[HN Gopher] Dementia risk linked to blood-protein imbalance in m...
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Dementia risk linked to blood-protein imbalance in middle age
Author : pseudolus
Score : 303 points
Date : 2023-07-21 13:34 UTC (9 hours ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| hirenj wrote:
| NDST1 is a funny one in the list. In principle it shouldn't be
| out in circulation, so it's probably a sign that actually what
| you are seeing is a dysregulation in activity of SPPL3 in
| shedding of this enzyme from the Golgi.
|
| More on reflection: Looks like NDST1 has a protective effect, so
| maybe this is reflecting the shedding going up for some reason.
| Would need to check what is regulating SPPL3 activity.
| FollowingTheDao wrote:
| NDST1 metabolizes glucosamine.
|
| I'm wondering, if taking glucosamine supplements could increase
| the risk of dementia then.
| hirenj wrote:
| NDST1 is a bifunctional sulfotransferase and de-acetylase.
| It's a gatekeeper enzyme (well as much as it can gatekeep
| with other isoenzymes), that catalyses a sulfation on heparan
| sulfate (HS) chains. HS makes up a big chunk of the
| extracellular matrix, and it is this matrix that various
| signaling molecules travel through to get to the cell.
| Reducing availability of NDST1 in cells would likely reduce
| binding of growth factors etc (or increase it, who knows!).
| It's likely a bunch of subtle effects, and maybe this is
| actually pointing to some whole other thing that is
| happening. It's difficult to say without digging into the
| literature.
| justsocrateasin wrote:
| Exciting pieces of research coming out right now. I could see
| using a blood test to find these specific biomarkers, and then
| getting started earlier on a drug like donanemab that has better
| results the earlier you start it. Combining a blood test with a
| preventative/early stage drug like donanemab or lecanemab would
| have a lot better results than just starting those immuno drugs
| at the first sign of symptoms.
| hirvi74 wrote:
| > a drug like donanemab that has better results the earlier you
| start it.
|
| Do you think there will ever be a point where Donanemab or
| similar drugs will be recommended for all people after a
| certain age?
|
| If I am thinking of the same medication, doesn't it have pretty
| nasty side-effects -- 30% chance of brain bleeding, right?
|
| It's tough, because after a certain age, I think it would be
| worth the risks (in my non-medical professional opinion), but I
| am not sure if that is how medicine works in practice. I mean,
| you wouldn't want to give one medicine for a condition that he
| or she might never end up getting, but you probably also do not
| want to wait until it's too late.
|
| I am just hoping that we find some kind of treatment in our
| lifetimes.
| thereticent wrote:
| Individual differences in neuronal and glial cell metabolism and
| excretion, and presumably toxic effects from those changes and
| associated inflammation.
|
| I just got funded as PI to study blood proteomics and long term
| cognitive outcomes after large vessel stroke, with a focus on
| early identification of post-stroke dementia. It's a very cool
| area to be in.
| mrtomservo wrote:
| As someone who has had a (brain stem) stroke, and also as
| someone with close family members that have/had dementia, thank
| you for your work.
| jxramos wrote:
| I've always been curious about this. Can you briefly summarize
| how you take peripheral blood and fractionate it out to these
| small bits. What's the deal exactly? Is it like centrifuged and
| the plasma pulled out and everything is solution there or it's
| in the buffy coat or down deeper? Where are these proteins
| found exactly and how are they purified?
| Aurornis wrote:
| What an awesome space to be working in. I have a lot of
| appreciation for people working on addressing unknown areas of
| human health and well-being. Always makes what I'm working on
| feel insignificant in comparison.
| echelon wrote:
| Congrats! That sounds amazing! Thank you for doing this
| important work.
|
| What are your thoughts and the general consensus within your
| field for how individuals might prevent dementia?
|
| Are there untested, but plausible hypotheses for the causal
| mechanisms -- perhaps chronic inflammation, liver or metabolic
| disease, bad gut microbiota, a multitude of factors? Or does
| more data need to be gathered?
| ddorian43 wrote:
| A hypothesis is also linked to metabolic psychiatry (having
| diabetes, mental illnesses like depression/paychosis),
| diabetes, insulin resistance in the brain.
| [deleted]
| hirvi74 wrote:
| Thank you for your efforts. It's unsung heroes like you and all
| the other researchers behind the scenes that improve the lives
| of countless individuals.
