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Brain inflammation sows the seeds of Alzheimer’s (cosmosmagazine.com)
140 points by fraqed on Dec 21, 2017 | hide | past | favorite | 78 comments



Inflammation seems to be at fault for a whole host of huge medical problems.

The problem is that this is not illuminating. It's like saying that the reason your car blew a rod is because it had no oil in it.

Okay, cool, but why didn't it have oil?

Inflammation is the body's first step in "repairing" a problem. Often times, like with cancer, the body fucks up the repair. So inflammation "causes" so many disorders, but what causes the inflammation?

Saying inflammation causes anything is seemingly clickbait at this point.


Inflammation is like a bad mechanic. It's meant to fix things but sometimes messes it up.


>Okay, cool, but why didn't it have oil?

Good point.

Five Whys:

https://en.wikipedia.org/wiki/5_Whys#Example


Here is a great talk from a doctor who has had success in reversing Alzheimer's: https://www.youtube.com/watch?v=6D5aA_-3Ip8&list=WL&index=20


A tl;dr would be nice. That's an hour+ video.


[Edit]

From the video description:

Dr. Bredesen sees Alzheimer’s disease,- as an imbalance rather than a toxicity resulting in amyloid beta plaques which block nerve cell signaling and lead to memory loss.

Among the measures he recommends:

- A diet that eliminates processed foods and other unhealthy ingredients, and boosts fruits, vegetables and healthy fish

- Stress reduction with meditation, yoga, music or other means

- Eight hours of sleep a night

- At least 30 minutes of exercise four to six times a week

- Very good oral hygiene

- Improvement of gut health with probiotics and prebiotics

- Fasting for 12 hours between dinner and breakfast, and three hours or more between dinner and bedtime, to keep insulin levels low

Published in the September Journal Aging, he did a study on ten patients. Nine of the 10 patients improved. The one patient who did not improve was in the late stages of Alzheimer’s Disease.

---

Additional info

Reversal of cognitive decline: A novel therapeutic program

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/


> Very good oral hygiene

It is surprising how much inflammation can stem from your gums. Floss! I know it's boring. But, it can be rewarding to dig gross gunk out of your mouth that you didn't even know was there. Gross, yes. But, less gross than leaving it there!


"very good oral hygiene" -- I hadn't heard anything about this being linked to systemic health before. My interest is piqued!


My dentist mentioned in passing that seriously (deadly) infections can enter the blood stream via the gum line, so I don’t think this is an obscure notion.


Heart health and gum disease have been linked to https://www.colgate.com/en-us/oral-health/conditions/heart-d...


I would think sleep is pretty important. It's when the brain recovers. Yet I wonder how many drugs prescribed to people later in life disrupt their sleep. I'm going to spitball and say: probably far more than we realize.

And in (say) obesity, which effects a high percentage of adults and is bad for the body (of which the brain is a part) and also effects sleep.

Long to short, plenty of people abuse their bodies as well as theirs minds. Yeah, it's sad. What i don't understand is the general surprise that there might be a cost to that. It's like wanting to party all night and then somehow expecting not to have a hangover. The body doesn't work that way, afaik.


I didn't see alcohol on the list though! :D


The Bredesen protocol probably slows the decline, but I doubt that it reverses the disease.


The reversal seems more along the lines of the effects of the disease + side effects of the previous drug(s). Although if the new treatment stops the damage to the brain then over the course of years, not weeks or months, I could see a recovery of functionality.


Bredesen has published about the reversal and with the small sample of 10 patients showed full reversal in 9 patients. There is no doubt at all when you read that patients were extremely forgetful, unable to do their job and unable to learn a new language were completely opposite after the short treatment: good memory, able to do the old job, and having pleasure learning a new language. Bredesen followed the 9 patients for 4 years after the treatment and there is no new decline. The treatment is a true cure.

There is nothing magical. Inflammation makes a mess of a brain and a healthy body is able to recuperate from almost any disease.


How does the brain become inflamed in the first place? Couldn't find that in their write-up.


Diet. And probably something to do with gut bacteria, which just ties back into diet.


There's also reportedly a connection with bad teeth.


Yes, and this is obvious when you think about it. Sugar causes both inflammation (actually any carbohydrate will eventually) and sugar is why you brush your teeth.

Fascinating books on this include "pure, white and deadly" and "cancer: disease of civilization" (this one is hard to find, written in 1962 I think). The former was written before sugar fully took over, the latter was written back when some cultures didn't get cancer.


