#043 Dr. Dale Bredesen on Preventing and Reversing Alzheimer's Disease
Dr. Dale E. Bredesen, a professor of neurology at UCLA, discusses Alzheimer's disease subtypes (inflammatory, atrophic, toxic) and introduces his RECODE protocol. This approach uses a "cognoscopy" to identify risk factors and customizes diet (Ketoflex 12-3), lifestyle, and other interventions to prevent and reverse cognitive decline.
Deep Dive Analysis
18 Topic Outline
Introduction to Dr. Bredesen's Work and Alzheimer's Disease
Pathological Features and Causes of Alzheimer's Disease
Amyloid Plaques: Neurotoxin and Protectant
Three Main Subtypes of Alzheimer's Disease
Zinc Deficiency and Type 3 (Toxic) Alzheimer's
APOE4 Gene: Risk Factor and Implications
The Cognoscopy and RECODE Protocol for Reversal of Cognitive Decline
Key Biomarkers for Alzheimer's Risk Assessment
The Ketoflex 12/3 Diet for Cognitive Health
Ketosis, Fasting, and Dietary Considerations for APOE4 Carriers
Mechanisms of Amyloid Clearance and Inflammation Resolution
Role of Omega-3s and Antioxidants in Phagocytosis
Herpes Viruses and Their Contribution to Alzheimer's Subtypes
Sauna Use for Detoxification and Brain Health
Limitations of Monotherapy and Importance of Multi-Factorial Approach
Prevalence of Alzheimer's Subtypes and Toxin Exposure
Testing for Mold and Mycotoxins in the Home
Gut Health Markers and Personalized Medicine
7 Key Concepts
Alzheimer's Subtypes
Dr. Bredesen describes three main subtypes of Alzheimer's: Type 1 (inflammatory/hot) associated with an overactive immune system, Type 2 (atrophic/cold) characterized by a lack of proper signaling for synapse generation and preservation, and Type 3 (toxic/vile) with a robust environmental toxicity component. Glycotoxicity (insulin resistance) is considered Type 1.5, blending features of both inflammatory and atrophic types.
Amyloid Beta as Protectant
Beyond being a neurotoxin, amyloid beta is also a protectant made by the brain in response to specific insults. It acts as an antimicrobial, a binder of divalent metals like copper and zinc, and a response to reduced trophic support, leading to a downsizing of the neural network.
Synaptoblastic vs. Synaptoclastic Activity
This refers to the ratio of brain activity involved in making and storing synapses (synaptoblastic) versus actively pulling back and reorganizing synapses (synaptoclastic). In Alzheimer's, this ratio changes due to inflammation or decreased trophic support, leading to a downsizing of the neural network.
Antagonistic Pleiotropy (APOE4)
This concept explains how a gene like APOE4 can be beneficial in certain environments (e.g., squalid, parasitic, where inflammation is needed) but detrimental in others (e.g., modern, clean environments), leading to chronic inflammation and increased risk for diseases like Alzheimer's later in life.
Cognoscopy
A term coined by Dr. Bredesen, similar to a colonoscopy, recommending a suite of baseline biomarkers for everyone aged 45 or over. It involves testing for genetic factors (like APOE4), homocysteine, inflammatory markers, nutrient levels, and toxin exposures to assess Alzheimer's risk.
Glymphatic System
This is a system in the brain that actively sweeps out waste products, including amyloid, during sleep. Adequate sleep and fasting windows are crucial for its proper function, as the brain's architecture changes during sleep to facilitate this clearance.
Chronic Inflammatory Response Syndrome (SIRS)
Described by Dr. Richie Shoemaker, SIRS is a chronic inflammatory condition often caused by exposure to biotoxins, such as those produced by mold species. It can contribute to cognitive decline and is a key component of Type 3 (toxic) Alzheimer's.
7 Questions Answered
By definition, Alzheimer's disease is characterized by the presence of amyloid plaques and phosphorylated tau tangles in the brain, though these are markers and not necessarily the root cause.
Amyloid is not just a neurotoxin but also a protectant, produced by the brain in response to various insults. Many people produce it to protect themselves and do not experience cognitive downsizing unless other factors like inflammation are also present.
APOE4 is the most significant genetic risk factor for Alzheimer's. Having one copy (heterozygous) increases lifetime risk to about 30%, while having two copies (homozygous) increases it to over 50%, and potentially as high as 90% in some studies.