| theptip wrote:
| Any hints in the literature as to whether these protein
| imbalances are downstream of some other cause that is itself
| harmful, or harmful in themselves? (I.e. direction of causative
| arrow)
| SubiculumCode wrote:
| Do you use neuroimaging as one of your outcome measures? I'm
| curious as a neuroimaging scientist.
|
| Also: Congrats on the funding!
| JPLeRouzic wrote:
| As someone having a blog on neurodegenerative diseases (and
| someone in their 60s), thank you for working in this area.
| moneywoes wrote:
| Amazing
|
| Thank you for your work
|
| Aside from good sleep are there any evidence based practices
| for mitigating these risks?
| ddorian43 wrote:
| Kinda hard for evidence based. Maybe look into low carb
| diets. There are small studies for increase life quality and
| cognition (I do it).
| mcdonje wrote:
| Anyone know what could cause these types of protein imbalances?
| 1MachineElf wrote:
| The HN submission _Could leak in blood-brain barrier cause poor
| memory?_ (2021) may provide a clue:
| https://news.ycombinator.com/item?id=26520453
|
| >People with ApoE4 have a hard time getting rid of amyloid beta
| peptide in their brains, which causes an accumulation of
| plaque. With healthy aging, the pumps in the blood-brain
| barrier work less efficiently in getting rid of the amyloid
| beta peptide. The pumps work even less well in people with
| Alzheimer's disease.
|
| >Recent work suggests that the leak in the blood-brain barrier
| that occurs with Alzheimer's may be due to an age-related loss
| of pericytes. Astrocytes, by contrast, seem to be overactive.
| Recent work suggests that preserving pericyte function by
| giving the factors that they secrete or even transplanting them
| could lead to a healthier blood-brain barrier.
|
| >Other findings raise the question of whether the brain's
| source of nutrition and its grip on control of the immune and
| endocrine systems could deteriorate with aging. Another finding
| raises the possibility that the rate at which many drugs are
| taken up by the brain may explain why older folks sometimes
| have different sensitivities to drugs than their children or
| grandchildren.
|
| Pair that with this part of OP:
|
| >This regulation is important in preventing proteins from going
| rogue and clumping together, which is what happens to the
| amyloid and tau proteins in the brains of people with
| Alzheimer's disease, the most common cause of dementia.
|
| I'm just a layman, but it sounds like BBB health is a major
| factor for regulating this in the brain. In some individuals,
| including those with identified genetic biomarkers for
| increased Alzheimer's risk, the BBB ages faster, leading to
| decreased regulation of protein/peptides. So learning more
| about how to improve BBB health could eventually help people
| maintain a healthy brain longer.
|
| Avoiding excessive alcohol seems to be an important factor for
| BBB health, according to this 2021 study performed on mice:
| https://pubmed.ncbi.nlm.nih.gov/33516661/ ; also this research
| published in 2022:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204474/
|
| OP refers to "amyloid and tau proteins" while the 2021 article
| I referenced refers to "amyloid beta peptide" - at this point,
| I'm really not sure how precisely these terms are being used.
| Are they interchangeable in this context, or is there an
| important nuance that I'm missing?
| dsign wrote:
| I learned a lot about aging by watching this Minecraft
| video[^1] and building the kelp farm. That farm stops working
| after some (long) time, given the way that kelp grows in
| Minecraft. If Avomance had done the math beforehand, he would
| have discovered that he needs a costly full row of observers
| for the farm to work forever.
|
| Biological systems are not designed, but evolved, and evolution
| ends up selecting systems (which we call "organisms" or
| "individuals") which are good enough for it to be
| reproductively successful. In practice that means "low-
| maintenance" and "energy-efficient". Functional errors and
| their organism-wide effects slowly accumulate, and although our
| biology has everything material it needs to fix each and every
| error[^2], its healing program/intelligence is far from
| perfect.
|
| [^1]: https://www.youtube.com/watch?v=Sf9I3YORSzM
|
| [^2]: Compare this with a car, for example. If your lights go
| bust, the car won't grow a new one; you need to change them.
| But biological organisms have a lot of self-healing capability.
| FollowingTheDao wrote:
| Nonsteroidal anti-inflammatory drugs increase GDF15 which was
| one of the key markers in the study
| garganzol wrote:
| But NSAIDs do not worsen dementia. Quite the contrary, the
| symptoms improve due to lowered inflammation.
|
| So, as other posters suggested, those proteins can be the
| effect markers but not the root cause indicators.
| FollowingTheDao wrote:
| What?
