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This is a trash article that belongs in a tabloid. All of those supplements showed preliminary progress but then were refuted by evidence showing that they were garbage.

Saying "these steps might" is as bad as the initial pimping of the supplements in the first place. The failures in this space should put is in a mode of "extraordinary claims" -- until these results get exhaustively researched and replicated it is irresponsible to report on them as any more effective than using hexes and energy crystals to stave off dementia.

Did you even read the headline? “Supplements won’t prevent dementia...”

The first half of the article is all about various dietary supplements and how there is no good evidence for them. But there is decent evidence for exercise, controlling blood pressure, and congnitive training.

I mention the supplements as a comparison. Like the nonsense peddled here, the techniques (increased physical activity, blood pressure management, and cognitive training) have shown preliminary promise. But all three (I boldly predict) will fail on further testing, and even now, as the article itself notes, have failed to produce results that exceed statistical significance.

This is irresponsible reporting that is falling for the exact same magical thinking that led to the hype around supplements. Because attempts to prevent dementia have been previously shown to be without merit, we should report on new ideas with a great deal of skepticism until the evidence becomes very strong.

> we should report on new ideas with a great deal of skepticism until the evidence becomes very strong

A nutritionist with Ph.d with good credibility claims that he got good results with using black sesame seeds. The way he used it is - roast 2 spoons of black sesame seeds and eat once a week for 6 months (no need/should not take every day). He claims to have cured them in 6 months. If I have someone I know I would try as there is no harm in having a regular food item taken once a week. Don't know how it works or if any studies already done to back it up.

Great! Until he does a double-blind pre-registered randomized study (with a control group) and it is published in a serious peer review journal (and reproduced a few times by independent research groups), it should be treated like snake oil.

The harm is indirect, because they are mixing real medicine wit pseudoscience. There are a lot of miracle "cures" that appear every month. Many of them steal the patients or the family money, other steal just time and hope. And in some cases, people following the alternative cures avoid following the standard treatment that is better ot at leas reduces the suffering.

May be you forgot the context I mentioned it in. We have to look for alternatives when there is no definitive one present for the time being.

He's been curing patients for past 20 years with diet changes alone. So, I am impressed with his results and shared his idea. Doing a study on it and not using it until you study is your problem. In other words, I sense your worry of how your medicine will react since it's posion (full of unnatural chemicals) compared to a natural food item in it's unaltered form which is being used in daily food consumption in many cultures. Are you suggesting people taking medicine to stop eating food on a daily basis? I never suggested to stop any medication.

I am more than willing to contact him, will you be able to fund the study?

> He's been curing patients for past 20 years with diet changes alone.

From your other comment:

> He claims to have cured them in 6 months.

I'm not sure how long it takes to transform a 6 month treatment to a paper. I guess 1 year before for designing, filling all the forms and preparations. And I guess 1 year after to process all the statistics, write the results in a nice form, fighting with the referee/editor. So in 2.5 years it could be published. Let's round it to 3 years because it's not my field of study. [1]

So in 20 years he has enough time to publish a serious paper on a cure an a popular illness that has a lot of people working on it. (Perhaps if the evil Big Pharma is blocking his study, he can replace the pre-registration to a single big announcement in a blog post an a hash of the post in the bitcoin blockchain. It's not official, but any good registration is enough. Most of the other steps, like double-blind, can be made anyway.)

[1] In Physics the typical time is 3 month, but there are very few paperwork because the study doesn't use humans. In Math the typical time is more than 1 year, perhaps 2, because math is forever and the review is proportional.

I totally agree. It will be beneficial for everyone.
Where’s his paper in Nature or some other high profile journal? Even as a preliminary result in mice, this would have been big news. The lack of said news means something is wrong with the study.
The field of cognitive training has moved way beyond preliminary promise.

Here's a meta-analysis of 97 published randomized controlled trials, showing reliable improvements in cognitive function and transfer to real-world function [1]

Here's an NIH-funded study of more then 2,800 older adults followed for 10 years showing that speed-of-processing training reduces the risk of dementia by 29% [2]

Disclosure: I work at a cognitive training company.

