impairment and, if they are already showing signs of it, to stop mental decline in its tracks and restore their ability to remember, to think, and to once again live a cognitively healthy life.
But if the results I describe overcome your skepticism, then please open your mind and consider changing your life—not only if you have already begun the slide into cognitive decline, but even if you haven’t. Needless to say, the people who will find this book most immediately and directly life-changing are those whose memory and cognition are already suffering (and their family members and caretakers). By following the protocol I describe, those with cognitive impairment that is not yet Alzheimer’s disease, as well as those who are already in the grip of Alzheimer’s, can not only halt but often actually reverse the cognitive decline they have already suffered. For those so stricken, progression to severe dementia has until now been inevitable, with nothing but bad news from every expert. The anti-Alzheimer’s protocol my colleagues and I developed consigns that bleak dogma to the dustbin of history.
There is a second, very specific group for whom this book can mean the difference between the grim future they have probably been told to expect and a future filled with health and joy. These are the people who carry a gene variant (allele) called ApoE4 (ApoE is short for apolipoprotein E; an apolipoprotein is a protein that carries lipids—i.e., fats). ApoE4 is the strongest known genetic risk factorfn3 for Alzheimer’s disease. Carrying one ApoE4 (that is, inherited from one parent) increases your life-time risk of Alzheimer’s to 30 percent, while carrying two copies (inheriting copies from both parents) increases it to well over 50 percent (from 50 to 90 percent, depending on which study you read). That compares to a risk of only about 9 percent in people who carry zero copies of this allele.
The vast majority of ApoE4 carriers don’t know about this potential ticking time bomb in their DNA, and typically find out only after the onset of symptoms of Alzheimer’s disease spur them to undergo genetic testing. It is certainly understandable that, as long as there is no prevention or treatment for Alzheimer’s, most people would not want to know their ApoE status. In fact, when Nobel laureate Dr. James Watson (codiscoverer of the DNA double helix) had his genome sequenced in 2007, he said he did not wish to be told whether he carried ApoE4; why expose yourself to devastating news if there’s nothing you can do about it? However, now that there is a program that can reduce the risk of Alzheimer’s, even in those carrying ApoE4, dramatic reductions in the prevalence of dementia could be achieved if more people underwent genetic testing to determine their ApoE status and initiated a preventive program long before any symptoms appeared. It is my fervent hope that this is exactly what will happen, and that ApoE4 carriers in particular learn from this book that their situation is not hopeless: you too can take steps to prevent Alzheimer’s disease or reverse cognitive decline.
There is a perhaps less obvious group, for whom I believe this book can be life-changing: everyone past the age of 40. The number one concern of individuals as we age (and yes, when we talk about brain aging, the downhill slide begins at about 40) is the loss of our cognitive abilities. For it is those abilities—to read a letter from a loved one and comprehend it; to watch a movie or read a book and follow the plot; to observe the people in our lives and understand them; to perceive the events around us and maintain a sense of our place in the world; to perform the basic functions of daily life so we are not mere sacks of protoplasm dependent on others to feed, dress, move, and bathe us; to remember the events of our life and the people who have been precious to it—that define us as human. When they go, so does our very identity as someone with a meaningful life. To all of you lucky enough to have avoided even a hint of these losses even as you are acutely aware that they may be lurking in your future, my message is this: take a deep breath and realize that cognitive decline is—at least for most of us and, especially, early in its course—addressable. Despite what you may have been told, it is not hopeless or irreversible. To the contrary. For the first time, hope and Alzheimer’s have come together.
And the reason for that is one fundamental discovery: Alzheimer’s “disease” is not the result of the brain doing something it isn’t supposed to do, the way cancer is the result of cells proliferating out of control or heart disease is the result of blood vessels getting clogged with atherosclerotic plaque. Alzheimer’s arises from an intrinsic and healthy downsizing program for your brain’s extensive synaptic network. But it is a program that has run amok, sort of the way Mickey Mouse’s efforts to get enchanted brooms to carry buckets of water for him in “The Sorcerer’s Apprentice” segment of the 1940 classic Fantasia eventually lead to the brooms running amok. In Alzheimer’s, an otherwise normal brain-housekeeping process has gone haywire.