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690966/
|
| I'm not saying that it isthe root cause at all either, I'm
| saying they're a marker as well. I'm saying there a marker
| as well, possibly from NSAIDS.
| bitwize wrote:
| Probably the usual suspects: inflammation, gut bacteria, the
| American diet.
| Aurornis wrote:
| That is the question.
|
| These are correlated to dementia risk, but that doesn't mean
| they're directly involved causing dementia. They could be a
| related effect of the root cause(s) of dementia.
|
| There are many examples in medicine where we've attempted to
| directly modify measurable markers like this without fixing the
| underlying disease.
|
| They could be useful clues for discovering the root cause,
| though!
| carbocation wrote:
| Bingo. More explicitly, there is no strong reason to think
| that the proteins from the correlational analysis are causal
| for dementia.
|
| The proteins from the Mendelian randomization also don't have
| to be (can be in a pleiotropic pathway) but there is at least
| reason to think that they could be causal.
| mcdonje wrote:
| If these are correlated, then not every treatment for them
| would necessarily be as effective against dementia. However,
| if the cause of the protein imbalances is something people
| can take steps to prevent, then doing so would logically have
| a greater than zero chance of mitigating dementia risk.
| Aurornis wrote:
| > However, if the cause of the protein imbalances is
| something people can take steps to prevent, then doing so
| would logically have a greater than zero chance of
| mitigating dementia risk.
|
| Or correcting the protein imbalance could interfere with an
| important feedback loop that we don't yet understand, which
| could possibly make the situation worse. Or maybe the
| protein imbalances are involved in counteracting the issue
| that causes dementia, and that's why they're elevated.
|
| This is a common theme in biological systems. A good
| example would be cortisol, which has become known as the
| "stress hormone". Many people assume that lowering cortisol
| must therefore be a good thing, but if you were to
| indiscriminately lower cortisol during periods of stress
| you'd end up in a far worse condition than you were before.
| Cortisol is part of your body's reaction to stress and part
| of the system that responds to it, so artificially lowering
| it can interfere with your stress response process.
| mcdonje wrote:
| Good points. Thank you.
| nonethewiser wrote:
| It makes me think of running a fever. Its easy to think
| of fevers as bad but I imagine it would be a lot worse to
| simply stop the fever (if that were even possible).
| smolder wrote:
| > (if that were even possible)
|
| Indeed it is. Tylenol, for instance, is marketed as a
| fever reducer.
| nonethewiser wrote:
| Well perhaps this proves my intuition wrong. Is it OK to
| reduce a fever then? But how so if its purpose is to kill
| off something worse?
| smolder wrote:
| IANAD, so someone please correct me, but I think there's
| some truth that treating a mild fever will just interfere
| with what the immune system is doing, to its detriment.
| On the other hand, very high fevers in themselves are
| quite dangerous and so being able to lower someone's
| temperature is a benefit.
| petercooper wrote:
| This is unscientific anecdata, but my dad had celiac disease.
| After a few years, he got "bored" of it and refused to go along
| with the diet. Within a couple of years, he got vascular
| dementia (at a relatively young age) and ended up having a
| brain haemorrhage. The studies are pretty early stage on
| finding connections between celiac disease and brain damage but
| the TGM6 protein, common in people with gluten related
| sensitivities, has been implicated. So, and this is all
| spitballing for now, I think diet, and inflammation in
| particular, could prove to be a big deal. At least, I believe
| it's not following the diet that "got him", as it were.
| aszantu wrote:
| I agree, I fall into depression after I eat anything seed
| based
| pella wrote:
| (Guinea Pig) : diet, gut microbiota, ... ( ?? )
|
| "The Effects of Different Diets on Guinea Pig Health, Hair
| Morphology and Blood Protein Concentration"
|
| ~ "Guinea pigs (Cavia porcellus) have biological similarities
| to humans, which make them a suitable animal model in multiple
| fields of research. "
|
| https://lsmu.lt/cris/handle/20.500.12512/115773
| stefantalpalaru wrote:
| [dead]
| bilsbie wrote:
| How might this interact with the APOE4 genotype?
