The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline

by Dale E. Bredesen

In this paradigm shifting book, Dale Bredesen, MD, offers real hope to anyone looking to prevent and even reverse Alzheimer's Disease and cognitive decline. Revealing that AD is not one condition, as it is currently treated, but three, The End of Alzheimer's outlines 36 metabolic factors (micronutrients, hormone levels, sleep) that can trigger "downsizing" in the brain. The protocol shows us how to rebalance these factors using lifestyle modifications like taking B12, eliminating gluten, or improving oral hygiene.

The results are impressive. Of the first ten patients on the protocol, nine displayed significant improvement with 3-6 months; since then the protocol has yielded similar results with hundreds more. Now, The End of Alzheimer's brings new hope to a broad audience of patients, caregivers, physicians, and treatment centers with a fascinating look inside the science and a complete step-by-step plan that fundamentally changes how we treat and even think about AD.

Genres: Health, Nonfiction, Science, Medicine, Self Help, Medical, Brain

320 pages, Hardcover

First published August 22, 2017

About the author

Dale Bredesen, M.D., is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer’s disease. He graduated from Caltech, then earned his M.D. from Duke University Medical Center in Durham, North Carolina. He served as chief resident in neurology at the University of California, San Francisco (UCSF) before joining Nobel laureate Stanley Prusiner’s laboratory at UCSF as an NIH postdoctoral fellow. He held faculty positions at UCSF, UCLA, and the University of California, San Diego. Dr. Bredesen directed the Program on Aging at the Burnham Institute before coming to the Buck Institute in 1998 as its founding president and CEO. He is the chief medical officer of MPI Cognition.

Reviews

[Maggie Stiefvater · Rating 5 out of 5]

Last year, I was diagnosed with adrenal insufficiency, autoimmune, and a hookworm infestation after losing the ability to stay awake, think, digest food, grow hair, or perform easy physical tasks like lifting a backpack. I couldn't remember my home address; I certainly couldn't write novels. I was failing as a human and as a creator. My functional physician put me on a dauntingly strict regimen of diet, supplements, and cortisol management, and slowly my physical health returned. More slowly, my brain followed. When the brain fog still lingered, however, I picked up this book in hopes of understanding why I hadn't gotten my cognition back completely.

It was an incredibly informative and exciting read. Bredesen's protocol is strikingly similar to the autoimmune protocol my doctor put me on, and incorporating the differences into my own regime has given me even more functionality is just a few weeks.

The incidence of autoimmune disease, Alzheimer's, and Parkinson's has skyrocketed in developed countries, and science gallops alongside it looking for answers. Old theories on lupus, depression, and hormone imbalances are rapidly changing as research increasingly points to how we're making ourselves sick as a society. Very cool, very exciting, and very daunting times. This book collects some of the newest stuff. I'm recommending it to everyone with any kind of autoimmune, brain fog, or dementia.

[Craig & Heather Norris · Rating 5 out of 5]

Critically important reading

My wife was diagnosed with mild cognitive impairment while a member of the Kaiser network. They did a few diagnostic tests ,get a MOCA score on my wife of 19, got her drivers license revoked, and essentially said, "this is a terrible disease, there is nothing tone done for it, good luck".

None of the Bredesen Protocol is part of the Kaiser program, and the physicians we spoke with did not even know what a functional medicine physician is, but did not think that Kaiser had one.

Fortunately, we were able to qualify for a Bredesen Immersion program with Dr. Bredesen and a team he assembled of trained functional medicine physicians. Subsequently, we are " all in" with the Bredesen protocol. It is not a diet, bit a complete lifestyle change. My wife' symptoms have not progressed and in many area have improved, just sine April 2017. Yes, the program is challenging and has some expense associated with it, but compared to what? An Alzheimer's unit in a nursing home, not to mention the emotional toll on everyone - does this seem like an easier and cheaper alternative to anyone?

This book and the ReCode protocol offers something that cannot be measured, real hope. I urge you to read the book and take the protocol seriously, it can change you and your loved ones lives.

[Doug Bradshaw · Rating 5 out of 5]

A friend brought this book to me and asked me to read it and then to help him incorporate the protocol into his life to fend off mild cognitive impairment symptoms. The book was recommended to him by a well known MD.

The author is well qualified with an MD degree, a residency in Neurology along with other related postdoctoral work. He has been studying the disease for 20 plus years.

MD's and pharmaceutical companies have been looking for a drug to help Alzheimer's patients for a long time. There are a few drugs that help a little bit, but unfortunately, this type of one drug solution so common in medicine won't work because there are dozens of potential causes of the disease. He has identified 36 causes and that list is growing. He compares the causes to holes in the roof that need to be patched. Patching one or two holes won't do the trick.

The three main categories of the causes of the disease are:

1. Inflammation caused by a multitude of different factors including unhealthy foods, drug interactions, and many others. This inflammation triggers the immune system that can then cause an unhealthy brain environment.

2. Metabolic issues, also caused by a multitude of factors, insulin resistance, lack of the vitamins needed to properly break down foods, unhealthy foods, lack of exercise, daylight, etc. etc.

3. Sometimes there are toxins that can cause serious problems such as mold and a list of others such as lead poisoning, etc.

I have merely touched the surface of each category and the various components of each. The first thing to do to start the "ReCODING" process is to identify which of the 36 holes you have in your roof. Many of the holes are fairly simple to identify, low levels of certain vitamins, high A1C levels, high homocysteine level, BMI over 30, low testerone levels, low cholesterol levels (surprised at that one), and many more. These can be identified with blood labs. Once identified, there is good information involving diet, exercise, supplements and vitamins which will reverse these problems over time.

There are also or toxin tests, pet scans, genetic testing and many more that will probably require help from a doctor. There is also the MOCA Montreal tests that you can do online to measure your impairment level.

It seems to me that this book is excellent for anyone over the age of 45 to read and then to incorporate as much as possible into a healthier lifestyle and prevention, even if you show no signs of cognitive issues. I am excited to get my own blood labs done. I especially enjoyed reading about the many patients who started Recoding and then sometimes reversed the disease and stopped the progression in its tracks.

I'm also planning to watch several YouTube videos that have been posted by the doctor himself and other doctors who are implementing the work into their practices.

[Bharath · Rating 5 out of 5]

If you have known people who have battled Alzheimer’s disease, you understand the toll it takes on the person as well as the family/caregivers. A cruel disease which robs people of their sense of identity and confidence to face others. This is a book I liked – I feel the advice is rooted in good experience & evidence.

It has been known since some time that brains of people with Alzheimer’s have build-up of amyloid-beta plaques – scans have conclusively shown that. Over the years, drug companies have invested large sums of money and found many compounds which can reduce the build-up. And yet, the number of drugs which can arrest or cure Alzheimer’s is still at 0. A sense of helplessness has come to people diagnosed with the disease. While there has been considerable progress in the treatment of other dreaded diseases like heart ailments and even cancer, drugs to treat Alzheimer’s has made no headway. Dr Bredesen offers the following reasons – Alzheimer’s is probably not one disease; at the minimum it seems to have at least three variants and he & his team have identified 36 factors which need to be addressed to effectively arrest progression and even reverse the symptoms. The three types (Inflammatory, Atrophic, Toxic) are recognizable through a combination of genetic, blood and other tests, though most doctors do not consider it worthwhile, as in any case Alzheimer’s is regarded as uncurable.

How modern lifestyle invites Alzheimer’s with a combination of poor diet, lack of exercise & inadequate sleep is also true for general health. The culprits this book identifies – sugar, processed food, meat, dairy, gluten largely match those in other good books I have read – How Not to Die: Discover the Foods Scientifically Proven to Prevent and Reverse Disease and Brain Food: The Surprising Science of Eating for Cognitive Power. There is fairly good and detailed information on the tests you should take, assessments you can do yourself and the treatment options. Since Dr Bredesen offers a holistic multi-pronged treatment approach combining – diet, supplements, ayurveda, herbs, yoga, fasting & exercise, not all in the medical community are convinced that this can be effective, as everybody would be happier if there were just one ‘pill’ which could reverse the disease.

I consider this an important book, especially since I am sure much of this is also sound advice for good all-round health, especially mental health, of course. A regimen well worth adopting, especially if you are in your 40s or later.

[Gina · Rating 1 out of 5]

This is a harsh rating, but feels appropriate.