Not surprising if true. It seems swallowing the bacteria that flourish when you don't brush/floss your teeth leads to damage to your heart valves (wild!) so other immune responses, typically leading to inflammation, are quite likely.


I always figured they entered your bloodstream through your gums.


I am not aware that the oral mucosa are particularly permeable in this regard.


It bleeds when you floss so it seems like it’s pretty open. But I’m not positive.


"minor insults to the brain – perhaps a virus or mild injury"


Thanks! I was just skimming. I wonder if the anti-inflammatory properties of coffee are enough to help ward off AD. Not sure if the phenols interact with the proteins they discuss here.


A huge number of studies have consistently shown a strong protective effect of moderate to high coffee consumption against AD and Parkinson's


Fine as long as you can remember to turn on the espresso machine...


One alternative theory is borreliosis (Lyme disease).


Any evidence of this?

In the United States, Lyme disease is mostly confined to the north east.

https://www.cdc.gov/lyme/images/maps/2015-dot-map-title.jpg

But Alzheimer's is not confined to the north east. It's not even more prevalent there.

http://www.slate.com/content/dam/slate/articles/arts/culture...


There are claims by an american pathologist, Dr. Alan MacDonald. You can find his research and videos online.


And it should be non existent in other places like Australia if true.


Lyme Disease has been known to mimic the symptoms of so many diseases that in medicine it has the distinction of being known as "The Great Imitator".

Also, tests for it are not completely reliable, some people have it and go undiagnosed or are misdiagnosed for many years, and there are all sorts of anti-medical-establishment conspiracy theories surrounding it. As a result some people think that symptoms or diagnosis of just about anything could really be caused by Lyme Disease.


If true, what can people who already have Lyme disease do to prevent Alzheimer’s?


Not enough sleep.


Dementia is a multifaceted disease, of which sleep plays a big part in the exhaustion of waste products. Inflammation also prevents the exhaustion of waste products.


There's been articles posted on HN about how sleep reduces inflammation.

It's also scary to me because there was a sleep disruption leads to dementia/Alzheimer's piece this week, and I only had five hours last night. Guess I'll have to hope Dr. Bredesen will be able to help, or the electrodes that restore sleep patterns.


You can try melatonin and magnesium.


Paper: https://doi.org/10.1038/nature25158

The research noted here improves the understanding of how inflammation acts to drive the progression of Alzheimer's disease, despite being secondary to the well-known deposition of amyloid-β observed in the condition. Alzheimer's disease is considered to be in part an inflammatory condition. Rising levels of chronic inflammation occur with aging, in the brain and elsewhere in the body, and there is plenty of evidence for inflammation to contribute to a good many age-related conditions. The ordering of cause and effect in Alzheimer's is still somewhat up for debate, but there is evidence for the cascade to begin with amyloid-β, that then produces inflammation as the immune cells of the brain react to it, which in turn leads to tau aggregation. The paper here adds nuance to that possible ordering, suggesting that amyloid-β and inflammation form their own feedback loop, spurring one another forward.

The immune system of the central nervous system is its own creature, quite different in its details from the immune system of the rest of the body, and arguably much more integrated and necessary for the correct function of the brain than is the case in other organs. Nonetheless, similar classes of age-related dysfunction arise, and inflammation is one of the results regardless of protein aggregation such as the formation of amyloid deposits. Immune cells become overly active, but at the same time less effective at carrying out their assigned tasks. Inflammation is a necessary part of the immune response to many of the issues it might have to deal with, typically those that involve destruction, as as removal of senescent or potentially cancerous cells, and mounting attacks upon the pathogens that constantly try to invade the body and brain. If permanently switched on, however, inflammation begins to disrupt all of the other necessary tasks of the immune system, such as those relating to regeneration or shepherding the correct function of brain cells.

For a number of years now, some researchers have departed a little way from the mainstream focus on removal of amyloid-β to consider an anti-inflammatory approach to building therapies for Alzheimer's, but this line of research hasn't made a sizable impact yet. Reducing inflammation in a usefully targeted way is still quite challenging, as the immune system is very complex, though promising noises are emerging from research groups investigating NLRP3 as a target. That also happens to show up in the research here as a part of the connection between immune cells, amyloid, and inflammation.