| submeta wrote:
| For those who, like me, tried to find ways to influence this
| imbalance positively, the article mentions one specific protein
| called GDF15 as having a strong association with dementia risk.
| The researchers identified 32 proteins in total that were
| strongly associated with an increased risk of developing dementia
| if their levels were unbalanced in middle age.
|
| The article doesn't provide specific steps on how to influence
| the levels of these proteins. The purpose of this research seems
| to be more about identifying potential biomarkers for early
| detection and risk assessment of dementia rather than outlining
| therapeutic interventions.
|
| Edit:
|
| GDF15, or Growth Differentiation Factor 15, is a protein that is
| naturally produced by our bodies. It's a stress-responsive
| cytokine, meaning that it's part of the body's response to
| conditions of stress or damage. It has roles in various
| physiological and pathological processes, including inflammation,
| metabolism, and apoptosis (a form of cell death).
|
| In terms of influencing GDF15 levels, most research so far has
| been in the context of pharmaceutical interventions, particularly
| in relation to conditions such as cancer and cardiovascular
| disease.
| TaupeRanger wrote:
| Well, it's just a correlation. No causal link has been
| established, and anything you do to get "less" GDF15 could put
| you at greater risk for other types of diseases, since we have
| no idea what the relationships between these things are. I
| wouldn't lose sleep over this - like many things in health and
| nutrition, we must simply admit our ignorance while seeking and
| hoping for a breakthrough.
| steelframe wrote:
| > I wouldn't lose sleep over this
|
| Good, because poor sleep habits earlier in life have been
| strongly correlated with development of dementia later in
| life.
| Tempest1981 wrote:
| Ha! So raising kids is likely correlated. And attending
| college... (or maybe I was doing it wrong)
| chad_c wrote:
| And just living!
|
| Our time is short.
| gunapologist99 wrote:
| Thankfully, we only have so long. Also thankfully, we
| have so long!
| FollowingTheDao wrote:
| GDF15 is a gene that is activated by NSAIDs.
|
| So avoiding them would be a good place to start.
|
| https://www.uniprot.org/uniprotkb/Q99988/entry
|
| https://www.sciencedirect.com/science/article/abs/pii/S01637...
| .
|
| Is also causes insulin release.
|
| But NSAIDs have been linked to dementia in the past, so...
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690966/
|
| it would be pretty crazy if drug companies were causing all of
| the dementia and Alzheimer's, wouldn't it?
| Supermancho wrote:
| > it would be pretty crazy if drug companies were causing all
| of the dementia and Alzheimer's, wouldn't it
|
| This makes sense from 10k feet. If you perennially treat
| conditions in the body to reduce symptoms, but the conditions
| persist, aren't you just masking the inflammation/trauma that
| accumulates? Perhaps this is the best we can do for the human
| condition, with current technology.
| FollowingTheDao wrote:
| I agree that the modality of treating symptoms and not
| curing disease is probably causing more problems then just
| having the disease.
|
| I disagree that it is the best we can do. I have
| essentially cured my self of an "incurable" disease, one
| which was treated with drugs that masked the symptoms while
| my nervous system kept collapsing. when doctors see my labs
| and I tell them my story they are uninterested. That has
| nothing to do with technology and everything to do with
| curiosity and compassion.
|
| My mother was told to take a baby aspirin everyday for her
| heart. Then the doctor one day to her just to stop taking
| them. It turns out that "just stopping" casued her to have
| a mini stroke (TIAs) which was well known issue when
| stopping long term low dose aspirin. That, and the fact
| that psychiatrists killed my nephew with medications, has
| led me to truths about the medical and pharmaceutical
| industries that see them as an obstacle to human health.
| Supermancho wrote:
| I happen to have been taking a blood thinner since I was
| 9 (almost 40 years now) due to a congenital defect and
| then the ongoing surgeries. I am aware of the evils of US
| pharma. Perhaps "the best we can do" was flippant.
| Apologies.
| criddell wrote:
| There are a lot of conditions for which treatment of
| symptoms is really the only option. I take ibuprofen and
| tylenol fairly frequently to deal with cluster headaches.
| If anybody can recommend a different course of action, I'm
| all ears.
|
| Dementia terrifies me. My dad died last year with Lewy Body
| Dementia. After witnessing this, I totally understand why
| Robin Williams decided to end his life.
