Bredesen Protocol

From ApoE4.Info Wiki
Revision as of 07:37, 26 July 2023 by Theresab (talk | contribs) (→‎Papers that include discussion of ApoE4: bold font fixes)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search

Introduction

The protocol in this wiki is based on Dr Bredesen’s first book, The End of Alzheimer’s. With the exception of some new findings as well as some tweaks and refinements, his second book, The End of Alzheimer’s Program maintains the ReCode protocol, but presents practical information and steps to implement the protocol. Changes or new information from Dr Bredesen’s second book:

  • The cognoscopy now has some new tests and some biomarker goals have been refined, the table below in the resources section reflects these updated tests and values
  • The original 3 types of Alzheimer’s has been expanded to 6 types: Type 1 Inflammatory or hot, Type 2 atrophic or cold, Type 1.5 glycotoxic or sweet, Type 3 Toxic or vile, Type 4 vascular or pale, Type 5 – traumatic or dazed
Ketoflex 12/3 Pyramid. Source: https://www.apollohealthco.com/ketoflex-12-3/
  • A step by step guide on the order of events for reversing cognitive decline. From chapter two: 1.address insulin resistance 2. get into ketosis 3. optimize nutrient, hormone and trophic factor (growth factor) support 4. resolve and prevent inflammation 5. treat chronic pathogens 6. identify and remove toxins 7. rule out sleep apnea and optimize sleep
  • A discussion of the KetoFLEX 12/3 Brain Food Pyramid. The bottom layer, the foundation, is overnight fasting. Above that is non starchy vegetables and healthy fats. Next is prebiotics, resistant starch, and probiotics. Second from the top is animal protein and fruit. And the top of the pyramid is indulgences. For a video discussing this pyramid: Video "JG#2" from Facebook page "Dale Bredesen, MD" For a summation of KetoFLEX 12/3, see KetoFLEX 12/3 from Apollo Health
  • The role of oral health in cognitive decline
  • Detailed information about dementogens
  • Personalized nutritional supplements
  • Plan for gut health and how to optimize your microbiome and holobiome
  • Plus interspersed throughout the book are inspiring stories of patients who have successfully reversed cognitive decline


Dr. Dale Bredesen has created the ReCODE protocol that involves multiple strategies to address specific health issues that contribute to Alzheimer's Disease (AD). He followed on with the PreCode Protocol intended for individuals who are asymptomatic and interested in preventing cognitive decline and promoting brain health optimization for such reasons as genetic risk, family history, risk factors such as pre-diabetes or inflammation. The results of each strategy in these protocols are measured by using blood tests, cognitive evaluations, and other markers of overall health improvements. Actions are tweaked over time to aim for optimal lab and evaluation results. His analogy is to think of AD as a leaky roof - there are as many as 36 leaks in the AD roof that need to be addressed to stop the problem. Not every patient will have the same leaks, and the protocol is customized based on the patient’s genetics, current health, and lifestyle.

In 2014, his first published paper on the protocol, Reversal of Cognitive Decline, highlighted 10 case studies. Of those 10 people, nine showed enough improvement to return to normal life activities. Several hundred people with cognitive impairment have since followed the protocol, and most have seen a reversal of cognitive impairment. He published results of reversing various levels of cognitive decline in Reversal of Cognitive Decline: 100 patients, published October 2018. His book The End of Alzheimer's, published August 2017 discusses his protocol and explains many of the mechanisms of Alzheimer's.

Bredesen’s protocol has not been tested as a preventative, however in a May 2019 podcast interview, Dr Bredesen did say that he’s never had someone at risk come in for prevention and develop even mild cognitive impairment. Research has shown that amyloid-β is deposited in E4 carriers as early as their thirties, so addressing components prior to experiencing cognitive impairment symptoms will likely lead to better health and cognition in aging. Members on the APOE4.Info forum who follow the protocol report improvements not only in health but also in cognition, even if they do not have an SCI or MCI diagnosis.

Although Bredesen does not see private patients, he has made his protocol available to those seeking doctor assistance through AHNP: Precision Health. MPI Cognition, his previous affiliation, was acquired by AHNP and his prior affiliation with Muses Labs has ended.


