[HN Gopher] Organ transplant patients may not get dementia
___________________________________________________________________
Organ transplant patients may not get dementia
Author : klevertree
Score : 230 points
Date : 2021-11-03 14:42 UTC (8 hours ago)
(HTM) web link (trevorklee.com)
(TXT) w3m dump (trevorklee.com)
| [deleted]
| treeman79 wrote:
| Theory. People who take immune suppressing drugs have less
| dementia. Perhaps undiagnosed autoimmune conditions are a cause /
| trigger for dementia.
|
| My experience. Had out of control undiagnosed autoimmune
| condition.
|
| Started developing major dementia.
|
| Eventually (20 years) got autoimmune diagnosed and under control.
| Also started blood thinners. Dementia resolved quickly.
| mhalle wrote:
| As a liver transplant recipient (7.5 years out), I find how
| transplant patients are stereotyped in this somewhat informal
| article a bit misleading.
|
| First, transplants are about as close to a life-changing miracle
| as you can imagine. By which I mean night and day change for a
| reasonable subset of patients. The fact that we now have anything
| like access to interchangeable parts that can let people live
| extremely normal lives is absolutely remarkable. Before
| transplant there were times when I was too weak to walk. One
| month after transplant I could walk a mile, three months after
| five miles.
|
| There is zero question I'd be dead by now without my transplant.
| I might have lived a year or so more with my old one, but it
| would have been an unpredictable high-wire act between GI bleeds,
| encephalopathy, coma, and fear that any simple action might
| trigger an emergency trip to the emergency room. Internal
| bleeding and encephalopathy put my in a coma for three days and,
| when I came out, this PhD computer scientist couldn't remember my
| own kids' names. Now I'm writing this. I am simply so fortunate
| to be able to have this second chance in life.
|
| As for the misleading parts, "Organ transplant patients are, by
| their nature, sick patients." Yes, but that's why they get
| transplants. Many get better. Look at livers. Viral hepatitis (in
| my case, Hep C) is one of the most common reasons for liver
| transplant. But we can cure Hep C. I was one of the first people
| cured before transplant with Gilead's Hep C antivirals. The new
| liver fixed my cirrhosis. Now I get sick less often than my kids,
| and my life is extremely normal except for a couple pills a day
| (tacrolimus) and lab tests every three months. I was a mild
| hemophiliac, and that was cured by the new liver as well.
|
| If you looked at my lab tests, besides a low platelet count, I
| would look perfectly normal. And especially for livers, which
| deal with processing a lot of foreign substances in the body, so
| it probably more tolerant than other organs, the lifespan on them
| may be quite long. Older liver transplant patients can sometimes
| even drop their immunosuppressants completely.
|
| So, for people who have curable diseases, the health of a
| transplant patient can be quite good, potentially better than
| their peers. There's no specific reason they as a single less
| healthy class (as opposed to a set of classes, which also
| includes people who abuse alcohol or have diseases we can't
| cure).
|
| To answer some other questions in the discussion, the transplant
| process tries hard to keep someone from being able to literally
| buy their way onto the transplant list. For livers, priority of
| transplant goes by a lab test called MELD which estimates 90 day
| mortality. You have to be sicker than other people but healthy
| enough not to waste an organ. It's a fairly macabre competition.
|
| There are, however, advantages to those with means. In the US,
| organ transplant is administered nationally but organs are still
| basically allocated regionally. If you can travel to another
| region in the country with a surplus of organs, you can get a
| transplant sooner. I did it. It saved my life.
|
| You also need to go through a battery of tests to make sure you
| are, basically, a good host for the rare organ. In general you
| have to stop substance abuse. You need to lose weight. You need
| to take a physical which can disqualify you. You need to have a
| social support mechanism to help take care of you after surgery
| (in the hospital, after discharge, and long term).
|
| Finally, you need to have insurance that will cover the
| potentially million dollar surgery and and complications that
| might follow. And that means there's another hidden process that
| happens in the insurance company to assess whether you're a good
| risk or not.
|
| Most of those conditions strictly require wealth. All of them
| benefit from it, especially access to health care. On the other
| hand, it isn't clear that access to health care is strongly
| correlated with an absence of dementia, is it?
| supperburg wrote:
| People talk about inflammation vs metabolism. They are linked.
| Inflammatory signals can turn cellular metabolism up or down.
|
| African sleeping sickness is an infection that results in a
| person going into a kind of coma. The parasite constantly changes
| its molecular interface with the host which is supposed to
| confuse the hosts immune system. This places a huge burden on the
| immune system and results in the host becoming hungry all the
| time, despite already being full. These patients will stuff
| themselves while growing progressively more tired. And eventually
| they fall asleep permanently. Inflammatory signals slow
| metabolism or something to that effect and this change in
| metabolism causes the body to feel as though it's starved of
| energy and so the patients feel hunger. Inflammation and
| metabolism are linked.
|
| A man with schizophrenia was cured after a bone marrow
| transplant. The New York Times wrote about it recently. Symptoms
| of age including cognitive decline have been reversed in mice and
| humans through blood dilution/ blood transfusion probably due to
| reduction in the concentration of inflammatory molecules in the
| blood that are produced by ones own body. Inflammation/metabolism
| is the biggest medical revolution on the horizon. Especially
| since COVID has made it a grant-worthy topic now and doctors
| can't deny that chronic fatigue syndrome is real anymore. It's
| funny how all those people who insisted that CFS wasn't real are
| now nowhere to be found to answer for their mistake.
| fumar wrote:
| How do you influence inflammation to increase metabolism? Are
| you saying high inflammation increases cognitive decline?
| erentz wrote:
| > It's funny how all those people who insisted that CFS wasn't
| real are now nowhere to be found to answer for their mistake.
|
| Oh a many of them are still out there. Now pushing CBT and GET
| as a cure all for Long COVID.
| circlefavshape wrote:
| I have direct experience of this. My wife has had long covid
| for the last year, has had dozens of medical tests, and none
| of them have showed up anything except for POTS.
|
| I can understand why a neurologist would suggest CBT. All my
| wife's test results are normal, so the neurologist has no
| remedies available. People _do_ get psychosomatic illnesses,
| and in those cases CBT _does_ help. That doesn 't mean that
| my wife has a psychosomatic illness, but there's no test for
| that either - can't hurt to try
|
| (FWIW this is not the way my wife saw it - she was pretty
| furious and felt like the neurologist was demeaning her
| condition)
| tweedledee wrote:
| I have hEDS which can cause POTS and had the exact same
| experience. The Golden Girls covered it over 30 years ago
| https://www.youtube.com/watch?v=vVyLZTKDy2E and it is still
| the default response.
| yosito wrote:
| Results aside, I give this article points for clear and
| persuasive writing!
| fbanon wrote:
| Is it safe to buy this stuff over the internet/dark web? I want
| to try it, maybe it has nootropic effects on healthy brains too.
| klevertree wrote:
| To add to what everyone else said: it's not just an
| immunosuppressant, it's an immunosuppressant with
| unpredictable, severe side effects. It's really interesting,
| and I hope to reformulate it to make it possible for healthy
| people to use, but you will cause severe damage to yourself if
| you self-administer.
| TedDoesntTalk wrote:
| Are you looking for any kind of help besides funding?
| somesortofthing wrote:
| It's an immunosuppressant, and it seems like the mechanism of
| action is preventing brain cell death. You'd have to be pretty
| old to benefit at all, and you're risking potentially fatal
| infection to maybe possibly get some nootropic effects. I
| _really_ wouldn 't risk it if I were you.
| gpm wrote:
| > 3. There's something different about how the University of
| Texas hospital administers calcineurin inhibitors vs. the
| average hospital.
|
| > This is entirely possible. Calcineurin inhibitors are
| dangerous and difficult to administer correctly,
|
| I know nothing about this drug... but probably not a good
| idea..
| bencollier49 wrote:
| Given that it suppresses organ rejection, my untrained
| speculation is that it might make you more prone to cancer.
| macNchz wrote:
| Yes, per https://www.ncbi.nlm.nih.gov/books/NBK304321/
|
| > There is sufficient evidence in humans for the
| carcinogenicity of ciclosporin. Ciclosporin causes cancer of
| the skin (squamous cell carcinoma), cancer at multiple other
| sites, and non-Hodgkin lymphoma.
| InfiniteRand wrote:
| It's an immunosuppressant, so you might want to make sure you
| don't need your immune system too healthy before taking it ;)
| alasdair_ wrote:
| According to my Facebook feed, All I need is to replace my
| immune system with Invermectin and Colloidal Silver and I'll
| be fine.
| thrill wrote:
| As an opposing anecdata, my aunt got a heart transplant in the
| late 70's, is still kicking, but has severe dementia now in her
| mid 70's.
| oaktrout wrote:
| There are multiple types of dementia, a woman with known heart
| disease might have vascular dementia (dementia related to
| decreased blood flow to the brain). This article is really
| about alzheimers (although that's not clear from the title, it
| should probably say "(maybe) don't get alzheimers").
| patall wrote:
| That would be (most likely) an absolute world record in
| surviving with a heart transplant. In 2016, someone died with a
| survival Guinness Record of 33 years [1], your Aunt would
| exceed that quite far. Current (non-official) US record
| supposedly is 35 years [2]. I am not saying your are mistaken,
| just noting that she might be an outlier.
|
| [1] https://www.bbc.com/news/uk-england-beds-bucks-
| herts-3554369... [2] https://www.wbay.com/2021/06/29/green-bay-
| man-nations-longes...
| [deleted]
| panzagl wrote:
| Maybe he means just a valve?
| Traubenfuchs wrote:
| Does she take calcineurin inhibitors?
| [deleted]
| thrill wrote:
| I have no idea.
| whoknowswhat11 wrote:
| Wow - that is an absolutely incredible result for a heart
| transplant! Very unusual situation. Be interesting to
| understand the specifics - and the team doing this kind of
| work!
| OscarCunningham wrote:
| Not everyone who needs an organ transplant gets one. So could it
| be that recipients are privileged in some way that also prevents
| them getting dementia?
| bbulkow wrote:
| Very nice to read a balanced paper, but a hospital might very
| well ( and, I think, illegally ) give some transplant people
| priority. Isn't that what happened to Steve jobs? No one is
| supposed to jump the queue, but he did. If 'queue jumping' is
| illegal, and happening at one hospital, I could imagine that as
| the kind of stunning bias shown in the data, and everyone
| involved would say it isn't happening
| wombatpm wrote:
| Transplants are coordinated regionally. Jobs just purchased
| homes in multiple areas with shorter wait times than
| California. One of the advantages of being rich.