The RECODE protocol (Reversal of Cognitive Decline) is a sophisticated, multi-pronged approach developed by Dr. Bredesen and colleagues to identify and treat several subtypes of Alzheimer's disease and mild cognitive impairment by addressing the multiple contributing factors.
Amyloid is considered a mediator, not the primary cause, of Alzheimer's. Simply removing amyloid without addressing the underlying causes (pathogens, toxins, metabolic changes) is like treating a symptom without curing the disease, and can sometimes even worsen outcomes.
One can use the EPA Relative Mold Index (ERMI) test, available through companies like MycoMetrics.com, which uses PCR analysis of dust samples to identify mold species and assess potential toxin production.
Tests like Genova's GI Effects or Cyrex Array 2 can assess gut health by looking at stool analysis or various antibodies, such as those responding to LPS or gluten/gliadin, which can indicate a leaky gut.
50 Actionable Insights
1. Get Tested for APOE4 Gene
Get tested for the APOE4 gene (e.g., via consumer genetic tests like 23andMe and then using foundmyfitness.com/genetics for a free report) to understand your genetic risk factor for Alzheimer’s, as knowing your status allows for proactive intervention.
2. Get a Cognoscopy at 45+
Get a ‘cognoscopy’ (a suite of baseline biomarker tests) at age 45 or over to understand your risk factors for cognitive decline, including APOE4 status, homocysteine, inflammatory issues, nutrient issues, and toxin issues, as these can all be addressed.
3. Personalize Your Health Program
Develop a personalized health program based on your specific risk factors and underlying causes of cognitive decline or risk, rather than a one-size-fits-all approach.
4. Address All Alzheimer’s Contributors
Do not rely on monotherapeutics for complex chronic illnesses like Alzheimer’s; instead, identify and address all contributing factors, which can be dozens, to effectively manage or reverse cognitive decline.
5. Adopt Ketoflex 12-3 Diet
Follow the Ketoflex 12-3 diet, which emphasizes mild ketosis, a flexitarian approach treating meat as a condiment, and at least 12 hours of daily fasting starting three hours before bed, to improve cognition and metabolic flexibility.
6. Practice Daily Intermittent Fasting
Implement a daily fasting period of at least 12 hours between dinner and breakfast to allow for autophagy and brain cleansing; if ApoE4 positive, extend this fast to 14-16 hours.
7. Cease Eating 3 Hours Before Bed
Finish dinner at least three hours before bedtime to prevent high insulin levels, which can hurt cognition, contribute to insulin resistance, and promote fat storage.
8. Aim for Mild Ketosis
Aim for mild ketosis (1.5 to 4 millimolar beta-hydroxybutyrate) through a very low carbohydrate, high good fats diet (e.g., avocados, nuts, seeds) to improve cognition.
9. Treat Meat as a Condiment
Adopt a flexitarian approach where meat is treated as a condiment rather than the main course, and if consumed, choose pastured chicken, grass-fed beef, or wild-caught fish (avoiding large, long-lived fish high in mercury).
10. Prioritize Organic Food
Consume organic foods to minimize lifelong exposure to dementogens and other toxins present in conventional food.
11. Avoid High-Mercury Fish
Stay away from large-mouthed, long-lived fish like tuna, shark, and swordfish due to their high mercury content, which can contribute to cognitive decline. Instead, opt for ‘smash fish’ (salmon, mackerel, anchovies, sardines, herring).
12. Optimize Homocysteine Levels
Monitor and optimize homocysteine levels, aiming for less than 7 (not 13), because high homocysteine is an independent risk factor for neurodegeneration and a more rapid decline in cerebral gray matter and hippocampal volume.
13. Optimize Fasting Insulin
Monitor and optimize fasting insulin levels, aiming for less than 5, as higher levels contribute to glycotoxicity and insulin resistance, which impact cognition.
14. Optimize Hemoglobin A1c
Monitor and optimize hemoglobin A1c, a marker of average serum glucose over two months, to address glycotoxicity and insulin resistance.
15. Optimize Fasting Glucose
Monitor and optimize fasting glucose levels to address glycotoxicity and insulin resistance.
16. Optimize Vitamin D Levels
Monitor and optimize vitamin D levels to ensure they are optimal, not just within normal limits, as it is critical for supporting synaptogenesis and brain health.