| GonzoVeritas wrote:
| I've taken Ibuprofen for years for my recurrent
| headaches, and only recently (after decades) discovered
| that I had two underlying issues that seemingly caused
| them. The first was gluten intolerance, which presented
| as inflammation, and apparently I was also chronically
| dehydrated. I cut out wheat and started drinking tons of
| water and the headaches, which plagued me all my life,
| have almost completely disappeared.
|
| Had I not found the cause, I would still be popping Advil
| almost daily. Of course, my issue and solution is almost
| certainly vastly different from yours or any other
| person, but the key was finally discovering the
| underlying cause. That was the tough part.
|
| All that said, the damage has been done, hopefully the
| dementia doesn't set in anytime soon. My mother just died
| this year with dementia, it was NOT an easy ride.
| criddell wrote:
| Dehydration is definitely one of my triggers. I think I'm
| fine on the gluten front (although I've never removed it
| from my diet). I think some dust or grass or mold
| allergies are another trigger of mine.
|
| I'm very sorry to hear about your mom.
| berdon wrote:
| Have you tried diltiazem for cluster headaches? I got
| them after coming off of the medicine for heart related
| issues. Started taking it again and they vanished.
| criddell wrote:
| Nope, but I'll look into it. Thanks!
| hazmazlaz wrote:
| There is some interesting early research into psilocybin
| and cluster headaches:
| https://americanmigrainefoundation.org/resource-
| library/can-....
| bebopfunk wrote:
| This supplement stack + oxygen + verapamil + magic
| mushrooms has turned clusters into almost a non issue for
| me. I went through several years of being too broke to
| really address them, and too pig headed to think
| something as simple as vitamin D would help. But my last
| set of clusters was a walk in the park compared to the
| ones before it.
|
| https://web.archive.org/web/20210119212133/https://vitami
| ndw...
|
| If you decide to try Verapamil make sure you get the
| extended release pills. I don't have the link handy but
| you can find research journal articles that help nail
| down dosage. As for the oxygen, you may have to get your
| own regulator and mask to get what you need. 15lpm and a
| rebreather mask works amazingly for me. If your doctor is
| difficult about it just get them to write a script for
| oxygen, find a local supplier and pay out of pocket. It
| was only $80 to rent the tanks I needed to get me through
| my last cluster season.
|
| A couple of home remedies I've tested and found effective
| were cardio and putting my feet in some super hot water.
| Both sound silly but seem to work in my experience. So if
| you don't have the other stuff yet, or aren't able to get
| to it in time, give either a try. I do burpees as soon as
| I feel one coming one (and after I've chugged a 5 hour
| energy).
|
| The last and most effective solution is LSD or Magic
| mushrooms. If you micro dose then periodically you can go
| a lot longer between cluster headaches. A tiny bit of
| mushroom also seems to work as an abortive for me when I
| feel one coming on.
|
| I'm still experimenting and learning. But hopefully this
| info may give you some things to research or try
| (assuming you haven't already, but I'd much rather share
| this information repetitively then not share something
| that could help you).
|
| Feel free to reach out if you ever want to chat. Always
| down to provide research I've found out just lend an ear,
| I know how debilitating and isolating they can be.
| criddell wrote:
| Thank you so much for sharing all of this. I've copied it
| to my phone so I can refer to it later.
|
| I take quite a lot of vitamin D (6000 IUs daily),
| cetirizine (zyrtec), and nicotinamide riboside (300 mg),
| and a cheap multivitamin. I'm a little wary about adding
| stuff to that but I'm definitely going to look into all
| the things you've mentioned.
|
| Psychedelics are super interesting to me but I really
| wouldn't know where to start. I'm 53 ferchrisakes. Last
| time I was around people buying mushrooms was 35 years
| ago at a skate park.
|
| > just lend an ear
|
| Say... that reminds me. Tinnitus isn't something you are
| dealing with as well, is it?
| mfer wrote:
| I think it would be really useful to understand what influences
| these proteins so we can potentially stop dementia from
| happening or reduce it.
|
| From other research, I suspect we can influence things. Certain
| populations (based on lifestyle choices / environment) have
| lower rates of dementia than other places.
| croes wrote:
| The imbalance could just be a symptom of the reason for
| dementia not the reason as such.
| wongarsu wrote:
| Which is a good argument against medication that just lowers
| GDF15 levels. But if you approach it as "what lifestyle
| changes lower GDF15" then there's a good chance that those
| changes would also attack the actual reason for dementia.
