Blog 3 of 6
By Terry Willard Clh, PhD
This material will be presented at the Kootenay Herb Conference on July 8th, 2023 (https://herbconference.com/kootenay-herb-conference/).
Sorry about the delay! I had technical problems with my web page for the last 2 weeks. This has been resolved so we go forward with the rest of the instalments.
In the first two blogs( Blog 1, Blog 2) in this series, we looked at some of the causes and started to unwind various possible changes to lifestyle that can improve a person’s chance of reducing Alzheimer’s symptoms. We will start this blog with looking at the Dr. Bredesen’s Protocol.
Before finding the right protocol for you, or a loved one, you need to know a bit more about the symptoms that are presented in the particular type of Alzheimer’s disease (AD). Yes, there is more than one type of AD. This is one of the great jewels that can be found in the Dr. Bredesen’s look at AD.
If you are experiencing or are at risk for cognitive decline, or if the goal is to enhance cognition, then you want to increase all of the contributors to your synaptoblastic signaling and reduce all of the contributors to your synaptoclastic signaling. To do this, you’ll want to know about the potential contributors:
- Is there ongoing inflammation? This is easy to check via a doctor-requested blood test. One of the most common causes of chronic inflammation is leaky gut—the leaking of bacteria, fragments of bacteria, other microbes, incompletely digested food molecules, and other molecules, into the bloodstream which incite an inflammatory response. Another common cause is metabolic syndrome, which is a combination of hypertension (high blood pressure), high cholesterol, high glucose (diabetes or prediabetes), and inflammation, associated with a diet high in sugars or other simple carbohydrates.[1] A third common cause is poor dentition—periodontitis (inflammation around the teeth) or gingivitis (inflammation of the gums).
- Is there insulin resistance? This is easy to check with a fasting insulin level. If diabetes runs in the family, they may wish to add one final test—the most sensitive—which is an oral glucose tolerance test with insulin levels.
- Is there optimal level of nutrients, hormones, and trophic factors (growth factors)?
- Is there specific pathogens—microbes that cause the brain to respond by producing the amyloid of Alzheimer’s disease?
- Are they immunosuppressed? If their immune system is not working well, then every infectious agents—e.g., viruses, molds, bacteria, parasites, and spirochetes described above—are able to survive in their body and gain access to their brain. The brain then protects itself by making—you guessed it—the amyloid that we associate with Alzheimer’s.
Bredesen Protocol
The Bredesen protocol is the most controversial of all the ideas about AD. It is based around the work from the decades of research by Dr. Dale Bredesen, MD, a neurologist. It can be seen in more detail in his proliferate body of work, especially his book, The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age.[2] His system has become quite popular, in fact there is a whole industry based around it. As you will see in future blogs, his protocols are based mostly in evidence and science, using natural remedies, purporting that yes, Alzheimer can be reversed which flies in the face of the mainstream narrative about dementia medicine (which claims dementia is irreversible). As stated earlier, he presents records of over 100 patients to strengthen his case. Some of his critics take aim at his popularity, TED talks, and the great amount of marketing from the industry that has grown around him, and among his detractors you see attacks over small things in his research. There is no question that a lot of money is trading hands around his protocols and that seems to make his colleagues both accusatory and jealous.
What is the Bredesen Protocol?
The Bredesen Protocol is a personalized approach to prevent and reverse cognitive decline through a PreCODE (Pre [starting point] of cognitive decline) or ReCODE (for reversal of cognitive decline) process. The PreCODE begins with a “cognoscopy” at the age of 45, if possible. This is done using the MoCA test (MoCA is an abbreviation for Montreal Cognitive Assessment – https://www.parkinsons.va.gov/resources/MOCA-Test-English.pdf).
The PreCODE also includes a set of simple blood tests which gives the doctor the ability to customize a treatment plan for better brain health.
The overall goals of the Bredesen Protocol are to remove exposure triggers that lead to cognitive decline, optimize health support, and rebuild the neural network. Dr. Bredesen subdivides Alzheimer’s into 6 subtypes and identifying which one is more relevant for an individual can be helpful for adjusting the treatment plan.
