11 ms·

Reversal of cognitive decline: A novel therapeutic program

195 points by lawrenceyan 5y ago

garganzol 5y ago
There is a long discussion about the metabolic underpinnings of neurological diseases but the paper's reasoning about the underlying mechanism of disease is weak. For example, the paper stresses that there is a dysfunctional signaling in AD and comes to a conclusion that it is inducted by a metabolic dysfunction. While this is a true statement, the amount of overall cellular damage happening under the conditions of insufficient metabolism goes way beyond that. The patients have not only "bad signalling", but also autoimmune-like response to damaged tissues. The paper fails to discuss that but suggests as a treatment target in "Therapeutic System 1.0". The suggested treatment, however, contains the crucial elements that should bring the improvement to patients. This is not a bad paper by all means. It is useful and even enlightening to some degree, but the theoretical part is tiny and not sound. Regarding the critical article from The Lancet [1], it's full of emotions and nihilism. I.e. it is bad. I mean, really bad. For example, here are some excerpts from critical article. "high out-of-pocket cost to implement" - bullshit. While the whole protocol may be costly depending on country, the mitochondrial (the most essential part of it) is dirt cheap, like tens-of-dollars per month cheap. Anti-inflammatory part of protocol can be implemented even with Aspirin. "Readers might not be aware that the three case series evaluating the Bredesen protocol appear in journals considered by some to be predatory open access journals. Predatory open access journals are scientific-sounding publications that hijack the open access model for profit" - come on. The predatory closed-access model, on the other hand, has its own downsides, e.g. slow progress, walled gardens of authority, review rings. "There are elements of the Bredesen protocol that could be beneficial and are largely free to patients. It is standard of care in dementia clinics to educate patients, without cost, on the lifestyle interventions" - and that's it. No mentions to metabolic corrections other that "lifestyle change". Which is not sufficient by itself. It only works in conjunction with mitochondrial + anti-inflammatory parts. "When presented with this information, there are people who continue to hold a strong belief in the protocol’s efficacy." - because it is. Rather than loudly criticizing other's work, it is way better to join the ranks and improve the research by covering the missing parts. "When carefully examined, multiple red flags appear in the scientific studies supporting the Bredesen protocol." - that's true. "To date, the evidence does not support its claim to prevent and reverse cognitive decline" - oh well, don't get me started. To date, the neurologists try to treat such patients with... antidepressants. And that's it. Most of them do not even know about neuro-metabolical cause and effect connections. [1] https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-44222030113-7.pdf https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-442...
sradu 5y ago
I've done a bit of research here. It's not snake oil. They did a trial, https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v1.full https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v..., and it worked very well. It's being commercialized here: https://www.apollohealthco.com/ https://www.apollohealthco.com/, and the guy has patents on everything.
- pmoriarty 5y ago
  "They did a trial, https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v..., and it worked very well." Only 25 patients, not double-blind, no controls.
  - krrrh 5y ago
    The protocol is mostly lifestyle changes, there’s no meaningful way it could be double-blind. It has to be compared to standard of care outcomes.
    - adrianN 5y ago
      The control group could use a different set of lifestyle changes. Changing something always has an effect. You need to somehow figure out whether the changes you propose are better than just doing anything.
- deleted 5y ago
  [deleted]
lawrenceyan 5y ago
A followup paper to the original one as well: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931830/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931830/
o_____________o 5y ago
tldr personalized techniques: - Optimize diet: minimize simple CHO, minimize inflammation. - Patients given choice of several low glycemic, low inflammatory, low grain diets. - Enhance autophagy, ketogenesis - Fast 12 hr each night, including 3 hr prior to bedtime. - Reduce stress - Personalized—yoga or meditation or music, etc. - Optimize sleep - 8 hr sleep per night; melatonin 0.5mg po qhs; Trp 500mg po 3x/wk if awakening. Exclude sleep apnea. - Exercise - 30-60′ per day, 4-6 days/wk - Brain stimulation - Posit or related - Homocysteine <7 - Me-B12, MTHF, P5P; TMG if necessary - Serum B12 >500 - Me-B12 - CRP <1.0; A/G >1.5 - Anti-inflammatory diet; curcumin; DHA/EPA; optimize hygiene - Fasting insulin <7; HgbA1c <5.5 - Diet as above - Hormone balance - Optimize fT3, fT4, E2, T, progesterone, pregnenolone, cortisol - GI health - Repair if needed; prebiotics and probiotics - Reduction of A-beta - Curcumin, Ashwagandha - Cognitive enhancement - Bacopa monniera, MgT - 25OH-D3 = 50-100ng/ml - Vitamins D3, K2 - Increase NGF - H. erinaceus or ALCAR - Provide synaptic structural components - Citicoline, DHA - Optimize antioxidants - Mixed tocopherols and tocotrienols, Se, blueberries, NAC, ascorbate, α-lipoic acid - Optimize Zn:fCu ratio - Depends on values obtained - Ensure nocturnal oxygenation - Exclude or treat sleep apnea - Optimize mitochondrial function - CoQ or ubiquinol, α-lipoic acid, PQQ, NAC, ALCAR, Se, Zn, resveratrol, ascorbate, thiamine - Increase focus - Pantothenic acid - Increase SirT1 function - Resveratrol - Exclude heavy metal toxicity - Evaluate Hg, Pb, Cd; chelate if indicated - MCT effects - Coconut oil or Axona