| autokad wrote:
| yeah strongly agree. it was thought that those plaques in
| the brain was the cause of alz; however, some research has
| indicated that's the body's defense against what is going
| on, not the cause. so you could take a medication that
| lowers GDF15, and its possible it actually increases the
| onset of dementia.
| croshan wrote:
| Exactly. I know if medication were to be developed,
| checking "are GDF15 levels significantly lowered" would be
| part of the trials.
|
| But how often does the medication development process check
| the result we care about: "does this medication then go on
| to reduce the chance of dementia?"
| wbl wrote:
| Always. Secondary endpoints are heavily disfavored in FDA
| approval.
| markstos wrote:
| Is GDF15 found in animal foods, plant foods, both or maybe
| neither because we create it?
| FollowingTheDao wrote:
| not only do we create it, but it's stimulated by nonsteroidal
| anti-inflammatory drugs. You know like ibuprofen that
| everyone takes all the time.
|
| Edited to remove Tylenol and replace it with ibuprofen. For
| some reason I thought Tylenol wasn't ibuprofen. Thanks!
| Spooky23 wrote:
| Best honestly to minimize use of this type of medication.
| Tylenol is rough on your liver.
| reducesuffering wrote:
| NSAID's have issues with your stomach, ears, and stroke
| risk. Best to minimize them all, with the smallest
| combination dose of tylenol + 1 NSAID.
| petemill wrote:
| Tylenol / Acetaminophen / Paracetamol is not an NSAID.
| Ibuprofen and Aspirin is.
| elamje wrote:
| For those of you here that care about what's going on inside of
| you - Function is tracking 100+ biomarkers over time, bi-
| annually, and has additional testing available for state-of-the-
| art early cancer detection (Grail) and Alzheimer's risk.
|
| https://www.functionhealth.com/whats-included
|
| I work here and it's amazing to watch this space unfold. Lots of
| great stuff going on in the diagnostic space. Measurement is the
| first step towards understanding your biochemistry and making
| changes!
| scottyah wrote:
| This looks great, I'm just hesitant to sign up with any
| startup-y looking company these days that says they're going to
| be around for my lifetime. You might get more traction from
| people like me if you guarantee that our data will be easily
| exportable and testing methods reproducible.
|
| I imagine the testing methods might be your bread & butter, but
| it's so hard to trust any claims if the results aren't
| auditable. I think about how these results will matter a lot
| more to me in 40-50 years, and how unlikely it is for ANY
| business to last that long.
| elamje wrote:
| Yeah, our internal engineering team in the US are members (me
| included) that want the same thing! Do you have any
| suggestions on file format with the ideal schema? I've done
| deep dives on PubMed and GitHub but haven't found a great
| answer for all use cases.
|
| I personally track a lot of my stuff in a spreadsheet right
| now but am on a personal hunt for a standard format
| hn_throwaway_99 wrote:
| I wouldn't really be concerned about the longevity of the
| business as long as I can get just a print out of the data,
| which I'm assuming is a pretty obvious feature because I'd
| want to share results with my doctor.
|
| Note that, on an individual level, the format of the export
| really doesn't matter much with the rise of LLMs. I had some
| past bloodwork results in PDF format, and I was amazed how I
| could just copy and paste the test results into ChatGPT and
| it was able to correctly parse and interpret the results.
| Others may have privacy concerns but I LLMs being able to
| read and parse a PDF dump of bloodwork is going to be an easy
| commodity.
| dusanh wrote:
| I got excited about this and then I noticed it's US only.
| johndavi wrote:
| Any early access codes you're spraying around? Also how does
| Function compare to something like your out of the box test-
| ordering companies? https://www.ultalabtests.com
| elamje wrote:
| Not at the moment, but the waitlist is a real waitlist that
| moves forward, not the typical smoke and mirrors email
| marketing grab.
|
| Not familiar with that provider, but our core offering tracks
| this over time. I would recommend comparing the pricing of
| their tests to the equivalent for us. We are bi-annual for
| biomarkers that our CMO selected - i.e. some aren't
| interesting to track in 6 month intervals. You can always add
| testing at higher frequency if you'd like.
| yieldcrv wrote:
| nice, like I always say
|
| no conflict == no interest
| hospitalJail wrote:
| Huh, I wonder if this explains why Fasting could prevent
| Dementia. Although hard to imagine autophagy only targets the
| excess.