The idea is that there are 36 factors that can result in dementia, and so dealing with those factors can reverse it, especially if you catch it early. The 36 sounds like a lot, and it is, but I don't automatically object to that. There can be a lot of complex interactions.

I did have an issue with some of the connections drawn, which seem a little iffy, not to mention trendy.

I have a bigger issue with the contradictions, like the book saying that there is no backup for metals being a cause of dementia, but you should try having mercury fillings removed. Okay, mercury can have toxicity issues (not necessarily for fillings, but fine), but then it is further specified that aluminum doesn't seem to contribute, yet one of the sample routines includes the elimination of aluminum from her deodorant.

In a way that makes sense, because the people who are most likely to jump on bandwagons of clean eating and pure living are the people who will be most drawn to this book. I also do not doubt that when people improve their nutrition and sleep that they do better in many ways. I do doubt that adding all of these supplements as you eliminate some pretty good foods is helpful.

I can almost excuse that everyone cheating on their diet - as determined by visiting health coaches - does not automatically rule out the connection between the protocol and their improvements, given that you might not have an issue with all 36 factors. However, that level of unverifiability, and the scare tactics that are used regarding stopping, and other factors feel like they are adding up to someone not improving just not having found the right essential oil yet, and if it doesn't work you just didn't try hard enough.

I might have given it two stars if it were just kind of scientifically shoddy, but the way it ended up being angered me.

A much better book along similar lines would be The Brain Fog Fix by Mike Dow, which covers similar ground with less pretension.

[Doris Jean · Rating 4 out of 5]

He has a program called ReCODE stands for “reversal of cognitive decline”. ReCODE means to change your lifestyle to recode your brain to stop or reverse Alzheimer's disease (AD). As I read the book, I thought it read as though two authors were collaborating, then at the end he thanked his team of three editor-writers and I think that this team did not work closely enough since the writing was choppy and inconsistent. For example, one section said 50 mg., and another said 100 mg. There were many diagrams and charts and some toward the beginning of the book were so confusing that they were incomprehensible. There were several parts in need of editing for clarity.

Chapter 1 addresses metabolic imbalance of 36 factors affecting AD. Chapter 2 says that the plaques and tangles of AD are a defense for the brain against the 36-factor imbalance. Chapter 3 relates symptoms of AD as recalled by patients who have improved enough to tell how they felt before they improved. Chapter 4 was how to give yourself AD – I would have omitted this chapter completely. Chapter 5 had diagrams of the neuron with plaques and tangles and explained "dependence receptors" and APP (amyloid precursor protein). He explained that APP is a "dependence receptor" (poor diagram, poor explanation) which can be enzymatically cut into either two or four pieces. The two-piece cuts are healthy, the four-piece cuts are Alzheimer's. APP is a prion and with beta-amyloid one gets a self-replicating prionic loop cascade – and Alzheimer's. Chapter 5 was a good chapter.

Chapter 6 was unclear, he is trying to define AD into four types: type 1, 2, 1.5 and 3 which did not make sense – editors? Chapter 7 talked of factors, supplements, advanced glycation end-products (AGE's - from sugar!), inflammation markers, insulin-degrading enzyme (IDE), hormone, thyroid, metals, antibody arrays, the blood-brain barrier, mitochondrial damage, testing, genetics (ApoE4/3), and antioxidants.

Chapter Eight is entitled "Reversing Cognitive Decline" - ReCode seems to be to take vitamin B 6,9, and 12 and trimethylglycine and avoid meat, nuts and beans which give the amino acid methionine which yields homocysteine which is inflammatory. This does not convince me.

Next, he has "DESS" which is diet, exercise, sleep and lack of stress. His "12/3" means one stops eating at least three hours before sleep, so no midnight snacks. The "12" part means that one waits at least twelve hours after the last meal of one day to eat breakfast the following day to help the body into the fat-burning stage of ketosis.

I have been reading many of the newer books on health and it seems that epigenetics is gaining respect. Many now encourage using food in a ketogenic diet to influence genes to improve health. In my opinion the useful information in this book boils down to change your lifestyle to guide your genes toward health. A ketogenic diet will lower insulin (which is being identified as an enemy of longevity because it shortens telomeres). This author also explains that insulin is needed in the brain to clear out sugar but there is an insulin-clearing enzyme (IDE) which is also needed to clear out the beta-amyloid plaques and the insulin will always get the enzyme before clearing the plaques. So high sugar means high insulin which means no enzyme left to clear out the plaques, it will all be used up on the sugar.

He demonizes gluten, but I think it's not only the gluten that is a problem – it's also the glyphosate (RoundUp) which is genetically inside the grain cell and sprayed on the outside of grains to dehydrate for a fast harvest. Glyphosate causes holes in body membranes (leaky gut and leaky blood-brain barrier) and molecules leak through these holes and go into places where they do not belong and cause inflammation and metabolic imbalances. He seems to be a vegetarian, he never recommends eating meat or butter. He recommends "wild-caught" fish which ARE FARMED fish caught in a net out of the fish farm in the ocean, they are NOT wild, but he doesn't seem to realize this. I do not think he means to recommend farmed fish which are not fit for food, they are fed poorly and dyed and genetically manipulated.

Chapter 10 is a summary recommending 1) reduce insulin, 2) reduce inflammation/infection, 3) balance hormones/nutrients, 4) reduce toxins/stress and 5) restore synapses. He didn't say how to restore synapses specifically. Chapter 11 is crutches for cravings: glutamine, MCT's (butter or coconut oil), and more happiness. So eat protein (for glutamine) and animal fat (butter, etc.) to curb cravings is the conclusion, but the author seems afraid to state this outright. Chapter 12 gave brands of supplements and websites. Appendix A gave more websites. Appendix B told about ketone meters. Appendix C told about 23andme for genetics. Appendix D was a fairly good chart summarizing store/forget (blastic/clastic) balance, APP, AD (a plasticity defense against lack of fat, too much glucose, toxins, failure of DESS) and ReCODE to balance the signalling.

This book has mostly useful information, some minor errors, weak editing, weak organization but I think anything that can help someone (especially from the disaster of AD) deserves an extra star, so I now changed my rating from 3 to 4 stars.

[Maureen Smith · Rating 5 out of 5]

This is one of the most important books I have ever read; and I will read it over and over again (in between loaning it out to others). It seems we all know someone who has been diagnosed with Alzheimer's Disease, so this should be a must-read for anyone who doesn't want to accept the current death sentence usually associated with it.
This was an advanced reader's copy, and I expected to find many editing mistakes, but I was pleasantly surprised to find an extremely well written and edited book. I think it would be easy to understand for the average lay person, yet is not boring for someone with medical knowledge.
Dr. Bredesen has been studying and documenting his amazing life work, that is no longer a theory; people have reversed their Alzheimer's Disease by changing their lifestyles.
Dr. Bredesen is sharing important information and is not selling you anything but the book. I already have a list of people who want to read my copy. I wish every medical person I know, every hospital and nursing home dietician, everyone who has a relative with Alzheimer's, and everyone over forty who cares about maintaining their optimal cognitive ability, would read this book.

[Donna · Rating 4 out of 5]

This book is Health & Science. This was between 3 and 4 stars but I'll round up for a few reasons. I've read more than a handful of books lately in this genre, covering all different approaches to our well-being. And this has got to be the first one that didn't feel like it was a giant soap box with agendas. The author covered a lot of material, but not once did he point the finger at someone else's book and put them down....he actually mentioned these other books in case the reader wanted more info on that particular line of thinking.

He made his points.....gave the research that supported it and moved on. At times he even mentioned the pros and cons of a certain food or supplements. Other authors never did that. So this was kind of refreshing. For that alone, I'm willing to round up.

Now this author is heavy on adding supplements. I'm personally not a fan of that when it is heavily relied upon. Sure if there is a deficiency somewhere ... great. But I did like his approach to eating better. Eat whole foods, mainly veggies....exercise....be mindful...and journal.

Overall, I enjoyed this one but here is one BIG cautionary note I'd like to mention. More than a few times, it felt like having a PhD would have been extremely useful in understanding what he was saying. He rarely paused to explain the plethora of acronyms and/or medical jargon. So 4 stars anyway.

[marie · Rating 3 out of 5]

I listened to the audio book and this is one case where I definitely recommend getting the actual paper version and read it since it would be a reference volume. This is far too technical for listening as there are long lists of supplements and their recommended doses being read out. So, my 3 stars is referring only to the audio version. Will change it when I get the hard copy.