The following list links to summaries of why each strategy is important, what you can do, and a selection of research references.

Diet Strategies

Optimize diet

Enhance autophagy and ketogenesis

Improve GI Health


Lifestyle Strategies

Reduce stress

Optimize sleep

Exercise

Rule out sleep apnea

Optimize mitochondrial function


Lab Tests to Track and Treat

Homocysteine

B vitamins

Inflammation

Insulin sensitivity (insulin and blood glucose)

Hormones

Zn:fCu ratio

Vitamin D

Rule out heavy metal toxicity

Optimize antioxidants  ??


Brain Strategies

Brain stimulation

Reduction of Aß

Cognitive enhancement

Increase NGF

Provide synaptic structural components

Increase focus

Increase SirT1 function


Inhalational Alzheimer's (editing note: update to types of AD)


Resources

Lab tests: Lab testing information


Supplements: Supplement ordering


Tracking results: Our member "optimize" made a Google spreadsheet using the recommended Cognoscopy test values in The End of Alzheimer's. This spreadsheet is a simple table to help you track your latest test results, with values flagged as "high", "low", or "in range". It's intended as a quick way to organize test results, and see at a glance where to make improvements.

The link to make your own copy of the spreadsheet for your private use is here: https://goo.gl/8t2dxi

Please note!

1) The copied spreadsheet will let you type in the white areas, but this may cause errors in the formulas. If you accidentally type in a white area, hit "ctrl-Z" a few times to remove the typing, or download a fresh copy of the spreadsheet.

2) The visitor might want to look at this thread about the limitations of using Promethease for some of the genetic findings as recommended on this sheet.


Summary of key tests for ReCode Protocol

Taken from table 1 of Dr Bredesen's second book The End of Alzheimer's Program provided for quick reference, refer to the book for specific information. If you are following his first book, note that some of the biomarkers have changed.

Critical Tests Target Values Comments
Inflammation, protection, and vascular hs-CRP <0.9 mg/L Systemic Inflammation
Fasting insulin

Fasting Glucose
Hemoglobin A1c
HOMA-IR

3.0-5.0 μIU/mL*

70-90 mg/dL
4.0-5.3%
<1.2

Glycotoxicity and insulin resistance markers
*For those who are insulin sensitive, with fasting glucose <90 mg/dL, fasting insulin of < 3.0 is still a healthy range 
Body mass index (BMI) 18.5-25 Weight (lbs) x 703/height (inches)2
Waist to hip ratio (women)

Waist to hip ratio (man)

<0.85

<0.9

Homocysteine ≤7μmol/L Reflects methylation, inflammation, and detox
Vitamin B6

Vitamin B9(folate)
Vitamin B12

25-50 mcg/L (PP)

10-25 ng-mL
500-1500 pg/mL

Improve methylation and reduce homocysteine
Vitamin C

Vitamin D
Vitamin E

1.3-2.5 mg/dL

50-80ng/mL
12-20 mg/L

Omega-6 to omega-3 ratio 1:1 to 4:1 (beware that <0.5:1 may be associated with bleeding tendency) Ratio of inflammatory to anti-inflammatory omega fats
Omega-3 index ≥10% (ApoE4+)

8-10% (ApoE4-)

Proportion of anti-inflammatory omega-3 fats
AA to EPA ratio (arachidonic acid to eicosapentaenoic acid ratio) <3:1 Ratio of inflammatory AA to anti-inflammatory EPA
A/G ratio (albumin to globulin ratio)