| hpagey wrote:
| Incorrect. You don't have to be rich. I am currently being
| evaluated for deceased donor transplant outside my home
| state of California. You just have to register at another
| center and you are allowed to multi list. Some states have
| residency requirements but lot of them do not.
| pkaye wrote:
| You can multi list at different transplant clinics across the
| country. They just require you to be able to travel quickly
| on call. Steve Jobs has a private jet so he pick anywhere in
| the US.
|
| And each type of organ has different priority criteria.
| Kidneys for example you have a wait time and compatibility
| score. Liver is by MELD score and how healthy the person it
| (sick enough to need it but not too sick!)
|
| Also a lot of transplant patients fall under Medicare and are
| not rich at all.
| bink wrote:
| As I recall it he didn't so much "queue jump" as he used his
| private plane to travel to another state within a specific
| window of time from where he lived, which most people who
| lived outside of the transplant state couldn't do. So he was
| able to get on multiple transplant waiting lists.
| asow92 wrote:
| Also wondering if lifestyle choices of those post-op have
| anything to do with this. i.e. better diet, exercise, etc.
| tacobelllover99 wrote:
| Couldn't read after they said Huffpo is Journalism
| jhales wrote:
| Isn't Rapamycin generally used as part of an immunosuppressant
| cocktail for organ transplants?
|
| Curious why that isn't mentioned in the article as a contributing
| factor.
| klevertree wrote:
| I thought it'd be too much in the weeds. The UTexas paper goes
| into their prescribing data and comes out with the conclusion
| that calcineurin inhibitors are the only common factor in their
| patients who don't get dementia.
|
| Rapamycin also does not have any evidence of efficacy on
| neurodegeneration, while there's evidence for CNI on other
| forms of neurodegeneration.
| TedDoesntTalk wrote:
| What are the side-effects of calcineurin inhibitors ?
| gzer0 wrote:
| Cyclosporine has some very serious long-term toxicity
| (especially renal dysfunction and hypertension) and the
| availability of newer biologic agents has restricted the
| use of cyclosporine to patients who have not responded to
| conventional treatment. *Mild tremor is
| common with both cyclosporine and tacrolimus use, occurring
| in 35 to 55 percent of patients [ 79,80 ]. *Rarely,
| patients develop severe headache, visual abnormalities, and
| seizures. This syndrome is associated with acute
| hypertension and resembles hypertensive encephalopathy [ 77
| ]. *Posterior leukoencephalopathy is usually seen on
| brain imaging [ 82 ]. *Cyclosporine may contribute to
| bone loss after organ transplantation [ 88 ]; this effect
| may be due to the induction of high bone turnover.
| *Cyclosporine can cause hyperkalemia and hypomagnesemia,
| via effects on renal tubular function. Hyperuricemia and
| exacerbation of gout are well-described with cyclosporine.
|
| [77]. Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine
| neurotoxicity and its relationship to hypertensive
| encephalopathy: CT and MR findings in 16 cases. AJR Am J
| Roentgenol 1995; 165:627.
|
| [78]. Eidelman BH, Abu-Elmagd K, Wilson J, et al.
| Neurologic complications of FK 506. Transplant Proc 1991;
| 23:3175.
|
| [79]. Randomised trial comparing tacrolimus (FK506) and
| cyclosporin in prevention of liver allograft rejection.
| European FK506 Multicentre Liver Study Group. Lancet 1994;
| 344:423.
|
| [80]. A comparison of tacrolimus (FK 506) and cyclosporine
| for immunosuppression in liver transplantation. The U.S.
| Multicenter FK506 Liver Study Group. N Engl J Med 1994;
| 331:1110.
|
| [81]. Wijdicks EF, Wiesner RH, Krom RA. Neurotoxicity in
| liver transplant recipients with cyclosporine
| immunosuppression. Neurology 1995; 45:1962.
| leokeba wrote:
| I'm surprised the author does not mention taking steps to verify
| the "unique University of Texas protocol" hypothesis. It really
| looks like the most probable alternative explanation, and it
| doesn't seem very difficult for someone already in the medical
| industry to get in touch with one of the people there who could
| be able to verify it. Maybe I'm missing something ?
| krisoft wrote:
| > Maybe I'm missing something ?
|
| I'm afraid it appears so.
|
| The article says they contacted the authors of both
| publications but haven't got a response back yet. Relevant bit:
|
| "For my own part, I've contacted authors of both papers, but
| haven't received substantive responses from either. I'll update
| this post when/if I do."
| gzer0 wrote:
| It is very difficult to engineer animals with symptoms mimicking
| human dementia so they can effectively be trialed with drugs
| before testing on people.
|
| This is the exact reason dementia / Alzheimer's research is
| littered with dozens of high-profile failed clinical trials;
| after billions and decades poured into this area and nothing to
| show.
|
| I would be interested to see non-murine, primate-based(?)