- giantg2 5y ago
  Should also add cobalt to the list of metals to look at if one has a joint replacement using it. What is MgT?
  - jwond 5y ago
    Magnesium L-Threonate, also known as “Magtein”
    - giantg2 5y ago
      I think it needs a different notation. Could be easily confused with Mg Taurate.
giantg2 5y ago
Bredesen has a book called The End of Alzheimer's, or something.
- catlikesshrimp 5y ago
  Unfortunately, the end of alzheimer is death :/
wawayanda 5y ago
Maybe I'm a cynic but it strains credulity that the miracle cure is also a laundry list of fad health trends from the the last decade. Gluten free, intermittent fasting, yoga, melatonin, probiotics, etc etc
- catlikesshrimp 5y ago
  Gluten free is not snake oil.... if you have a Immune Celiac disease. Melatonin helps with sleep disorders... for people with sleep disorders. There is a synthetic analog called Ramelteon. Intermitent fasting has curious effects on insulin resistance, but not clinically relevant. Probiotics reduce incidence and severity of traveler's diarrhea... for travelers. It has been comercially available for a while. Like Ivermectin, which is not snake oil, but is also being sold for the same purposes as snake oil.
  - Earw0rm 5y ago
    Re intermittent fasting - "not clinically relevant" in that its effect on insulin in itself isn't relevant, or that insulin resistance itself doesn't have a clinically significant relationship to dementia? I'm not a faster, don't have a dog in this fight, just curious as have seen a few papers & articles in recent years that seem to suggest a relationship between T2D / metabolic syndrome and dementia, but these may have since been debunked?
- varelse 5y ago
  If what you're telling me is that eating healthy, getting enough sleep and exercising can halt or reverse Alzheimer's it's not going to exactly shock me. The real fad is how amazingly stupid Americans are about their own health.
  - easytiger 5y ago
    I come from a family with Alzheimer's running through it like clockwork. I have some uncles who tried to live the right lifestyle. It didn't help. If anything in my observations it made things worse. Though it's a meaningless sample size.
dayofthedaleks 5y ago
Needs a (2014)
jonmc12 5y ago
Here are a couple more recent papers exploring the efficacy of hyperbaric oxygen treatment and autophagy on Alzheimer's disease: 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293997/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293997/ 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049408/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049408/
suyash 5y ago
So what was the diet and lifestyle changes that patients did? Didn't much much information about that in the article.
- suyash 5y ago
  (comment below answered this)
someguydave 5y ago
Seems like hype, this article was cited by others as an example of non-validated treatments https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935739/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935739/ and another paper that criticizes this paper heavily https://pubmed.ncbi.nlm.nih.gov/33459944/ https://pubmed.ncbi.nlm.nih.gov/33459944/
lvs 5y ago
Snake oil.
wolverine876 5y ago
The paper is from 2014.
jasonhansel 5y ago
A thorough debunking of this protocol from The Lancet: https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-44222030113-7.pdf https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-442... A few quotes: > Despite the certainty inferred by the book’s subtitle, there is no published study that tests or proves the hypothesis that the Bredesen protocol can prevent and reverse cognitive decline. > Readers are informed that participants with subjective cognitive impairment or mild cognitive impairment are included in the studies; however, both conditions can have causes unrelated to neurodegenerative processes. These studies are therefore not targeting a common underlying neuropathological process of Alzheimer’s disease, as the papers suggest. > Readers might not be aware that the three case series evaluating the Bredesen protocol appear in journals considered by some to be predatory open access journals. [...] The journal Aging, where the first two articles were published, appears on the Beall’s list of potential, possible, or probable predatory open access journals [...] > it is notable that the Bredesen protocol has been made commercially available; however, the authors do not disclose any conflicts of interest in their scientific reports.
- tgtweak 5y ago
  It feels like, in general, 10 data points are not enough to justify efficacy of a protocol. One would also assume that simply exercising and eating properly on their own would have some measurable improvements. As the paper suggests, a larger case study would be in order, specifically with some combinations of the various measures in the protocol to determine individual and compound efficacy on a statistically relevant scale.
- knaik94 5y ago