| Yoric wrote:
| Is there any reason to believe that fasting could prevent
| dementia?
| ccvannorman wrote:
| There seems to have been a few studies as described here:
| https://www.discovermagazine.com/health/the-growing-
| science-...
|
| But, in my opinion there is more research to be done here to
| establish whether or not (and to what degree) there is a
| strong link
| garganzol wrote:
| Fasting increases insulin sensitivity, which in turn helps to
| prevent dementia. Fasting activates growth hormone, which in
| turn helps to heal damages that might lead to dementia.
| Fasting activates autophagy which eradicates marginal
| tissues, thus helping to prevent dementia.
|
| So fasting has quite a few cards upon its sleeve and the
| effect is enormous. But, a therapeutic fasting should be done
| right and should include water, minerals and vitamins. So
| it's not quite a full fasting per se, it's more about
| creating the right conditions for an organism to reboot the
| broken parts.
| mycall wrote:
| > Yu and his team have previously found that people with immune
| diseases are more vulnerable to Alzheimer's later in life [2]"
|
| Does this include autoimmune issues like developing allergies in
| life?
|
| [2] Zhang, Y.-R. et al. Alzheimers Res. Ther. 14, 130 (2022).
| SpaceManNabs wrote:
| Not a doctor or a researcher in this base, but I think they are
| using immune to include auto immune as a subset. lots of people
| call some subcases of Alzheimer's as diabetes 3.
| eloq wrote:
| [flagged]
| treeman79 wrote:
| Got exposed to lot of natural gas over a 3 month period. (Long
| story) Eventually figured out that my blood begin clotting like
| crazy. I have factor 5, so I was predisposed to it, but I was
| having 2-3 TIAs a week for a couple of years. Huge cognitive
| decline.
|
| Only when a large clot showed up in lungs did they figure out
| what was going on.
|
| Week after being on blood thinners and simple programming
| problems that were taking me weeks to solve were back down to
| minutes.
| ncr100 wrote:
| Wild.
|
| Blood clots can be scary. (personal exp). Glad to hear you know
| why they are happening and how to fix it.
|
| Happy clear-thinking !!!
| garganzol wrote:
| It has an official name - vascular dementia. A kind of dementia
| that is caused by vascular problems like blood clots in vessels
| making it hard to deliver the blood to the brain.
|
| Oftentimes it is close to impossible to spot this in a usual
| bloodwork, but were they able to spot D-dimer anomalies in your
| case?
| hn_throwaway_99 wrote:
| Would definitely like to hear more about how they were able to
| narrow down to find a root cause. I also have factor 5 and have
| suffered some other non-specific symptoms (primarily extreme
| fatigue) but haven't been able to nail down a root cause. I'm
| curious if there was a test to find out how "thick" your blood
| was before you went on blood thinners.
| treeman79 wrote:
| Trial and error. Symptoms start back up every-time I go off
| blood thinners. Visual issues , TIAs, cognitive. Clears up
| when I start back up. Covid started when I was just getting
| treatment so lost access to doctors, so no further
| investigating was done.
| Pr0ject217 wrote:
| That's crazy.
| ramblerman wrote:
| Since protein is a key factor in building muscle, is there any
| reason to assume keeping up with strength training in middle age
| would direct most of that protein to a better use and keep the
| balance?
|
| I realize the question is "bro-science", but I'm genuinely
| interested, perhaps someone educated could expand on it.
| radicaldreamer wrote:
| Ever seen dementia in someone who lifts? Me neither...
| aszantu wrote:
| seen cancer in someone who'd eat white bread and banana in
| the morning, then go lift weights afterwards. Within 3 months
| he war breathing heavily when comming up the stairs. I
| noticed. Within 2 more months he was dead. Guy was 70 or so.
| 98codes wrote:
| The article doesn't say anything to infer that it's odd, but the
| rate of incidence of dementia being 20% seems awfully high to me.
| skybrian wrote:
| How old are the people you're imagining? Among people who live
| long enough, it seems fairly common.
| agentgumshoe wrote:
| [flagged]
| [deleted]
| pella wrote:
| related:
|
| "Blood protein levels predict leading incident diseases and
| mortality in UK Biobank"
|
| https://www.medrxiv.org/content/10.1101/2023.05.01.23288879v...