Do you know much about nlrp3? I read an interesting paper by some investigators who later formed a company called inflazome, but am not sure how the biology or chemistry has evolved since then


It is getting more attention these days, and the older discoveries have had enough following attention to be fairly widely known in the field. It isn't a line of research I've followed specifically, but if you look at PubMed you can follow the trail over the past decade.

https://www.ncbi.nlm.nih.gov/pubmed/?term=nlrp3

They have a histogram by year, and papers looking it over in the context of inflammation are getting quite common. I'd expect some sort of trial to emerge in the next few years, it seems to be getting to that point.


Extended results of the Alzheimer's disease anti-inflammatory prevention trial (2011)

https://www.ncbi.nlm.nih.gov/pubmed/21784351


So it is useless to consume ibuprofen and the like, to avoid the disease :(


From my own research (ie googling), your best bet is to build up the brain, so if the decline starts, you have a stronger starting point. This means exercise[1], B12, folate, CDP-choline[2], turmeric[3], coconut oil (medium chain triglycerides) [4]. Also, I avoid paracetamol, there are some claims about it being linked to dementia. There are some promising drug trials (aducanumab for example), but we'll have to wait and see.

[1]https://www.health.harvard.edu/blog/regular-exercise-changes...

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

[3]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781139/

[4]https://coconutketones.com


paracetamol is acetaminophen(Tylenol) for the Americans in the audience.


It's interesting medicine would pursue this symptom in determining brain and nervous system problems - inflammation has been linked to depression, suicidal thinking and other mental disorders in recent research.


A plant-based diet is naturally anti-inflammatory and thought to be a great way to prevent and help reduce the symptoms of Alzheimer - https://www.youtube.com/playlist?list=PL5TLzNi5fYd8E6GHQcmIW...

I wonder if Alzheimer, just like heart disease and diabetes is mostly a western diet-related disease.


Vegetarian propaganda would say so. But Western societies are far from the biggest meat-eaters out there. Do the Maasai and the Inuit suffer from inordinate rates of Alzheimer’s?

The common factor in the diseases you mention is sugar.


The inuits did have high artero esclorosis and heart disease, as seen in 500 years old mummies.

The idea that inuits are healthy despite their high meat diet is a myth, have a look here https://www.youtube.com/watch?v=9LvGiiZyn-M


Just spitballing here, but the Inuit eat a lot of omega-3 which is anti-inflammatory.


There are a number of fallacies in your statement. 1) Western societies are large populations that eat meat and eat meat more than other large populations, by far.

2) Inuits live 10 on average less than the local nearby populations and 900 year old Inuit mummies also show signs of advanced osteoporosis.

3) Processed sugar is not a health product and is not the polar opposite of meat. It is in the same category of meat as 'unhealthy' and 'causes inflammation'

4) A whole-foods low-GI plant-based diet has been show to open up arteries and that is important for Alzheimers as people with that disease do show blocked arteries to the brain post-mortem. So while not a 100% prevention, it certainly reduces risk and may even reverse issues.


The "pro meat" (or should I say "meat health and environmental damage negationists") circle jerk on HN is sure strong, looking at your post and below's slowly fading away. I'm amazed everytime how the majority here, people who seem in other conditions able of logical reasoning, are just impermeable to unpleasant facts. You bring up good arguments.


So the tens of thousands of people who have successfully used a keto diet to induce autophagy and lose weight are all just.. making it up, in your mind?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/

Maybe you should admit it's a bit more complicated than you seem to realize.


"Long-term effects of a ketogenic diet in obese patients".. read the first line. Its 16-24 weeks. Thats not exactly long term. Also, the study was done for people at home, not in a clinical ward.

Try this 8 year study instead https://www.ncbi.nlm.nih.gov/pubmed/20592131 Or if you want a long term RCT, try this 74 week one: https://www.ncbi.nlm.nih.gov/pubmed/19339401


Does keto diets have anything to do with the arguments presented by above poster, that could explain the downvotes ? Did I mention keto diets ? What is your point ?


Discussing a "circle jerk" (not a term consistent with the standards of discussion here) amongst an unnamed deluded majority that "seems to" exist is a rhetorical strategy that I will downvote, despite my generally vegetarian/sustainable meat consumption leanings


Do you have another explanation as to why the post which I responded to is solidly downvoted, with no answer or contest of its arguments which could explain this phenomenon ?


There is a range of research to suggest that Alzheimer's is a metabolic disorder with high level similarities to type 2 diabetes. You might look up "type 3 diabetes" - which is not an official designation, but sufficiently discussed in the research community and associated with Alzheimer's disease that when a different form of (definitely) age-related diabetes was discovered recently, it had to be called type 4.

