Reversal of cognitive decline: A novel therapeutic program | Hacker News Reader

Reversal of cognitive decline: A novel therapeutic program

ncbi.nlm.nih.gov

195 pointslawrenceyan102 comments

A thorough debunking of this protocol from The Lancet: 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.

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.

While I appreciate the sci-hub link, the author manuscript can also be found at 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.

> the author manuscript can also be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377549/ which I think should be encouraged over sci-hub.

Why? Which one has better policies?

PMC is where papers go that are required to be open access due to funding or chosen to be open access in the life sciences, generally speaking. It's the official place for these and a legal copy. Sci-hub generally isn't. If you support Sci-hub you might as well save them the bandwidth for serving papers that are genuinely open access. And supporting PMC is good to support the further expansion of actually open access papers and the funding of them.

PMC also makes everything uniformly formatted which is often a benefit, though sometimes equations can be worse.

> however, the authors do not disclose any conflicts of interest in their scientific reports

I find it amusing the Lancet complains about this considering Peter Daszak's et al covid origins letter was published without disclosing conflicts of interest.

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

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

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

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

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

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

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/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.

> 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.

These are harmless until they become harmful. What if we develop a good cure for Alzheimer's in 10 years, this method gets debunked but the method makes many refuse to use the conventional treatment? That isn't a made up scenario, it happens all the time. Announcing that something is a cure without evidence is hurting people.

It would be better if the article described it as a general cognitive decline without a diagnosis of AD. A lot of symptoms we attribute to AD could very well be caused by other factors which are reversible, such as inflammation, lack of sleep, poor diet, metal toxicity, or a deficiency of CoQ-10 or Ubiquitol due to statin use.

Anecdotally, I experienced a rather severe cognitive impairment after statin use, which, when discontinuing the statin was reversed. I believe this could be attributed to mitochondrial damage. Were I an older individual, this might be improperly diagnosed as age-related cognitive decline.

In another example, 60 Minutes ran a story on a group of people who were suffering from late-stage AD. After autopsy, some showed amyloid beta plaques in some cases and the total absence of it in others. This leads me to believe that AD, as it is currently understood, is better classified as a syndrome which may have no single definitive cure.

Sure that's possible. But it's also overweighting potential harms in an imaginary future scenario over potential benefits today. One can come up with other imaginary scenarios, not to be too dramatic, but the same arguments were likely made against Semmelweis [0] when he promoted hand washing before delivering babies, or the people who discovered the ketogenic diet helped manage epilepsy in the 1920s. [1]

Scientific progress has often been speculative and messy. The few thousand people with ApoE4 genes who read his book and then actually commit to time-restricted feeding, exercising 4 times a week, sleeping 8 hours, and semi-ketogenic diets might have better outcomes a decade from now than those who don't. If that discourages another few tens of thousands of people from taking a potential blockbuster drug in the early years after its release, fine. It's worth the natural experiment to find out because millions of people are not getting much relief from current treatments [2]. This is even more true given that Alzheimer's isn't communicable.

[0] https://en.wikipedia.org/wiki/Ignaz_Semmelweis

[1] Which is lately experiencing a renaissance see https://charliefoundation.org

[2] Official bodies also continue to approve therapies with evidence that appears inconclusive with a higher degree of certainty than Bredeson's protocol. https://hub.jhu.edu/2021/06/21/fda-aduhelm-approval/

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/ and another paper that criticizes this paper heavily https://pubmed.ncbi.nlm.nih.gov/33459944/

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

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.

Given that Americans work more than most other countries it’s a wonder how they get enough sleep or time to cook healthy.

México, Costa Rica, Korea, and Greece would like a word, on both working harder and eating better:

https://www.weforum.org/agenda/2018/01/the-countries-where-p...

Mexico is more overweight than the US and tops your list of reported working hours.

That's very far from the truth: https://en.wikipedia.org/wiki/List_of_countries_by_obesity_r...

In fact, the only other country with a population of more than 200,000 people with a higher obesity rate than the US is Kuwait.

Ah yes, every single one of them. And none of the people in any other country.