[1] PDF link: https://www.researchgate.net/profile/Catherine_Mewborn/publi...

[2] https://www.sciencedirect.com/science/article/pii/S235287371...

From [2], above: (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50–0.998, P = .049)

Yowzers -- just squeaked by on that one, didn't they. Given the unknowns around dropouts, I would be frankly astonished if these results stood up. It mainly looks like the "speed" category dubiously "benefited" from a higher death rate; the ~20 excess deaths in that subset can neatly account for ~2 additional cases that drives significance to random-chance levels again.

In addition, the meta-analysis seems to indicate that only memory-based interventions work, while the individual study linked showed differently. Hopefully as pre-registration becomes mandatory it should become clearer how many of these studies were abandoned because of null results.

Can you recommend a book or course that can help me understand stats on clinical trials (if not a stats book with emphasis on clinical trials)?

I feel like I am of those that can easily be fooled by misleading claims.

From [1] (the meta-analysis), "Working memory interventions proved most effective (g = 0.479), though memory, processing speed, and multi-domain interventions also significantly improved cognition."

From [2] (the crash results), deaths and drop-outs were handled by adjusting crash rates to total person-year exposure times. In this study as a whole, non-completion rates were not significantly different across groups.

Yes, pre-registraton is an excellent idea.

Peter Attia did a podcast with Francisco Gonzalez-Lima. Its a pretty fascinating listen where he explains the vascular hypothesis of Alzheimer’s which describes one the problem of impaired blood flow to the brain. The podcast is called "The Drive" if anyone wants to look it up.
The brain is 60% fat and basically the rest if cholesterol; ignoring water.

If you eat a diet which is low in fat and cholesterol, you are going to lack the building blocks for your brain. You're going to have a degrading mind.

That is grossly oversimplified: there are multiple types of cholesterol, and you are very likely eating the wrong one.
There is only one chemical entity called cholesterol. More formally known as (3β)-cholest-5-en-3-ol. Different dietary fats (or other constituents) may play a role in the blood levels of the different _lipoproteins_, such as HDL and LDL.
Nitpick all you want, but this misses the forest for the trees. When we talk about health and cholesterol levels, it is almost always in the context of lowering LDL and increasing HDL. Even Center for Disease Control and Prevention calls them "cholesterols" because that currently is the public understanding of how it affects their health:

> Cholesterol travels through the blood on proteins called “lipoproteins.” Two types of lipoproteins carry cholesterol throughout the body:

> LDL (low-density lipoprotein), sometimes called “bad” cholesterol, makes up most of your body’s cholesterol. High levels of LDL cholesterol raise your risk for heart disease and stroke.

> HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and carries it back to the liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for heart disease and stroke.

https://www.cdc.gov/cholesterol/ldl_hdl.htm

Except that when you eat cholesterol, it is digested and absorbed from the food as cholesterol, not lipoproteins. So it's really silly to say there's "bad" or "good" cholesterol in food.

The main purpose of lipoproteins such as LDL and HDL is to carry fatty fuel around the body. Cholesterol just gets a ride-share along with the fat since it is not water (and by extension blood) soluble.

And the thing that makes levels of HDL and LDL in the blood "bad" has more to do with high blood sugar messing up the lipoproteins' ability to identify itself to the liver (search oxidation & glycation of lipoproteins) which causes excess levels in the blood, than it has to do with cholesterol.

IMO the focus on cholesterol (edit: as the source of disease) in popular science and medicine has been a huge mistake.

I disagree. I'm point out simple facts. We have mental illness growing as a problem, the more that people eat less fat and less cholesterol.

This is a matter of chemistry.

This article seems to have come out in a vacuum while there has been notable research published in the last months. All of these articles have been published on HN.

* On Prions and Alzheimer's being transmissible https://news.ycombinator.com/item?id=19127520

* On insulin resistance linked to the disease https://www.psychologytoday.com/ca/blog/diagnosis-diet/20160...