| clinical findings before I get my hopes up again. We have seen
| this pattern too many times; a compelling agent, pathway, or
| signaling mechanism is found, targeted, and shows great promise
| in mice, even sometimes in primates. And once we get to human
| trials it fails because we cannot replicate dementia accurately
| in these test vehicles.
| genewitch wrote:
| I'm not seeing much mention of diet and gut biome in these
| comments, over the last decade they're linking satisfactorily
| the gut to so many different ailments in later life, including
| Alzheimer's and dementia. Additionally studies are linking
| diet/gut Flora to stuff like autism, some inflammatory
| diseases, etc.
|
| If I was born 15 years later I'd probably have gone into that
| field of study as it probably makes the most fiscal sense -
| from a national medicine standpoint - to combat these disorders
| and diseases at the actual source.
|
| I wonder if there's been a metastudy on the median lifespan
| going up and incidence of these cognitive or neurological
| disorders. That is, now that humans on average are living
| longer, perhaps our diets are more important; and with his
| knowledge we can get some enhancements on regulations from the
| FDA or something.
| easytiger wrote:
| There is a genetic component that seems very much ignored too
| caymanjim wrote:
| This is an interesting pop-science read, but who is Trevor Klee?
| As far as I can tell, he's a college exam tutor who's written a
| few "how to pass the GRE" booklets. He's writing about trying to
| start a biomedical business around this idea, but if his LinkedIn
| is accurate, he's never had a job beyond tutoring college
| students. His list of "failed projects," linked to from the blog,
| contains a bunch of similar biomed business ideas, none of which
| have anything at all to do with each other on a technical level
| ("Using RNAi for agriculture", "Exploring ketamine for blood
| pressure").
|
| This basically reads as "I got a masters in molecular bio, have
| never worked in the field, and want you to give me money for my
| next crackpot idea". That doesn't mean the idea is wrong, but
| this guy isn't the one who's gonna make it happen.
| tibbetts wrote:
| Anybody asking me for money to cure Alzheimer's I just at this
| point assume is Theranos 2.0. There are plenty of well informed
| life sciences investors with very deep pockets.
| 300bps wrote:
| Yeah I'd be as likely to buy a magical anti-dementia rock as
| invest in this.
| jointpdf wrote:
| This is quite the display of unnecessary credentialism. It's a
| blog. A nicely-designed and seemingly useful one at that (I'm
| finding this post on IBS to be a handy summary and pointer to
| studies: https://trevorklee.com/a-complete-guide-to-self-
| diagnosing-a...).
|
| From what I can tell, this is a humble, curious, and well-
| meaning guy that funds his menagerie of research interests with
| a successful tutoring business (a noble career in and of
| itself). I see absolutely no need to frame him as an unworthy
| crank.
| meowface wrote:
| I don't think the parent was taking much issue with the blog
| posts or the fact that he's a tutor. I think it's his
| previous companies, plus this paragraph from the post:
|
| > So, first of all, the confession: I'm not a neutral
| observer here. In talking about this paper, I'm talking my
| own book. My company, Highway Pharmaceuticals, is currently
| raising funds to get a safer, easier to use, extended-release
| version of cyclosporine, the most common calcineurin
| inhibitor, into first-in-human trials. If this paper is
| correct, investors should probably consider throwing money at
| me.
| caymanjim wrote:
| Yes, this. I enjoyed the blog post. It was an easy read,
| the idea is intriguing, it linked to a related paper. I
| found the plug for the company mildly offputting, and
| decided to see if the author was someone actively working
| in this space.
|
| I don't think anyone needs credentials to have an
| interesting idea, but it's laughable that someone with no
| lab or research or business experience is an actual player
| in this space. I guess people can invest in him if they
| want. The idea that he's fundraising for human trials is
| laughable.
| mcguire wrote:
| As they say, ideas are easy. Execution is hard.
| [deleted]
| [deleted]
| cellis wrote:
| I don't know much about how the biotech industry works, but are
| you saying that he should "work in the field" before pitching
| this idea? In software that would be almost laughed at as a
| suggestion, if the idea is indeed promising.
| mcguire wrote:
| And how many times have you been faced with "I have this
| great idea, I just need a few programmers to build it"?
| Barrin92 wrote:
| >In software that would be almost laughed at as a suggestion
|
| yes because we don't care if our software breaks every five
| minutes and if its clobbered together by people who have no
| idea what they're doing because 99% of the time it's just
| consumer gadgets anyway. If you deal with technologies that
| affect people's health that's not really how things work, or
| in any other serious engineering discipline.
|
| If the semiconductor or aeronautics industry would work like
| the software industry your computer wouldn't boot up and the
| planes would double their fuel consumption every year
| meowface wrote:
| >yes because we don't care if our software breaks every
| five minutes and if its clobbered together by people who
| have no idea what they're doing because 99% of the time
| it's just consumer gadgets anyway. If you deal with
| technologies that affect people's health that's not really
| how things work, or in any other serious engineering
| discipline.
|
| Yeah, you're not really gonna get away with an "oopsie
| woopsie!! we made a widdle fucky wucky! our elves are
| working vewy hard to fix this!" after you kill a few people
| due to negligence.
| coldtea wrote:
| No, in software terms, he's saying that is somebody comes and
| tells you "Software that has enough spaces, never crashes",
| and he "happens" to be selling the "Extra-spaces-adder" IDE,
| then maybe don't believe him...