American culture is staggeringly unhealthy. Denying this is impossible.

Not sure we're alone. Take the UK, for example. 2/3 are either overweight or obese. Better than the US? Sure. But what a weak victory that is.

I'm definitely biased by living in the southern hemisphere for almost half a decade. The places I've lived are visibly healthier than the US. People have less chronic health problems, take fewer sick days, etc.

I imagine a lot of that depends on where in the US you go. I live in an area that is statistically similar to Europe. If your idea of the US is south and east, it will be considerably different.

I've lived in major cities in the southeast and the west coast. The west coast of the US is still extremely unhealthy.

Learning how unhealthy the culture I grew up in is has been a gradual process. Shock moving to the west coast, and then shock at each of the subsequent moves around other parts of the world.

I think it is pretty easy to deny. The CDC breaks out obesity by demographics[1]. White adults have an obesity rate of ~29%. This is the same as other predominantly white/Anglo countries like Canada, Australia, and the United Kingdom[2].

Maybe 29% is staggeringly unhealthy, but it isn't American culture to be that overweight. Being overweight is fairly widespread and not unique to America.

Probably it has more to do with lifestyle changes (e.g. cars and working at computers) and diet changes (rise of processed and fast food). These things have disparate impact on racial groups, e.g. hispanics and blacks are considerably more overweight than whites. America having more hispanics and blacks than places like the UK, the US seems like it is more obese.

1 - https://ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2015...

2 - https://en.wikipedia.org/wiki/List_of_countries_by_obesity_r...

12th most obese nation in the world, I'd call that staggeringly unhealthy given our GDP:

https://obesity.procon.org/global-obesity-levels/

Also, 46th in life expectancy:

https://www.worldometers.info/demographics/life-expectancy/

Happy with those numbers? I'm not.

> it isn't American culture to be that overweight

> hispanics and blacks are considerably more overweight than whites

Are these people not American?

Those implicit biases can be pretty explicit...

You may want to edit this comment. It reads as though you don't think Hispanics or Blacks count as American. I don't think you intend to express this racist sentiment, but it's easily inferred from the text as written.

I don't see how that sentiment can be read into what I wrote. I looked at three racial groups in America and observed they had different obesity rates. In abstract terms - "You think this quality is specific to the whole. If you divide the whole into three parts you can see the quality differs between the parts. This implies the quality is not specific to the whole."

To take that claim and infer that I mean to suggest the parts are not part of the whole is clearly nonsense.

There were 3 different responses that read your post similarly, as though the higher levels of obesity among Hispanic and Black people are unrelated to American culture, as though it doesn't matter what the rates of obesity are among people who aren't White.

I suppose the reason why some bristle at your partitioning of American obesity rates into racial groups is that it's unclear that it's particularly relevant. Obesity varies by income, urban/suburban/rural-ness, red state/blue state, and more.

Any of these dimensions could be used to partition America into tranches. Then, throw out the bottom tranches. Then, say that America isn't especially unhealthy.

Imagine person A says: There's an epidemic of gun violence in America.

Person B responds: No. Just ignore the urban gang violence, the mentally ill mass shooters, and the suicides. It turns out that among mentally stable Whites, America isn't that violent.

There could have been three million such responses. It still wouldn't change the fact that that's a logically incoherent reading of my comment.

The reason to use racial groups in my example, is first because I happened to know obesity differed between the groups, and second because it offers the opportunity to look at similar groups in different countries. This example shows that there is variance within the country and similarity beyond it, which I think makes a good case that the culture of the country is not what's responsible.

Regarding your point on violence, suppose it were the case that left handed people had a murder rate 100x higher than right handed people. Now, imagine too that the OECD countries, or whichever group you would like to compare America too, were 99% right handed and America were only 90% right handed.

Would it make sense in this case to say that American culture was the root of the problem with American violence if right and left handed Americans committed violence at the same right as their OECD counterparts? I wouldn't think so. I would think the explanation would be as simple as "greater proportion of more violent left handers".

I realize in the violence example that I've simplified and exaggerated the case compared to obesity. I am not claiming that obesity rates are similar to my example.

