In the last few days, a major book has been published by Dale Bredesen, MD. Dr. Bredesen has developed a new approach to the illness, and has shown, for the first time as far as I know, that it is possible, in a number of cases, to reverse the symptoms. He, and his team, have helped 200 cases. Some of these people have gone from barely functioning, to returning to work. As well, he has given us new insights into how to prevent the illness. A serious neuroscientist and neurologist, who trained with a Nobel Laureate, he has learned from both basic research and complementary medicine. His book is a must-read, and brings many disciplines together. The complex protocol has worked for people who have the Alzheimer’s gene, ApoE4, and he shows that there are variants of the disease, which is an illness in which the brain loses its plasticity. Funds are currently being raised for a substantial clinical trial.
Click this to link to book, The End of Alzheimer’s by Dale Bredesen, MD
Dr. Bredesen is a neurologist and neuroscientist who worked in the lab of Nobel laureate Stanley Prusiner, and who has had appointments at U.C.L.A. and U.C.S.F.. The patients had well-documented Alzheimer’s Disease, including on brain scans and other forms of testing. According to Dr. Bredesen, it appears that the same techniques that helped these patients, can prevent Alzheimer’s Disease (or AD) from developing in the first place, if applied early enough. The earlier the techniques are applied to people who already have AD, the more effective they appear to be. The protocol usually takes 3-6 months to work for most people, but they must stay on it, or their Alzheimer’s symptoms return. The protocol also sheds new light on the nature of the illness. Two hundred plus patients have gone through the protocol, with benefits. Small studies have been published, one following the very first patients to receive the protocol, other papers shedding light on the nature of the disease. Because the protocol is non-invasive, and there are no other effective treatments for this fatal disease, I am choosing to discuss it in detail, even though these are early days, and a substantial clinical trial has not yet been conducted. In situations where there are no treatments available for a fatal illness, a researcher, who is also a physician, as is Dr. Bredesen, is wise to balance research imperatives with the potential clinical benefits to patients who have a fatal illness, and the potential harm to them by withholding information which might help save lives. I think his comprehensive reconceptualization of the illness is, in itself, a seminal breakthrough, and sharing this information may hasten further research.
Clinical evidence, so far, is that the Bredesen Protocol, also called ReCODE (for reversal of cognitive decline) appears to lead to sustained remission of Alzheimer’s symptoms, and some of the pathology, as long as the patients stay on it. The first patient to undergo the protocol, is five years into recovery now, after having reversed her symptoms. Her mother had died of dementia, and when she came to treatment, she couldn’t function well. She couldn’t find the light switch in her home, called her pets by the wrong names, couldn’t drive. She can now drive, is back to work, and doesn’t feel she has a memory problem any longer. Several times she went off the protocol, (explained below) and several times the symptoms returned. What this means, I think, is that in such cases, this is not a “cure”; but staying on the protocol, one can live with the cognitive function one would have if one were “cured.” That is still extraordinary, if it holds up.
While we have known about how to reduce the risk of Alzheimer’s in a population, with certain lifestyle changes, reversing symptoms in people who already have it, is a new, monumental finding. This is not to say all cases, or extremely advanced cases, can be helped; but we are going from a situation where none were helped, to credible descriptions of significant numbers having been helped.
The protocol works for those with the Alzheimer’s gene, ApoE4, which is the strongest known risk factor for the illness in the majority of people who get the illness. Until now, many people were, quite sensibly, wary of being tested for ApoE4, because there was nothing they could do with that knowledge, since Alzheimer’s has been incurable. Now, one might argue that knowing one’s status is helpful for treatment, and can fine tune prevention, not to mention motivate one to do that prevention.
WHY THIS APPROACH IS DIFFERENT
Dr. Bredesen and his colleagues have shown that there are at least three different types of Alzheimer’s Disease, and each requires a different overall approach. But there is more variation than that. They have found that there are at least 36 different factors contributing to this complex disease, and they must each be addressed, if awry, in patients. So, in the end, the approach is tailor-made for each patient.
For years, the working assumption of most Alzheimer’s researchers has been that the disease was caused by a buildup of amyloid plaque, and another protein, which interfered with the functioning of the neurons. If one looked at the brain of a patient with Alzheimer’s, one could see a pathological increase of amyloid plaque. The goal of most recent therapies was to find a drug to remove the plaque. So, amyloid, (and tau protein), was seen to be the major pathology present in AD.
