Study Reveals Immune Driver of Brain Aging
med.stanford.edu
med.stanford.edu
Often one of the first symptoms that cause people to seek a diagnosis.
Have Sjogrens. Cognitive decline is a real issue for me. Treatment and lifestyle changes make a huge difference.
Basically controlling inflammation becomes your life. Or you won’t have much of one.
I seem to have some dietary autoimmune stuff going on as well which is incredibly difficult to deal with, my friends know me as that person who brings home cooked food around everywhere, as I know there are no spices or grains that will set me off. Eating out I usually just order a salad with no croutons, no cheese, no nightshades, no dressing outside of olive oil, and a meat to go on it. But even then, if the meat has spices, I'm in trouble.
[1] http://brainhealthbook.com/ -- also available on the large book piracy site
But what do you think mental illness is, if not an autoimmune disorder?
I try not to think about it, but when I was diagnosed 15 years ago, I had a reaction to a psychotropic drug and the pharmacist said "oh yeah, that's an antihistamine, so don't take more OTC antihistamines to try to deal with the reaction". And I switched to something that wasn't so bad, and never thought much more about it for a long time.
Then after a decade and a half, for various reasons, but particularly to check for celiac, I finally went to an allergist to be tested for common allergies, who said "oh yeah, your medication is an antihistamine, so you'll have to stop taking it for a few days in order to be tested". Which I decided I really can't.
I feel like nobody says it most of the time, or acts on it, and many don't have any idea, but it is widely known at the same time. Which is eerie.
As a researcher, Dr. Kharrazian earned a PhD degree in Health Science with concentrations in immunology and toxicology and a Doctor of Health Science (DHSc) degree from the Department of Health Care Sciences at Nova Southeastern University. He completed his post-doctoral research training as a research fellow at Harvard Medical School and worked as a researcher at the Department of Neurology at Massachusetts General Hospital, where his research focus was in autoimmunity and neuroimmunology. Dr. Kharrazian also earned a Master of Medical Science degree (MMSc) in Clinical Investigation from Harvard Medical School. Dr. Kharrazian is an active member of the Harvard Medical Alumni Association and the American Association of Immunologists.
Most doctors don't go too deep. They do the equivalent a support call center employee does when "helping" you by reading from a number of pre-made support scripts.
Similar to you, CRP tests were fine and bloodwork was all good, however they did find I was positive for the HLA-B27 antigen which is a known marker for autoimmune conditions and only present in about 5% of the population, but present in 90-95% of those with spondylitis, so there's one red flag. The issue is as you mention, there is no definitive diagnoses until they see joint damage on X-ray, and by then you've missed years of potential intervening treatment.
Eventually I developed brain fog like you describe, but it was gradual and difficult to tell if the symptoms were related. It's not always debilitating but I'd say 4/5 days I'm foggy to varying degree, and then one day where I'm about 3x sharper. I've learned to just ride the productivity wave those days and do mundane stuff other days.
I thought it may be sleep related, and although getting more sleep does seem to give me a higher probability of a "good" day, it's not a panacea. There are days where even after 10 hours I'm still foggy, and I can tell immediately upon waking up how the day will go.
While I'm sympathetic to those who say googling your way to diagnoses can be harmful (and no doubt it may frustrate some doctors), I don't entirely agree. You have to live with your body and mind 24/7, and you have one and only one patient to care for - yourself. You will always be more motivated to find the answer than your doctor. A doctor cannot read your mind or feel your pain, and simply pattern matching symptoms is something anybody can do. It can never hurt IMO to go into the discussion informed and ask pointed questions.
The medical field is an evolving science, they don't have all the answers, they don't even have most of the answers.
Most recently a rheumatological told me some people are just "bone formers" which might be true, but is still frustrating to hear as it kind of came across as very hand-wavy.