17. Optimize Hormone Levels
Monitor and optimize levels of hormones such as pregnenolone, progesterone, estradiol, testosterone, and free T3, as they are critical for supporting synaptogenesis and brain health. Bioidentical hormone replacement may be necessary for some.
18. Exercise Regularly
Engage in regular exercise to support brain health, as it is likely to increase brain-derived neurotrophic factor (BDNF) and contribute to overall cognitive support.
19. Prioritize Quality Sleep
Prioritize quality sleep to support the glymphatic system, which actively cleanses the brain of waste products like amyloid plaques, and is crucial for overall cognitive health.
20. Actively Manage Stress
Actively manage stress levels, as they are surprisingly important factors influencing cognitive health and overall well-being.
21. Test for Mold & Mycotoxins
Test your living environment for mold exposure using the EPA Relative Mold Index (ERMI) via services like mycometrics.com (aim for a score less than 2), and consider urinary mycotoxin tests to check for personal exposure, especially if you suspect type 3 Alzheimer’s.
22. Remove Yourself from Moldy Environments
If tests confirm mycotoxin production in your home or workplace, it is crucial to remove yourself from these environments to eliminate chronic exposure to dementogens.
23. Address Metallotoxin Exposure
Identify and address exposure to metallotoxins like mercury, which can contribute to cognitive decline, especially if you are a poor excreter or have dental amalgams.
24. Address Organic Toxin Exposure
Identify and address exposure to organic toxins like DDE, which can contribute to cognitive decline.
25. Address Pathogen Infections
If specific pathogens like Borrelia (Lyme disease) or co-infections are present, they must be addressed as part of the protocol to reverse cognitive decline.
26. Address Leaky Gut
Investigate and address leaky gut, as it is a common problem that contributes to chronic inflammatory conditions, including cognitive decline.
27. Utilize Gut Health Tests
Utilize gut health tests such as Genova’s GI Effects, Doctor’s Data stool analysis, or Cyrex Array 2 (for leaky gut/LPS response) and Array 3 (for gluten/gliadin sensitivity) to assess and address gut health.
28. Consider Omega-3s & Antioxidants
Consider supplementing with omega-3s and antioxidants, along with vitamin D, as they have been shown to improve amyloid plaque phagocytosis and cognition, and are involved in resolving inflammation.
29. Prefer Whole Fish over DHA Supplements
When seeking omega-3 benefits, prefer consuming whole fish (e.g., ‘smash fish’) over isolated DHA supplements, as fish provide additional protective antioxidants and nutrients that may be more effective, especially for ApoE4 carriers.
30. Ensure Synapse Precursors
Ensure adequate intake of synapse precursors like DHA and citicoline to support synaptogenesis and maintain a large network of synapses.
31. Incorporate Regular Sauna Use
Incorporate regular sauna use into your routine, especially if you have type 3 Alzheimer’s or high toxic burden, as it helps detoxify the body by eliminating toxins like cadmium, mercury, and BPA through sweat, and contributes to resilience.
32. Shower with Non-Emollient Soap Post-Sauna
After sauna use or sweating, immediately shower with a non-emollient soap (e.g., Castile soap) to wash away toxins released in sweat and prevent their re-penetration into the skin.
33. Address Head Trauma History
Consider and address any history of head trauma as a contributing factor to cognitive decline.
34. Address Vascular Compromise
Investigate and address any vascular compromise as a contributing factor to cognitive decline.
35. Seek Optimal, Not Just Normal, Biomarker Ranges
When interpreting lab results, aim for optimal biomarker ranges rather than merely ‘within normal limits,’ as standard reference ranges may not reflect physiological optimum for health and cognitive function.
36. Cultivate Metabolic Flexibility
Cultivate metabolic flexibility, allowing your body to efficiently switch between burning carbohydrates and fats for fuel, which is beneficial for brain health and reduces reliance on glucose.
37. Reduce Simple Carbohydrate Intake
Reduce your intake of simple carbohydrates, as human organisms are not designed to consume the high amounts typically found in modern diets, and excess sugar acts as a toxin.
38. Be Proactive in Prevention
If you have known risk factors like ApoE4, be proactive in trying lifestyle and dietary interventions to prevent cognitive decline, even if you currently have good health markers.
39. Monitor Cardiovascular Biomarkers
Continuously monitor cardiovascular biomarkers such as LDL particle number and size, and triglycerides, to ensure that dietary and lifestyle changes are beneficial for both heart and brain health.