The problem is, that over 99% of the drugs designed to remove amyloid have failed to meet approval and make it to the market because they simply don’t work. Nor have other non-drug techniques to remove it been effective. This failure has occurred despite billions spent on this line of research. The few drugs that have made it to the market may briefly improve symptoms for a number of weeks, by boosting brain chemicals, but they don’t stall the progress of the illness. If they did, Alzheimer’s would not be incurable. Hundreds of millions of dollars are invested at any one time, in the gamble that the amyloid hypothesis is correct.
But recent findings show that amyloid plaque is not properly thought of as the cause of Alzheimer’s. Given the failure of all attempts to remove amyloid to cure AD, one might even say that the amyloid hypothesis has become a dogma that has been getting in our way.
We now know, from recent work by neurologist-neuroscientist Rudi Tanzi at Harvard, and others, that amyloid plaque is the brain’s way of protecting itself from infection. You need amyloid. It helps survival. Tanzi’s lab has shown amlyloid plaques give off little particles, that form a net around pathogens that invade the brain, to wall them off. There are all sorts of reasons that infections might get into the brain as we age. The blood brain barrier (that protects the brain, and is a kind of filter) may break down with age. Our gut health may also influence the brain. The gut is like a filter, that protects the body from pathogens. If it becomes leaky, pathogens may get into the blood, and the brain.
THE REAL CAUSES OF AD
So, though plaques are extremely prominent in Alzheimer’s, and interfere with functioning, the primary cause, or pathogenesis of Alzheimer’s is, according to Bredesen, threefold, and includes factors that predispose to the buildup of amyloid:
- inflammation (from infection, diet—foods that trigger it, or other causes)
- toxins (including chemicals and molds)
- decreased nutrients, hormones and other molecules (one subgroup of patients included those, for instance, who suddenly got AD after removal of a hormone producing organ)
In short, one might argue that the research and medical community made the same mistake with AD that I have argued we made with Parkinson’s. We have confused the pathology (abnormal tissue) that occurs in the illness, and its pathogenesis (what causes the abnormal tissue), and targeted the former, instead of the latter. It’s like coming on a burned out forest, and saying, “the ash” destroyed the forest, and if we just get rid of the ash, everything will be fine. No, it was fire that got it going, and that keeps it going.
It has long been known that in AD, the brain loses its plasticity in many ways. It loses the ability to make new connections, and it shrinks. Bredesen’s view of AD, is the above processes disturb the neuroplastic balance in the brain. The brain is always making new connections, but also deleting others. This process has to be balanced. But in AD, the deletion process becomes unregulated, and the brain begins to prune itself to death. Fortunately, basic research has begun to understand these pathways sufficiently, to be able to sort out what is triggering it and stop it. Pathological inflammation is one key factor.
ReCODE is very much in keeping with the five stages of neuroplastic healing I have described in The Brain’s Way of Healing. It primarily targets Stage 1, General Cellular Health; but after cellular function is restored, it also makes use of the stages which involve Neurostimulation and Neurodifferentiation, to restore lost connections. In AD, the brain shrinks, and the connections between the neurons, or synapses, wither. Short-term memory goes because the hippocampus shrinks.
One of their early small studies, published in Aging, http://www.agingus.com/article/100981/text, described a man with Alzheimer’s precursor (Mild Cognitive Impairment). He had a PET scan showing much amyloid plaque, and his hippocampus had shrunk to the 17th percentile in size when he was diagnosed. He also had the Alzheimer’s gene. After the protocol, his hippocampus regrew to the 75th percentile. This level of increase in hippocampal volume was far greater than that seen, for example, with exercise. That is neuroplasticity in action, in a highly diseased brain.
If the list of causes of AD seems more reminiscent of the factors that functional medical physicians and naturopaths attend to, that is no accident. Though Dr. Bredesen trained as a mainstream physician and researcher, and was focused on the standard approach of finding a single medication, to beat AD, he was married to a woman who persuaded him this wasn’t the whole story.
It was his wife, Dr. Aida Lasheen Bredesen, who introduced him to functional and integrative medicine. Functional medicine is a new approach that combines mainstream medicine, with more integrative or complementary approaches (based on basic science). I heard him say that though he was initially skeptical of more holistic-integrative practices, over the years he learned of how her patients responded with more attention to diet, exercise, toxin elimination, and attention to inflammation, and so on. Because he had a very strong research background, he was able to go back to basic neuroscience, and see that these functional interventions affected the chemical pathways affected by AD. His vast knowledge of AD pathophysiology was thus united with this more holistic approach. For instance, a bad diet, poor gut bacteria, or a leaky gut can lead to a breakdown of one of the barriers between us and the world, and our brain and the world.