[Designlover · Rating 5 out of 5]

THIS IS A GREAT BOOK !!!

Actually I had received the uncorrected proofs from the publisher,
but that version did not have an (all important) index or some of the graphics.
I ordered and received 5 copies of the hardback version of the book,
which I have distributed to friends.

Here is a review from University of Georgetown Professor, Dr Robert Hedaya, MD:
Dr. Bredesen has written the first comprehensive guide to preventing, halting, and reversing Alzheimer's Disease. It is a must read as it provides you with the tools necessary to understand what Alzheimer's disease is, how to prevent it, and how to treat it. I am a clinician who has been using these methods for more than 2 decades and I know the methods work. This book gives you the blue print you need. Since nearly all of us will be affected directly or indirectly by dementia, this book is required reading if you care about your health, or the health of your loved ones. Robert Hedaya, MD, DLFAPA

more:
https://www.wholepsychiatry.com/lette... /
Alzheimer’s Disease Letter to the Editor Wall Street Journal
Time for a Better Approach To Alzheimer’s Treatments
Alzheimer’s research has failed because of adherence to a flawed model.
April 16, 2017 12:32 p.m. ET


ONE IMPORTANT THING THAT WAS LEFT OUT OF THE BOOK:
Dr. Bredesen's outstanding resume:
http://www.eastonad.ucla.edu/about-us...
( look for it at the end of this review )
Reading this, convinced me Dr. Bredesen is the real deal, an unparalleled example of steadfast research and dedicated determination to find the contributing causes of this insidious disease.

I also spoke with the purchasing departments of the Los Angeles Public Library and the L.A. County Library (Science & Technology reviewers) highly recommending the book (sent email screenshots of some of the text). I am happy to report L.A. County already has 30 copies on it's shelves. LAPL is currently processing it into their system. You can put a hold on it now . . .

I also recommended it for the University of California libraries and the Hawaii State Public Library.

Please ask you local library to purchase it.

It is available in different formats: Hardcover, eBook and AudioBook CDs and downloadable.

Post your review after your read it . . . Pass it on to a friend . . .

Dr. Dale E. Bredesen
CV

http://www.eastonad.ucla.edu/about-us...
Visiting Professor of Neurology, Director of Neurodegenerative Disease Research, UCLA
Education, Training and Appointments
B.S., Biology and Literature, California Institute of Technology, Pasadena, CA, 1974.
M.D., Duke University Medical Center, Durham, NC, 1977.
Resident, Medicine, Duke University Medical Center, Durham, NC, 1978-1980.
Resident, Neurology, Chief Resident, UCSF, San Francisco, CA, 1980-1983.
Clinical Instructor, Neurology, UCSF, San Francisco, CA, 1983-1987.
Hughes Associate, Laboratory of Dr. LY Jan (Drosophila Neurogenetics) Howard Hughes Medical Institute, San Francisco, CA, 1985-1986.
NIH Postdoctoral Fellow, Laboratory of Dr. SB Prusiner (Neurodegenerative Disease) University of California, San Francisco, San Francisco, CA, 1986-1989.
Assistant Adjunct Professor, UCSF, Department of Neurology, San Francisco, CA 1987-1989.
Assistant Professor, UCLA, Department of Neurology, Los Angeles, CA, 1989-1994.
Associate Professor, UCLA, Department of Neurology, Los Angeles, CA, 1994-1995.
Elizabeth R. and Thomas E. Plott Chair, UCLA, Center on Aging, Los Angeles, CA 1993-1995.
Professor and Director, Program on Aging, The Burnham Institute, La Jolla, CA, 1994-1999.
Associate Adjunct Professor, UCLA, Department of Neurology, Los Angeles, CA, 1995-1997.
Associate Adjunct Professor, Neuroscience Department, UCSD, San Diego, CA, 1996-1998.
Adjunct Professor, Neuroscience Department, UCSD, San Diego, CA, 1998-2000.
Adjunct Professor, The Burnham Institute, La Jolla, CA, 1999-2005.
President and CEO, Buck Institute for Age Research, Novato, CA, 1999-2005.
President and CEO, Buck Institute for Age Research, Novato, CA, 1999-2005.
Adjunct Professor, UCSF, San Francisco, CA, 1999-present.
Scientific Director and CEO, Buck Institute for Age Research, Novato, CA, 2005-2006.
Director and CEO, Buck Institute for Age Research, Novato, CA, 2006-2008.
Professor and Founding President/CEO, Buck Institute for Age Research, Novato, CA, 2008-present.
Honorary Professor, Dominican University, San Rafael, CA, 2008-present.
Director, Mary S. Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, CA, 2013-2015.
Activities and Awards
1970, 1993-1997 Athletic Letters, Caltech (Football, Track)
1970-1974 Alfred P. Sloan Scholar, Caltech
1971 Research Assistant, Caltech (Dr. H. Gray, Inorg. Chemistry)
1972 Research Assistant, MIT (Dr. M. Wrighton, Inorg. Chemistry)
1972 Member, Board of Control, Caltech
1973 NSF Summer Fellow, Caltech (Dr. R. Sperry, Psychobiology)
1974 McKinney Prize for Humanities, Caltech
1974 Graduation with Honor, Caltech
1975-1977 Mary Duke Biddle Scholar, Duke
1977 Brody Scholar in the History of Neurosciences, Duke
1977 Trent Prize in the History of Medicine, Duke
1982 Chief Resident, Neurology, UCSF
1983 Scholarship Recipient, Cold Spring Harbor Neurobiology Seminars
1983 Sandoz Award for Outstanding Neurology Resident, UCSF
1984 Outstanding Faculty Teacher Award, UCSF
1992 Honorable Mention, UCLA Neurology Residents' Teaching Award
1992 Cotzias Award, American Parkinson Disease Foundation
1993-1995 Elizabeth R. and Thomas E. Plott Chair in Gerontology, UCLA
1996 Child Neurology Society Lectureship
1996 Lou and Eleanor Gehrig Lectureship, Columbia University (given for the most outstanding work on amyotrophic lateral sclerosis within the previous year)
1997 United Way Combined Health Agencies Health Hero (annual award for outstanding medical research in San Diego)
2000 Arthur Cherkin Award for Research in Neurodegenerative Disease, UCLA
2005 Gilman-Barbour Distinguished Lecturer, University of Michigan
2010 Editorial Board Member, JBC
2011 Associate Editor, J Alzheimer's Disease
2013 Turken International Lecturer, Neurology Grand Rounds at UCLA
2014 Steven DeArmond Lecture, American Academy of Neuropathologists, Portland, OR

