More than five million Americans today have Alzheimer’s. This debilitating disease is also one of the most heartbreaking, as loved ones slowly slip away and become unreachable. Dr. Dale Bredesen of the Buck Institute is at the forefront of Alzheimer’s research. His new book, The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline, has just been published. I recently spoke with Dr. Bredesen to find out more about his groundbreaking program.
Dr. Bredesen is an internationally recognized expert on neurodegenerative disease. He held faculty positions at UCSF and UCLA and directed the Program on Aging at the Burnham Institute. He joined the Buck Institute in 1998 as its founding president and CEO. Two of his recently published papers include “Reversal of cognitive decline in Alzheimer’s disease” and “Inhalational Alzheimer’s disease: An unrecognized—and treatable—epidemic.”
I interviewed Dr. Bredesen for a podcast a year ago, and I’m excited to bring you more information about his program and his new book. If you have a loved one with Alzheimer’s—or who is just starting to get forgetful—The End of Alzheimer’s is a fantastic resource.
1. What’s wrong with the conventional approach to Alzheimer’s disease?
The conventional approach to Alzheimer’s disease does not address the actual cause—the contributors to this complex chronic illness, which may be dozens and vary from person to person—and attempts to improve symptoms with a monotherapy, a single drug. This is something like trying to patch 36 holes in your roof by putting a patch over one hole and finding that water is still coming through the other 35 holes. In addition, the conventional approach is a one-size-fits-all approach, when a personalized, precision approach is needed, based on the different critical targets for each person.
Finally, the conventional approach is often backward—the surprise is that the very amyloid that is associated with Alzheimer’s disease is a protective response to insults such as microbes and toxins. Therefore, any attempt to remove the amyloid should be preceded by the removal of the insult(s) that are inducing this protective response.
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2. What led you to a functional/evolutionary perspective on AD?
This came directly from the test tube, from years of basic laboratory research—we had no idea when we started that we would end up with a functional medicine approach. We were studying the molecular biology of APP, the amyloid precursor protein that gives rise to the amyloid-beta that collects in the brains of patients with Alzheimer’s disease. Surprisingly, we found that APP functions like a molecular switch—when it is cleaved at the alpha site, two peptides are produced (sAPPalpha and alphaCTF) that support neurite outgrowth, neuronal survival, and synaptic maintenance—essentially, these support memory. Conversely, when APP is cleaved at the beta, gamma, and caspase sites, it yields four peptides (sAPPbeta, amyloid-beta, Jcasp, and C31) that mediate neurite retraction, synaptic reorganization, and ultimately, neuronal death—essentially, these support forgetting. In other words, the two supportive peptides are “synaptoblastic,” whereas the four retractive peptides are “synaptoclastic.”
We then wanted to know what determines this critical balance—a plasticity balance—and it turned out that dozens of parameters affect this balance, many quite directly. For example, vitamin D, estradiol, testosterone, NF-kappa B (as part of the inflammatory response), BDNF (brain-derived neurotrophic factor, which increases with exercise), sleep (which helps to clear the amyloid-beta, among many other effects), and dozens of others, all affect this critical balance. Therefore, we realized that we needed to measure all of these parameters for each person in order to determine what is contributing to cognitive decline or risk for cognitive decline. Then we need to address each contributor—to reduce the synaptoclastic signaling and increase the synaptoblastic signaling. This is a functional medicine approach, so we realized that the basic research had shown us that, for a complex chronic illness such as Alzheimer’s disease, a functional medicine approach makes mechanistic sense. This has been supported now by hundreds of patients who have shown positive responses to this approach to cognitive decline.
3. Can AD be prevented and even reversed?
Yes, contrary to the current dogma, Alzheimer’s disease can be prevented, and the cognitive decline associated with AD can be reversed, although in the late stages of the illness this becomes progressively more difficult and less common. However, there is a large window of opportunity—about a decade of SCI (subjective cognitive impairment), when people note cognitive changes yet still score normally on cognitive tests; then often several years of MCI (mild cognitive impairment), when cognitive testing shows abnormalities, yet people are still capable of doing ADLs (activities of daily living); then early in the course of full-blown Alzheimer’s disease. Therefore, it is important to seek evaluation and treatment as early as possible.
4. You’ve proposed five different types of AD. What are they, and how are they distinct?
Type 1 is inflammatory (“hot”), and the inflammation may be due to pathogens or other inflammatory factors such as trans fats. Type 2 is atrophic (“cold”) and is associated with reductions in trophic support such as nerve growth factor, brain-derived neurotrophic factor, estradiol, vitamin D, and other trophic, hormonal, or nutritional support. Then there is a common combination of type 1 and type 2—type 1.5, or glycotoxic (“sweet”)—that combines the inflammation of high glucose (e.g., via AGEs, advanced glycation endproducts) with the trophic loss of insulin resistance. Type 3 is toxic (“vile”) and is associated with exposure to toxins such as mycotoxins (e.g., trichothecenes or ochratoxin A) or chemotoxins (e.g., mercury). Type 4 is vascular (“pale”) and is associated with reduced vascular support. Type 5 is traumatic (“dazed”) and is associated with previous head trauma. The typical symptoms and signs of these types are described, and clinical cases are described, in the book.