THIS BOOK IS not a scientific tome—though I include the scientific evidence that supports my conclusions—but instead a practical, easy-to-use, step-by-step manual for preventing and reversing the cognitive decline of early Alzheimer’s disease or its precursors, mild cognitive impairment and subjective cognitive impairment, and for sustaining that improvement. It is also a guidebook by which the 75 million Americans who carry the ApoE4 gene can escape the fate written in their DNA. The protocol for achieving this led to the first-ever scientific publication of a study, in 2014,fn4 reporting the reversal of cognitive decline in patients—nine out of ten of them—with Alzheimer’s disease or its precursors, thanks to a sophisticated personalized protocol based on our decades of research on the neurobiology of Alzheimer’s disease. Called ReCODE,fn5 for reversal of cognitive decline, the protocol not only achieved the reversal of cognitive decline in Alzheimer’s disease and pre-Alzheimer’s that no one thought possible; it also allowed patients to sustain that improvement. The very first patient treated with what is now the ReCODE protocol is, as I write this, five years into the treatment, and at 73 remains cognitively healthy, traveling the world and working full-time. Our extensive subsequent work, with hundreds of patients, proves that she is far from unique.
After publication of the 2014 study, we received many thousands of emails, phone calls, and visits from physicians and other practitioners, potential patients, and family members from all over the United States, the UK, Australia, Asia, Europe, and South America, wanting to learn more about the successful protocol. The journal that had published the study is called Aging, and the staff called to inform us that, of the tens of thousands of scientific papers the journal had published over the years, ours had scored in the top couple—and thus in the 99.99th percentile—in the system of metrics that gauges impact and interest. Although in that initial scientific paper I did not include a detailed step-by-step description of the protocol (scientific journals have page limitations for each paper), in this book I do. I also recount how I developed ReCODE and explain its scientific basis. In the appendix, I list sources of the foods, supplements, and other components of ReCODE as well as links to physicians and other health-care practitioners who are knowledgeable about it and can help you implement it in your own life—or in the life of a loved one.
There is nothing more important than making a difference in the lives of patients, and that is what has driven me in the decades-long quest to find a way to prevent and reverse Alzheimer’s disease. But if enough people adopt ReCODE, they will be helping far more than themselves. Because Alzheimer’s disease strikes an estimated one in nine Americans 65 and older, or 5.2 million people as I write this, the aging of the baby boom generation threatens to bring a tsunami of Alzheimer’s immense enough to bankrupt Medicare and Medicaid and overwhelm the nation’s long-term care facilities—to say nothing of the toll it will take on tens of millions of families whose loved ones are swallowed by this merciless disease. Globally, a projected 160 million people will, by 2050, develop Alzheimer’s. That makes the need for prevention and treatment greater than ever. The hundreds of patients I have seen battle back from cognitive decline—battle back despite the medical dogma that such a recovery is impossible—have convinced me that the prevention and treatment of Alzheimer’s is not some pie-in-the-sky fantasy.
We know how to do it—now, today.
That’s what I mean when I say that if enough people adopt ReCODE, the consequences would ripple across the nation and the world, cutting medical costs by many billions of dollars a year, preventing Medicare’s bankruptcy, reducing the global burden of dementia, and enhancing longevity. All of these are feasible.
Here, finally, is nothing less than the first good news about Alzheimer’s disease. It is a chronicle of joy, of the blessing of getting your life back. One of the patients you shall read about said he has allowed himself to think about the future once again when he talks to his grandchildren. Another said her memory is better than it has been in thirty years. One musician’s wife said his guitar playing has returned; the daughter of another said her mother, who had been disappearing slowly each time the daughter returned from college, is once again part of the family. What you read about here is the beginning of a changed world, the beginning of the end of Alzheimer’s disease.
Here’s what’s ahead:
Chapters 2 to 6 relate the scientific odyssey that led to ReCODE. They describe the discoveries that form the scientific basis of the treatment protocol—what Alzheimer’s disease actually looks like “under the hood,” where it comes from, and why it is so common. These are the discoveries that support the first effective approach to preventing cognitive decline, identifying the metabolic and other factors that increase your risk, and reversing cognitive decline if it has already begun. These are also the discoveries that challenge the central dogma of Alzheimer’s: they showed that this devastating disease is the result of a normal, healthy brain process that has gone haywire. That is, the brain suffers some injury, infection, or other assault (I’ll explain the many kinds) and responds by defending itself. The defense mechanism includes producing the Alzheimer’s-associated amyloid. Yes, you read that correctly—the amyloid that has been vilified for decades, the very amyloid that everyone has been trying to get rid of, is part of a protective response. No wonder trying to get rid of it hasn’t been very helpful to those with Alzheimer’s disease.