40. Address Amyloid Causes Before Removal
Before attempting to remove amyloid plaques (e.g., with antibodies), first identify and address the underlying causes of their production, as amyloid is a mediator and protectant, not the sole cause of Alzheimer’s.
41. Support Inflammation Resolution
Actively support the resolution phase of inflammation, not just addressing the inflammatory triggers, to prevent chronic inflammatory states that contribute to cognitive decline.
42. Understand Your Alzheimer’s Subtype Mixture
Understand your personal ‘mixture’ of Alzheimer’s subtypes (inflammatory, atrophic, glycotoxic, toxic) to tailor the most effective treatment protocol, as most people have a combination of contributing factors.
43. Optimize Brain Trophic Support
Optimize trophic support for your brain by ensuring appropriate levels of hormones (e.g., through bioidentical hormone replacement if needed) and brain-derived neurotrophic factor (BDNF) to counteract atrophic processes.
44. Use MCT/Coconut Oil for Ketones
Initially use MCT oil or coconut oil to help raise ketone levels and transition to a ketone-based metabolism for the brain.
45. Transition Fats (ApoE4)
If ApoE4 positive, after 1-2 months of using MCT oil to establish ketosis, transition to more monounsaturated and polyunsaturated fats to maintain heart health while supporting cognition.
46. Manage Keto Flu During Transition
Be aware that transitioning to a ketogenic diet can cause ‘keto flu’ if ketones aren’t adequately raised while carbs are lowered; it takes a few weeks to convert to a fat-based metabolism, and exercise can help during this period.
47. Liberalize Diet if Low BMI
If you have a very low BMI and are on the Ketoflex 12-3 diet, liberalize your diet about once a week with more carbohydrate-related foods like sweet potatoes to prevent unwanted weight loss.
48. Optimize HSCRP Levels
Monitor and optimize your HSCRP levels, a marker of inflammation, as part of addressing inflammatory issues contributing to cognitive decline.
49. Monitor LDL-P (ApoE4)
If ApoE4 positive, monitor your LDL particle number (LDLP) and aim to keep it below 1,000, adjusting your intake of MCT oil, monounsaturates, and polyunsaturates to balance heart and cognitive health.
50. Take Responsibility for Your Health
Take personal responsibility for your longevity and health by actively seeking data, understanding your body, and making informed lifestyle choices.
6 Key Quotes
cognitive decline is, at least for most of us, and especially early in its course, addressable. Despite what you may have been told, it's not hopeless or irreversible. To the contrary, for the first time, hope and Alzheimer's have come together.
Dr. Dale Bredesen
The whole world is turning upside down now when it comes to our understanding of Alzheimer's.
Dr. Dale Bredesen
I think more and more of amyloid as being like napalm. You got the bad guys coming across the border. So you're now going to put down stuff that kills the bad guys, the napalm. But in so doing, you're now going to reduce your arable soil. You're now living in a smaller country.
Dr. Dale Bredesen
We've been trying to treat this disease without knowing what causes it.
Dr. Dale Bredesen
The reality is Alzheimer's should be a rare disease. It should essentially decrease to a very low level with the current generation.
Dr. Dale Bredesen
It's not that the tau is not the cause of the problem. It is a mediator based on what's going on genetically with pathogens, with toxins, with metabolic changes, with innate immune system, and with trauma.
Dr. Dale Bredesen
1 Protocols
Ketoflex 12/3 Diet
Dr. Dale Bredesen- Achieve mild ketosis through a very low carbohydrate, high-fat diet using good fats like avocados, nuts, and seeds.
- Adopt a flexitarian approach, treating meat as a condiment (pastured chicken, grass-fed beef, wild-caught 'smash' fish like salmon, mackerel, anchovies, sardines, herring) while avoiding large, long-lived fish high in mercury.
- Maintain a minimum of 12 hours of daily fasting between dinner and breakfast/brunch/lunch.
- If APOE4 positive, extend the daily fasting period to 14-16 hours.
- Ensure at least 3 hours pass between finishing dinner and going to bed to avoid high insulin levels during sleep.
- Consume organic foods to minimize toxin exposure.
- For APOE4 positive individuals, initially use MCT oil to induce ketosis, then transition to more monounsaturated and polyunsaturated fats after 1-2 months, while monitoring LDL particle number to keep it below 1,000.