Albumin

≥1.8:1

4.5-5.4 g/dL

Markers of inflammation, liver health, and amyloid clearance
LDL-P

Small dense LDL
Oxidized LDL

700-1200nM

<28 mg/dL
<60 ng/mL

LDL-P is LDL particle number
Total cholesterol

HDL cholesterol
Triglycerides
TG to HDL ratio

150-200 mg/dL

>50 mg/dL
<150 mg/dL
<1.1

CoQ10 1.1-2.2 mcg/mL Affected by cholesterol level
Glutathione >250 mcg/mL (>814 μM) Major antioxidant and detoxicant
Leaky gut, leaky blood-brain barrier, gluten sensitivity, autoantibodies Negative
Minerals RBC-magnesium 5.2-6.5 mg/dL Preferable to serum magnesium
Copper 90-110 mcg/dL
Zinc 90-110 mcg/dL
Selenium 110-150-ng/mL
Potassium 4.5-5.5 mEq/L
Trophic Support Vitamin D 50-80 ng/mL (250H-D3)
Estradiol

Progesterone

50-250 pg/mL

1-20 ng/dL (P)

Women; age dependent
Pregnenolone

Cortisol (AM)
DHEA-S (women)
DHEA-S (men)

100-250 ng/dL

10-18 mcg/dL
100-380 mcg/dL
150-500 mcg/dL

Age dependent
Testosterone

Free Testosterone

500-1000 ng/dL

18-26 pg/ml

Men; age dependent
Free T3

Free T4
Reverse T3
TSH
Free T3 to reverse T3
Anti-thyroglobulin antibodies
Anti-TPO

3.2-4.2 pg/mL

1.3-1.8 ng/dL
<20 ng/dL
<2.0 mIU/L
>0.02:1
Negative
Negative

Toxin-related Mercury

Lead
Arsenic
Cadmium

<5 mcg/L

<2 mcg/dL
<7 mcg/L
<2.5 mcg/dL

Heavy Metals
Mercury Tri-Test <50th percentile Hair, blood, urine
Organic toxins (urine) Negative Benzene, toluene, etc.
Glyphosate (urine) <1.0 mcg/g creatinine Herbicide
Copper to zinc ratio 0.8-1.2.1 Higher ratios associated with dementia
C4a

TGF-β1
MMP-9
MSH

<2830 ng/mL

<2380 pg/mL
85-332 ng/mL
35-81 pg/mL

Associated with inflammatory response
Urinary mycotoxins Negative May include contributions from inhalation, ingestion, and infection
BUN

Creatinine

<20 mg/dL

<1.0 mg/dL

Reflects kidney function
AST

ALT

<25 U/L

<25 U/L

Reflects liver damage
VCS (visual contrast sensitivity) Pass Failure associated with biotoxin exposure
ERMI test <2 Mold index from building
HERTSMI-2 test <11 Index of most toxic molds
Pathogen-related CD57 60-360 cells/μL Reduced with Lyme
MARCoNS Negative
Antibodies to tick-borne pathogens Negative Borrelia, Babesia, Bartonella, Ehrlichia, Anaplasma
Antibodies to Herpes family viruses Negative HSV-1, HSV-2, HHV-6, VZV, EBV, CMV
Neurophysiology Peak alpha frequency on quantitative EEG 8.9-11 Hz Slows with cognitive decline; useful for following progress
P300b on evoked response testing <450 ms Delayed with cognitive decline; useful for following progress
Other Tests MoCA (Montreal Cognitive Assessment) 28-30
Nocturnal oxygen saturation (SpO2) 96-98% Affected by living at high altitude
AHI (apnea-hypopnea index) <5 events per hour >5 indicates sleep apnea
Oral DNA Negative for pathogens P. gingivalis, T. denticola, etc.
Stool analysis No pathogens or dysbiosis
ImmuKnow (CD4 function, indicated by ATP production) ≥525 ng/mL Indicates function of helper cells of the cellular arm of adaptive immune system