I have noticed a drastic difference since catching COVID and fear the days of my youth being able to churn anything out on a whim is over
I try to prioritize creative work, e.g. building something new, really hard problems, etc. for "good days", and I focus on work that I've already begun and can see the completion path for on bad days. I do occasionally have days where I'm totally useless, and if that happens I'll just do mundane rote tasks that I've been putting off.
I also understand the need for doctors to be measured in their diagnosis, so I don’t begrudge them for following protocols established for disease qualification. I don’t think of it as invalidating experiences of patients (though it can feel that way to patients) but everyone is aware of those that want a diagnosed health problem, and to a more frequent extent, those that want a tidy answer to their experiences even if there isn’t one. Denying a diagnosis of a known disease is not denying a diagnosis at all.
My wife struggled with weird autoimmune symptoms that eventually progressed enough to get a diagnosis. At the time of her diagnosis, her life expectancy without treatment was 1-2 years. I empathize a lot with patients and doctors who are trying to dial-in on a mysterious illness.
In these cases, the psychological toll is pretty heavy - the uncertainty of your future while your very identity is being challenged. I've seen people respond badly - instances where people engage in a tragically comic route of turning to chronic alcohol intake, becoming inactive/sedentary, bandaging emotional pain with bad diet, etc. Precisely activities that are known to aggravate autoimmune disorders. This is a horrible reaction.
Now, even with a specific diagnosis, the first thing your rheumatologist is going to tell you is that you need to make lifestyle changes - diet, sleep quality, stress levels, etc. That's going to be solid medical advice regardless of what drugs you go on.
For those without a specific diagnosis, adopting these lifestyle changes is still good advice and within reach. There is no instance I've seen where someone with an autoimmune disorder can rely solely on drugs and be otherwise "normal". The drugs (especially those beyond hydroxychloroquine) have unpleasant side effects of their own that need to be managed. In all cases with drugs, the goal is to get the disease itself into a managed state, and ideally into remission. That's not possible for everyone, but for plenty of people it is possible to manage mild instances of disease without drugs, and enough of a possibility that I think it's at least worth a try. This doesn't mean stopping your drugs and doing reckless experiments, but in consultation with a rheumatologist weaning off drugs while having adopted lifestyle changes that avoid known triggers for flare ups. If it doesn't work, go back on the drugs.
Dramatically reduces rashes, swelling. Great substitute for viagra. Improves energy.
So it’s a weird balance.
Had to push hard for further testing. Plus just trying the treatment. Had a big positive response. If I hadn’t pushed they would have just had me come in once a year to “check”.
One of the factors that got me a diagnosis.
I’m not sure these tests are good for diagnosing triggers though, compared to quarterly or biannual management of a disease (to make sure you’re not headed off the rails). The range for CRP, for instance, is relatively broad. What’s serious is when you’re exceeding the reference high.
In these cases (like maxed out SED rate) chronic inflammation is a thing and more than “feeling bad”. It does lasting damage so the quicker you can respond to it the better, and IME that kind of inflammation sneaks up on a person and often goes undiagnosed until other downstream problems start to present themselves.
There’s a bit of fashion to talking about “cytokine storms” and inflammation that is partly healthy to be aware of (and interesting to the seriously curious) but also a lot of faddish health nuttery lately. Be careful of the snake oil salesmen out there, folks.
Diets, supplements, exercise equipment, OTC meds, are as often nets to harvest disposable income more than they are serious approaches to managing disease.
For people suffering autoimmune disorders, much can be done with simple balanced diets and regular low stress body weight exercising. The key is avoiding things like excessive drinking, high mental stress levels, sleep dep. All the good advice for Puritan living that really applies to all of us, just that they have far, far lower tolerances for deviation. Response to NSAIDs may indicate what you’re fighting but if you’re there you’ve already failed upstream from where you are now. Chronic NSAID use isn’t all that great either but is often an unavoidable supplement for those trying to hold a normal career these days. This kind of internal feedback loop is more cost effective and probably more accurate for behavior correction than looking at daily blood work.