You've linked me a list that shows the US nearly in the top 5% of the world for obesity and claimed that we're not unhealthy. Also the implication that white people are somehow genetically predisposed to obesity is strange, with plenty of countries existing as counterexamples.

You've listed the obesity rate, not the rate of people who are overweight. Beyond that, you haven't limited to adults. According to the CDC [1]:

Percent of adults aged 20 and over with obesity: 42.5% (2017-2018)

Percent of adults aged 20 and over with overweight, including obesity: 73.6% (2017-2018)

It absolutely has to do with lifestyle. America is one of the cultures most reliant on cars in the developed world. Physical activity is also ridiculously low. The problem is there's no way to reliably measure physical activity across countries. There's just survey data, and people in the US know they _should_ exercise.

[1] https://www.cdc.gov/nchs/fastats/obesity-overweight.htm

I think you are misunderstanding most, if not all, of what I wrote.

I never claimed that we weren't unhealthy but that being unhealthy isn't "American culture" as evidenced by different demographics in America having markedly different obesity rates. The obesity rates are similar among similar demographic groups in different countries - e.g. white people in the US have similar obesity rates as UK, Canada, and Australia. It's very weird to say that this thing that is constant among demographic groups across countries is dependent on the culture of one country. Especially when it is different among demographic groups in the same country.

I am not implying that white people are genetically predisposed to obesity. Actually, what I wrote is the exact opposite. I suggested the obesity rates were due to environmental factors and, crucially, I pointed out that other racial groups have greater obesity rates. So, I explicitly stated I believed the difference was not genetic and that white people have less obesity in the US than non-white.

For the other points you seem to prefer using a different metric, overweight instead of obesity. You haven't said why that factor is more relevant or how it changes what I wrote above.

I am studying in Russia and one of my teachers told me that it must be so that North Americans have some disease that has made them all so large. It was after I told him two of my neighbours had tummy tucks in the same month... he did not know what that was.

I would contend that physical activity is probably not a large determinant of weight, although physical activity is an important determinant of health.

Yes and no.. on a strict thermodynamics basis, it's not. If you're say 30lbs overweight (i.e. some, but not much), straight up burning that is going to require considerable patience and discipline to not destroy your body in the process. Each lb of fat is - very roughly - equivalent to running a marathon.

However, being physically active makes you more aware and mindful of the input side of the equation; building muscle mass, cardiovascular fitness and endurance in turn improves your metabolic ability to burn calories. So it's absolutely part of the picture. "The Miracle Pill" by Peter Walker is an excellent introduction to the topic.

> America having more hispanics and blacks than places like the UK, the US seems like it is more obese.

Whether or not you actually meant it, this very clearly comes off as you saying that they aren't American.

How? The UK has more anglo people than the US. Am I implying that Anglos aren't United Kingdomers or Americans? The US has more white people than Sudan. Does that imply white people aren't American?

It's logically implied by your words, "the US _seems_ like it is more obese." (Emphasis added.)

"Seems", as in "appears to be, but is not actually." The only way the US is not actually more obese is if Hispanics and Blacks do not count as "the US".

The only other way to read "seems" here is in the "I'm not totally sure, but this is what it looks like" sense. But this doesn't seem to be the way you're using this word, especially given that your entire comment is denying that the US is more obese purely in virtue of white obesity statistics.

If you are intent on finding offensive meanings you will be able to regardless of if they are there or not.

It's pretty clear that "seems" means that obesity seems to be a US problem unless you start looking at demographics, where similar demographics in different countries have the same rate of obesity (e.g. white people in the US, Australia, and Canada) and demographics in the same country have different rates of obesity (e.g. in the US blacks, whites, and Hispanics all have different rates of obesity).

I was not denying that the US is obese, to the extent that it is. I was explaining that it is not "American culture" that is the issue. Multiple groups that share "American culture" have different rates of obesity and groups that don't share American culture do share obesity rates.

The UK is not a good yardstick to judge healthy weight by. High levels of overweight here among all races (also, a lot of UK TV drama portrays the UK as a lot whiter than it actually is - our major cities & more modern towns are as ethnically diverse as the US equivalent). However, there's less extreme obesity here - likely as portion sizes tend to be smaller (soda cups larger than 20oz are a rarity, for example).