  While I appreciate the sci-hub link, the author manuscript can also be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ which I think should be encouraged over sci-hub. I love sci-hub and understands its necessity but my cursory look through saw now difference in text or tables provided.
  - thaumasiotes 5y ago
    > the author manuscript can also be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ which I think should be encouraged over sci-hub. Why? Which one has better policies?
abdel_nasser 5y ago
in patient one they list fasting for extended periods of time and also "MCT effects" which refers to the administration of MCT oil. so in other words, this is a very convoluted way of doing what the ketogenic diet does. the fact that the ketogenic diet can reverse alzheimers in part or in full has been well established by Dr. Mary Newport. as well as it can be without support from the mainstream medical establishment -- they refuse to conduct proper studies on it out of sheer stupidity and stubbornness. i add "stupidity" because of how long theyve let the oversight go for. ketosis does something to the immune system. in many people who have schizophrenia, touching the immune system sometimes has a direct impact on symptoms. there is a famous case of a young man whos symptoms went away after having his bone marrow removed as reported in the NYT. the articles goes on to connect many interesting cases and facts that orbit this idea. its official everyone, the NYT knows more about medicine than your doctor. another article, published by a practicing harvard psychiatrist in psychology today, presents three case studies of schizophrenics who go into remission upon entering ketosis. other people find fleeting relief after donating blood and thus diluting their blood. and blood dilution has been shown to directly impact tons of things at UCB especially things having to do with aging. its an indication of whats to come. our own bodies are producing inflammatory molecules that cause disease. i have schizophrenia and i can say that these things are true and i have tested them. whether AZ disease improvement upon entering ketosis is due to inflammation reduction or metabolic improvements due to using BHB rather than glucose in some cells, im not sure anyone knows. i wonder if any doctor will stop to reflect on his own behaviour for a single second after he hears that the titan of AZ medications, which reduces plaques, does not fucking work? people like me have been saying for ages that AZ is caused by metabolic dysfunction and the plaques are a downstream artifact. well now the evidence against them and for me is so massive that they will have to write it in the sky. pure vindication.
- tuomasb 5y ago
  >they refuse to conduct proper studies on it out of sheer stupidity and stubbornness Not stupidity and stubbornness. There is exactly zero money to be made from fasting. Much better to try to make some miracle compound and sell it for $50 per pill and bill it from insurers.
krrrh 5y ago
Lots of comments dismissing this out of hand because of lack of evidence, but there aren’t any conventional treatments that are very helpful for Alzheimer’s. The lifestyle adjustments suggested in the protocol are largely healthy, not that hard to do, and offer other health benefits. They are also relatively uncommon so it’s not impossible that a broad based adoption of specific habits along with testing for mycotoxins and heavy metals, etc could provide some marginal benefits. Aside from maintaining your spare tire and fatigue from not getting enough sleep and exercise, there’s not much reason to ignore the main advice. Anyway, here’s a Rhonda Patrick interview with Bredeson for the curious. So few people will actually do the protocol, time will tell if there’s anything to it. https://www.foundmyfitness.com/episodes/dale-bredesen https://www.foundmyfitness.com/episodes/dale-bredesen
- crdrost 5y ago
  Similar claims were also made by Dr. Lustig’s book Metabolical earlier this year, which of course is more concerned with the diabetic aspects but indeed considers Alzheimer's etc. metabolic disorders. Not seeing Bredesen on the bibliography so I think the research is independent, some related citations from that bibliography: G.J. Biessels and F. Despa. “Cognitive Decline and Dementia in Diabetes Mellitus: Mechanisms and Clinical Implications,” Nat. Rev. Endocrinol. 14 (10) (2018): 591. https://www.nature.com/articles/s41574-018-0048-7 https://www.nature.com/articles/s41574-018-0048-7 B.J. Neth and S. Craft. “Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages,” Front. Aging Neurosci. 9 (2017): 345. https://doi.org/10.3389/fnagi.2017.00345 https://doi.org/10.3389/fnagi.2017.00345 S.S. Dominy et al. “Porphyromonas gingivalis in Alzheimer’s Disease Brains: Evidence for Disease Causation and Treatment with Small-Molecule Inhibitors,” Sci. Adv. 5 (1) (2019): eaau3333. https://www.science.org/doi/10.1126/sciadv.aau3333 https://www.science.org/doi/10.1126/sciadv.aau3333 M.P. Pase et al. “Sugary Beverage Intake and Preclinical Alzheimer’s Disease in the Community,” Alzheimers Dement. 13 (9) (2017): 955. https://doi.org/10.1016/j.jalz.2017.01.024 https://doi.org/10.1016/j.jalz.2017.01.024 V. Berti et al. “Nutrient Patterns and Brain Biomarkers of Alzheimer’s Disease in Cognitively Normal Individuals,” J. Nutr. Health Aging 19 (4) (2015): 413. https://doi.org/10.1007/s12603-014-0534-0 https://doi.org/10.1007/s12603-014-0534-0 S.M. Raefsky and M.P. Mattson. “Adaptive Responses of Neuronal Mitochondria to Bioenergetic Challenges: Roles in Neuroplasticity and Disease Resistance,” Free Radic. Biol. Med. 102 (2017): 203. https://www.sciencedirect.com/science/article/abs/pii/S0891584916310814?via%3Dihub https://www.sciencedirect.com/science/article/abs/pii/S08915... So the claim is that ultraprocessed food is essentially making your mitochondria sick, and the recommended diet adjustment is not very different from Bredesen’s approach.