Publications (selected peer-reviewed publications)
• Butterfield DA, Galvan V, Lange MB, Tang H, Sowell RA, Spilman P, Fombonne J, Gorostiza O, Zhang J, Sultana R and Bredesen DE. In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid beta- peptide of APP. Free Radic Biol Med 2010;48:136-144. PMID: 19854267; PMCID: PMC2818480
• Harris JA, Devidze N, Halabisky B, Lo I, Thwin MT, Yu GQ, Bredesen DE, Masliah E and Mucke L. Many neuronal and behavioral impairments in transgenic mouse models of Alzheimer's disease are independent of caspase cleavage of the amyloid precursor protein. J Neurosci 2010;30:372-381. PMID: 20053918; PMCID: PMC3064502
• Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D Richardson A, Strong R and Galvan V. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One 2010;5:e9979. PMID: 20376313; PMCID: PMC2848616
• Zhang J, Gorostiza OF, Tang H, Bredesen DE and Galvan V. Reversal of learning deficits in hAPP transgenic mice carrying a mutation at Asp664: a role for early experience. Behav Brain Res 2010;206:202-207. PMID: 19751769; PMCID: PMC2783897
• Sperandio S., Poksay, KS, Schilling B, Crippen D, Gibson BW, Bredesen DE. Identification of new modulators and protein alterations in non-apoptotic programmed cell death. J Cell Biochem 2010 Dec 15;111(6):1401-1412. doi 10.1002/jcb.22870. PMID: 20830744
• Bredesen DE, John V, Galvan V. Importance of the caspase cleavage site in amyloid-ß protein precursor. J Alzheimers Disease 2010;22(1):57-63. PMID: 20847422; PMCID: PMC3968071
• Descamps, O, Zhang, Q, John V, Bredesen DE. Induction of the C-Terminal Proteolytic Cleavage of AßPP by Statins. J Alzheimers Dis 2011;25(1):51-57. doi: 10.3233/JAD-2011-101857. PMID: 21422530
• Mehlen P and Bredesen DE. Dependence receptors: from basic research to drug development. Sci Sign 2011 Jan 25;4(157):mr2.
• Poksay, KS, Madden DR, Peter AK, Niazi, K, Banwait, S, Crippen D, Bredese DE, Rao RV. Valosin-containing protein gene mutations: cellular phenotypes relevant to neurodegeneration J Mol Neurosci 2011 Jun:44(2):91-102. PMC: PMC3084943
• Orcholski, ME, Zhang, Q, Bredesen DE. Signaling via amyloid precursor-like proteins APLP1 and APLP2. J Alzheimers Dis 2011:23(4):689-699. PMID: 21178287
• Robinson RA, Lange MB, Sultana R, Galvan V, Fombonne J, Gorostiza O, Zhang J, Warrier G, Cai J, Pierce WM, Bredesen DE, Butterfield DA. Differential expression and redox proteomics analyses of an Alzheimer disease transgenic mouse model: effects of the amyloid-beta peptide of amyloid precursor protein(Xi). Neuroscience 2011;177:207-222. PMID: 21223993; PMCID: PMC3058851
• Poksay KS, Banwait S, Crippen D, Mao X, Bredesen DE, Rao RV. The Small Chaperone Protein p23 and Its Cleaved Product p19 in Cellular Stress. J Mol Neurosci 2011;9574-9577. PMID: 21691801; PMCID: PMC3246043
• Zhang J, Rao RV, Spilman P, Mangada J, Xie L, Vitelli C, Gorostiza OF, Madden DT, Zeng X, Jin K, Hart MJ, Bredesen DE, Galvan V. Endogenously EGFP-Labeled Mouse Embryonic Stem Cells. Aging Dis 2011;2:18-29. PMID: 21874159; PMCID: PMC3160738
• Madden DT, Davila-Kruger D, Melov S, Bredesen DE. Human Embryonic Stem Cells Express Elevated Levels of Multiple Pro-Apoptotic BCL-2 Family Members. PLoS One 2011;6, e28530, 10.1371/journal.pone.0028530 PONE-D-11-19250. PMID: 22174832; PMCID: PMC3235131
• Libeu CP, Poksay K., John V, Bredesen DE. Structural and Functional Alterations in Amyloid-B Precursor Protein Induced by Amyloid-B Peptides, J Alzheimers Dis 2011;25:547-566. PMID: 21471643; PMCID: PMC4001850
• Rao R, Patent A, Zhang Q, Flores S, Bredesen DE. Cellular effects of APOE4: Implications for Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011;7:S569.
• Libeu CP, Descamps O, Zhang J, John V, Bredesen DE. Altering APP proteolysis: increasing sAPPalpha by targeting dimerization of the APP ectodomain. PLoS One. 2012;7(6):e40027. doi: 10.1371/journal.pone.0040027. PMID: 22768208; PMCID: PMC3386930
• Choi SW, GA, Ng R, Flynn JM, Melov S, Danielson SR, Gibson BW, Nicholls DG, Bredesen DE, Brand MD. No consistent bioenergetic defects in presynaptic nerve terminals isolated from mouse models of Alzheimer's disease. Journal of Neuroscience 2012;32(47):16775-16784. doi: 10.1523/JNEUROSCI.2414-12.2012. PMID: 3175831; PMCID: PMC3736741
• Rao R, Descamps O, John V, Bredesen DE. Ayurvedic medicinal plants for Alzheimer's disease: a review. Alzheimers Res Ther 2012 Jun 29;4(3):22. doi: 10.1186/alzrt125. PMID: 22747839; PMCID: PMC3506936
• Rodríguez Plaza JG, Villalón Rojas A, Herrera S, Garza-Ramos G, Torres Larios A, Amero C, Zarraga Granados G, Gutiérrez Aguilar M, Lara Ortiz MT, Polanco Gonzalez C, Uribe Carvajal S, Coria R, Peña Díaz A, Bredesen DE, Castro-Obregon S, Del Rio G. Correction: Moonlighting peptides with emerging function. PLoS One 2013;8(10). doi: 10.1371/annotation/fc687f18-ce8e-4704.... eCollection 2013. PMID: 24194802; PMCID: PMC3806584
• Sultana R, Robinson RA, Lange MB, Fiorini A, Galvan V, Fombonne J, Baker A, Gorostiza O, Zhang J, Cai J, Pierce WM, Bredesen DE, Butterfield DA. Do proteomics analyses provide insights into reduced oxidative stress in the brain of an Alzheimer disease transgenic mouse model with an M631L amyloid precursor protein substitution and thereby the importance of amyloid-beta-resident methionine 35 in Alzheimer disease pathogenesis? Antioxid Redox Signal 2012;17(11):1507-1514. PMID: 22500616; PMCID: PMC3448937
• Poksay KS, Banwait S, Crippen D, Mao X, Bredesen DE, Rao RV. The small chaperone protein p23 and its cleaved product p19 in cellular stress. J Mol Neurosci 2012;46(2): 303-314. doi: 10.1007/s12031-011-9574-7. PMID: 21691801; PMCID: PMC3246043
• Bredesen DE, John V. Next generation therapeutics for Alzheimer's disease. EMBO Mol Med 2013;5(6):795-798. doi: 10.1002/emmm.201202307. PMID: 23703924; PMCID: PMC3779441
• Descamps O, Spilman P, Zhang Q, Libeu CP, Poksay K, Gorostiza O, Campagna J, Jagodzinska B, Bredesen DE, John V. AbetaPP-Selective BACE Inhibitors (ASBI): Novel Class of Therapeutic Agents for Alzheimer's Disease. J Alzheimers Dis 2013;37(2):343-355. doi: 10.3233/JAD-130578. PMID: 23948888; PMCID: PMC3971881
• Zhang J, Spilman P, Chen S, Gorostiza O, Matalis A, Niazi K, Bredesen DE, Rao RV. The small co-chaperone p23 overexpressing transgenic mouse. J Neurosci Methods 2013;202(2):190-194. doi: 10.1016/j.jneumeth.2012.09.022. PMID: 23022695; PMCID: PMC3562756
• Theendakara V, Patent A, Peters-Libeu C, Philpot B, Flores S, Descamps O, Poksay K, Zhang Q, Cailing G, Hart M, John V, Rao R, Bredesen D. Neuroprotective sirtuin ratio reversed by ApoE4. PNAS 2013;110(45):18303-18308. doi: 10.1073/pnas.1314145110. PMID: 24145446; PMCID: PMC3831497
• Spilman P, Descamps O, Gorostiza O, Peters-Libeu C, Poksay K, Matalis A, Patent A, Rao R, John V, Bredesen D. The multi-functional drug tropisetron binds APP and normalizes cognition in a murine Alzheimer's model. Brain Research 2014;1551:25-44. Issue Cover. doi:10.1016/j.brainres.2013.12.029. PMID: 24389031; PMCID: PMC4001856 [Available on 2015/3/10]
• Zhang Q, Descamps O, Hart MJ, Poksay K, Spilman P, Kane D, Gorostiza O, John V, Bredesen DE. Paradoxical Effect of TrkA Inhibition in Alzheimer's Disease Models. J Alzheimers Dis 2014;40(3):605-617. PMID: 24531152; PMCID: PMC4091737
• Galluzzi L, Kroemer G, Bredesen DE, et. al. Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ 2015;22(1):58-73. PMID: 25236395; PMCID: PMC4262782
• Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging 2014;6(9):707-717. PMID: 25324467; PMCID: PMC4221920
• Zhang Q, Du G, John V, Kapahi P, Bredesen DE. Alzheimer's Model Develops Early ADHD Syndrome. Journal of Alzheimer's Disease, 2014 May. (Submitted)
Chapters
• Bredesen DE. (2010) BACE, APP Processing, and Signal Transduction in Alzheimer's Disease. John, V. (ed.), BACE: Lead Target for Orchestrated Therapy of Alzheimer's Disease. John Wiley & Sons, Inc., Hoboken, NJ, pp. 1-14.
• Bredesen DE. Role of Programmed Cell Death in Neurodegenerative Disease. Reed, J.C. and Green, D. (eds.), Apoptosis: Physiology and Pathology of Cell Death. Cambridge University Press, New York.
• Bredesen DE. Prionic Loops, Anti-Prions, and Dependence Receptors in Neurodegeneration, Prusiner Beitrag 2013.
• Jagust W, Bredesen DE, Campisi JC, Lithgow G, Vijg J. Molecular and Cellular Biology of Aging (2013) in press.