Contrary to the current dogma, therefore, what is referred to as Alzheimer’s disease is actually a protective response to, specifically, three different processes: inflammation, suboptimal levels of nutrients and other synapse-supporting molecules, and toxic exposures. I’ll say more about each of these in chapter 6, but for now, let me underline this simple message: the realization that Alzheimer’s disease can exist in three distinct subtypes (and often in combinations of these subtypes) has profound implications for the way we evaluate, prevent, and treat it. That discovery also means that we can better treat the subtler forms of cognitive loss, mild cognitive impairment and subjective cognitive impairment, before they progress to full-blown Alzheimer’s disease.
In chapter 7, you’ll learn about the tests that identify what is causing your cognitive decline or putting you at risk for it—how you may already be giving yourself Alzheimer’s disease. The tests are necessary because the often numerous contributors to one person’s cognitive decline are very likely different from the contributors to someone else’s. These tests therefore give you a personalized risk profile, letting you know which factors to address to optimize improvement. You will learn the rationale behind each test—that is, how the physiological parameter it evaluates contributes to brain function and Alzheimer’s disease. Chapter 7 summarizes the tests involved in this “cognoscopy” and explains the guiding principles behind them.
Chapters 8 and 9 explain what to do in response to the test results. These discuss the fundamentals that must be addressed in order to reverse cognitive decline and reduce risk for future decline: inflammation/infection, insulin resistance, hormone and supportive nutrient depletion, toxin exposure, and the replacement and protection of lost or dysfunctional brain connections (synapses). This is not a “one size fits all” approach. Everyone’s version of ReCODE is personalized, based on their test results: your version will be different from that of others because it is optimized to your unique physiology. Of course, the very fact that ReCODE works—that it prevents and reverses cognitive decline—makes it unique and novel. But so does its focus on personalization.
In chapters 10 through 12, I explain the keys to achieving the very best results and to sustaining that improvement. These chapters offer workarounds, not only to help you succeed in reversing cognitive decline, but also to address the questions and criticism that have been directed at this approach.
Since the advent of “modern” medicine in the nineteenth century, physicians have been trained to diagnose disease—for example, hypertension or congestive heart failure or arthritis—and prescribe a standard one-size-fits-all treatment, such as an antihypertensive for hypertension. That is slowly changing, as with precision cancer treatments in which the genetic profile of a patient’s tumor dictates what drug to prescribe. The push for personalized medicine could bring us closer to a core aspect of Eastern medicine such as TCM (traditional Chinese medicine) and Ayurvedic medicine: although the ancient practitioners of these healing traditions were not aware of the molecular biological details of particular diseases, they were experts at treating the whole person instead of focusing on a single “disease” such as hypertension.
The new medicine—twenty-first-century medicine—brings together the best of the modern Western and the traditional Eastern approaches. It combines a knowledge of molecular mechanisms with an understanding of the entire person. This allows us to go beyond simply asking what the problem is to asking why the problem is. Asking why makes all the difference—including, as you’ll see, in the prevention and treatment of Alzheimer’s disease.
What the research from my laboratory colleagues and me adds up to is this: No one should die from Alzheimer’s disease. Let me say that again: No one should die from Alzheimer’s disease. To accomplish this will require that we—clinicians as well as patients—update our practices from twentieth-century medicine to twenty-first-century medicine, and that we be proactive about our own cognitive and general health.
Books on medical science are supposed to be dispassionate, objective expositions of “facts,” as peer-reviewed and approved by the experts, so I beg your indulgence for failing to remain completely dispassionate. As history has proven time and again, all too often the facts that we as a biomedical and scientific community accept, endorse, and propagate as gospel turn out ultimately to be incorrect. (Newborns cannot feel pain. Ulcers are caused by stress. Hormone replacement therapy for postmeno-pausal women prevents heart disease. And on and on.) The field of neurodegenerative diseases has not been immune from such recursive crashing and burning of its own dogmatic assertions. Depending on which expert you ask and when, Alzheimer’s disease is due to free radicals or metal binding or misfolded proteins or diabetes of the brain or tau protein or detergent-like effects or … well, the list goes on. There is simply no consensus. Moreover, none of the current hypotheses explains all of the published data, which is contained in more than 50,000 published papers. Is it any wonder that Alzheimer’s disease is on track to take the lives of 45 million of the 325 million Americans alive today?
So yes, I am very passionate about this cause, this disease, the underlying neurodegenerative process, the many overly simplistic approaches taken to address it, the political and financial nature of the decisions made, and the millions dying. As physicians, we worry that sentiment and passion may color our medical decisions, robbing us of objectivity. This is an appropriate concern. However, anyone following the Alzheimer’s field, watching the heartbreak and desperation, might rationally conclude that dispassion colors far too many of our daily decisions. Have we as a society become numb to the tragedy of dementia? Have we given up on trying to pull out all the stops? Have we decided that the same kind of scientific genius that developed cardiac bypass, antibiotics, plasmapheresis, artificial limbs, stem cells, and organ transplants is powerless against Alzheimer’s disease? Are we, as scientists and clinicians, such prisoners of medical dogma that we focus completely on single-drug, one-size-fits-all approaches to Alzheimer’s no matter how many times they fail?