zanethomas 5y ago
Brandon could use that.
ike77 5y ago
The major issue with this paper and this protocol is that it is not reproducible. As the protocol is not accessible / published, we cannot determine how the difference in the set of measures between participants were determined and as such no researcher can independently replicate this study. This is why those licensed diet / lifestyle change are never science: by definition. Even if they actually produce the desired outcome, all the research is produced either by the creator or by researchers that entered a license agreement and thus have conflicting interests and bias.
- garganzol 5y ago
  > The major issue with this paper and this protocol is that it is not reproducible. Sorry, such claim is a pure bullshit. It is reproducible, even the parts of the suggested treatment lead to significant improvements in quality of life for affected patients. What we have here is: 1) the paper has some claims 2) it has weak theoretical coverage 3) it does not perform orthogonal hypothesis validation (validating each parameter in isolation) 4) the size of trial is small Plus some political plays between scientific society participants. But it is far from non-reproducible. There are a few people in the field who had big successes with similar therapies. (Dr. Derrick Lonsdale)
  - prepend 5y ago
    The treatment varies for the patients. How would someone reproduce treatments if they don’t know how the particular elements are selected?
dbredesen 5y ago
Jason et al., Looks like no one has any training in neuroscience (or scientific analysis) here, so let's go over the basics: (1) The "debunking" you quote from the Lancet does not address data--it's all opinion. Look at the cases themselves, the changes in cognitive scores, the objective data. In addition to this ancient (2014) paper, which described the first reversals of cognitive decline in patients with AD or pre-AD, we have published 100 documented cases of improvement (in J. Alz Dis and Parkinsonism, publicly available) and posted a successful proof-of-concept trial (https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v1.full https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v...). Note that in the trial, 84% improved their cognitive scores, and even the MRIs improved. We are now doing a larger, randomized, controlled clinical trial. (2) We've published over 220 papers and 3 books; please read these before making silly comments. (3) AD has been completely untreatable, and the best data from pharma simply show a slight slowing of decline, not improvement or even stabilization. We've achieved improvement that has been sustained for years--the first patients started in 2012 and are still improved. So the complaints should take into account the alternatives. (4) How do you think medicine changes? A 100-million-dollar Phase 3 trial as the first step? Please. You need a model, then anecdotal, objective data, then a proof-of-concept trial, then a randomized controlled trial. We are doing all of that, step by step. If you have better results, please publish them; if not, don't impede progress, since there are millions in need. (5) The idea that we are using "fads" is ridiculous--we spent 30 years in the laboratory determining the molecular pathways that drive neurodegeneration, and we then translated those data into a workable clinical approach that has already achieved better clinical outcomes than any other approach. Admittedly it is not simple enough yet, but the disease is dictating the simplicity at this point; we have more work to do to prioritize and scale. (6) Our data and approach are simply systems medicine, and the pushback is coming from the stakeholders in outdated single pharmaceutical medicine--do you really believe that something as complicated as a human brain, beset by a disease as complicated as Alzheimer's, is going to be cured by a single small molecule? Ignoring the various pathways involved? Come on now, The Lancet can afford to act like idiots because they've been around for a while, but most of us need data and outcomes. (7) Our approach is simply to identify the drivers of decline (the current standard of care does not even look for them) and then target those. This type of network analysis is the future of medicine, and frankly it needs a lot more Silicon Valley input and a lot less pharma monotherapy influence. (8) The Alzheimer's field is experiencing many of the same issues as the Opioid Epidemic did--coercion, billions of dollars at stake, pharma-established infrastructure, and needless deaths. The recent FDA decision on aducanumab provides further evidence of this. Please look at the data and compare the various approaches, instead of accepting the opinions of the stakeholders at face value. Thanks.
aniola 5y ago
My conclusion, after reading the book, was that the author knows what test results you need in order to prevent or reverse cognitive decline, but he is no expert in how to get those results. Feel free to ignore whatever he says about how you optimize your test results, but I trust him a lot more on what happens when you have successfully optimized those results.

195 points by lawrenceyan 5y ago

There is a long discussion about the metabolic underpinnings of neurological diseases but the paper's reasoning about the underlying mechanism of disease is weak. For example, the paper stresses that there is a dysfunctional signaling in AD and comes to a conclusion that it is inducted by a metabolic dysfunction. While this is a true statement, the amount of overall cellular damage happening under the conditions of insufficient metabolism goes way beyond that. The patients have not only "bad signalling", but also autoimmune-like response to damaged tissues. The paper fails to discuss that but suggests as a treatment target in "Therapeutic System 1.0". The suggested treatment, however, contains the crucial elements that should bring the improvement to patients. This is not a bad paper by all means. It is useful and even enlightening to some degree, but the theoretical part is tiny and not sound. Regarding the critical article from The Lancet [1], it's full of emotions and nihilism. I.e. it is bad. I mean, really bad. For example, here are some excerpts from critical article. "high out-of-pocket cost to implement" - bullshit. While the whole protocol may be costly depending on country, the mitochondrial (the most essential part of it) is dirt cheap, like tens-of-dollars per month cheap. Anti-inflammatory part of protocol can be implemented even with Aspirin. "Readers might not be aware that the three case series evaluating the Bredesen protocol appear in journals considered by some to be predatory open access journals. Predatory open access journals are scientific-sounding publications that hijack the open access model for profit" - come on. The predatory closed-access model, on the other hand, has its own downsides, e.g. slow progress, walled gardens of authority, review rings. "There are elements of the Bredesen protocol that could be beneficial and are largely free to patients. It is standard of care in dementia clinics to educate patients, without cost, on the lifestyle interventions" - and that's it. No mentions to metabolic corrections other that "lifestyle change". Which is not sufficient by itself. It only works in conjunction with mitochondrial + anti-inflammatory parts. "When presented with this information, there are people who continue to hold a strong belief in the protocol’s efficacy." - because it is. Rather than loudly criticizing other's work, it is way better to join the ranks and improve the research by covering the missing parts. "When carefully examined, multiple red flags appear in the scientific studies supporting the Bredesen protocol." - that's true. "To date, the evidence does not support its claim to prevent and reverse cognitive decline" - oh well, don't get me started. To date, the neurologists try to treat such patients with... antidepressants. And that's it. Most of them do not even know about neuro-metabolical cause and effect connections. [1] https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-44222030113-7.pdf https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-442...

sradu 5y ago

I've done a bit of research here. It's not snake oil. They did a trial, https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v1.full https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v..., and it worked very well. It's being commercialized here: https://www.apollohealthco.com/ https://www.apollohealthco.com/, and the guy has patents on everything.

pmoriarty 5y ago
"They did a trial, https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v..., and it worked very well." Only 25 patients, not double-blind, no controls.
- krrrh 5y ago
  The protocol is mostly lifestyle changes, there’s no meaningful way it could be double-blind. It has to be compared to standard of care outcomes.
  - adrianN 5y ago
    The control group could use a different set of lifestyle changes. Changing something always has an effect. You need to somehow figure out whether the changes you propose are better than just doing anything.
deleted 5y ago
[deleted]

lawrenceyan 5y ago

A followup paper to the original one as well: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931830/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931830/

o_____________o 5y ago

tldr personalized techniques: - Optimize diet: minimize simple CHO, minimize inflammation. - Patients given choice of several low glycemic, low inflammatory, low grain diets. - Enhance autophagy, ketogenesis - Fast 12 hr each night, including 3 hr prior to bedtime. - Reduce stress - Personalized—yoga or meditation or music, etc. - Optimize sleep - 8 hr sleep per night; melatonin 0.5mg po qhs; Trp 500mg po 3x/wk if awakening. Exclude sleep apnea. - Exercise - 30-60′ per day, 4-6 days/wk - Brain stimulation - Posit or related - Homocysteine <7 - Me-B12, MTHF, P5P; TMG if necessary - Serum B12 >500 - Me-B12 - CRP <1.0; A/G >1.5 - Anti-inflammatory diet; curcumin; DHA/EPA; optimize hygiene - Fasting insulin <7; HgbA1c <5.5 - Diet as above - Hormone balance - Optimize fT3, fT4, E2, T, progesterone, pregnenolone, cortisol - GI health - Repair if needed; prebiotics and probiotics - Reduction of A-beta - Curcumin, Ashwagandha - Cognitive enhancement - Bacopa monniera, MgT - 25OH-D3 = 50-100ng/ml - Vitamins D3, K2 - Increase NGF - H. erinaceus or ALCAR - Provide synaptic structural components - Citicoline, DHA - Optimize antioxidants - Mixed tocopherols and tocotrienols, Se, blueberries, NAC, ascorbate, α-lipoic acid - Optimize Zn:fCu ratio - Depends on values obtained - Ensure nocturnal oxygenation - Exclude or treat sleep apnea - Optimize mitochondrial function - CoQ or ubiquinol, α-lipoic acid, PQQ, NAC, ALCAR, Se, Zn, resveratrol, ascorbate, thiamine - Increase focus - Pantothenic acid - Increase SirT1 function - Resveratrol - Exclude heavy metal toxicity - Evaluate Hg, Pb, Cd; chelate if indicated - MCT effects - Coconut oil or Axona

