This Journal entry picks up with more clinical science about brain health and revisits Alzheimer’s disease.
Clinical researchers have been investigating the biochemical mechanisms of this disorder and their investigations have led them to propose functional holistic lifestyle choices and practices as the therapeutic means to both prevent and reverse the disease process.
Of course, functional medicine practitioners have practiced from this perspective for decades. This is one of the first times that major research has come down from the conventional medical towers to grace us with holistic conclusions about how to treat one of our most dreaded diseases.
I am posting links to 3 different recent interviews with Dr. Dale Bredesen in this Journal writing.
Dr. Dale Bredesen, M.D. is the foremost clinical researcher on the mechanisms of the degenerative brain disease that now affects more than 5 million Americans. More people will die from Alzheimer’s disease in this year than from breast and prostate cancer combined. The suffering and expense is immense in scope. It is commonly thought that Alzheimer’s disease is an incurable condition, but this assumption is not true.
Bredesen was recently interviewed by functional medicine practitioner Chris Kresser, whose interview I am posting in its entirety below. Kresser’s interview with Dr. Bredesen is entitled “New Hope that Alzheimer’s Can be Prevented–and Even Cured.” Here is a link to the original article.
This interview is timely and coincides with the release of Dr. Bredesen’s book The End of Alzheimer’s, The First Program to Prevent and Reverse Cognitive Decline. Because we will all be affected by this particular degenerative disease in one way or another, either directly or indirectly, I recommend that everyone buy this book and become familiar with the solid science which leads right into functional medicine concepts…and then begin implementing these concepts into your lives.
As I have explained in a prior Journal entitled “Brain Health and the Degenerative Disease Spectrum” (linked below), all of the degenerative chronic diseases have common pathological mechanisms as the foundational basis which leads to their expression.
Good diet, good exercise, good stress management, and good sleep hygiene will solve most of the common diseases in our culture. Building emotional and mental clarity and becoming spiritually aligned with one’s life passions and purpose rounds one’s life out into a life well lived.
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 for research on aging in 1998 as its founding president and CEO, and is now on its Emeritus Faculty. Here is a summary of his curriculum vitae.
Here is the Kresser-Bredesen interview…
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.”
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.”
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.”
You’ve proposed 5 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.”
Where have you seen the biggest impacts in terms of diet, lifestyle, and functional medicine treatments 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.”
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.”
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.”
Where can people find practitioners who 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.”
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.”
————————end of interview————————–
Blood testing studies which Dr. Bredesen recommends are as follows:
|Ferritin||40 to 60 ng/mL|
|GGT||Less than 16 U/L for men and less than 9 U/L for women|
|25-hydroxy vitamin D||40 to 60 ng/mL|
|High-sensitivity CRP||Less than 0.9 mg/L (the lower the better)|
|Fasting Insulin||Less than 4.5 mg/dL (the lower the better)|
|Omega-3 index and omega 6:3 ratio||Omega-3 index should be above 8 percent and your omega 6-to-3 ratio between 0.5 and 3.0|
|TNF alpha||Less than 6.0|
|TSH||Less than 2.0 microunits/mL|
|Free T3||3.2-4.2 pg/mL|
|Reverse T3||Less than 20 ng/mL|
|Free T4||1.3-1.8 ng/mL|
|Serum copper and zinc ratio||0.8-1.2|
|Serum selenium||110-150 ng/mL|
|Vitamin E (alpha tocopherol)||12-20 mcg/mL|
|Body mass index (which you can calculate yourself)||18-25|
|ApoE4 (DNA test)||See how many alleles you have: 0, 1 or 2|
|Hemoglobin A1c||Less than 5.5 (the lower the better)|
Crestone and Beyond
Several days after I received the Kresser interview, Dr. Joseph Mercola posted another interview of Dr. Bredesen on his website under the title of ReCODE: The Reversal of Cognitive Decline. In this posting you can see a video of Dr. Bredesen being interviewed. The same information and principles are covered in a different manner.
And finally, here is an excellent 35 minute interview of Dr. Bredesen conducted by renowned holistic neurologist, Dr. David Perlmutter, M.D., posted here on October 8, 2017. Here is this episode of The Empowering Neurologist.
Dr. Bredesen’s work is now receiving immense attention, justly so, and this is a good thing because his functional and holistically based science approach will do the most good for those who embrace it. By following the principles he outlines, one can also expect to enjoy the prevention of a number of common degenerative disorders. Dr. Bredesen admits that his conventional science based research led him right into knowing that natural lifestyle choices and practices were foundational to prevention and healing of dementia conditions.
I attempted coverage of a broad scope of holistic functional considerations in brain health in 3 previous Journal entries:
All of the reading references listed at the end of those writings are appropriate for this Journal.
In a recent webinar entitled “Awakening from Alzheimer’s” I listened in as 11 M.D.s and 3 Ph.D.s described their clinical experience and research in treating Alzheimer’s dementia. This information has been gathered into a book by the same name.
One of the best interviews was of Dr. Bredesen, whose research and book I enthusiastically recommend. Another expert who was interviewed was Dr. Perlmutter. Please see reference #1 in the reading list below for a link to his nice website summary of how to prevent and treat Alzheimer’s disease.
Another person interviewed was Dr. Mary Newport, M.D., who explained her treatment and reversal of her husband’s advanced Alzheimer’s disease. Her book about this experience is Alzheimer’s Disease: What If There Was A Cure?