I hope not, for if necessity is indeed the mother of invention, then perhaps passion is its father.
“Everyone knows a cancer survivor; no one knows an Alzheimer’s survivor.”
MEET KRISTIN.
Kristin was suicidal. Years before, she had watched in despair as her mother’s mind slipped away, forcing her to enter a nursing home after she could no longer recognize family members, let alone care for herself. Kristin had suffered along with her mother, who at the age of 62 had begun an 18-year decline into Alzheimer’s disease. And at the end Kristin had suffered alone, for her mother was no longer sentient.
When Kristin was 65, she began to experience her own cognitive problems. She got lost when driving on the freeway, unable to remember where to get off and on, even on familiar routes. She could no longer analyze data critical to her job, or organize and prepare reports in a timely fashion. Unable to remember numbers, she had to write down even four digits, not to mention phone numbers. She had trouble remembering what she had read, and by the time she reached the bottom of a page had to start at the top again. Reluctantly, Kristin prepared her resignation. She began to make mistakes more and more frequently, often calling her pets by the wrong names and having to search to find the light switches in her own home, even though she had flipped them on and off for years.
Like many people, Kristin tried to ignore these symptoms. But they got worse and worse. After two years of unremitting cognitive decline, she consulted her physician, who told her she was becoming demented just as her mother had, and there was nothing he could do for her. He wrote “memory problems” on her chart, and because of that, she was unable to obtain long-term care insurance. She underwent retinal scanning, which revealed the Alzheimer’s-associated amyloid. She thought about the horror of watching her mother decline, about how she would live with progressive dementia and no long-term care, about the lack of treatment. She decided to commit suicide.
She called her best friend, Barbara, explaining, “I watched what my mother went through as she slipped away, and there is no way I will allow that to happen to me.” Barbara was horrified to hear Kristin’s saga. But unlike when other friends had fallen victim to dementia, this time Barbara had an idea. She told Kristin about new research she had heard about, and suggested that rather than ending her life, Kristin travel several thousand miles to the Buck Institute for Research on Aging, just north of San Francisco. In 2012, Kristin came to see me.
We talked for hours. I could offer her no guarantee, no example of any patient who had used the protocol—nothing more than diagrams, theory, and data from transgenic mice. In reality, Barbara had been premature in sending her to the Institute. And to make matters worse, the protocol I had developed had just been turned down for its first proposed clinical trial. The review board felt that it was “too complicated,” and pointed out that such trials are meant to test only a single drug or intervention, not an entire program (ah, if only diseases were that simple!). So all I could do was to go over the various parts of the protocol and recommend that she take these to her physician back home, asking him if he would work with her. She did that, and so began what has become the ReCODE protocol.
Three months later, Kristin called me at home on a Saturday to say she could not believe the changes in her mental abilities. She was able to work full-time again, to drive without getting lost, and to remember phone numbers without difficulty. She was feeling better than she had in years. When I put the phone down, what rushed into my mind were the decades of research, the countless hours at the whiteboard with lab members and colleagues, the arguments with myself about each detail of the theory and treatment approach. All of this had not been in vain; it had pointed us in the right direction. Of course Kristin was only one person—as they say, an “n of one”—and we needed to see similar results in thousands and ultimately in millions. I thought back to the doctor who told his patient, “You are just an anecdote; you are not statistically significant.” To which his patient replied, “Well, my family says that I am significant. Besides, I’m healthy once again, so I don’t care about statistics.” Indeed. Every fundamental change needs to start somewhere—every successful approach must start with Patient Zero—and Kristin was Patient Zero.
She confided in a family member, “Did you know I had Alzheimer’s disease?” He said, “Of course, it was obvious. I just did not want to say anything to you about it—I did not want to make you feel bad.” Kristin, who is now 73, has been on ReCODE for five years. She still works full-time, travels the world, and continues to be asymptomatic. Furthermore, she has discontinued the program, albeit briefly, four times, for various reasons—a brief viral illness, running out of some of the pills, traveling—and each time her cognition began to decline. But when she resumed ReCODE, it again returned to normal.