giantg2 5y ago
Should also add cobalt to the list of metals to look at if one has a joint replacement using it. What is MgT?
- jwond 5y ago
  Magnesium L-Threonate, also known as “Magtein”
  - giantg2 5y ago
    I think it needs a different notation. Could be easily confused with Mg Taurate.

giantg2 5y ago

Bredesen has a book called The End of Alzheimer's, or something.

catlikesshrimp 5y ago
Unfortunately, the end of alzheimer is death :/

wawayanda 5y ago

Maybe I'm a cynic but it strains credulity that the miracle cure is also a laundry list of fad health trends from the the last decade. Gluten free, intermittent fasting, yoga, melatonin, probiotics, etc etc

catlikesshrimp 5y ago
Gluten free is not snake oil.... if you have a Immune Celiac disease. Melatonin helps with sleep disorders... for people with sleep disorders. There is a synthetic analog called Ramelteon. Intermitent fasting has curious effects on insulin resistance, but not clinically relevant. Probiotics reduce incidence and severity of traveler's diarrhea... for travelers. It has been comercially available for a while. Like Ivermectin, which is not snake oil, but is also being sold for the same purposes as snake oil.
- Earw0rm 5y ago
  Re intermittent fasting - "not clinically relevant" in that its effect on insulin in itself isn't relevant, or that insulin resistance itself doesn't have a clinically significant relationship to dementia? I'm not a faster, don't have a dog in this fight, just curious as have seen a few papers & articles in recent years that seem to suggest a relationship between T2D / metabolic syndrome and dementia, but these may have since been debunked?
varelse 5y ago
If what you're telling me is that eating healthy, getting enough sleep and exercising can halt or reverse Alzheimer's it's not going to exactly shock me. The real fad is how amazingly stupid Americans are about their own health.
- easytiger 5y ago
  I come from a family with Alzheimer's running through it like clockwork. I have some uncles who tried to live the right lifestyle. It didn't help. If anything in my observations it made things worse. Though it's a meaningless sample size.

dayofthedaleks 5y ago

Needs a (2014)

jonmc12 5y ago

Here are a couple more recent papers exploring the efficacy of hyperbaric oxygen treatment and autophagy on Alzheimer's disease: 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293997/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293997/ 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049408/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049408/

suyash 5y ago

So what was the diet and lifestyle changes that patients did? Didn't much much information about that in the article.

suyash 5y ago
(comment below answered this)

someguydave 5y ago

Seems like hype, this article was cited by others as an example of non-validated treatments https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935739/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935739/ and another paper that criticizes this paper heavily https://pubmed.ncbi.nlm.nih.gov/33459944/ https://pubmed.ncbi.nlm.nih.gov/33459944/

lvs 5y ago

Snake oil.

wolverine876 5y ago

The paper is from 2014.

jasonhansel 5y ago

A thorough debunking of this protocol from The Lancet: https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-44222030113-7.pdf https://sci-hub.se/downloads/2020-04-23/63/10.1016@S1474-442... A few quotes: > Despite the certainty inferred by the book’s subtitle, there is no published study that tests or proves the hypothesis that the Bredesen protocol can prevent and reverse cognitive decline. > Readers are informed that participants with subjective cognitive impairment or mild cognitive impairment are included in the studies; however, both conditions can have causes unrelated to neurodegenerative processes. These studies are therefore not targeting a common underlying neuropathological process of Alzheimer’s disease, as the papers suggest. > Readers might not be aware that the three case series evaluating the Bredesen protocol appear in journals considered by some to be predatory open access journals. [...] The journal Aging, where the first two articles were published, appears on the Beall’s list of potential, possible, or probable predatory open access journals [...] > it is notable that the Bredesen protocol has been made commercially available; however, the authors do not disclose any conflicts of interest in their scientific reports.

tgtweak 5y ago
It feels like, in general, 10 data points are not enough to justify efficacy of a protocol. One would also assume that simply exercising and eating properly on their own would have some measurable improvements. As the paper suggests, a larger case study would be in order, specifically with some combinations of the various measures in the protocol to determine individual and compound efficacy on a statistically relevant scale.
knaik94 5y ago
While I appreciate the sci-hub link, the author manuscript can also be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ which I think should be encouraged over sci-hub. I love sci-hub and understands its necessity but my cursory look through saw now difference in text or tables provided.
- thaumasiotes 5y ago
  > the author manuscript can also be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ which I think should be encouraged over sci-hub. Why? Which one has better policies?

abdel_nasser 5y ago

in patient one they list fasting for extended periods of time and also "MCT effects" which refers to the administration of MCT oil. so in other words, this is a very convoluted way of doing what the ketogenic diet does. the fact that the ketogenic diet can reverse alzheimers in part or in full has been well established by Dr. Mary Newport. as well as it can be without support from the mainstream medical establishment -- they refuse to conduct proper studies on it out of sheer stupidity and stubbornness. i add "stupidity" because of how long theyve let the oversight go for. ketosis does something to the immune system. in many people who have schizophrenia, touching the immune system sometimes has a direct impact on symptoms. there is a famous case of a young man whos symptoms went away after having his bone marrow removed as reported in the NYT. the articles goes on to connect many interesting cases and facts that orbit this idea. its official everyone, the NYT knows more about medicine than your doctor. another article, published by a practicing harvard psychiatrist in psychology today, presents three case studies of schizophrenics who go into remission upon entering ketosis. other people find fleeting relief after donating blood and thus diluting their blood. and blood dilution has been shown to directly impact tons of things at UCB especially things having to do with aging. its an indication of whats to come. our own bodies are producing inflammatory molecules that cause disease. i have schizophrenia and i can say that these things are true and i have tested them. whether AZ disease improvement upon entering ketosis is due to inflammation reduction or metabolic improvements due to using BHB rather than glucose in some cells, im not sure anyone knows. i wonder if any doctor will stop to reflect on his own behaviour for a single second after he hears that the titan of AZ medications, which reduces plaques, does not fucking work? people like me have been saying for ages that AZ is caused by metabolic dysfunction and the plaques are a downstream artifact. well now the evidence against them and for me is so massive that they will have to write it in the sky. pure vindication.

tuomasb 5y ago
>they refuse to conduct proper studies on it out of sheer stupidity and stubbornness Not stupidity and stubbornness. There is exactly zero money to be made from fasting. Much better to try to make some miracle compound and sell it for $50 per pill and bill it from insurers.

krrrh 5y ago

Lots of comments dismissing this out of hand because of lack of evidence, but there aren’t any conventional treatments that are very helpful for Alzheimer’s. The lifestyle adjustments suggested in the protocol are largely healthy, not that hard to do, and offer other health benefits. They are also relatively uncommon so it’s not impossible that a broad based adoption of specific habits along with testing for mycotoxins and heavy metals, etc could provide some marginal benefits. Aside from maintaining your spare tire and fatigue from not getting enough sleep and exercise, there’s not much reason to ignore the main advice. Anyway, here’s a Rhonda Patrick interview with Bredeson for the curious. So few people will actually do the protocol, time will tell if there’s anything to it. https://www.foundmyfitness.com/episodes/dale-bredesen https://www.foundmyfitness.com/episodes/dale-bredesen

crdrost 5y ago
Similar claims were also made by Dr. Lustig’s book Metabolical earlier this year, which of course is more concerned with the diabetic aspects but indeed considers Alzheimer's etc. metabolic disorders. Not seeing Bredesen on the bibliography so I think the research is independent, some related citations from that bibliography: G.J. Biessels and F. Despa. “Cognitive Decline and Dementia in Diabetes Mellitus: Mechanisms and Clinical Implications,” Nat. Rev. Endocrinol. 14 (10) (2018): 591. https://www.nature.com/articles/s41574-018-0048-7 https://www.nature.com/articles/s41574-018-0048-7 B.J. Neth and S. Craft. “Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages,” Front. Aging Neurosci. 9 (2017): 345. https://doi.org/10.3389/fnagi.2017.00345 https://doi.org/10.3389/fnagi.2017.00345 S.S. Dominy et al. “Porphyromonas gingivalis in Alzheimer’s Disease Brains: Evidence for Disease Causation and Treatment with Small-Molecule Inhibitors,” Sci. Adv. 5 (1) (2019): eaau3333. https://www.science.org/doi/10.1126/sciadv.aau3333 https://www.science.org/doi/10.1126/sciadv.aau3333 M.P. Pase et al. “Sugary Beverage Intake and Preclinical Alzheimer’s Disease in the Community,” Alzheimers Dement. 13 (9) (2017): 955. https://doi.org/10.1016/j.jalz.2017.01.024 https://doi.org/10.1016/j.jalz.2017.01.024 V. Berti et al. “Nutrient Patterns and Brain Biomarkers of Alzheimer’s Disease in Cognitively Normal Individuals,” J. Nutr. Health Aging 19 (4) (2015): 413. https://doi.org/10.1007/s12603-014-0534-0 https://doi.org/10.1007/s12603-014-0534-0 S.M. Raefsky and M.P. Mattson. “Adaptive Responses of Neuronal Mitochondria to Bioenergetic Challenges: Roles in Neuroplasticity and Disease Resistance,” Free Radic. Biol. Med. 102 (2017): 203. https://www.sciencedirect.com/science/article/abs/pii/S0891584916310814?via%3Dihub https://www.sciencedirect.com/science/article/abs/pii/S08915... So the claim is that ultraprocessed food is essentially making your mitochondria sick, and the recommended diet adjustment is not very different from Bredesen’s approach.