He also was able to break free of the wish to find a single drug, as it became apparent that Alzheimer’s is a number of diseases. We might say that AD is a kind of final common pathway, to a number of processes, which all, by different means, can interfere with the brain’s regulation of its plasticity.
Normally the brain, as it performs its own housekeeping, removes some of the connections between cells. But in a number of kinds of AD, this process gets out of control, decreasing its plasticity. Yet there are many ways to cause that breakdown. And, in keeping with the holistic principles, some of the factors that trigger it, go on in the body. For instance, insulin resistance is a key risk factor. Insulin is neurotrophic, meaning it helps grow the brain. But when the body is insensitive to it, the brain suffers.
One of the reasons that we are this late in the day sorting it out, is that many medical researchers have had the wrong model for how to test treatment. The model they had was based—without any evidence—on the idea that a major disease should have one major pathway going wrong, and require only one intervention, or magic-bullet, to fix it. I believe this came about because of two reasons. First, there are a few problems in medicine that are that simple, and they stick in the mind, such as a B12 deficiency. One problem, one pathway, one remedy. Or snakebite: there’s one antidote, and it’s fixed.
But, these problems are “the low hanging fruit” of medicine. The illnesses we have not figured out, are often inscrutable to us because they are much more complicated. Alzheimer’s, autism, even depression, are like that. Many different things can cause each condition. We say these illnesses are “final common pathways,” meaning a number of different things lead to a similar picture. You can get depressed because you lose someone you love, fail to get a promotion you counted on, have low thyroid hormone, crash on cocaine, or from certain strokes (but not others). The causes are all different, but all depressed people feel down, have low energy, and so on.
Granting agencies are still often caught in the one-disease, one-treatment model, and they expect studies to examine one variable. When Dr. Bredesen first proposed a grant to study his program, with its many different variables, he was told it wasn’t scientific to test a number of interventions at once. Just test one of your interventions, then we will know if it works or not.
Where does one begin, replying to such simple-mindedness? Human beings require air, water and food to live. If you wanted to prove all three were essential, and proposed a study to a granting agency in which you give all three to a subject to prove it, such rigidly constrained thinkers, would say, “No. That’s not scientific. You can only give the person one of them, to see if that person lives. We can only study one variable at a time, otherwise, we won’t understand which variable is effective.”
Of course, if you just gave them food, but not water and air, and they died, these linear thinkers would conclude: food is not essential for life, then say, “Now, let’s test water.”
Thoughtful scientists have left this linear mono-variable thinking behind long ago. AIDS was tamed with three drugs, not one, for instance. Many cancers requires multiple interventions. Life, by definition, is complex. What we require, when there are many variables that contribute to an illness, are “programmatic” studies, i.e., studies that test an entire program, and all the variables at once, to see if the proposed program works. This is one reason there has not yet been a large clinical trial of Bredesen’s important work; that, and the fact that the findings are very new, challenge the dogma, and require a complex method. Currently, they are 1/3 of the way to $10 million for a large clinical trial.
There are, in fact, a number of protocols, each based on the type of Alzheimer’s the patient has, and which of the 36 variables need correcting.
One first requires detailed cognitive, chemical, hormonal, metabolic and toxicity testing to determine the presence of, and type of, Alzheimer’s disease involved. Then, based on the type of AD, and which of the 36 factors need attention in that individual, a tailor-made protocol is developed. Some of the 36 factors (such as correcting insulin resistance, hormone deficiencies, pathological inflammation) will be familiar; but most will not be familiar to physicians or lay people, who haven’t studied Alzheimer’s, and this is because they have emerged from the basic neuroscience research. For instance, interventions that “reduce synpatoclastic signalling” will not be known, (it involves reducing a pathway that decreases plasticity). This is specialized work, and one needs a clinician who has trained in the protocol.
Currently, about 450 physicians have been trained to conduct the protocol, which uses a much wider group of tests than most physicians are accustomed to, including a number of new tests.
A word of warning: while the protocol is non-invasive, there is often a dietary component, exercise, and many supplements to take. It is onerous. How onerous? About 1/1,000 as onerous as having Alzheimer’s, or having to care for someone you love with Alzheimer’s Disease and watching them lose pieces of themselves week by week.