* On gum disease's links

* On HIV and Herpes medication links to reducing https://news.ycombinator.com/item?id=17540094 https://news.ycombinator.com/item?id=19099157

> This article seems to have come out in a vacuum while there has been notable research published in the last months.

No. The article skipped early research based on weak studies that most likely won't hold up once it's looked at closer. That's a good thing. It means the journalist understands something about science.

All the links you mention may have something in common.

There seems to be bacteria in the gut and diabetes link or inflammation and diabetes link. Gum disease is known to have effects trough letting bacteria and byproducts into the blood. Antiviral medication (HIV and herpes medication) may fight Alzheimer for the same reasons (they kill viruses and reduce inflammation indirectly).

Infections (bacterial, viral or prion) and/or inflammation they cause may be the common link.

It could be that anything that increases inflammation has link to Alzheimer's.

Exercise, sleep, stress reduction and good nutrition may be linked to infections or inflammation as well. Link may be trough improving immune system to fight infections and/or reducing inflammation.

Inflammation and infection tend to go hand in hand. My best understanding is that each can promote the other and treating either successfully can reduce the other.

Chemical conditions that promote inflammation tend to promote infection. Infection tends to cause inflammation.

You likely cannot neatly separate these two health issues.

inflammation is biological response to infection (as well as other irritants).
I'm aware of that. But inflammation also can be caused by, for example, excess acidity. Reversing excess acidity has been shown to effectively break up biofilm, thereby reversing antibiotic resistance.

Seems pretty clear to me that the connection thus runs both ways. It isn't a one way street.

Can you explain what you mean with "excess acidity"? Excess acidity where? In the mouth? What is it in excess of?
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Throughout the body, though most medical sources seem to talk about blood pH.

My understanding:

Life was not able to leave the oceans until there were bony fish not simply because of the need for a frame on land, but also because of the need to regulate the blood chemistry. In the ocean, animals don't need this. The minerals in the water regulate their blood chemistry. Out of the water, bones serve as a store of calcium to draw upon to neutralize excess acidity.

If you are seriously and chronically acid, the body will strip the bones of calcium to keep you alive as long as possible, leading to osteoporosis. Blood needs to remain in a very narrow pH range or you quickly die. Diabetics diagnosed with acidosis are hospitalized. It is a medical emergency that can kill you in two or three days.

Most Westerners dismiss the idea of an alkaline diet as nonsense. It gets lumped in with "nutcase" anti-vaxxers for how "scientific" it is deemed to be. But the first defense against acidosis is diet. You need to not be eating too much of the wrong thing.

Correcting it is tricky because if the stomach gets too alkaline, you become incapable of digesting food and you begin throwing up. So brute force methods of consuming strongly alkaline stuff can go bad places. You really need to straighten out your diet as a first line of defense. Trying to "hack" this doesn't work well.

You can google it, though you will probably get a lot of hits that the HN crowd would outright mock. Here are a couple of "respectable" links to get you started:

https://www.livestrong.com/article/381592-normal-body-ph-ran...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137247/

This theory is total BS.

Acidosis is medical emergency. Human body contains several pH buffers, is someone would be able to saturate them by eating, they would die.

There is absolutely no connection between alkaline foods and blood pH levels. Eating acidic or alkaline foods has no effect on stomach pH, nor does it has effect on the pH of blood.

Alkaline food can alter urine pH, but there is no effect on elsewhere in the body unless you are really sick.

Inflammation is also the biological response to exercise.
True, which is why looking at so generally makes it seem paradoxical.

I can't recall where it read it, but I think it's the result of some phagocytic, either auto- (i.e. lysosomes, intracellular clean up) or macro- (i.e. macrophages, a type of white blood cell used from extracellular clean up).

Seems like there isn't a clear enough syntactical delineation between beneficial (exercise-linked) and harmful (disease/infection-linked) inflammation.

> “The same things we recommend for heart health turn out to be important for cognition,” she told me. “It’s a blossoming field.”

Well, the article just mentions exercise, but you can obviously also take dietary steps to improve artery function, and that includes certain food supplements. So either none of the tested supplements mentioned earlier in the article improve artery function, or there is something else going on that warrants further research.