Abbreviations used in the above table: AA – arachidonic acid AHI – apnea-hypopnea index ALT – alanine aminotransferase AST – aspartate aminotransferase BMI – body mass index BUN – blood urea nitrogen C4a – complement split product 4a CD57 – cluster of differentiation 57 CMV – cytomegalovirus CoQ10 – coenzyme Q10 (ubiquinone) DHEA-S - dehydroepiandrosterone sulfate DNA – deoxyribonucleic acid EBV – Epstein-Barr Virus EEG – electroencephalogram EPA – eicosapentaenoic acid ERMI – Environmental Protection Agency relative mold index HERTSMI-2 – Health Effects Roster of Type-Specific Formers of Mycotoxins and Inflammagens – 2nd version HHV-6 – Human herpesvirus 6 (A and B) HOMA-IR – homeostatic model assessment of insulin resistance Hs-CRP – high sensitivity C-reactive protein HSV-1 – Herpes simplex virus 1 HSV-2 - Herpes simplex virus 2 LDL – low density lipoprotein MARCoNS – mulit antibiotic-resistant coagulase negative Staphylococcus MMP-9 – matrix metalloproteinase-9 MoCA – Montreal Cognitive assessment MSH – alpha-melanocyte stimulating hormone P300b – positive wave at 300 milliseconds (event-related potential), component B PP – pyridoxal phosphate RBC – red blood cell SpO2 – peripheral capillary oxygen saturation T3 – triiodothyronine T4 – throxine TG – triglycerides TGF-β1 – transforming growth factor beta-a TPO – thyroid peroxidase TSH – thyroid-stimulating hormone VZV – varicella zoster virus

Dr Bredesen's research

Books



  • Third book, The First Survivors of Alzheimer's: How Patients Recovered Life and Hope in Their Own Words, published August 17, 2021. These first person accounts honestly detail the fear, struggle, and ultimate victory of each patient's journey. They vividly describe what it is like to have Alzheimer's. They also drill down on how each of these patients made the program work for them--the challenges, the workarounds, the encouraging results that are so motivating. Dr. Bredesen includes commentary following each story to help point readers to the tips and tricks that might help them as well. Amazon link for more info on this book, available for purchase at multiple sources


Social Media

  • Facebook Page: Dale Bredesen, MD includes a library of videos where Dr Bredesen discusses numerous subjects related to his research and findings.
  • Twitter: Dr Dale Bredesen


Videos and interviews

Not a complete list.

  • He cites 6 types of Alzheimer's: (1) inflammatory (2) atrophic (1.5) glycotoxic (3) toxic (4) vascular and (5) traumatic. Vascular and traumatic are new since publication of his book
  • In his markers for glycotoxicity, he cites fasted insulin of 5.0 (his book cites 4.5) or lower and HbA1c 4.5 to 5.2 (the book cites less than 5.6)
  • Dr Bredesen said that the Big Four to avoid are: grains, simple carbs, dairy, and lectins. Pro-inflammatory lectins have been added since publication of his book.
  • He added another mold/mycotoxin to his list: Wallemia. The big 5 molds are now: Stachybotrys, Aspergillus, Penicillium, Chaetomium, and Wallemia.
  • Interview with Dr Bredesen, conducted by Dave Asprey of Bulletproof Radio. Posted Oct 28, 2020. This interview promotes and discusses Dr Bredesen's second book, "The End of Alzheimer's Program. You Can Prevent and Even Reverse Cognitive Decline – Dr. Dale Bredesen with Dave Asprey : 753
  • Facebook live talks (recorded): "Special Considerations for ApoE4 Carriers" (March 12, 2021) and "Special Considerations for ApoE4 Carriers Part 2" (March 25, 2021) with Dr Dale Bredesen, Dr Ram Rao and Julie Gee. These recorded videos can be found on Dr Bredesen's facebook page, Dale Bredesen, MD - Facebook page click on the VIDEO link to find the talks.


Dr Bredesen's Papers

Papers that address Dr Bredesen’s protocol

The first version of Dr Bredesen’s protocol (which is similar to the above) can be found in this paper:

Reversal of cognitive decline: a novel therapeutic program (Dale E Bredesen, Sep 2014)


This paper addresses the common criticism that the original paper only covered a small number of patients. This paper documents improvement in cognition of 100 patients treated by several different physicians thus providing further support for a randomized, controlled clinical trial of the protocol and overall approach:

Reversal of Cognitive Decline: 100 Patients(Dale E Bredesen et al, 2018)


From this paper, "In summary, our findings from this pilot study reinforce the potential benefits of a multitherapeutic, personalized approach targeting metabolic risk factors and support our conclusion that the ReCODE program may be beneficial in delaying or arresting poor cognitive performance in most cases. The results also pave the way for larger controlled studies to provide further validation.”

ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline(Rammohan V Rao et al, 29 Sep 2021)


This paper set to determine whether a precision medicine approach implementing Dr Bredesen's Protocol to address Alzheimer's disease and mild cognitive impairment, in which potential contributors to cognitive decline are identified and targeted therapeutically, is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial.

Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project(Kat Toups et al, 16 Aug 2022)


This study used the Bredesen Protocol to observe the efficacy of the approach. From the conclusion: "Multiple measures of cognitive function improved after six months of intervention. Our results support the feasibility and impact of a multimodal, individualized treatment approach to OCI, warranting further research."

Observed Improvement in Cognition During a Personalized Lifestyle Intervention in People with Cognitive Decline (Sandison, Heather et al, 19 June 2023).


Not a paper, but due to the success cited in the above papers, Dr Bredesen is currently recruiting for a a pragmatic, randomized, multicenter, controlled trial in which participants will be randomized to a 9-month precision medicine treatment approach or a 9-month standard treatment approach. More info can be found here: https://www.dementiareversaltrial.com/


Papers that include discussion of ApoE4

Dr Bredesen is author/co-author of over 200 peer-reviewed papers and has over thirty medical patents to his name. His complete curriculum vitae (CV) detailing his education, professional experience, professional activities, honors & special awards, research grants and fellowships received, lectures and presentations (abridged from over 300), publications and more can be found here: https://www.apollohealthco.com/wp-content/uploads/2019/10/bredesen-cv.pdf.

Of his many publications, the following papers/posters were found to cite ApoE4 as found through Google Scholar:

Could Alzheimer's Disease Be a Maladaptation of an Evolutionary Survival Pathway Mediated by Intracerebral Fructose and Uric acid Metabolism? 2023


Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer's Disease and MCI: A Review 2023


Precision medicine approach to Alzheimer's disease: Successful pilot project 2022


ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline 2021


Alzheimer’s disease as a systems network disorder: chronic stress/dyshomeostasis, innate immunity, and genetics 2020


Alzheimer's Disease, the Microbiome, and 21st Century Medicine 2019


P2-176: IDENTIFICATION OF AN EXPERIMENTAL DRUG THAT ENHANCES BRAIN SIRTUIN 1 LEVELS AND IMPROVES COGNITION AS A POTENTIAL NEW THERAPEUTIC FOR AD 2019


Reversal of cognitive decline: 100 patients 2018


A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model 2018


O5-06-06: NORMALIZATION OF HIPPOCAMPAL SIRTUIN 1 LEVELS IN A MURINE APOLIPOPROTEIN E4-5XFAD MODEL OF AD RESTORES COGNITIVE FUNCTION 2018


Downregulation of protein phosphatase 2A by apolipoprotein E: Implications for Alzheimer's disease 2017


Transcriptional effects of ApoE4: relevance to Alzheimer's disease 2017


Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation 2017


Screening for small molecule inhibitors of statin-induced APP C-terminal toxic fragment production 2017


Direct transcriptional effects of apolipoprotein E 2016


Reversal of cognitive decline in Alzheimer's disease 2016


P3‐187: Neuronally‐Derived Exosomal Proteins Can Predict Brain Amyloidosis 2016


Development of ApoE4-‐Targeted Drug Candidates for Alzheimer's Disease 2016


Metabolic profiling distinguishes three subtypes of Alzheimer's disease 2015


Dynamic self-guiding analysis of Alzheimer's disease 2015


Alzheimer’s and Neurodegenerative Diseases 2015


Inhalational Alzheimer's disease: an unrecognized—and treatable—epidemic 2015


Reversal of cognitive decline: A novel therapeutic program 2014


Next generation therapeutics for Alzheimer's disease 2013


O2‐02‐02: Novel Transcriptional Role of APOE4 2016


Neuroprotective Sirtuin ratio reversed by ApoE4 2013


Next generation therapeutics for Alzheimer’s disease 2013


P3-164: Cellular effects of APOE4: Implications for Alzheimer's disease 2011