NEWSLETTER # 10
A BREAKTHROUGH IN THE UNDERSTANDING
AND TREATMENT OF ALZHEIMER’S DISEASE
Dale Bredesen, MD, has recently published what can only be described as his pioneering work to understand, and more importantly, to use that understanding to successfully treat Alzheimer’s disease. His book, The End of Alzheimer’s: The First Programme to Prevent and Reverse the Cognitive Decline of Dementia is an inspiration. (Published by Penguin/Random House, 2017)
Dr. Bredesen begins by reviewing the effectiveness of all known medications used for the treatment of Alzheimer’s disease and making it clear that these have not been very helpful—-they have, at best, delayed the progression of this illness by only months. Despite spending millions of dollars on research, this has left patients and families with little-to-no hope and has given a stigma to Alzheimer’s that it is incurable. So for all of those unfortunate individuals and their families and friends and communities it is perhaps the worst diagnosis possible.
Or it used to be.
Beginning in his laboratory, while studying the scientific basis of this illness, Dr. Bredesen began to piece together and new and more comprehensive understanding of what Alzheimer’s disease is. Let’s start there. Many of you are aware that the hallmark of this illness is the increased production of what is called amyloid, a sticky glop of protein fragments inplaques and tangles that destroy synapses in the brain. Until now, the medical approach to treating this illness has exclusively focused on how to dissolve amyloid. Many medications have been developed for this purpose, and essentially they do not work except for short periods of time. Perhaps the reason for this, Dr. Bredensen clarifies, is the mistaken concept that amyloid deposition is the cause of the illness, rather than the result of a variety of toxic, infectious, and nutritional deficiencies that stimulate the production of amyloid.
First his laboratory discovered the presence, in neurons, of dependence receptors. When these receptors did not receive sufficient neurotrophin molecules, they died. So, neurotrophins are nourishing to these neurons, but if something blocked the binding of these neurotrophins to neurons, they would be damaged and eventually die. It turns out that beta-amyloid does exactly that.
Dr. Bredesen and his group then asked the next obvious question: Where does amyloid come from? It is produced by the neuron itself and made by a larger precursor protein called APP (Amyloid Precursor Protein). After APP is made, it is cut by molecular scissors called proteases, which can break APP in two major ways: 1) if cut at 3 different sites, it creates 4 peptides, one of which is beta-amyloid and all of which play roles in the development of Alzheimer’s disease. 2) if cut at a single site, it creates only two peptides which have completely different effects on the neuron: they are nourishing to the neuron and prevent Alzheimer’s disease.
The bottom line here is that if we had ways of stimulating this cutting of APP to be singular and could minimize the cutting at 3 sites, we could theoretically (now we know, actually) reverse the processes that cause this disease.
Dr. Bredesen then searched for as many factors that he could find that would do exactly this, and discovered that there were three major processes, and 36 specific areas that could accomplish this. Since there are so many components, the idea that a single drug could cure or reverse Alzheimer’s now looks, in retrospect, silly. I know that medicine is in love with the idea that a single product will cure a given illness, but surely what we have learned in the last twenty years is that we have to accept the complexity of many illnesses and look at as many factors as we can grasp to stimulate healing. This is another important example of how we must look at this complexity. The good news is that although there are 36 areas to be considered, it can indeed be done…..and Dr. Bredesen has published proof that it works in medical journals. Since the publication of his original research, he has documented over 200 reversals/cures of Alzheimer’s with his program which is called ReCODE (Reversing COgnitive DEcline. At last, we are dealing with the cause of Alzheimer’s rather than its effects.
He has identified 3 primary types of Alzheimer’s:
Type I is inflammatory. It is found more often in people with carry one or
two ApoE4 alleles (a gene long associated with Alzheimer’s) and runs in
families. Laboratory testing will often demonstrate an increase in C-
reactive protein, in interleukin-2, tumor necrosis factor, insulin resistance
and a decrease in the albumin:globulin ratio.
Type II is atrophic. It also occurs more often those who carry one or two
copies of ApoE4, but occurs about a decade later. Here we do not see
evidence of inflammatory markers (they may be decreased), but rather
deficiencies of support for our brain synapses. These include decreased
hormonal levels of thyroid, adrenal, testosterone, progesterone and/or
estrogen, low levels of vitamin D and elevated homocysteine.