Anyway, to continue the "foods for a healthier vascular system" train of thought, nutritionfacts.org has a lot of information on what kind of foods cause stiffer arteries, and which ones help improve artery function. I know from past discussions that this is a controversial site on HN, presumably since it so makes extraordinary claims about a plant-based diet being a cure-all for many illnesses associated with Western lifestyles. However, it is not exactly controversial to call the Western diet unhealthy. Furthermore, the website actually cites nutrition research papers that it bases its claims on. That is a whole lot better than food blogs without scientific sources, or worse: people getting defensive over their food habits and sharing their unsourced opinions on what is and isn't a healthy diet.

The short version is: avoid meat, lots of foods rich in phytonutrients, fibres, and polyphenols. So vegetables, leafy greens, legumes, fruits and berries.

As for magical supplements: crushed flax seeds and the Indian gooseberry both appear to have very positive effects on artery health, cholesterol levels (healthy and unhealthy kinds) and hypertension[0][1][2][3].

Sugar spikes/crashes from foods that are too easy to digest can be mitigated when eaten together with the right ingredient, like blue-berries, cocoa, and vinegar[4][5][6][7][8][9]. On top of being a good thing on its own, it indirectly helps because it reduces overeating.

Both coffee and tea also improve artery function, as long as you avoid adding milk[10][11]. Hibiscus tea works even better, but contains so much manganese that you should probably not drink more than one cup of it per day[12][13].

Oh, and that "one or two glasses of wine is better than none" story? False: the research that this claim comes from did not control for people who don't drink alcohol for other health reasons. Fix that and drinking no alcohol at all is the healthiest option[14]. Sorry.

So yeah, all of that together probably will improve your chances at staying healthy into your old age, especially if you have a family history of hypertension (like me). And that might include a reduced chance of dementia.

[0] https://nutritionfacts.org/video/flax-seeds-for-hypertension...

[1] https://nutritionfacts.org/video/which-are-better-chia-seeds...

[2] https://nutritionfacts.org/video/amla-versus-diabetes/

[3] https://nutritionfacts.org/video/amla-vs-drugs-for-cholester...

[4] https://nutritionfacts.org/video/benefits-of-blueberries-for...

[5] https://nutritionfacts.org/video/The-Benefits-of-Acai-vs-Blu...

[6]

nutritionfacts.org is not a credible reference. It's a vegetarian propaganda site.
I'll echo another commenter's "trash" qualifier for the article.

Dr. Bredesen published a study in 2014 that found his protocol effective in people in the early stages of Alzheimer's disease. Some (all?) of his protocol is listed here: https://www.apoe4.info/wiki/Bredesen_Protocol

It includes interventions ranging from dietary (daily fasting, autophagy promotion, minimise inflammation & insulin resistance, prebiotics and probiotics), lifestyle (stress, sleep, exercise, sleep apnea, mitochondrial function), vitamins & minerals, hormonal balance, and more.

The recent articles linking Alzheimer's with insulin resistance, gum disease, HIV/herpes, and more are just bite-size recycling of what Bredesen talked about back then, but strangely without mentioning the whole protocol.

The article is trash not because vitamins aren't helpful (they are, but not on their own without the rest of the protocol), but because the Bredesen study has become quite well-known, and not mentioning it seems akin to malpractice. They might want to present the Bredesen study skeptically or critically, but pretending it doesn't exist, when it's shown success, is eerie. It's like writing an article about sugar in 2019 without mentioning its toxic effect on the body.

The point of this article was that a large part of the Bredesen Protcol doesn't work or is not backed by any studies...
ketogenic diet. Intermittent fasting. The science is catching up.
Nothing on fasting or low carb diet...I've read multiple studies that inducing autophagy through either is linked to reducing Alzheimer's risk...
Autophagy's great, but I prefer to boost mitochondrial function. Coconut oil is great to enhance fat burning. Eat a cup of salt to improve your osmotic potential. Watch out for keto flu!

"We're really on a roll catching all this food. We should fast for three days for autophagy and then post on the internet about it" - every good hunter ever