As far as diagnosing disease, there are many blood tests broadly that one would/could run to aid in diagnosing autoimmune diseases, including ANA pattern and titer, DS Antibody, SCL-70 antibody, ANA screen (IFA), SM antibody, Sjogren's antibodies, ANCA screen, P & C ANCA titer, rheumatoid factor, CRP, compliment levels (e.g. C3, C4), SED rate, white blood cell counts (neutorphils, lyphocytes, eosinophils, basophils, monocytes). Tests for organ function can also be critical in evaluation.
I don't know much about hypothyroidism, but my advice is to do a lot of self-education, reading as much literature as you can about it. Journal your behaviors, habits, stress levels, sleep, and food and identify patterns yourself. You can do this by eliminating certain environmental or dietary factors for four or six months, then do TSH tests again. You have to be careful of changing too many variables at once. I know it's a pain in the butt, but desperate times call for desperate measures. You want your disease to stay in a managed state and prevent any immune system issues from spidering into other disorders. If you have these potential warning signs of your immune system starting to crack, my advice is to do everything you can to protect it from reaching additional failure points.
Time to see a rheumatologist
The SED rate doesn't identify its cause, so ANA and CRP can be ordered after a high SED rate (along with tests such as CBC, urinalysis, etc that would indicate other possible causes). CRP and ANA tests are pretty specific to autoimmune diseases.
ANA is most often associated with SLE (lupus). Not all AI diseases have positive ANA screen, and even in SLE once it's in a managed state both SED and ANA titer would ideally be back within spec.
I'd be curious (if you do regular blood work) do you have a SED rate within spec but an ANA titer out of spec? Or "just" a positive ANA screen test?
Does this mean this is a typical of someone to be prescribed with autoimmune disorder? I was curious to know how one might discover on their own if they have it. As well as the effects of how someone feels (or changes) by taking NSAID ...
Diagnosing an autoimmune disease on your own isn't advised, you should really see a specialist, not a GP. Specifically, get a referral to a rheumatologist. Blood work, sometimes xrays are required to properly diagnose. There are some 200+ known autoimmune disorders if I recall correctly, many people end up with a two-for-one deal. Sjögren's and Raynaud's seem to be not uncommon companions of other disorders, for instance.
“non-steroidal anti-inflammatory drug”, a class that includes many popular non-opioid painkillers including aspirin, advil (ibuprofren), and aleve (naproxen), but not tylenol (acetaminophen/paracetamol).
CRP, is limited value test.
In general my blood work is great, yet I have lots of internal damage. It’s just not progressed enough to show up on typical blood tests.
Various antigen tests can pick up on it.
In case of pancreases, I got pancreatitis. Turned out that was an early sign of Sjogrens. At that point ultrasound was clean. Years later, Now it shows damage.
For me.
In order of improvement. Prescription: plaqunial. Blood thinners.
Avoiding flare triggers, Sun, heat, most foods.
Diet is huge. Autoimmune protocol diet is best for me. Similar to keto, etc. Personally I’ll eat a lot of sweet potatoes when I need relief. Safest food I have found.
Supplement: Vit D, magnesium, Vit E, fish oil, B complex, CQ-10 turmeric.
Autoimmune often means a lot of secondary conditions, or autoimmune is the secondary.
Increased cranial pressure is somewhat common with Sjogrens for example. High pressure is brutal on the mind and body.
Went from bed ridden in horrific agony all day to kayaking or equivalent every weekend.
I second the Anti-inflammatory diet and exercise (even just walking contributes greatly). I echo the supplement suggestions and also recommend glucosamine+chondroitin (which happens to lower all-cause mortality significantly).
Red meats (high omega 6 content), deeply fried foods, gluten (plenty of grain alternatives to wheat and corn), uncultured dairy (cheese seems ok, plenty of alt-milks out there), and sugar not from fruit can trigger inflammation for me. I might describe my diet as vegan+eggs+fish (ovo-pescaterian?)