| bawolff wrote:
| The irony of ranting about starting with the most interesting
| part of your thesis for 5 paragraphs, before actually starting.
| mcguire wrote:
| It's a good way to hide the fact that your thesis is pretty
| sketchy. Say you have one result that has replication issues,
| but don't want to appear too crackpotty or dishonest while
| emphasizing that brilliant result. So you do a little song and
| dance beforehand.
| p00l00 wrote:
| Im surprised nobody has suggested MicroRNA. In particular mir-29.
| But that remains to be thoroughly interpreted.
| https://www.frontiersin.org/articles/10.3389/fnins.2020.0056...
| [deleted]
| erdo wrote:
| These stats are only useful if we know how many people get
| dementia in the first place.
|
| What are the chances of a random control group of 14 over 85 year
| olds also not getting dementia?
|
| If it's very common, and you would usually expect 7 of them to
| develop dementia, then 0 cases in the test group is potentially
| impressive. If it's quite rare and you would usually expect only
| one of the control group to get dementia, then it's not that
| impressive that the test group had 0, and easily down to chance
| Epenthesis wrote:
| That's what the first image in the article is purporting to
| show (~33% of people in the general population over 85 have
| dementia)
| erdo wrote:
| Ha of course it does, thanks :) I don't know why I didn't see
| that
|
| so we could expect about 5 people with dementia in that
| control group, and the test group got 0, so not bad
| mcguire wrote:
| That is a tiny sample.
| jannyfer wrote:
| It'd be nice to take out the clickbaity "here's why" from the
| title.
| datameta wrote:
| The statistical prevalence of dementia is absolutely shocking to
| me... It is bar none one of the worst experiences one can go
| through. This [0] is an album that is an auditory approximation
| of it. I sincerely hope for more discourse and research dedicated
| to understanding, preventing, and treating it.
|
| [0] https://youtu.be/wJWksPWDKOc
| nojs wrote:
| "The Father" is another excellent portrayal of the emotional
| turmoil.
| GhettoComputers wrote:
| Music can help dementia and Alzheimer's.
| https://youtu.be/G7vkKHYosuQ
| datameta wrote:
| Yes, absolutely! My grandfather, even in the very late
| stages, could deeply enjoy music from his youth and appeared
| to regain some lucidity while listening to it.
| fbanon wrote:
| An auditory approximation of dementia - what does that even
| mean?
|
| This is just an album that was inspired by what James Leyland
| Kirby (The Caretaker) read on dementia. It does not have
| anything to do with actually experiencing dementia.
| meowface wrote:
| You're right, but I think the part that's ostensibly
| analogous is the slow, progressive decline. Which is
| something that happens with many chronic illnesses, but the
| notion of slowly losing your mental capacities is one of the
| worst kinds of decline.
|
| The music's coherence and form very gradually breaks down in
| an unsettling way as an abstract metaphor for the
| neurological dilapidation. It's of course nothing at all like
| the experience itself, but it's just an attempt to
| artistically portray it very abstractly and indirectly.
|
| (Side note: I was actually never a fan of this album or its
| concept after seeing it saturate music forums over the past
| several years, and all its associated "this album broke me"
| memes made me consider it pretentious and melodramatic, but
| the process of writing this post somehow changed my opinion.
|
| I think maybe because I suddenly found myself in the frame of
| feeling compelled to defend it from what I felt was an overly
| unfair and dismissive critique and became aware of my own
| cognitive dissonance. I suppose that's one way HN's
| stereotypical pessimism and negativity also has some benefit.
| I could see myself in the mirror of your post and I didn't
| like what I saw.)
| datameta wrote:
| It means it is intended to evoke something approaching the
| feelings and mindspace associated with dementia.
|
| We have works of art that allude to or generate all sorts of
| human feelings. While perhaps "the real deal" would be a
| piece of music written by someone who was actually going
| through the ordeal themselves it absolutely reminds me of
| collections of paintings or books created by artists with
| progressing dementia.
|
| As someone who lost a family member to it, I couldn't stand
| to listen to much of the album because it is just too on the
| dot.
| asow92 wrote:
| Is it weird that I was listening to music kind of like this
| right before clicking on this?
| https://www.youtube.com/watch?v=aMJyQK4xBUQ
| asow92 wrote:
| Honestly though I'm sort of loving this music. I'm 29 years
| old and feel like I have a false nostalgia for this kind of
| music.
| burning_hamster wrote:
| I am not sure I buy into the author's calcineurin/mitochondria
| hypothesis.
|
| There is a much more direct causal link as auto-immunity has been
| implicated in AD progression for years, e.g. [1-11]. I can't find
| the paper right now, but I once saw a very compelling
| longitudinal study where they regularly measured cognitive
| performance as well as several immunity markers in older
| subjects. Basically, every transient increase in antibody levels
| (IIRC, but they may have been tracking some other marker of
| immune system activation) was followed by a step decline in
| cognitive performance.