Was that zing really necessary? I'm trying to start a new diet plan over here, c'mon. There's just way too much good food in California.

Every problem is a solution in disguise: start a good food diet plan—people will certainly buy that.

lol. A tangent, but it so happens that my dad literally tried that because he hated CICO with a passion. An undiagnosed genetic condition took his life (this is a long time ago) before he could publish his book.

I'm sorry for your loss and for the loss of his effort (presuming you or another heir have not taken up the reins of his intellectual property).

Another step to consider in lateral thinking about (personal diet -> diet book) is the marketing of such. Instead of allowing it on the marketplace, it could be sold by word of mouth in the manner of multilevel marketing. Many MLM systems act as giant siphons for unethical people. I wonder if a forking blockchain could act as method to promote honest transparency, where each level of organization becomes a fork.

I mentioned sleep, exercise, and a healthy diet and IMO they're all connected. Nowhere did I mention anything about weight. But since we're on the topic now, I disagree with BMI alone as the single indicator of health. Canada seems to be moving in that direction as well. I try to eat healthy myself, but restaurants borderline conspire against that because healthy dishes just don't sell as well as those California Cream Sauce Specials with limitless bread.

https://www.verywellhealth.com/canada-guidelines-redefine-ob...

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.

My own mom has it right now. It's a godawful disease but her choices are equally godawful and they are getting monotonically worse with her decline. Her brother got it too and died horribly. Her other brother became a health not late in life and did not succumb to dementia but rather died of natural causes around 90 a happy and content soul. So I guess in both instances here we are both anecdotal single data points. But I think we can agree this is a horrible disease.

Absolutely. In the case of one uncle he was tea total, healthy diet, distance running, skiing up to his 70s when he got Alzheimer's. Declined in 2 years to the point where he couldn't be at home as he was too strong for his wife to handle. Covid proved the end of any attempt to cling on to his past as it was made illegal for family to visit him. He's gone completely now. But I suspect his physical fitness will see him last longer than he should.

My mother going this way now too.

Suspect it will be me one day.

Certainly genetic factors involved.

Yes. I don't take all those supplements but I have performed most of the eating/sleeping/exercise rituals because it's normal to do that and not normal to not sleep 8 hours, overeat and not exercise. There are endless new markets to be created from telling people how to be healthy that is not: every day do the same healthy things forever. I think it is sad that this implies that we should wait until we have cognitive decline before we do anything.

"Gluten free, intermittent fasting" are pseudoscience health trends and trying to strawman them as "eating healthy" is disingenuous.

The linked paper is from 2014 - it might even be the source of some of those health trends

No you are not a cynic. But this regimen could be relabeled “good living”. Amazing number of words to get to the actual interventions. And stop smoking too.

It would be wrong to characterize this as a miracle cure, especially given the significant time and effort required to get any effect. It also makes a lot of sense that dementia would end up being like cancer and heart disease in terms of being complex, systemic, and fundamentally related to metabolic activity.

It's quite easy to label something as a fad rather than to attempt to parse the data that supports the interventions they prescribed to the patients in the study (of which there is plenty).

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.

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?

Just wait for another paper claiming that the ketogenic diet is what really works.

While you wait, how about a book from a neuroscientist? https://www.drperlmutter.com/books/grain-brain-by-david-perl...

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/ 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049408/

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

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.

> 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)

The treatment varies for the patients. How would someone reproduce treatments if they don’t know how the particular elements are selected?

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

Should also add cobalt to the list of metals to look at if one has a joint replacement using it.

What is MgT?

Magnesium L-Threonate, also known as “Magtein”

I think it needs a different notation. Could be easily confused with Mg Taurate.

Magnesium Threonate. Seems like it’s specifically meant for cognitive enhancement rather than magnesium deficiency like other forms.

The magnesium l-threonate is better able to pass the blood brain barrier as opposed to other magnesium sources. There are some interesting studies on PubMed around it being helpful for Parkinsons, alcohol related issues, and even short term memory in chronic pain sufferers (some are non-human studies).