Equally, don't look for single causes. There are multiple contributing factors, all of which interact with one another, and many of which have multiple causes. E.g. amyloid buildup can be in part failure of clearance by immune cells, in part failure of drainage of cerebrospinal fluid through the cribiform plate, in part generation by lingering spirochete infection, etc.


Well, sugar does cause inflammation, and the western diet is kind of built on sugar


Thats not true. Western diet is build on processed foods - which includes lots of processed sugars and processed fats together.

Example, I don't see people eating teaspoons of white granulated sugar all day long.

Doughnuts and ice-cream on the other hand...


Why Western diet? Cultures other than western eat meat


Western diets have more meat and less plant material. Meat consumption (and plant consumption) isn’t boolean-valued, unlike (for example) vegetarianism.


In this context I wonder whether the problem is meat per se, or the heavily processed nature of much of the meat consumed in the West.


Modern "western" meat is very lightly processed compared to what we were eating a hundred years ago. Refrigeration has removed the need for carcinogenic preservatives and has nearly eliminated stomach cancer.


>> I wonder if Alzheimer, just like heart disease and diabetes is mostly a western diet-related disease.

Nope.

One of the professors I worked with in grad school did some groundbreaking Alzheimer research on Germans from Russia:

We have studied 28 kindreds with familial Alzheimer’s disease (FAD) that are all descended from the ethnic group of Germans from Russia. Eighteen families were of Volga German ancestry, originating from the same two villages and containing 132 demented individuals.

These families represent a model of genetic heterogeneity when compared with other reported FAD kindreds. Because of their common, isolated ethnic background, the Volga German families are likely to represent the founder effect and a single, as yet unidentified, autosomal dominant mutation. The Black Sea German kindreds may represent additional heterogeneity.

https://link.springer.com/chapter/10.1007/978-3-642-46776-9_...


The keys to anti-aging and anti-brain degradation are daily intermittent fasting, plant/fruit based diet, low sodium, low fatty foods, and low stress. Many monks in the far east follow this and live well into their 120s


No they don't live well in to their 120s. You just made that up.


> "In fact, it is not uncommon for a Tibetan monk to live to 120 years of age"

Just one of many sources its very well documented that monks live very long lives. Not sure why hes being downvoted.

blog.peterbaksa.com/post/9719815756/tibetan-monks-my-lama-temple-interviews


It's totally true.. links to Law of Attraction blog

Come on now.


He's being downvoted because it's not true. The oldest person on record was 122. If there were a bunch of Tibetan monks walking around at 120+ we'd know about it.


Just like everyone knows about the drastically different disease rate in orthodox monks?

https://www.thetimes.co.uk/article/a-foolproof-anti-cancer-d...


Many eastern tibetan monks claim to be 120+ years old. Due to the nature of their lives its very hard to document birth to death. Of course people deny it because its not "on record." likely due to longevity bias that humans naturally have.

https://en.wikipedia.org/wiki/Longevity_myths


There's true, false, not proven. It (claim to be 120+ years old) is not proven. Necessarily, it's not true. If it becomes true in the future, the studies would be interesting. That's obvious. Basing any sort of continued argument or worse, research, on wishful thinking is something left up to you.


According to Dr. James DiNicolantonio, we should be eating more salt, not less (https://twitter.com/drjamesdinic), but I agree about the intermittent fasting.


I think the dangers of a high sodium diet are pretty well documented, especially in the west where they have very high obesity rates. I would take Dr. DiNicolantonio's advice with a "grain of salt" haha


Documented in what way? All studies focus on people who already have heart disease. Just because sedentary couch potatoes on a high salt diet get sick does not prove causation from the salt. Everyone's body has built in regulatory systems to maintain isotonic balance and excrete the excess. We couldn't have crawled out of the sea without this fundamental ability. But, of couse, everybody knows salt is bad.


> Documented in what way?

Some of the most reputable organizations in medicine have documented the dangers of an high sodium diet.

https://www.hsph.harvard.edu/nutritionsource/salt-and-sodium...

https://www.cdc.gov/salt/pdfs/children_sodium.pdf

There are still some people that believe that smoking doesn't cause cancer after decades of research. In the end you are free to believe as you wish. Godspeed


Sodium, while a main (50%) ingredient of salt, gets into us for example with the probably most popular ingredient ever, monosodium glutamate. I personally believe it's the excess of one polarity ion over another that's detrimental to our health.


Well, I've read that 2-3g per kg at once can actually kill you. It's even a method of suicide.




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