Type III is toxic. This occurs more often in those who carry the ApoE3
allele rather than ApoE4 so it does not tend to run in families. This type
tends to affect more brain areas, which may show neuroinflammation
and vascular leaks on a type of MRI called FLAIR, and associated with
low zinc levels, high copper, low cortisol, high Reverse T3, elevated
levels of mercury or mycotoxins or infections such as Lyme disease with
its associated coinfections.
The ReCODE treatment program was developed directly from Dr. Bredesen’s understanding of these three types of Alzheimer’s. Keep in mind that a given patient may have more than one Type. The testing, therefore, to determine which areas need to be addressed include measuring:
- Homocysteine (optimally less than 7)
- Vitamins B6, B12 and Folate (B12 over 500, B6 60-100, folate 10-25)
- Insulin resistance (fasting insulin should be 4.5 or less, Hgb A1c<5.6, blood sugar 90 or less.
- C-reactive protein less than 1.0
- Albumin:Globulin ratio greater than 1.8
- Omega 6:omega 3 ratio 0.5-3.0
- Interleukin-6 less than 3
- Tumor necrosis factor alpha less than 6
- Thyroid optimization (TSH < 2.0, free T3 3.2-4.2, reverse T3 <20)
- Estradiol (50-250 for women)
- Progesterone (1-20 for women)
- Testosterone (500-1000 for men)
- Cortisol (morning 10-18)
- Pregnenalone 50-100
- DHEA sulfate 350-430 in women and 400-500 in men
- Copper:zinc ratio 0.8-1.2 with zinc 90-110
- Red Blood Cell magnesium 5.2-6.5
- Selenium 110-150
- Glutathione 5.0-5.5
- Checking for heavy metals, especially mercury using chelation provocation or Quicksilver assay
- Testing for sleep apnea with AHI of fewer than 5/hr
- LDL-p 700-1000
- Total cholesterol greater than 150
- Vitamin E 12-20
- Vitamin B1 (thiamine) 20-30
- Cyrex Array 2 to evaluate leaky gut
- Cyrex Array 20 negative
- Testing for gluten sensitivity with tissue transgluataminase antibodies or Cyrex 3 and 4 Array negative
- Autoantibody testing with Cyrex Array 5 negative
- c4a of less than 2830
- TGF-beta 1 of less than 2380
- MSH greater than 35
- Urinary measurement of mycotoxins
- Igenix Western Blot testing for Lyme IgM and IgG
- BMI (Body mass index) of 18-25
- Genetics: Measurement of apo E4 and SNPs related to neurodegeneration, such as APP, PS 1, PS2, CD 33, TREM 2, CR1 and NLRP 1
- Quantitative neuropsychological testing (MoCA)
- Imaging: Brain MRI with volumetrics
There are a few more than 36 here, but the 36 are categories. Dr.Bredesen feels that ALL of these need to be addressed to be sure that you are not missing important pieces that might compromise treatment. While this might seem overwhelming initially, all of these are areas that are commonly evaluated in functional medicine and I believe that if one goes about this systemically, it is quite doable.
Before I put my own spin on this information, I would encourage all of my readers to study this book. It well written, clear, and inspirational. I agree with most of what Dr. Bredesen has written, and do not want to nit pick the differences. Over the years, I have provided the vast majority of these treatments to my patients, and I applaud that he has put this together in a much more comprehensive way, specifically for Alzheimer’s but I suspect it would work well for other neurodegenerative diseases.
There are some components of testing that I am not sure are necessary for all patients. I am primarily a clinician, so I do not think that the MRI or psychoneurological testing is of clinical value (other than documenting improvement, which is crucial to Dr. Bredesen’s research but less so for my patients). I have not found the Cyrex Arrays helpful clinically and they are expensive. If one were to focus on the basic chemistry (items 1-25) mold and Lyme I think this would cover the known causes of Alzheimer’s reasonably well and provide an excellent starting point for evaluation and treatment. Having said that, please do not lose sight of what is really important: Dr. Bredesen’s ReCODE program provides true hope for improvement and reversal of Alzheimer’s disease and this is something that no one else is offering. Yes, there may be some expense to testing and treatment, but that would be a drop in the bucket compared to the expenses for medical care and caregivers over many years. The benefits to patients and families who will see their loved ones improve and function better are incalculable. Given the options of watching your parents descend into a spiral of despair and hopelessness, or doing everything possible to heal them, is there really any other choice? Finally, we have one, thanks to Dr. Bredesen.