Bredesen’s 6 Alzheimer’s Subtypes[3]:
- Type 1 Alzheimer’s disease is inflammatory, or hot
Ongoing or chronic inflammation puts the patient at greater risk for developing Alzheimer’s.
- Type 2 Alzheimer’s disease is atrophic, or cold
Sub-optimal levels of nutrients, hormones, trophic factors (cell growth factors like NGF, nerve growth factor) increases the risk for Alzheimer’s disease.
- Type 1.5 Alzheimer’s disease is glycotoxic, or sweet
High blood sugar or high fasting insulin levels increases the risk for Alzheimer’s disease. It is termed Type 1.5 because it has features of both Type 1 and Type 2. High cholesterol (especially LDL) may also come into play.
- Type 3 Alzheimer’s disease is toxic, or vile
Exposure to toxins such as mercury, toluene, or mycotoxins (made by certain types of molds) leads to an increased risk for Alzheimer’s disease. Although we all experience this exposure to a greater or lesser degree, the key is to minimize it by identifying and removing exposures as much as possible.
- Type 4 Alzheimer’s disease is vascular, or pale
If the patient has cardiovascular disease, they are at an increased risk of Alzheimer’s disease. Vascular leakiness is one of the earliest changes identified in Alzheimer’s disease.
- Type 5 Alzheimer’s disease is traumatic, or dazed
A history of head trauma—from accidents, falls, or repeated sports-related head injuries—increases the risk for Alzheimer’s disease.
A person can, and often does, have more than one of these above types of AD.
Addressing Insulin Sensitivity
Insulin is a key growth factor for neurons, and the Bredesen Protocol addresses insulin resistance and restoring insulin sensitivity.
Insulin sensitivity can be restored by the following:
- Combining the KetoFLEX 12/3 diet and lifestyle
- Optimizing intake of essential nutrients, such as zinc
- Exercising regularly
- Reducing stress
- Treating sleep apnea if present
- Taking a supplement such as berberine, cinnamon, alpha-lipoic acid, or chromium picolinate, if needed
Fat Burning for Improving Cognitive Health
Burning fat is crucial: Alzheimer’s is associated with a decrease in glucose utilization. Remember we can get energy from our mitochondria through ingesting glucose or fatty acids. A three-pronged approach to begin burning fat, according to Dr. Bredesen’s diet plan KetoFLEX 12/3, includes (a Flexible, Ketogenic diet, with at least 12 hours of fasting and stop eating at least 3 hours before going to bed):
- Eating a plant-forward, fiber-rich, low-carbohydrate diet that is high in healthy fats
- Fasting overnight for at least 12 hours
- Exercising regularly, ideally for 30 minutes, 5 times per week
Fat plays a crucial role in prevention and even reversal of AD. Thus, a modified Ketogenic diet is indicated. Omega-3 oils and MCT oil have been shown to protect the neurons from AD and almost emulsify or clean our old plaque. This has been shown to dramatical change with the ratio HDL (good) to LDL (bad) cholesterol.
A ground-breaking study has revealed that individuals with elevated levels of “good” cholesterol (HDL) in the fluid enveloping their brain and spinal cord could be shielded against Alzheimer’s disease.[4] Research conducted by the University of Southern California’s Keck School of Medicine in Los Angeles demonstrated that quantifying small high-density lipoproteins (HDL) particles in the brain could serve as an efficient predictor of dementia risk.
The study included an analysis of 180 participants with a mean age of approximately 77 years. Researchers examined the concentration of HDL, also referred to as “good cholesterol,” in cerebrospinal fluid. Their results demonstrated that individuals who had a larger number of small HDL particles in this fluid had the crucial indicators of Alzheimer’s protection.
Dr. Hussein Yassine, co-author of the study and an associate professor of medicine and neurology at the University of Southern California, emphasized that the research opened up new avenues for cerebrospinal fluid analysis. This finding has vast implications for public health since dementia currently represents a major global health crisis, and early detection can significantly lower the impact of this illness.