THE THREE MAIN TYPES OF ALZHEIMER’S DISEASE
The three main types of AD are:
- The inflammatory type. This occurs in people who carry one or two copies of the ApoE4 allele. Having one copy, gives one a 30% chance of having AD. Twenty five percent of Americans have one copy. Having two copies, gives one over a 50% chance of getting AD. This form of the illness runs in families, and presents with the inability to store information, i.e. form new memories. A person who has one copy can start to get ill in their fifties or sixties, and there are many inflammatory markers for it, such as something called tumor necrosis factor, and C-reactive protein. Fortunately, this is also the subtype that responds quickest to the protocol.
Why might we have this gene? About 5-7 million years ago, a common ancestor of ourselves and chimps had some mutations, that promote inflammation. It has been proposed that when our ancestors descended from the trees to the Savannah, we were exposed to more foot punctures, dung, infections, and that being quick to get inflamed became an advantage. But what saves us from infection, over time promotes inflammation that gives rise to a number of diseases, including certain kinds of heart disease and Alzheimer’s. The protocol for this type, dials back our tendency to get inflamed, but it also addresses many other of the 36 factors. Those with two ApoE4 genes (one from each parent) are more prone to Alzheimer’s. But, as said, this form of the illness has responded to the ReCODE protocol.
- Atrophic type. “Atrophic” means wasting away, or absence of growth, or loss of tissue. This type also occurs in carriers of ApoE4, but Bredesen points out that it presents about 10 years later, and also presents with memory problems. Importantly, these people don’t show the inflammatory markers. Rather, this is a disease of absence. They lack the supporting chemicals to maintain connections in the brain because they have low levels of hormones, including low thyroid, adrenal, estrogen, progesterone, testosterone, and pregnenolone. Several of these may be low. They may have low Vitamin D (easy to correct), insulin resistance (or low insulin) and high homocysteine. They respond more slowly to the protocol. Two thirds of AD cases are in women, and this is not simply because they live longer. Estrogen goes down with age, and estrogen protects the brain. (As well, for reasons that are not well-understood, inflammation rates are higher in women, probably contributing to their increased risk of Type 1.)
Sometimes, people will get both type 1 and type 2. I.e., they will be carriers of ApoE4, have type inflammatory markers, and type 2 low hormone levels. One of the combinations, Bredesen calls type 1a, and it is “sweet” because glucose is very high, and insulin is very high. Insulin is normally a neurotrophic molecule, and it helps growth in the plastic brain. But these people have “insulin resistance” and don’t respond to their insulin, giving them characteristics of the atrophic type. One has to aggressively treat the insulin resistance, but in cases, supplements and diet are sufficient to reverse it.
In all the above types, there is plasticity imbalance in the brain. The brain far too aggressively begins to actively remove synapses or connections between cells, in effect, downsizing. The protocol reverses this process.
- Toxic (vile) type. This tends to occur in people from families without Alzheimer’s. They tend to have another common gene, ApoE3. Symptoms can begin as early as the late forties to sixties. The disease not only affects the ability to have short-term memories. Many brain functions are affected. Long-term memories are forgotten, and skill based (procedural) memories are lost, so a person might no longer be able to play a game he mastered, or do math procedures. It may show up as depression (or psychiatric problems) which may precede the cognitive decline. The group was found, on extensive testing, to have low zinc levels and high copper, neuroinflammation, small blood leakages on a special MRI test. Most of these patients were originally diagnosed as having something other than AD, such as frontotemporal dementia, but they really had AD, when their spinal fluid and PET scans were done. They may have abnormalities affecting the pituitary axis, hypothalamus, thyroid levels, and cortisol, and other low hormones.
So, why is it called “toxic”? Because these patients have high levels of chemicals. The have high mercury. Sometimes the toxins are mycotoxins, produced by mold. Mercury can be removed by a chelating agent, a practice done by naturopaths or functional medical physicians. There were anecdotal cases in the literature about AD patients who had amalgam filings removed, and got improvements. These were not taken seriously by mainstream medicine, but they should have been. Patients in whom it was removed, had radical improvements.
There are some other kinds of Alzheimer’s dementia; in some cases, vascular dementia (dementia caused by blood vessel problems) is also prominent. As well, repeated traumatic brain injuries can predispose to AD. We are far too casual about concussions, and the cumulative damage they can cause. Rudi Tanzi reads the evidence as showing that psychological stress also increases the risk of AD.
As we have said, Dr. Bredesen and colleagues have now trained 450 physicians.
Click this to link to book, The End of Alzheimer’s by Dale Bredesen, MD
Here is a copy of his initial Aging study in pdf form: https://docs.wixstatic.com/ugd/1a2e49_f479c410646548dc9d5a20ef26dc3b8c.pdf