[Elizabeth (Alaska) · Rating 5 out of 5]

I picked up this book a few years back and let it languish on my virtual shelves. I did not think then (nor do I now) that I'm headed for Alzheimer's, but the idea that that dreadful disease could be prevented or reversed was marvelous and I wanted to know more about it.

I have become aware that my memory isn't as good as it once was, but not awful. Some days are better than others. From this book I can self diagnose early subjective cognitive impairment. I very occasionally have to search for a word and other things. I know clearly that on those days when I am even somewhat sleep deprived, I could easily tape a sign to my forehead "I am stupid". I can look back to some of those days and understand why some nights I have trouble either getting to sleep or waking for 2-3 hours in the middle of the night. A lack of exercise and a lack of good nutrition will take their toll.

This is the first stage of decline. The second stage is called mild cognitive impairment (example given was a woman who had trouble remembering which was the correct freeway off-ramp) and then finally Alzheimer's. Bredesen tells us that Alzheimer's is not a single disease and that there are three main aspects: inflammatory, suboptimal levels of nutrients and other synapse-supporting molecules, and toxic exposures. That stuff we've always learned about sticky amyloid substances comes from a natural and necessary brain process run amok.

Bredesen recommends a whole host of medical tests, including the normal blood tests with which most of us are familiar. Not everyone arrives at dementia or Alzheimer's by the same path. I guess as varied as is the human species, we should not be surprised at that. Bredesen developed a program to help us both prevent and reverse dementia. But we need to start early because the longer we allow ourselves to decline the harder it is to get well.

Bredesen's program is much more than about getting a good night's sleep. Inflammation, for example, can come from several sources, even as simple as needing to see the dentist. With the "American diet" few of us are actually getting the full complement of needed nutrients regularly. Toxicity is harder for me to pinpoint, but it could be as simple as air pollution for those who live in cities or more difficult to identify if from household mold.

There is a lot of science in this book. Success has been accomplished by many who have followed the program. I admit that some of it went over my head. In other places I stopped to do a quick Google check and get some of the terms presented somewhat differently. Because it is so dense and because I felt that much of it didn't apply, I might be tempted to give this only 4-stars. But the entire conclusion is too important to slight it. And besides, I think I might find myself rereading.

[Rosemary Ward · Rating 5 out of 5]

Before summarizing Dr. Bredesen’s matchless research on treatment protocols for aggressive cognitive decline, I need to recap where we stand as a country in the face of this disease, which threatens the stability of our medical systems, our communities, and our family units.

We all know someone who has survived cancer, but no one knows a single person who has survived Alzheimer’s. There is no treatment for it. After a diagnosis, there is a clear message conveyed – You are not going to get better. This is the beginning of the end. It will probably be awful.

In America, only two medications are currently prescribed to “slow the decline of neural degeneration”. (Everything else offered is a knock-out pill of one kind or another.) If you know someone in the throes of neural degeneration, you also know that slowing things down and prolonging the exquisite decimation of this human being’s neural real estate, is no blessing.

No new Alzheimer’s drug has been approved since 2003. That’s 15 years of nothing. We are making great strides in cancer and in molecular biology, generally. Meanwhile, death by dementia is rapidly increasing. It robs victims of their humanity – sometimes over decades – it terrorizes and bankrupts their families, and we have no effective treatment. What? While the technology industry makes startling advances in Artificial Intelligence almost weekly, we have stood by and watched the human intelligence of our seniors wither away appallingly. This situation seems ghoulish to me.

You have likely heard neuro-specialists parroting the amyloid plaque hypothesis. In fact, only those toeing the amyloid line can get funding for their research. Meanwhile, amyloid plaque is also found in the brains of perfectly healthy individuals. Amyloid is only one piece of a very complicated puzzle. Scientists and doctors investigating the root causes of cognitive decline and braving the icy waters of non-amyloid based research are mostly ignored.

In this book, Dr. Bredesen addresses the other pieces of the dementia puzzle and lays out his protocol, which has helped many hundreds of people reverse their cognitive decline.

This book is 70% understandable to the average reader (like me) and 30% rather technical and sciencey. There were two chapters I had to read twice and, yes, I took notes. His protocol is rooted in lots of common sense but there are many supplements he recommends, after the patient has had extensive blood work done so that there is a detailed, personalized blueprint of the patient’s overall metabolic flexibility (or lack thereof). He connects his reader with support groups (which I have visited) where extensive help is offered in determining your cognitive health – his calls this a “cognoscopy”.

My best take-aways:

1. Exercise almost every day. Sweat. Make it count. 30 to 45 minutes. This stimulates BDNF (brain-derived neurotrophic factor) which supports new neuron growth.
2. Stop eating sugar. It is poison for neurons.
3. Protect your sleep. 7 to 8 hours of quality sleep is imperative.
4. Vitamin D3!!! Take it. (Or, be outside in the sun without sunblock every day, if possible. No, not for hours. No, don’t let yourself fry.)
5. Fresh, organic vegetables with every single meal, and lots of them.
6. Lots of good fat – coconut oil, avocados, fatty fish (like salmon), nuts, and grass fed beef or chicken, but in small servings
7. Eliminate gluten.
8. Get your BMI in a good range.
9. Exercise your brain by challenging yourself, move around throughout the day, and get out and socialize.

The supplementation he recommends is rather extensive and it is keyed to your health blueprint. You need to follow through on extensive bloodwork in order to know exactly how much inflammation your body (hence your brain) is dealing with and where you stand with insulin sensitivity. These two things – inflammation and insulin senstitivity – are dire enemies of cognitive health. And environmental toxins….he spends plenty of time talking about this, too.

He urges those with cognitive decline to try to maintain a mild state of ketosis by eating lots of fat, some protein, but very little carbs. This makes the brain use fat as its main source of energy, which optimizes cognitive health. This is a widely-accepted practice and many people without any cognitive decline at all eat a ketogenic diet for better performance in life.

Dr. Bredesen’s entire program is called ReCODE (Reversing Cognitive Decline). His results, which he details in the book, have been astounding. I have personally joined some of the online groups using his protocol – it is the real deal. It does not look easy. It looks like a big commitment. It looks like work.

In chatting with one of my kids about this, he said: “Well, easy choices – hard life. Hard choices – easy life. Right?” Right….

If someone you love is battling cognitive decline, read this book. Take action. Take control of the situation for him or her. Do all that you can. Do not wait for a new drug because anything new is going to be targeting only ONE of the many things which cause cognitive decline. You want a solution with addresses the whole mess.

[Becky · Rating 3 out of 5]

Have utmost respect for Dr. Bredesen and the research he has done. I am thrilled that there is a method to address Alzheimer’s but in my opinion this book is too difficult to understand, making the program unwieldy for most people. I appreciate that he uses analogies to express difficult topics and that not everyone wants to understand the details. But, the list of tests that he recommends is very confusing - there is no clear list that I can take to my physician to request these tests. The reader has to discern the actual test name from with in the text.

I believe that in order to follow the ReCode protocol I would need the help of my doctor to order the tests and understand the results. Unfortunately I don’t see that happening, I wouldn’t know what to ask my primary care physician for and I expect she might dismiss my interest. Since I don’t currently have any symptoms and don’t have the ApoE4 variant, it will be difficult for me to take any specific actions without some guidance.

I certainly hope that more doctors and practioners read this book and make the approach more mainstream. That is what is needed for this to take hold and help so many people in need.

[Ms. Reader · Rating 5 out of 5]

I received this book from Goodreads First Reads in exchange for an honest review...

A very important and powerful book, that is a huge eye-opener. Strongly recommend everyone reading it, even if you don't know anyone personally who suffers from Alzheimer's.

[Repix Pix · Rating 1 out of 5]

Indecente usar los sentimientos así.

[Brendon Gray · Rating 1 out of 5]

https://www.ucsf.edu/news/2020/05/417...