Overall, this study’s findings offer optimism that dementia’s onset can potentially be avoided by promoting “good” cholesterol levels. With more research and study, healthcare professionals can eventually develop targeted treatment for reducing the risk of dementia.
A model for exchangeable apolipoproteins across the blood-CSF (cerebrospinal fluid) and brain barriers. The small HDL hypothesis proposes that small HDL components can exchange into the brain and that the interaction between plasma-derived and brain-derived apolipoproteins stabilize ATP-binding cassette 1 (ABCA1) function to form small HDLs in the brain. The brain-systemic circulation crosstalk is illustrated here by an interaction of plasma-derived apolipoprotein A-I (ApoA-I) with brain-derived apolipoprotein E (ApoE) to form ApoE/ApoA-I small HDLs. The formation of small HDLs in the brain promotes membrane lipid remodeling, clearance of Aβ, and synaptic plasticity.
Another indicator of lowering occurrence of AD is better performance on tests of memory and thinking skills. Of the 141 participants who completed a series of cognitive tests, those with higher levels of small HDL particles in their cerebrospinal fluid had better scores. Even more remarkable, this link remained independent of age, sex, education, or whether they carried the ApoE4 gene (which boosts Alzheimer’s risk, as mentioned previously). The link was even stronger among those who had no cognitive impairment.
Vitamin, Supplement, & Nutrient Support
It is important to optimize all nutrient, hormone, and trophic (growth factor) support. This support enables us to create resilience, optimize our immune systems, support our mitochondria, and begin to rebuild our brains’ synaptic networks.
Low levels of trophic factors (growth factors) such as vitamin B1 (thiamine), vitamin B12, vitamin D, testosterone, estrogen, and nerve growth factor are all associated with cognitive decline.
Other necessary nutrients for optimal cognitive function include vitamin C, vitamin E, vitamin K2, omega-3 fats, choline and other neurotransmitter precursors, and key metals such as zinc, magnesium, copper, and selenium.
Optimum hormone levels are critical for making and maintaining synapses. Optimal nutrition and lifestyle will lead to optimal hormone production for many of us; however, some patients will need to support optimal brain function by taking supplements to encourage healthy levels of the thyroid, pregnenolone, estradiol, progesterone, testosterone, DHEA, and cortisol.
Reducing Inflammation
We want to optimize the way the body uses inflammation. It’s important to allow the body to increase inflammation when it’s necessary and resolve inflammation when it’s no longer needed.
It is important to minimize inflammation that does not have a purpose (which is commonly referred to as “chronic inflammation”). Amyloids often associated with Alzheimer’s disease are part of our body’s inflammatory response.
Leaky gut is the most common cause of chronic inflammation, and can be a result of:
- Stress
- Alcohol
- Excessive sugar intake
- Processed foods
- Aspirin and related anti-inflammatories
- Soft drinks
- PPIs (proton-pump inhibitors—used to treat reflux or heartburn)
- Other damaging agents
Therefore, we need to know the status of our gut health.
Chronic inflammation with or without a leaky gut may also be caused by periodontitis, gingivitis from suboptimal dentition, or an infection of a root canal in your mouth.
In fact, chronic periodontitis, an inflammatory condition of the gums, may be a direct cause of Alzheimer’s disease.
In our next blog post, we will go into more detail on diet and how it can greatly improve our changes for overcoming AD.
[1] Christian K. Roberts, Andrea L. Hevener, and R. James Barnard, Comprehensive Physiology 3, no. 1, 1–58, May 2013 Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
[2] Bredesen, D., Perlmutter, D. (2020). The End of Alzheimer’s Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age. United States: Penguin Publishing Group.
[3] From https://primehealthdenver.com/bredesen-protocol/
[4] Martinez AE, Weissberger G, Kuklenyik Z, et al. The small HDL particle hypothesis of
Alzheimer’s disease. Alzheimer’sDement.2023;19:391–404. https://doi.org/10.1002/alz.12649