Man, that sounds exactly like something you'd see one of the guests on the Tim Ferriss podcast talking about.

What ever happened to ballroom dancing and bridge?

Speaking of which, I think if you want to be smart, don't do brain games. Do what the smartest people do: play an instrument and read challenging books.

I'm learning piano and it's a never ending brain game. You sit there for an hour trying to coax new neurons in various areas to grow.

Can we get one supplement pill that merges all of those that need to be consumed? Kthx.

This is probably sarcastic, but it has long been said that if exercise could be made into a pill it would be one of the best medicines ever and it is true that exercise is known to help with a majority of these issues though not necessarily all. So take an exercise and wash it down with some water and you may get some of these positive effects.

someone always wants a shortcut :P

To a rough approximation, I'd wager that someone == everyone.

Eating real food is better than supplements. That can help a ton.

Eat a can of beans and an entire bunch of bitter greens every day. That covers most of your vitamins and minerals.

Some exceptions apply: Sprinkle flax seeds on top for omega 3s, use iodized salt for iodine (seaweed is high in iodine but also high in bad heavy metals), get fresh air and sunshine for vitamin D, pick out your favorite source of vitamin b12. I believe you'll still need potassium.

For exercise: A good place to start is to walk and bike for transportation. Read this book if you're wanting to be convinced that exercise is a magic pill: Spark: The Revolutionary New Science of Exercise and the Brain

Oh and sauerkraut or something for the microbiome.

Surprised not to see anything about sociality here. I imagine this is a large determinant of health and life span.

visit a new place every day

That's actually part of the "full" Bredesen protocol, I read it in his book, and you're right it is a big part of slowing and reversing the Alzheimer's decline.

Can you expand/replace some of the numerous acronyms/initialisms in here? Like "CHO", just write "carbohydrates". This list could be helpful but it's written too opaquely to be easily digestible by someone who isn't already well-versed in health/diet terminology.

thanks for sharing this, lot of good food, exercise, no late night eating, fasting ...all the things that several people have been telling us recently! Nice to see Ayurvedic herbs too

Needs a (2014)

The paper is from 2014.

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.

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

(comment below answered this)

I've done a bit of research here. It's not snake oil.

They did a trial, https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v..., and it worked very well.

It's being commercialized here: https://www.apollohealthco.com/, and the guy has patents on everything.

"They did a trial, https://www.medrxiv.org/content/10.1101/2021.05.10.21256982v..., and it worked very well."

Only 25 patients, not double-blind, no controls.

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.

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.

Snake oil.

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.

>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.

Your comment is an example of good knowledge without public recognition as it was downvoted. Probably the public goes by keywords like "schizophrenia" and concludes "oh well, that guy is mad I shoulda downvote him for all's good". But I think your comment is good and worthy, as it brings a small bit of data to a metabolic-neurological connection theory.

>ketosis does something to the immune system

Keto utilizes a bit different metabolic pathway compared to the aerobic glycolysis [1, 2]. The reason you observe immune system response when you lower keto and increase hydrocarbons is because glucose metabolic pathway is broken in such patients. Their bodies cannot consume glucose in full and start to starve in ATP, up to the point of tissue damage, all that with excessive lactic acid excretion. When the tissues are damaged, immune system gets activated and attacks them. By doing so, it also affects nearby healthy tissues, leading to wavy but gradual disease progression.

This process is believed to play the crucial role in progression of neurological and cardiovascular disorders.

The part of glucose metabolism that gets often broken in a human is aerobic cellular respiration [2]. It may be an inherited genetical condition or an acquired mitochondrial dysfunction.

By the way, do you happen to have an insulin resistance? If this parameter is not ok, this can be an additional hint. But even if it is ok, the given pathological process may be in place and slowly progress, eventually leading to insulin resistance as well.

[1] https://en.wikipedia.org/wiki/Glycolysis

[2] https://en.wikipedia.org/wiki/Cellular_respiration

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

Brandon could use that.

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/10.1101/2021.05.10.21256982v...). 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.

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@S1474-442...

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