From ApoE4.Info Wiki

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

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"

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). The results of each strategy 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! 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.



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 B 6

Vitamin B 9 (folate)

Vitamin B 12 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 (SpO 2 ) 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

Dr Bredesen's first book, The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline, published August 22, 2017. Amazon link to Dr Bredesen's book





Dr Bredesen's second book, The End of Alzheimer's Program: The First Protocol to Enhance Cognition and Reverse Decline at Any Age, published August 18, 2020. His first book laid out the science, this book updates his program and provides "how to" advice to implement the science of his program. Amazon link to this second book



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

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.



Dr Bredesen's Papers

The first version of Dr Bredesen’s protocol (which is similar to the above) can be found in his paper: Reversal of cognitive decline: A novel therapeutic program, published September 2014, https://www.ncbi.nlm.nih.gov/pubmed/25324467

Subsequent papers of Dr Bredesen do not address his protocol, but further examine his findings. They include:

Metabolic profiling distinguishes three subtypes of Alzheimer's disease, published in August 2015, https://www.ncbi.nlm.nih.gov/pubmed/26343025

Direct Transcriptional Effects of Apolipoprotein E published January 2016, Dr Bredesen is co-author. https://www.ncbi.nlm.nih.gov/pubmed/26791201

Inhalational Alzheimer’s Disease: An unrecognized – and treatable epidemic, published February 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789584/

Transcriptional Effects of ApoE4: Relevance to Alzheimer's Disease, published September 2017. https://www.ncbi.nlm.nih.gov/pubmed/28879423

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: