The Bredesen Protocol™ categorizes the modifiable risk factors that drive the degenerative process involved in Alzheimer’s can be generally divided into 5 groups. Before discussing those it is appropriate to recognize that there are other factors that are involved in the disease process, but they tend to be non-modifiable. The two most important of these are age and genetics. Age is obvious. The risk of development of the disease is 1 in 10 by age 65. It increases to 1 in 3 by age 80. As life expectancy has gone from about 68 years of age in the early/mid 1900s, it is now approximately 80.
Genetics is the other with a variation in an apoprotein called apoE being the most common. This apoprotein is involved in a number of processes in the brain that offer some protective function from degeneration. The 1 in 10 adults that possess the apoE4 variant have an increased risk of the disease between 3 and 10 times higher depending on whether they have 1 or 2 copies of the variant gene.
The important concept to appreciate about what drives the overall risk of Alzheimer’s disease is that it is a combination of modifiable and non-modifiable factors. Those with genetically increased risk may not develop the disease with age if their attention to minimizing modifiable factors is well managed. The old adage in health care is “genetics loads the gun, but lifestyle pulls the trigger”.
So what are the modifiable factors that drive the disease?
- Trophic loss or withdrawal
Glycotoxicity is the collection of factors associated with impaired blood glucose control, diabetes being the end of that spectrum. It is, however, a spectrum with some degree of damage occurring progressively over time. The spectrum begins typically a decade or more before any blood glucose abnormality is seen. It begins with insulin resistance, a phase where the insulin receptors on cells that respond to insulin begin to become poorly responsive.
The body will try to resolve this by secreting progressively high levels of insulin trying to force the cell response.
Unfortunately, routine testing only looks at blood glucose which is normal in this phase and not at insulin which is abnormally high.
Eventually the insulin resistance progresses where even high amounts of insulin signal cannot keep glucose levels normal and the diagnosis of pre-diabetes is made. This still represents an abnormal blood glucose level and is associated with some degree of tissue damage. As blood glucose continues to worsen and rise over time, it hits the cutoff point of 140 which then defines diabetes.
We should really look at “pre-diabetes” as early diabetes. The terminology is similar to calling the 1st trimester of pregnancy “pre-pregnant”. Pre-diabetes is in many ways early diabetes.
With time the progressive load on the pancreas to produce progressive amounts of insulin to attempt to control the rising blood glucose causes it to fail, a phase termed insulin dependent diabetes.
The problem with high blood glucose is “glycation”. Glucose has a tendency to attach to proteins in the body damaging them. The standard diabetes monitoring test, hemoglobin A1C, is glycated or damaged hemoglobin. This is not a concern as we make new hemoglobin fairly quickly, but it reflects the level at which other proteins in the body are being damaged. The common diabetic complications reflect the areas of the body that cannot repair damaged proteins quickly including the retina, blood vessel linings, the kidneys and nerve cells including the brain cells.
Several markers of glycotoxic stress are part of the protocol lab studies including fasting insulin. From the pattern of imbalance a specific lifestyle corrective program is developed for each person.
Inflammation is a response the immune system generates to fight infection and in response to injury. In the short term it is a helpful process. However, when it is active, it injures our own tissue to some degree. This is not a big problem for a week to fight a virus or to initiate healing in a sprained joint, but chronic inflammation is an important mechanism of almost all chronic degenerative diseases. This is particularly true in Alzheimer’s.
Over 5400 studies discussing both “Alzheimer’s” and “Inflammation” appear in a search of PubMed, the search engine of the National Library of Medicine. A striking new study looked at inflammatory markers in middle age and followed subjects for 24 years. Those with the highest inflammatory markers present at middle age had significantly higher brain volume loss at follow-up as well as greater declines in a test of episodic memory which is the memory of events including when, where, what and other details.
Two steps are involved in the Bredesen Protocol™ regarding inflammation. The first is the use of a number of markers in the blood panel to determine if inflammation is part of the problem and to what extent. The second is to examine and correct what modifiable lifestyle factors are causing these markers to elevate and develop a specific protocol for each person to address those mechanisms. They may include diet, chronic infections, excessive body fat, omega-3 fatty acid imbalances and others.
Circulatory is fairly straight forward to understand. Acute circulatory interruptions are a major cause of brain injury such as stroke and transient ischemic attacks, or TIAs. Gradual loss of circulation to the smaller blood vessels can cause progressive brain injury over time including being a mechanism of Alzheimer’s. This is evaluated with lab studies looking at risk factors for circulatory damage such as blood lipids, inflammation and glycation as discussed above. Additionally, areas of damage may be identified by brain imaging such as MRI showing old “silent mini-strokes” or areas called white matter hyperintensities.
Treatment centers around corrective lifestyle changes addressing blood lipids, inflammatory triggers and blood glucose problems.
Trophic loss or withdrawal
All cells need ongoing trophic stimulus to remain healthy and function. This stimulus triggers cell functions including function, growth and repair. Without these signals cells become diseased and eventually die. Trophic signals include those from hormones (thyroid and steroid), and from certain nutrients such as B12 and other vitamins.
The protocol involves extensive testing of trophic factor levels and treatment focused on optimizing any levels not in the ideal range.
Unfortunately, all of us receive ongoing exposure to many toxins throughout life. The body has several systems to manage these exposures through detoxification mechanisms. Variations in toxic exposure combined with detoxification capability results in the varying net toxic load from person to person. Some individuals may have higher than normal exposure to a particular toxin such as can occur from occupational exposure, mercury containing dental amalgam fillings, biotoxins (mold toxins), etc. Others may have a tolerable exposure to most people but because of lifestyle, genetics or disease their detoxification mechanisms are impaired.
Each patient has a different degree of contribution from these 5 factors that drive their disease process. Similarly, each patient will have a specific therapeutic program to ensure the maximum resolution of their involved factors and the resulting disease. The Bredesen Protocol™ begins with extensive testing of markers that show the degree of activity and involvement of these factors in the neurodegeneration. The program’s success is based on its comprehensiveness to specific targets in each individual.