Some of the many important holistic principles which were consistently covered by all presenters in this webinar were the importance of:
- low carbohydrate, higher fat diet
- appropriate nutritional supplements
- sleep health
- stress management
Alzheimer’s disease is a very important disease to understand in terms of how it can be prevented by practicing healthy common sense lifestyle choices, even if one carries an ApoE4 gene variant.
All degenerative diseases exist on a spectrum with common causal factors as is explained in my writing, linked above, entitled “Brain Health and the Degenerative Disease Spectrum.” Like all cells and tissues in our body, the central nervous system is able to heal itself. As always, the best cure for any of the common diseases which plague our society is prevention.
“The best time to repair the roof is when the sun is shining.”….John F. Kennedy
Thank you for reading.
Signing off from Crestone and Beyond
A Very Good Supplement Resource…Keto-Nootropic
The new supplement from Designs for Health, Keto-Nootropic, is especially good for any aging brain, and of will supply readily available ketones to all brain cells, especially in brain cells which are starving for fuel because of insulin resistance; i.e., most brains in pre-dementia and dementia states.
Keto-Nootropic provides exogenous ketones as beta-hydroxybutyrate salts. This product offers the benefits of elevated ketones, such as cognition-supportive and energy-boosting effects, without the need to always follow a ketogenic diet, which can be challenging without an experienced guide and coach.
Ketones have been shown to produce energy in the mitochondria more efficiently than glucose or fatty acids. They are produced primarily in the liver and are exported around the body to serve as fuel in other tissues, especially the high energy demanding cells of the brain, heart, and skeletal muscle. In order to generate levels of beta-hydroxybutyrate (βOHB) considered to reach nutritional ketosis, a deliberate strategy is required, such as fasting or a ketogenic diet. However, many individuals find a ketogenic diet difficult to sustain, and even for people who enjoy this very low-carbohydrate, high-fat diet, it can be difficult to achieve and maintain. The exogenous ketones in Keto-Nootropic are ideal for these situations. American ginseng is also included to further assist with healthy cognition.
Highlights of this ketogenic supplement include:
Carbohydrate-free fuel for muscle and brain
Helps control hunger and will support weight loss
Supports healthy cognition
Stimulates “metabolic shift” away from glucose dependence and provides more balanced metabolic control
Yields immediate and sustained energy fuel for exercise
In addition to Keto-Nootropic, all of the supplements previously listed in the Brain Health Journal are important to consider. The synergistic effect of added complementary supplements accentuates the effectiveness of any one of them.
Here is an associated writing about the positive brain health qualities of American ginseng which is an important ingredient in the Keto-Nootropic powder.
Additional Reading and References:
Please revisit this Reading and References section in the future as new updated and current article links will be posted.
- Alzheimer’s–The Most Fundamental Principle…respected holistic neurologist Dr. David Perlmutter, M.D. reveals the simple lifestyle approaches which prevent and reverse Alzheimer’s disease…worth a look…many nice simple links are given for substantiation of the basic principles.
- Two of Dr. Bredesen’s recently published papers include Reversal of cognitive decline in Alzheimer’s disease and Inhalational Alzheimer’s disease: An unrecognized—and treatable—epidemic.
- Lithium’s Billion Year Journey: A Cinderella Story for Brain Health…a very good article on lithium’s history, chemistry and benefits. This is the part I article of reference #3 below.
- Nutritional Lithium: Orchestrating Our Genes & Optimizing Our Moods…how lithium works at the genetic level to increase BDNF and prevent Alzheimer’s disease.`
- Has Ancestral Health Gone Mainstream?…interesting information about the APOE4 gene in the Tsimane people of Bolivia.
- Alzheimer’s Disease: New Genetic Culprit Found…information about the TOMM40 genetic variant and more information about Dr. Dale Bredesen’s recommendations.
- Getting 30 Minutes of Daily Exercise Could Prevent 1 in 12 Deaths…good ideas for exercise to combat the problems caused by sedentary lifestyles. The nitric oxide (NO) release exercise is demonstrated. I recommend starting with the set shown by Dr. Zach Bush, M.D.
- Digital Dementia…an important article about a growing toxicity. Note the comment about doctors and nurses spending more time looking at digital devices than interacting with patients.
- The Magic of the Unconscious Mind…since the subconscious mind manages about 90% of what we do it is an important aspect of our brain to understand and assist in its health. A 52 minute documentary explains some of the facts.
- Is There a Role for Ketones in Traumatic Brain Injury?…TBI is a significant caused of dementia. The value of ketones as a brain fuel is explored in this article.
- Does Parkinson’s Disease Begin in the Gut?…very interesting and important recent findings are presented here.
- There are 4 writings on this website about how the heart functions outside of its role of pumping blood. These considerations are very important for body-mind-emotion-spirit health, and are the most important considerations for living a happy and healthy life that I know of. There are many many people who live happy and healthy lives in our world who would never need to read such writings. They are the living examples of a glowing heart…1) The Pulse of Life, 2) The Spiral of Life, 3) The Prayer of Life, and 4) The Beginning of Life.
- Recent research suggests that repeated hits, not concussions are to blame for CTE…the editor for a website devoted to the football program at the University of Alabama posts a nice summary article which has a look at some important new research findings about the pathogenesis of CTE.