[Frederick Gault · Rating 5 out of 5]

There is a lot of good common sense life-style advice that everyone should do. EG: exercise, don’t smoke, get your BMI to a good place, eat less meat and more veggies, reduce stress, reduce sugar, etc. Just THAT would improve the lives of most people. I thought his model with 36 different routes to the APP Protease enzyme snipping in a blastic vs clastic mode was explained well and was backed up by hard science. I do kind of understand why the FDA balks at a multi-modal clinical regime in the typical 3 phase trial, there are just so many variables based on epidemiology that it is difficult to say with absolute certainty what mechanisms are in play. That being said, how DOES one test his hypothesis? I suspect that his book is based on his pique at being shot down by the Australian equivalent of the FDA. In time, clinical data will have to be teased out of studies that are not conducted in the 3 phase approval model. My friend a PhD microbiologist will tell you that it is only worth testing one mechanism at a time . . . I’ve had arguments with him about this . . . why not collect data without complete mechanistic understanding?

I like the idea of checking hormones, glucose, vitamins, heavy metals and tailoring a treatment schedule. It is just a more comprehensive process than what your typical clinician (i.e. Insurance Company death panel) will approve. Where I have to start disagreeing is his advocacy of so many herbal remedies. The science behind and purity of that stuff is suspect. The right thing to do would be to set up double-blind studies of each product with purity assays and prove that they do something positive. Naturally, that ain’t gonna happen anytime soon. Big Pharma can’t make money off supplements so they won’t finance the studies and the providers of supplements don’t need to do the studies, even if they can afford to, because their market doesn't insist on this kind of data.

That means I think the process is solid, the supplements, more suspect. I think my wife and I are going to try and find one of these practitioners and go through the blood work/treatment model . . . the herbs I may reserve judgement. Two exceptions on the supplements; Resveratrol and Curcumin have SOME good studies that seem to support their usage. Vitamins are in-between with their use subject to blood work that shows you really need them. Vitamins are subject to hype and can be harmful. The data available for vitamin C seems to support it not doing anything unless you have scurvy.

[Natali · Rating 5 out of 5]

I picked this up for extra research for a project I was working on and I am so glad that I did! If this doesn't inspire you to a healthier lifestyle, I just don't know what will! This doctor's research is fascinating and refreshingly holistic. It is very east-meets-west - western medicine meets eastern healing. I hope that this catches on so that we can arm people with the tools to avoid this painful disease, which has claimed two of grandparents' lives.

The doctor introduces the word "dementogens," which is like a "carcinogen" for brain health. It refers to things that lead to cognitive decline such as a diet full of gluten and sugar, high exposure to toxins, chronic inflammation, and head trauma. These are things we have a measure of control over. I do encourage reading this book so that you can commit to the best health that you possibly can and help reverse any cognitive decline you may be suffering in your own family.

[kimera · Rating 5 out of 5]

Deep bows and respects

[Robert Luebke · Rating 5 out of 5]

This is a must read for anyone who fears the threat of getting Alzheimer's. Dr. Bredesen is a neurologist and researcher who lays out a plan called RECODE for preventing and even reversing some of the symptoms of Alzheimers. Nutrition plays a big role in his program, but the stories of patients who have improved from Dementia after being on this program is very promising.

[Carol Bakker · Rating 4 out of 5]

I have SO much to write about this book, but no time.

For so long, type 2 diabetes was framed as an incurable, progressive disease. We now know that it is a metabolic disease the responds beautifully to dietary changes to lower insulin. Similarly (but with far more complexity) Alzheimer's disease responds to lifestyle changes and supplements.

This is a book of hope, and if dementia is part of your family history I highly recommend giving it a read. A few chapters almost swamped me with the science, but there are many many many good ideas. It's complicated: not one disease, but three. Not monotherapy (the one pill that fixes all) but a multilevel approach.

My principle for any therapy/change is: If it can't hurt, why not see if it helps? For example, dental hygiene is a risk factor. Oil pulling (swishing coconut oil in mouth for three minutes) sounds woo-woo, but it can't hurt and may help.

No time, but there I just wrote three paragraphs!

[Payal Sachdeva · Rating 5 out of 5]

Read this awesome book ..Alzheimer’s disease (AD) has become part of the zeitgeist. Millions are devoured by this draconian disease and once one gets sucked into the blackhole of AD, the life becomes grim, doomed and there is unrelenting descent into a mental abyss and decline , depriving the human from its very identity; emotionally, mentally and physically. It affects not only the patient but even the family and caretakers .
Earlier it was considered to be the disease of old age but as said rightly , diseases don’t follow the books , AD has started affecting the people as young as 40, all thanks to sedentary lifestyle , high sugar and carbohydrate diet, diabetes , stress , lack of sleep and exercise .

Dr Bredesen is the professor of neurology at the university of California , and he has been working on AD for decades and he explained beautifully how humans get AD and ways to keep it at bay .

As thought earlier that AD results due to accumulation of amyloid beta plaques in the brain , leading to mental confusion, MCI And SCI ( mild and subjective cognitive impairment) but it is not so , amyloid has been vilified for the decades Like cholesterol , infact both are important for the body . This disease occurs just like diabetes , hypertension, cancer , obesity and can be prevented or treated just by incorporating simple lifestyle modifications.

Readers who have read Jason Fung’s , obesity code and diabetes code , would love reading this book.

The worst part is ,this disease starts insidiously and it takes atleast 8-10 years to manifest the full blown Decline , and people tend to hide the symptoms , considering them as part of the aging , stress , fuzzy senior moments. Anyone above 40 should follow simple regimen to keep this at bay .

This book gives the reader a multi pronged approach , yet simple , to prevent this disease and I found the content pertinent. The discussion flouts decades of conventional wisdom , that it cannot be avoided and treated . Time to unlearn this dogmatic assertions .
I highly recommend this book.
I have read Fung’s , obesity code, diabetes code, cancer code , the complete guide to fasting , life in the fasting lane ; Gary Taubes good calories , bad calories … what is common in all the books is the importance of intermittent fasting and sleep.

AD occurs due to consumption of sugar and processed carbohydrates, dairy , lack of sleep and exercise , all leading to rise in insulin , leading to insulin resistance and brain atrophy . There are various ways to diagnose this disease , simple being MRI and PET scan .

Lack of deep sleep for 8-9 hours is the major culprit for diabetes , cancer and AD, as sleep induces ketosis, which helps in overall well being of human body and mind .

Dale has made some appendices as what should be done and what not to eat ; mainly stressing on intermittent fasting , avoiding sugars and carbs , one hour daily walk or exercise , avoiding dairy , use of probiotics and few supplements, good dental hygiene and flossing , and the most important being good uninterrupted sleep of 8-9 hours .

This disease can affect anyone of us but the people who have genetic risk factors have ten fold increase to acquire this disease . No one is impervious to it , so Time to take care of our health .

People who read daily our less likely to develop AD, as neurons are always active so less chance of neuron death 😊

[Ann · Rating 5 out of 5]

Please read this book.
If you, or anyone you care about, suffers from any form of cognitive decline — or even if you or a loved one has a family history of cognitive decline — I implore you to read about Bredesen's ReCode protocol.

Personally dealing with a loved-one's cognitive decline, I have seen the traditional approach's lack of support, hope, or help. As Bredesen says, the traditional approach is pretty much, "there's nothing that can be done." But, Bredesen outlines why this is no longer true. He details the science behind his approach to reversing cognitive decline (yes, not just halting, but reversing!). But he also includes case studies and personal stories for those of us without medical degrees.

For my very non-medical summary: the basis of Bredesen's approach is that there is not one sole cause of cognitive decline. Therefore, it cannot be reversed with one drug (at least, not at this time). Cognitive decline is caused by a number of factors that, when there are enough of them, tilt the scales too far to the wrong side. Once this happens, the brain produces more of the cognitive decline causing amyloid. And, the more amyloid the brain produces, the more decline it creates... which causes the brain to produce more amyloid. It's a downward spiral — unless you can chip away at those amyloid-creating factors and tip the scales back in your brain's favor. Which, as Bredesen details, can be done.

Do you have to read and understand the few technical chapters in the book? No. But I found them incredibly helpful to understanding the reasons behind the protocol outlined in the rest of the book. So, I would suggest you not be daunted by the technical chapters. I set aside plenty of time to read, reread, (and reread again if necessary) each paragraph so that I was sure I was understanding — to the best of my ability — what is actually happening within the brain. Again, you don't have to read these chapters to understand the rest of the book, but I think taking the time to digest the science made it easier to understand the protocol.

While my loved-one has not yet completed the entirety of the Bredesen protocol, I have seen the positive effects of aspects of this protocol first-hand. There is truth in this book. There is hope.

Please, please, please read and share this book and this approach, with yourself, your loved ones, and your doctors.