zanethomas 5y ago

Brandon could use that.

ike77 5y ago

The major issue with this paper and this protocol is that it is not reproducible. As the protocol is not accessible / published, we cannot determine how the difference in the set of measures between participants were determined and as such no researcher can independently replicate this study. This is why those licensed diet / lifestyle change are never science: by definition. Even if they actually produce the desired outcome, all the research is produced either by the creator or by researchers that entered a license agreement and thus have conflicting interests and bias.

garganzol 5y ago
> The major issue with this paper and this protocol is that it is not reproducible. Sorry, such claim is a pure bullshit. It is reproducible, even the parts of the suggested treatment lead to significant improvements in quality of life for affected patients. What we have here is: 1) the paper has some claims 2) it has weak theoretical coverage 3) it does not perform orthogonal hypothesis validation (validating each parameter in isolation) 4) the size of trial is small Plus some political plays between scientific society participants. But it is far from non-reproducible. There are a few people in the field who had big successes with similar therapies. (Dr. Derrick Lonsdale)
- prepend 5y ago
  The treatment varies for the patients. How would someone reproduce treatments if they don’t know how the particular elements are selected?

dbredesen 5y ago

Jason et al., Looks like no one has any training in neuroscience (or scientific analysis) here, so let's go over the basics: (1) The "debunking" you quote from the Lancet does not address data--it's all opinion. Look at the cases themselves, the changes in cognitive scores, the objective data. In addition to this ancient (2014) paper, which described the first reversals of cognitive decline in patients with AD or pre-AD, we have published 100 documented cases of improvement (in J. Alz Dis and Parkinsonism, publicly available) and posted a successful proof-of-concept trial (https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v1.full https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v...). Note that in the trial, 84% improved their cognitive scores, and even the MRIs improved. We are now doing a larger, randomized, controlled clinical trial. (2) We've published over 220 papers and 3 books; please read these before making silly comments. (3) AD has been completely untreatable, and the best data from pharma simply show a slight slowing of decline, not improvement or even stabilization. We've achieved improvement that has been sustained for years--the first patients started in 2012 and are still improved. So the complaints should take into account the alternatives. (4) How do you think medicine changes? A 100-million-dollar Phase 3 trial as the first step? Please. You need a model, then anecdotal, objective data, then a proof-of-concept trial, then a randomized controlled trial. We are doing all of that, step by step. If you have better results, please publish them; if not, don't impede progress, since there are millions in need. (5) The idea that we are using "fads" is ridiculous--we spent 30 years in the laboratory determining the molecular pathways that drive neurodegeneration, and we then translated those data into a workable clinical approach that has already achieved better clinical outcomes than any other approach. Admittedly it is not simple enough yet, but the disease is dictating the simplicity at this point; we have more work to do to prioritize and scale. (6) Our data and approach are simply systems medicine, and the pushback is coming from the stakeholders in outdated single pharmaceutical medicine--do you really believe that something as complicated as a human brain, beset by a disease as complicated as Alzheimer's, is going to be cured by a single small molecule? Ignoring the various pathways involved? Come on now, The Lancet can afford to act like idiots because they've been around for a while, but most of us need data and outcomes. (7) Our approach is simply to identify the drivers of decline (the current standard of care does not even look for them) and then target those. This type of network analysis is the future of medicine, and frankly it needs a lot more Silicon Valley input and a lot less pharma monotherapy influence. (8) The Alzheimer's field is experiencing many of the same issues as the Opioid Epidemic did--coercion, billions of dollars at stake, pharma-established infrastructure, and needless deaths. The recent FDA decision on aducanumab provides further evidence of this. Please look at the data and compare the various approaches, instead of accepting the opinions of the stakeholders at face value. Thanks.

aniola 5y ago

My conclusion, after reading the book, was that the author knows what test results you need in order to prevent or reverse cognitive decline, but he is no expert in how to get those results. Feel free to ignore whatever he says about how you optimize your test results, but I trust him a lot more on what happens when you have successfully optimized those results.