|
| ( May 03, 2023 ; open, pre-print; not-yet peer-reviewed ;
| Alzheimer's dementia included .. )
|
| Abstract:
|
| _" The circulating proteome offers insights into the biological
| pathways that underlie disease. Here, we test relationships
| between 1,468 Olink protein levels and the incidence of 23 age-
| related diseases and mortality, ascertained over 16 years of
| electronic health linkage in the UK Biobank (N=49,234). We report
| 3,123 associations between 1,052 protein levels and incident
| diseases (PBonferroni < 5.4x10-6). Forty-four proteins are
| indicators of eight or more morbidities. Next, protein-based
| scores (ProteinScores) are developed using penalised Cox
| regression. When applied to test sets, eight ProteinScores
| improve Area Under the Curve (AUC) estimates for the 10-year
| onset of incident outcomes (PBonferroni < 0.0025) beyond age, sex
| and additional health and lifestyle covariates. The type 2
| diabetes ProteinScore outperforms HbA1c (P = 5.7x10-12) - a
| clinical marker used to monitor and diagnose type 2 diabetes. A
| maximal type 2 diabetes model including the ProteinScore, HbA1c
| and a polygenic risk score has AUC = 0.90 and Precision-Recall
| AUC = 0.76. These data characterise early proteomic contributions
| to major age-related disease."_
|
| Alzheimer dementia * 10 proteins:
|
| (jpg)
| https://www.medrxiv.org/content/medrxiv/early/2023/05/03/202...
|
| And you can check the data ( protein * disease ) :
|
| _" Our Shiny https://protein-disease-ukb.optima-
| health.technology app [Username: ukb_disease, Password:
| shinyappUKB] provides visualisations for sensitivity analyses run
| across cases over successive years of follow up, allowing for
| interrogation of individual protein-outcome relationships."_
| denial wrote:
| (Paywalled link of paper:
| https://www.science.org/doi/10.1126/scitranslmed.adf5681)
|
| Abstract:
|
| A diverse set of biological processes have been implicated in the
| pathophysiology of Alzheimer's disease (AD) and related
| dementias. However, there is limited understanding of the
| peripheral biological mechanisms relevant in the earliest phases
| of the disease. Here, we used a large-scale proteomics platform
| to examine the association of 4877 plasma proteins with 25-year
| dementia risk in 10,981 middle-aged adults. We found 32 dementia-
| associated plasma proteins that were involved in proteostasis,
| immunity, synaptic function, and extracellular matrix
| organization. We then replicated the association between 15 of
| these proteins and clinically relevant neurocognitive outcomes in
| two independent cohorts. We demonstrated that 12 of these 32
| dementia-associated proteins were associated with cerebrospinal
| fluid (CSF) biomarkers of AD, neurodegeneration, or
| neuroinflammation. We found that eight of these candidate protein
| markers were abnormally expressed in human postmortem brain
| tissue from patients with AD, although some of the proteins that
| were most strongly associated with dementia risk, such as GDF15,
| were not detected in these brain tissue samples. Using network
| analyses, we found a protein signature for dementia risk that was
| characterized by dysregulation of specific immune and
| proteostasis/autophagy pathways in adults in midlife ~20 years
| before dementia onset, as well as abnormal coagulation and
| complement signaling ~10 years before dementia onset.
| Bidirectional two-sample Mendelian randomization genetically
| validated nine of our candidate proteins as markers of AD in
| midlife and inferred causality of SERPINA3 in AD pathogenesis.
| Last, we prioritized a set of candidate markers for AD and
| dementia risk prediction in midlife.
| refurb wrote:
| The key question is - how strong was the correlation? Was it
| associated with a 5% higher chance of dementia? Or several fold
| higher risk of dementia?
| olliej wrote:
| I know that's not what this is saying in any way, shape, or form,
| but I am waiting for FB posts using this as evidence support
| balancing humours to prevent dementia.
| thomashabets2 wrote:
| Is there a test for it?
| ccvannorman wrote:
| +1 - How would one get bloodwork done to specifically test for
| these proteins?
| 3cats-in-a-coat wrote:
| This is literally the same cause as "child dementia", which was
| reportedly called this due to similar symptoms, despite the cause
| is different, a genetic anomaly that causes accumulation of
| protein in nerve tissue and the brain. Well, it was thought to be
| different, but I guess not.
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