[Molly Ferguson · Rating 5 out of 5]

This book really changed the way I think about cognitive decline and what can be done to address it. I want to put it in the hands of several people in my life who may be resistant to it. It's clear, easy to read (he even tells you which are the two jargon-filled chapters and gives you permission to skip them), yet science-based. I especially appreciated that the book is full of 1.) examples from people's lives, and 2.) exactly what you need to do to follow the ReCODE system. Here's the thing: some of the parts of the system I already do, and other parts are *really* hard for me to follow--I will need to do a lot of changing of my lifestyle to follow them. For example, I do sleep well and exercise, but no way in hell do I (or do I want to) do the 12 hour ketosis period. I've always felt the keto diet was disordered eating, but this book might have changed that for me--it has a pretty good argument for why you should be in mild ketosis before you eat your first meal. There are other things that I feel like I can incorporate into my lifestyle with just a little effort, like brain games and reducing blue light and limiting dairy/gluten. If I start experiencing decline, I really think my first line of defense would be following this strictly, at least to try it. If you know anyone having difficulty with memory and focus or who has the APO4 gene, maybe direct them to this book!

[Jim Angstadt · Rating 4 out of 5]

The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline
Dale Bredesen

If you or someone you know has Alzheimer's then this book can be a very worthwhile read. Roughly the first half of the book is devoted to a medical and research understanding of the symptoms and causes. There is a lot of science here. For example, the Food and Drug Administration rejected a proposed drug trial because it didn't fit the notion of one drug to fix one problem. As the author points out, Alzheimer's has many problems and medications; the interaction of each can vary between individuals.

The second half of the book is much easier to understand and follow, but be warned. The recomended treatment will require major changes to one's medications, diet, exercise, and maybe sleeping patterns.

[Peter McCluskey · Rating 5 out of 5]

Alzheimer's can be at least postponed for years in most people, and maybe fully cured.

The main catches: It only works if started early enough (and Bredesen only has crude guesses about what's early enough), the evidence is less rigorous than I'd like, and it's not a medical treatment, it's a quantified self approach on steroids ketones.

My guess is that the book is roughly 70% correct. If so, that's an enormous advance.

The protocol involves more tests than I want to count. These are almost entirely tests that are standard for some health-related reason. Bredesen suggests small changes to how to interpret those tests, and large changes to how much we should value optimizing the things they measure. It's a strategy that says "normal" health is unacceptable, we need to do better. This part of the protocol seems to be backed by decent research indicating that we should expect some sort of health benefits from it. Most biomarkers are less reliable than is commonly reported, but as long as they point in the right general direction, it's better than not to improve them.

The protocol also includes an even larger set of ideas about how to optimize those biomarkers via lifestyle changes, vitamins, supplements, and maybe prescription drugs for a few people. Here, Bredesen appears to be using a much wider mix of science and fads. E.g. there's plenty of evidence that exercise is healthy. But for bone broth, he cites an article from mercola.com that's rather weak about providing evidence for bone broth's benefits. As these examples suggest, the protocol is probably safer overall than the average American lifestyle, even if a few parts do a little harm.

And we only need to trust him a tiny bit about the interventions he recommends, because he advises us to check carefully whether those interventions improve the biomarkers.

2.

How plausible is it that a complex set of interventions work where single interventions have consistently failed? My understanding of Bredesen's model implies that careful tests of individual interventions should show small benefits.

Wait a minute! Bredesen didn't actually say that single interventions have failed! He said that single drugs have failed.

So I did a little research. Wikipedia pointed me to evidence about exercise, including a small RCT which shows important benefits (but needs many caveats). A bit more searching, and I find an RCT of B-vitamins showed some benefit, and this paper says that benefit happened mainly in people with adequate Omega-3s. I've already blogged about zinc and copper, where a small RCT showed weak evidence of benefits. Overall, single interventions seem to have better evidence than Bredesen led me to believe. Where are the large-scale trials that would be prompted by this evidence if we had a medical community that cared about preventing Alzheimer's?

3.

My initial impression of the book was that it's too good to be true. So, how could its most important claims could be wrong?

- Could he be intentionally dishonest? There's no foolproof way to discredit this hypothesis, but also little reason to think it's more likely than with typical research. He's virtually guaranteed to attract more scrutiny than most - that would be a strange strategy to pursue if he had something to hide.

- Could he be cleverly only accepting patients who mistakenly think they're developing Alzheimer's? If true, this would imply that he has some pretty unusual skills, and that there are serious problems with how some other doctors diagnose dementia. I can't rule out this hypothesis.

- Could he be selective reporting only the good results? I can see how he might be overstating the benefits this way, but I don't see how it could explain his results if there were no benefits.

- Could he be measuring dementia poorly? There's a weak sense in which most of the measurements are subjective. Maybe a professional poker player with a diagnosis of mild cognitive impairment could be mistaken about whether his poker improved. But his case studies include some pretty strong claims, including one report of a big increase in hippocampal volume measured by MRI, and one patient whose neuropsychologist advised him to "wind down his business and plan for the full-time care he would soon need". Two years later that neuropsychologist measured the patient's memory as having improved from the 3rd, 13th, and 24th percentile on three tests to the 84th, 79th, and 74th percentile, and the patient expanded his business.

Those seem to be stretching the limits of what I can believe for measurement error.


Many people have strong priors about Alzheimer's which lead them to find Bredesen's claims less plausible than these hypotheses, based on past experiences with Alzheimer's "cures", plus stereotypes about what approaches to disease work.

Those priors might make some sense if researchers had tried many independent approaches. But it looks to me like the failure of most Alzheimer's research can be explained by a small set of problems: reliance on rodent models, when hindsight tells us that Mouzheimer's has different causes than Alzheimer's. The inadequate exploration of different paradigms can be explained by an ordinary amount of groupthink plus bias toward approaches that support continued funding of areas that existing experts know best.

So it's not wildly implausible that someone could find the equivalent of a trillion dollar bill (or maybe a ten billion dollar bill if he has overstated the benefits a lot). It's not as if the bill was in plain sight - it's more like it was torn into dozens of pieces, and hidden in leaves.

4.

What causes the widespread reluctance to adopt the kind of functional medicine that Bredesen advocates?

- Often patients wouldn't do anything valuable in response to most of the tests that he suggests. I don't expect doctors to like detecting suboptimal health and then watching helplessly as patients continue the lifestyle that caused the problem. Why would patients fail to follow the protocol? Partly because things like pizza and cookies are somewhat addictive. Partly because there are important social costs to admitting that we're not healthy enough to eat at a typical restaurant or party. [1]

- These tests are mostly not patented, done by markets that are competitive enough that no company would get much from marketing them, and combined with FDA restrictions on marketing that require expensive evidence if anyone wanted to market them.

- Status quo bias (it's hard to find other explanations of why people don't switch to cholesterol tests that focus on the harmful forms of cholesterol).

- Functional medicine is associated with some conspicuously reckless doctors. (Mainstream doctors are sometimes reckless - not washing their hands, or saying that patients can't do anything about Alzheimer's, when they could say something like "regular exercise may improve your odds". Somehow those mistakes stay less conspicuous than functional medicine's recklessness.)


I'm unclear what the current reaction is from mainstream Alzheimer's researchers. Bredesen seems to have gotten a mix of help and hostility in the past from mainstream institutions. The Buck Institute (of which Bredesen is the founding president) gets a good deal of NIH grant money, and he doesn't appear to have trouble publishing peer-reviewed papers related to his Alzheimer's ideas. But IRBs denied him permission to conduct a trial that involved an early version of his protocol (because it would have tested too many things at once).

That mainly seems like additional evidence that IRBs are unethical. It's quite possible that his protocol hasn't been stated clearly enough to qualify as a set of scientific hypotheses, and that it might end up testing some mix of articulated hypotheses and also the skills of the people involved [2]. If that was the IRB reasoning, it seems like a really awful reason for rejecting a trial. Even if it mostly ended up testing doctor's skill at giving advice, a positive result would falsify the claim that Alzheimer's cannot be prevented, cured or even slowed. [3]

5.

Bredesen presents a nonstandard biochemical model of Alzheimer's. I'm not sure what to make of it. It doesn't seem particularly helpful for understanding why the protocol works. It does explain why the simple amyloid-beta hypothesis is wrong, but it's hardly the only hypothesis to explain that.

He classifies Alzheimer's into three semi-distinct subtypes. I'm fairly convinced that Alzheimer's refers to more than one disease, but I don't get the impression that anyone knows how many subtypes can be usefully identified.