When my colleagues and I started the research that led to ReCODE in 1989, the Alzheimer’s dogma was well established. The disease, according to the theory that has prevailed since the 1980s, is caused by sticky gobs or plaques of amyloid, a protein molecule, gunking up the spaces between brain neurons. Since these spaces, or synapses, are where neurons communicate with one another, the damage caused by the sticky amyloid plaques has devastating consequences: synapses stop functioning. Indeed, the amyloid plaques were one of the abnormalities that neuropathologist Dr. Aloysius Alzheimer (1864–1915) saw in the autopsied brain of the first patient he diagnosed with presenile dementia, as he described it in 1906. (The other abnormality was a profusion of long stringy tangles of proteins called tau, but the importance of these neurofibrillary tangles has long been over-shadowed by the focus on amyloid plaques.) The dominance of the amyloid hypothesis led to a herd mentality. Many experimental compounds developed to treat Alzheimer’s worked the same way, by grabbing hold of the amyloid plaques (or in some cases of amyloid before it had stuck together into plaques) and attempting to remove it.
Scientists at medical centers, universities, and pharmaceutical and biotechnology companies have discovered hundreds of these amyloid-removing compounds. Scores of them looked promising enough in laboratory animals that powerhouse pharmaceutical companies such as Eli Lilly and Biogen have spent billions of dollars to test them in patients, in clinical trials. I don’t have to hedge or estimate when I tell you how many of the 200-plus experimental drugs have proven safe and effective enough in these trials—where effective means they have stopped the worsening of or, even better, reversed Alzheimer’s disease—to be approved by the Food and Drug Administration. That number is zero. Hence, according to the Alzheimer’s Association, no drug “can cure Alzheimer’s or stop it from progressing.”
Of course, all of these failures have cast doubt on what has been the central dogma in Alzheimer’s research, which is called the amyloid cascade hypothesis. This suggests that amyloid plays a central role in Alzheimer’s disease, which is a bit like saying that lumps of cells play a central role in cancer—it doesn’t tell you why the amyloid is there, what its normal function is, or how to prevent the disease. Most important, it doesn’t tell you what Alzheimer’s disease actually is.
Not surprisingly, while early results in Kristin and a handful of other patients on ReCODE led to a stampede of requests for more information from physicians, patients, and patients’ families, they also led to intense skepticism. That’s because they flew in the face of the long-held dogma that nothing will prevent, slow, or reverse Alzheimer’s disease—at least not until the first miracle drug arrives, and certainly not something like ReCODE’s extensive protocol. But the number of patients successfully treated with ReCODE is now over 200, and more and more medical professionals are using it successfully for their own patients. Since 2016 I have trained some 450 physicians, neuropsychologists, nurses, health coaches, and nutritional therapists from 7 different countries and throughout the United States in this approach.
Even more encouraging, increasing numbers of neuroscientists and physicians are beginning to recognize that Alzheimer’s disease is not what we thought it was. Rather than being caused by the buildup of those sticky amyloid plaques (or neuron-strangling tangles), the disease we call Alzheimer’s is actually the result of a protective response in the brain.
This is worth repeating. Alzheimer’s disease does not arise from the brain failing to function as it evolved to. It is not like cancer, where a genetic mutation—inherited or acquired during the course of life—turns a cell and all its progeny into out-of-control proliferators that take over an organ. It is not like rheumatoid arthritis and other autoimmune diseases, where the immune system turns on the body’s own cells and attacks them. In those and many other diseases, something is dangerously out of whack: a physiological system is not functioning as intended.
Alzheimer’s is different. As I explain in detail in chapter 4, one of the key discoveries to come out of my lab is that Alzheimer’s arises when the brain responds as it should to certain threats. Why would evolution give us a brain that works like this? Because in most cases this response to outside threats succeeds; the brain beats back the threat and goes on functioning just fine. The problem comes when those threats are chronic, multiple, unrelenting, and intense. In this situation, the defenses that the brain mounts are also chronic, multiple, unrelenting, and intense—so much so that these protective mechanisms cross the line into causing harm. Specifically, Alzheimer’s disease is what happens when the brain tries to protect itself from three metabolic and toxic threats:
In chapter 6 I will explain in detail how we discovered that these three types of threats—which have dozens of contributors—trigger this protective response in the brain—including what the three kinds of threats do and why the amyloid response that they incite is so toxic to the brain’s synapses. But for now let me simply say that once we recognize that Alzheimer’s disease is what happens when the brain struggles to defend itself against inflammation, to function despite a shortage of beneficial compounds, or to fight an influx of toxic substances, the optimal way to prevent and treat the disease becomes clear: identify which of the many potential contributors to these three classes of threats a particular patient’s brain is responding to defensively, remove the specific contributors, and help it fend off the remaining attackers.