|
| [1] Lopez (1991) Serum auto-antibodies in Alzheimer's disease
|
| [2] Aisen (1996) Inflammation and Alzheimer disease
|
| [3] D'Andrea (2005) Add Alzheimer's disease to the list of
| autoimmune diseases
|
| [4] Carter (2010) Alzheimer's Disease: A Pathogenetic Autoimmune
| Disorder Caused by Herpes Simplex in a Gene-Dependent Manner
|
| [5] Reddi et al (2011) Autoimmunity in Alzheimer's disease:
| increased levels of circulating IgGs binding Ab and RAGE peptides
|
| [6] Sardi et al (2011) Alzheimer's disease, autoimmunity and
| inflammation. The good, the bad and the ugly
|
| [7] Marchese (2013) Autoimmune Manifestations in the 3xTg-AD
| Model of Alzheimer's Disease
|
| [8] Li et al. (2018) Dementia and Alzheimer's disease risks in
| patients with autoimmune disorders
|
| [9] Arshavski (2020) Alzheimer's Disease: From Amyloid to
| Autoimmune Hypothesis
|
| [10] Itzhaki et al (2020) Do infections have a role in the
| pathogenesis of Alzheimer disease?
|
| [11] Lim et al (2020) Alzheimer Disease Pathogenesis: The Role of
| Autoimmunity
| renewiltord wrote:
| Sorry, haven't read these yet, but any antibodies? Like any
| immune response makes you duller and at greater risk? Eek.
| burning_hamster wrote:
| Like I said, I can't find the study right now, and I
| originally saw the data anywhere between 5-10 years ago. They
| may also have been measuring some cytokine. Even without AD,
| memories really aren't reliable over that time span.
|
| The point the authors were trying to make is that if you have
| AD, any inflammation, even asymptomatic ones, will
| potentially worsen your cognitive performance. The most
| interesting feature of that graph was to me that the
| cognitive performance actually remained fairly constant in
| between infections/inflammations, and decline was not gradual
| but in a step-wise fashion.
| axutio wrote:
| Also interesting is ISRIB [0,1], which is intended to
| negate the cognitive impacts of stress memory accumulated
| over years of immune response, and possibly as a result of
| TBI as well [2].
|
| [0] https://en.wikipedia.org/wiki/ISRIB
|
| [1] https://doi.org/10.1073/pnas.1815767116
|
| [2] https://doi.org/10.1073/pnas.1707661114
| [deleted]
| noyeastguy wrote:
| I absolutely agree with this. My great grandmother had
| Alzheimers as well as Hidradenitis suppurativa, which I have
| inherited from her. I switched to a yeast and wheat free diet
| many years ago to relieve symptoms of HS. Not only did it
| resolve my HS, but also migraines and many other inflammatory
| issues. Looks like there is research around Alzheimer's and
| Dectin-1 signaling which is involved in innate immunity to
| fungi, including bread yeast (Saccharomyces cerevisiae). It's
| absolutely insane to me that people eat a pathogen that
| triggers an innate immune response. A inflammation response to
| yeast is coded into our cells, if it weren't we'd be killed by
| unbaked bread. Why then do most processed foods contain it?
| We're taxing and confusing our immune systems by eating it.
| kortex wrote:
| That does not really make sense. Yeast from bread is not
| really a pathogen. Everything you eat, not just bread, is
| covered in wild yeast.
|
| Fermented foods, which are largely considered good for heath,
| are full of yeast.
|
| So you could refine that last bit to
|
| > We're taxing and confusing our immune systems by eating.
|
| if that were truly the case.
| TremendousJudge wrote:
| > We're taxing and confusing our immune systems by eating.
|
| Well this is not wrong. I'm no expert, but it seems as
| though not eating (or drinking) would result in less need
| for inmune system activity, at least in the digestive
| track. Of course, you'd die, but maybe that was the cost of
| healthy living all along
| sbierwagen wrote:
| Slightly off topic, but if this experiment
| https://www.thefreshloaf.com/node/37259/mythbusters-grain-
| ye... is correct, bread yeast is specialized, and doesn't
| spread by air very well.
|
| I can easily imagine someone with a genetic trait that
| malforms a single protein could end up with a heritable
| sensitivity to one particular yeast strain, and not all
| yeast, everywhere.
| noyeastguy wrote:
| This diet is hard to follow because yeast cuts through a
| lot of foods, especially in fermented foods as you've
| mentioned. A non-exhaustive list of yeasty foods looks
| like: Non-distilled vinegars, non-distilled alcohols, dried
| fruits, naturally-fermented soy sauce, cheese, many savory
| packaged goods, most vegan meat replacements, some dried
| spices, bread, etc.
|
| Fermented foods and mushrooms can be good at fighting
| cancer precisely because they ramp up the immune system. In
| fact yeast is used as an adjuvant inside of vaccines for
| this purpose.
|
| What's insane is that it is both known and not known that
| yeast causes inflammation by science. Used as adjuvant,
| used to "boost" immunity, yet not understood to be a cause
| of general low-grade systemic inflammation when in our food
| supply.
|
| Opportunistic Strains of Saccharomyces cerevisiae: A
| Potential Risk Sold in Food Products
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705302/
| klipt wrote:
| Is there less Alzheimer's in cultures that don't eat bread
| (e.g. where rice or potatoes are a staple instead)?
|
| Maybe in bread heavy cultures it's not a widespread issue
| because the majority of people have evolved some kind of
| resistance?
| ejolto wrote:
| You tend to get Alzheimer's after you are done having
| children, so resistance wouldn't evolve.