Not surprisingly, many people have combinations of these types, so we have developed a computer-based algorithm that calculates the percent contribution from each type. This then helps to develop the optimal therapeutic program for each person, and again we use an algorithm to generate an initial program.
5. Where have you seen the biggest impacts in terms of diet, lifestyle, and functional medicine treatment with AD?
The key is that the whole program works together, so there is a threshold effect, just as is seen with cardiovascular disease treatment. There seem to be major effects of reversing insulin resistance, optimizing sleep, exercising regularly, eliminating toxic exposures (especially for Type 3 AD), optimizing hormonal support (including bioidentical hormone replacement), optimizing nutrition (e.g., avoiding high homocysteine, low vitamin D, low vitamin B12, low magnesium, etc.), addressing pathogens (e.g., Borrelia), reducing inflammation (but most importantly, removing the cause(s) of the inflammation), optimizing brain training, and reducing stress.
6. What role does genetic testing play in the functional approach to AD?
Genetic testing plays an important role, and although there are hundreds of SNPs (single nucleotide polymorphisms) that are associated with AD, the most important genetic test for AD risk is ApoE: for those with zero copies of ApoE4 (e.g., those who are ApoE3/3), the lifetime risk of developing AD is about 9 percent; for the 75 million Americans with one copy (e.g., ApoE3/4), the lifetime risk is about 30 percent; and for the seven million Americans with two copies (ApoE4/4), the lifetime risk is well over 50 percent. This has led to a conventional approach of avoiding the determination of ApoE genotype, with the claim that there is “nothing” one can do about it. This is no longer the case, and therefore the goal is for everyone to know their ApoE status, to get on an active prevention program, and to make Alzheimer’s disease a rare disease.
In addition, for those with a strong family history of AD, especially for early onset AD (before 65 years of age), it is important to determine whether there are familial Alzheimer’s disease-associated mutations in APP, presenilin-1, or presenilin-2.
7. What are the most important steps people can take to reduce their risk of AD?
The most important thing to do is to get a “cognoscopy”—in other words, just as everyone knows that he or she should have a colonoscopy when turning 50, it is a good idea for everyone over 45 to have an analysis of biochemistry (what is your homocysteine, fasting insulin, hs-CRP, etc.?), genetics (ApoE4 positive?), and function (how are you scoring on a quick, simple test that can be done online). These tests will tell you where you stand, and from there, you can address the very items that are placing you at risk, such as inflammation, insulin resistance, poor nutrition, suboptimal hormone levels, toxin exposure, etc.
8. Where can people find practitioners that have been trained in your approach?
We have now trained more than 450 practitioners from seven different countries and all over the United States, and there will be more than 1,000 by the end of this year. We are training practitioners in our protocol (ReCODE, which is for reversal of cognitive decline) in collaboration with the Institute for Functional Medicine. You can find these practitioners at the website mpicognition.com.
9. What are you most excited about in terms of future developments? What challenges are we facing?
It is important to emphasize that we are just at the very beginning of all of this—literally the dawn of treatable and preventable Alzheimer’s disease. This is the same thing that is occurring with the use of functional medicine for other complex chronic illnesses—unprecedented improvements are being seen in type 2 diabetes, hypertension, cardiovascular disease, multiple sclerosis, lupus, rheumatoid arthritis, and other illnesses. There is a tremendous amount of development remaining to do—how do we optimize outcomes? For those who improve but then plateau at less than their normal cognition, how do we enhance improvement? How do we achieve better results for those who are late in the course of Alzheimer’s disease? Can we achieve similar results for the one million Americans with Lewy body dementia? How do we address other neurodegenerative diseases, such as ALS (Lou Gehrig’s disease) and Parkinson’s disease, optimally?
There are exciting developments that should help to address these questions: the analysis of neural exosomes by Prof. Ed Goetzl and his colleagues has offered the ability to evaluate brain chemistry with a blood sample. Prof. Milan Fiala has described the “phagocytosis index,” which also shows evidence of Alzheimer’s disease pathophysiology in a blood sample and offers real-time follow-up of metabolic improvement that associates with cognitive improvement. More sensitive tests for chronic pathogens, for biotoxins and chemotoxins, for barrier breaches (gut, blood-brain, etc.), and for optimal microbiomes (especially gut, oral, and rhinosinal) should all play important roles in the evolution of functional medicine approaches to neurodegeneration, as well as improved, precision medicine programs that include optimization of immune responses, stem cells, and neurotrophin delivery—not a silver bullet, but silver buckshot.
The End of Alzheimer’s is now available from Amazon.com and other book retailers.