6.

Bredesen seems confused about the diet that humans evolved to eat. "[H]umans evolved to handle only small amounts of sugars (about 15 grams per day", and his figure 10 says that humans had a low-carb diet for the 7 million years before agriculture (and what does "God Gene" mean?). We don't have good evidence about human diet over that period, but it looks pretty likely that humans relied mainly on fruit during the early part of that period, and relied on high-carb roots during some parts of that period. Some modern hunter-gatherers (Hadza) eat way more honey than that 15 gram limit would allow.

Maybe American lifestyles create a need for that strict limit, but that need isn't inherent in our biology.

While evidence from hunter-gatherers weakens some of Bredesen's specific advice, it strengthens his claim that Alzheimer's depends on lifestyle choices: there's moderately good evidence that hunter-gatherers don't get adult-onset dementia [4].

7.

The book has somewhat inadequate warnings for people who want to wait until they get more severe symptoms: readers might imagine that a delay in implementing the protocol will just make recovery slower and/or more expensive. NO!! The protocol is already pushing the limits of what we have the mental capacity to implement (in some people; the difficulty will vary unpredictably from person to person). Delaying until the symptoms become noticeable makes it harder to learn new habits, harder to track whether you've taken the right pills, harder to prepare new recipes, etc.

8.

What do I expect if he's right?

I expect an expanded number of doctors using his protocol over the next few years to reach something like 10,000 people who are at risk of Alzheimer's. I expect a similar number of patients to see doctors who doctors who try to follow the protocol without being trained by a Bredesen-approved teacher. I expect these doctors to report widespread improvement in these patients, and I expect those reports to be controversial due to risks such as selective reporting. I expect these doctors to report that around 30% of patients didn't comply well enough to get good results.

I expect some sort of clinical trial to be completed within three years, using an algorithm that implements something like 75% of the advice described in the book. I expect it to report results that look about 1/4 as impressive as this book reports, with a bit less that half the patients complying fully with the protocol.

I recommend that the trial be evaluated in two separate steps: a test for biomarker improvement, and test for cognitive changes given some pre-specified biomarker improvement. My hope is that will distinguish problems with patient compliance from issues of how improved biomarkers affect dementia.

I'm unclear how the average doctor will react after those trial results are released. But among doctors that are relatively open to new ideas, I expect a profusion of competing protocols, with poorly documented claims about how well patients comply with the protocol.

I expect that as the number of patients using these protocols exceeds 100,000, patient compliance will drop to about 50% for the most effective protocols (the earlier patients were way more motivated than the typical patient).

I expect that by around 2023 to 2025, at least half a million patients will use one of these protocols, and that will be sufficient to a decline in the overall number of people developing Alzheimer's.

Conclusion

The book seems slightly careless about details such as citing good references, as if it were rushed to print (rushing does seem appropriate). I suspect he exaggerates the benefits.

He errs slightly in the direction of allying too much with alternative medicine. Mainstream medicine has some major flaws, but it's still important to persuade mainstream institutions to listen to the book's ideas.

But it's good enough to persuade me to experiment with significant changes to my diet and supplements, and maybe enough to convince me to donate to the Buck Institute.

Footnotes

[1] - the book won't tell you directly whether it's safe for you to eat at restaurants and parties. It will tell you how to get evidence about whether those are safe for you.

[2] - the book outlines the protocol well enough that a highly motivated person will usually be able to follow it, but it doesn't look like a complete algorithm. E.g. my current guess is that the book doesn't include enough advice to get my sdLDL down to good levels. But the book did get me to look at apoe4.info, and find ideas that seem more directed toward my situation.

[3] - That's from the top result in my Google search for Alzheimer's. That page has an automated(?) list of recent news headlines. These two showed up on the same alz.org page as the "cannot be prevented" claim when I visited it:
Healthier living could reduce worldwide dementia by a third, report says – The Washington Post
One in three dementia cases 'could be prevented by lifestyle changes' – London Evening Standard

I hope this is a sign that cognitive dissonance on the subject has reached a maximum.

[4] - see Lindeberg, Food and Western Disease. There are important limits to how reliable this evidence is, but the researchers were able to get decent evidence that some hunter-gatherers lived into their 80s, that hunter-gatherers did have people whose cognitive ability was impaired from childhood, and consistently did not know of late-onset cognitive decline.

Beware that "it's due to modern lifestyles" doesn't guarantee there's a reasonable strategy to avoid Alzheimer's. Modern population densities support infectious diseases that hunter-gatherers don't get.

[Leah · Rating 2 out of 5]

Author is Chief Science Officer this company https://www.apollohealthco.com/ which sells a ReCODE program that costs $75/month without labs. Conflict of interest that absolutely needed to be addressed in this book.

Lots of recommendations, little citations. Let alone peer-reviewed ones.

Lacks of any form of clinical trial whatsoever.

Claims to cure Alzheimer's but writes that the program is more effective for people who are pre-Alzheimer's - "If you have moderate Alzheimer's, improvement is unfortunately more difficult."

Science part was okay, not explained the best (i.e. the author used the word "autophagy" with absolutely no explanation given- no one knows what this means except biologists!!!) Frequent analogies to cancer were not useful.

A lot of the vitamin/herb claims were pulled out of no where. No science behind these, and if there is, it was not explained at all. Overall, this book just tells you to live a healthy lifestyle, which almost everyone knows they should be doing. The main novel part of this book is the use of the ketogenic diet, which I really wasn't even convinced of. Is it the 15 hour fast that induces ketosis and autophagy necessary - is the high fat diet required? Reasons given in the book for necessity of ketogenic diet seem to deal with insulin signaling and glucose levels. However, if you are not diabetic, I think that a whole plant food diet consisting of healthy carbs would be fine. As there is no controlled trial on this, there is no way to know if ketogenic diet is required on top of the 15 hour fast.

There are people who this program has worked for, evidently. So I'll give it 3 stars. Will be interesting to see if this holds up overtime and what changes are made to this protocol.

[Kelly Wilson · Rating 1 out of 5]

Not impressed. I think the idea of this book is to make you think that the author has all the answers based on his discussion of genetic indicators hormone levels and such. But really all he has is a few cases that he counts as research. He might be right, but his evidence reads more like a medical text than a roadmap. And what he does provide in a way of roadmap, is baffling. At one point he says if your grandmother wouldn’t recognize an ingredient, then it’s highly processed and worth staying away from. Sounds like good advice to me. Until you get to his appendix where all of the supplements he recommends, I guarantee my grandmother has never heard of. There must be 40 supplements he suggests you take. His solution requires you to have extensive testing and monitoring under medical care, and take countless supplements. Again it might be the right answer, but it is certainly not something an individual can implement. Then there is the common every day wisdom that is nothing new… Get sleep, exercise, meditate, eat healthy. Not worth the read.

[Ei · Rating 5 out of 5]

BRILLIANT!!! ... and encouraging.
I do not have the APOE4 gene variant, however, I am very familiar with progressive Alzheimer's Disease and have an interest in keeping current with research. This book was the BEST book I've read in years! Anyone can read this book and understand the correlation with the science and the outcomes. Very grateful a doctor recommended this book to me! Lyme Disease has left me with mild cognitive impairment. The systems approach in this book, which has reversed Alzheimer's at the Buck Institute at UCLA, is applicable to anyone who is willing to implement this protocol. I was encouraged to find that I am already doing many of the steps in the protocol! I would like my entire family, and all of my friends to read this book. Decrease your risk of Alzheimer's and prevent cognitive decline - no matter what your current epigenetics are.
(The risk of Alzheimer's increases with age, regardless of your genetic markers.)

[Isaac Winterfeld · Rating 3 out of 5]

The Alzheimer's Society claims that Bredesen’s Recode Protocol offers false hope. It has not been peer-reviewed and to date, there have been no clinically validated systems, medications or lifestyle changes proven to reverse Alzheimer’s disease. This said, there is no harm in implementing his protocol and he has worked with hundreds of patients that have benefited from this protocol.

Although I was hoping for something more evidence-based that has been validated in larger studies I would still recommend this book if you're interested in learning about Alzheimer's. The author does a great job breaking down and simplifying what Alzheimer's is, how it works, and what causes it.

His protocol also seems like a great foundation for a health plan which promotes vitality and longevity in seniors so I think it is worth implementing at least some aspects of the protocol even if it does not prevent & reverse Alzheimer's like he claims.