| irthomasthomas wrote:
| Related: Type 3 Diabetes
| https://en.wikipedia.org/wiki/Type_3_diabetes
| canjobear wrote:
| Correlation.
| JamesBarney wrote:
| Are you're implying that there is a third factor that both
| reduces risk of dementia by 10x and increases risk of kidney
| failure by 10x? I think that's highly unlikely.
|
| Or theoretically getting dementia a decade later could protect
| against organ failure a decade earlier.
|
| But I really don't think that's it. If this data is right there
| is probably an effect. I agree with the author that the mostly
| likely reason this isn't true is because of bad data.
| omgwtfbyobbq wrote:
| Autoimmune issues may fit that bill in people with the right
| genetics. They can cause and/or contribute to CKD, which
| could push someone into kidney failure with other insults (eg
| dehydration), and can also contribute to dementia.
| JamesBarney wrote:
| That would give us the opposite result, higher rates of
| dementia among organ transplants. It would have to be
| something that causes kidney failure, but prevents
| dementia.
| mattkrause wrote:
| Two things I would want to dig into:
|
| - How are the patients selected for transplants? Scarce
| organs are probably not given to patients who have _other_
| serious impairments as well.
|
| - How were the (non)-dementia patients assessed? No formal
| diagnosis of dementia != no dementia.
| JamesBarney wrote:
| > - How are the patients selected for transplants? Scarce
| organs are probably not given to patients who have other
| serious impairments as well.
|
| Even though being healthy helps move you up the list of
| organ transplant recipients. It would still be really
| strange if people who got organ transplants were healthier
| than the general population, who mostly do not need organ
| transplants.
|
| >- How were the (non)-dementia patients assessed? No formal
| diagnosis of dementia != no dementia.
|
| But it would be weird if organ transplant recipients were
| 10x less likely to get a diagnosis of dementia (assuming
| the same base rates). I would think because of their heavy
| interaction with the healthcare system they'd have a high
| rate of diagnosis.
| CJefferson wrote:
| Firstly yes, they are already suggesting it a correlation --
| people who get transplants get given certain drugs which
| (might) stop you getting dementia.
|
| Secondly, even if the corrolation is caused by another effect,
| whatever it is it's a REALLY strong corrolation, so we should
| find out what it is!
| _game_of_life wrote:
| Initially I thought that the reason for this would be that most
| people with transplants live less than 10 years, and eligibility
| requirements of who gets transplants (and therefore who gets
| calcineurin inhibitors) might further complicate the results.
|
| Wow, was I ever wrong. This article says it's not too uncommon
| for people to live 30 years after their transplant. Other
| articles say that even the obese are eligible for transplantation
| now. Very impressive.
|
| https://wexnermedical.osu.edu/blog/how-long-do-transplanted-...
|
| That being said, I know life extension and nootropics and all
| that jazz is a really popular topic with tech bros, so its worth
| noting the side effects of calcineurin inhibitors are really bad.
|
| It's also neat ciclosporin was isolated from some scandanavian
| fungus living in the soil. Makes me sad thinking about how once
| we are able to significantly understand and appreciate genetics
| and related biotechnology later this century, half of the species
| on earth will already be gone, their amazing biological traits
| and compounds lost forever.
| [deleted]
| snapetom wrote:
| I'm a pessimist and when I look at the graft half-life in your
| article, it puts a wet blanket on things. For example, half of
| kidney transplants from a deceased donor fail in 7-9 years.
| That's not a lot of time. A lung gets you on average less than
| five years.
|
| I would be interested in whether it's survivorship bias, or
| lack of in this case.
| maxerickson wrote:
| I don't really understand your formulation here. How is your
| view about the benefit of organ transplantation pessimistic?
|
| Patients living 7 years instead of dying in short order is a
| pretty good trick for doctors to be working. For pessimism to
| make sense, there needs to be some better option than that
| available.
| snapetom wrote:
| Did you read the original article? The context of this is
| in regards to dementia.
|
| A dead 40 year old, regardless of whether they had a
| transplant at 30 or not, is probably not going to have
| dementia.
| maxerickson wrote:
| There's a reasonable sample of over 65s.
| hpagey wrote:
| The average lifespan of deceased donor kidney is 10 to 15
| years and for live donor is around 15 to 20 years. People
| normally get multiple transplants throughout their lives.
| jxramos wrote:
| I thought all donors had to be living with a beating heart,
| are deceased non-heartbeat donors viable for some subset of
| organ transplants? How does this work exactly?
| throwaway81523 wrote:
| They collect the organs from people who have just died,
| such as in car crashes. In the paperwork for getting a
| California driver license, you check a box saying whether
| you are willing to be an organ donor. If you check yes
| and you are later killed in a crash, they immediately
| bring your remains to a hospital that is always awaiting
| such deliveries, and a transplant operation gets going
| right away.
|
| Motorcycles are sometimes called "donorcycles" because of
| the high likelihood that any given crash will be fatal,
| and that the rider is young and healthy and thus a highly
| desirable source of transplant material.
| AmericanChopper wrote:
| A doctor friend of mine would joke about it being good
| organ transplant weather when it was raining, because
| they'd get dead motorcyclists turning up in the rain so
| frequently.
| mechanical_bear wrote:
| > called "donorcycles"
|
| Only by ghouls.
| short12 wrote:
| Organ donation is based on recently dead people. Heart,
| liver, kidneys, eyes etc are all up for grabs as soon as
| possible
|
| I learned yesterday that a heart has a shelf life of
| about 6 hours and liver is 12
| jdsully wrote:
| Where I am being on an organ donor list also makes you
| eligible to be used as a cadaver. I'm not comfortable
| being prodded by med students but would give an organ.
| klipt wrote:
| Fun social engineering fact: countries that make organ
| donation (on death) opt-out instead of opt-in have much
| shorter waiting lists for organs. The USA could save
| thousands of lives by switching to opt-out.
|
| https://en.wikipedia.org/wiki/Organ_donation#Opt-
| in_versus_o...
| njarboe wrote:
| Funnier social engineering fact: If it's legal for people
| sell their kidneys, wait lists for kidneys goes to
| zero[1]. Too bad only one country in the world does that.
|
| Another fun fact. The US government spends more on
| dialysis than the budget for NASA.
|
| [1]https://en.wikipedia.org/wiki/Kidney_trade_in_Iran
| ricardobeat wrote:
| From news sources I found, it looks like the system in
| Iran works exactly as one would expect: the poor and
| desperate end up with one less kidney while not
| significantly benefitting from the trade.
|
| Which is precisely the reason such sales are outlawed
| worldwide.
| manquer wrote:
| It is problematic yes, however so is most of medical
| care, poor don't get access to it as much as the rich do
| , whether it is countries or people.
|
| Sadly, economics dictate a lot of people's health is
| going to be like. Living/Work conditions lifestyle, diet
| are all influenced by wealth.
|
| Poor people work most of the dirty and unhealthy jobs
| that significantly cut short life spans. Wealth and
| lifespans are known to be strongly correlated.
|
| As countries we are perfectly comfortable reserving
| vaccines blocking poor countries with patents, polluting
| a lot more or exploiting their labor in terrible
| conditions we wouldn't tolerate. Compared to what we are
| willing to accept already this doesn't seem worse.
|
| If a commercial system could save more lives(probably
| more likely rich) it is not that much worse for poor than
| it already is.
| JamesBarney wrote:
| Kidney donors in Iran get ~6 month salary, kidney donors
| in the U.S. get 0 months salary.
|
| Are Iranian kidney donors the ones getting scammed?
| whimsicalism wrote:
| Presumed consent would effectively end waiting lists for
| most organs.
| singlow wrote:
| I learned today that one can be a living heart donor.
| There is a special type of donation where a person who
| needs lungs gets a lungs+heart donation from a deceased
| donor, while the living person's healthy heart is
| transplanted to another person whose heart needs to be
| replaced. It seems this has advantages both for the lung
| recipient and the heart-only recipient and allows for
| compatibility in cases where the lungs and heart of the
| deceased person will not work separately for the two
| recipients.
| ectopod wrote:
| Sure, but "dead" is a Humpty Dumpty word. Some organs
| need the donor to be legally but not colloquially dead.
| In other words, you are dead and your heart is still
| beating.
| jxramos wrote:
| can you share a link, I'd like to learn more about this
| "organ shelf life". Very fascinating. Maybe I was
| mistakenly applying the sudden death of the brain without
| blood perfusion to hold likewise for every other organ.
| Like a heart attack when blood ceases to flow into it
| turns the myocardium to scar tissue. But that must not be
| an instant process, probably takes some time. I know
| temperature can keep tissues viable longer too, so that's
| another variable to consider.
| generalizations wrote:
| Considering that some people have been revived without
| side effects after multiple hours of being brain-dead
| (e.g. famous example of women who drowned in icy water),
| how 'dead' is 'dead', in the context of being an organ
| donor?
|
| I've heard it said that "you're not dead until you're
| warm and dead", but 6-12 hours doesn't seem like a lot of
| time, to make sure you're not coming back.
|
| e.g., I drown in an icy pond, and I'm found after 5
| hours. I might be revived, I might not...but the heart
| only has an hour before it's toast.
| manquer wrote:
| Clinical Death != brain dead, Clinical death has a very
| well defined and nearly irreversible process [1].
|
| The longest human is known to be revived is only in the
| range 10-15 minutes. Brain damage is quite likely at this
| point. The longest for an animal is for cat - 1 Hour.
|
| Only clinically dead people are eligible for organ
| transplantation
|
| [1] https://en.wikipedia.org/wiki/Clinical_death
| sbierwagen wrote:
| >how 'dead' is 'dead', in the context of being an organ
| donor?
|
| Doctors occasionally jump the gun:
| https://www.fox6now.com/news/father-accused-in-hours-
| long-st...
| larrik wrote:
| I'm assuming it's that you can get a kidney transplant
| from a family member who is lying in the OR next to you.
| Deceased donors are transported from wherever they died.
| pkaye wrote:
| Sirolimus and Tacrolimus are two other common anti-rejection
| medicines. They were found in Easter Island and Japanese soil
| samples respectively.
| actually_a_dog wrote:
| For those less familiar, Sirolimus is a trade name for
| rapamycin.
| [deleted]
| tantalor wrote:
| Apples & oranges
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