There is a wealth of information online to tailor one's diet. Honestly - this is a diet that everyone can benefit from health wise.
The reason for the yellow/red flag system is to not impose a strict limit, but as a way to inform myself I'm in a danger zone. Primarily because many foods I love (ahem brownies!) are a flagged food. Telling myself "no", when I'm stressed or foggy state, often fails. However a "red" flag state helps bring out my inner engineer: “Can'nae take any more, Captain!”
There's probably a terrible joke to be made here about red shirts but I can't muster it
For those who can't tolerate dairy, or any kinds of nuts or seeds or grains, one kind of food that you might enjoy is coconut yogurt. Not cheap but it helps to break some of the dietary monotony.
It really is awesome that we can find what fits us with large store brands that deliver! Never knew how many forms of vegan protein exist out there
It's full of useful information even if you don't intend to go full carnivore.
Have you tried using the mushroom [extract] Cordyceps as a supplement? It seems to help abate some symptoms when I eat an autoimmune triggering food.
https://www.nowfoods.com/supplements/cordyceps-750-mg-veg-ca...
/r/Sjogrens /iih
Podcast Sjogrens Strong
Good resource Sjogrens foundation John Hopkins Sjogren foundation for more up to date testing and articles
Did you have muscle pain?
Then I took matters in my own hands, joined some forums and subreddits, turn out loads of people were like me. Literally thousands of people in online communities had undiagnosed Low Testosterone. Most docs are uneducated about this as they just look at the blood test lab results, and group everyone from age 20 to age 70 in the same category. Went to a mens health doc, gave me TRT, symptoms gone in a week. Literally saved my life and career, I almost dropped out of college. I put my dad on TRT too, and litterally I tell everyone about this. The Low T epidemic is a really serious issue!
My understanding is that T levels can vary based on the time of day they're taken, so they likely need to be taken multiple times.
In any event, glad you arrived at a solution!
Was the contrast brain MRI to make sure you didn't have tumors that were subsequently impacting your hormone production?
It doesn't have to be Redbull, but where else are you going to get 30g of sugar and a few helpful vitamins out in the wild.
Also there was a study that showed greater than 160mg of caffeine per day may increase inflammation in those predisposed to it, whereas the group that consumed <120mg had no negative effects. Can try to dig it up if someone is interested.
If I remember right, the only ingredients in Red Bull not listed by name are the artificial flavors (and maybe some colors). And those have to be drawn from GRAS don't they?
It's always seemed strange to me that we are more willing to trust plants with thousands of unknown chemicals, over a simple energy drink with like ten chemicals, all listed.
I was once a multiple-a-day energy drink consumer. The fizzy caffeine+sugar+choline+inositol mixture in a can has barely been around a few decades. Do you know what compounds the artificial flavors are? I've since switched to getting my caffeine from plants. It's been verified by a plethora of civilizations over thousands years.
Can I really just say some days I feel dumber than usual and he'll be able to diagnose and fix me?
I printed out 4 page list of all the weird symptoms I had, and what affected me.
One crazy old neurologist-ophthalmologist read the list and declared I had Sjogrens. Something I had not considered.
Through research and Support groups I found out my symptoms were normal, and mostly ignored by doctors.
Addison's is deadly if left untreated. According to my endocrinologist, I was scarily close to death.
Doctors are quick to discourage patients from "Googling their symptoms", but patients (and their veterinary friends, lol) need to advocate for themselves. If I hadn't taken the tip about Addison's seriously and demanded tests from my primary care, I could very well be dead.
Some tests took over a year for me to get run.
Some I still haven’t.
Other more exotic tests were super easy to get.
If this isn't the truest thing. It's very difficult when you have doctors--who society tells you to deeply respect--calling you a lazy liar.
I don't think I would have been diagnosed if I didn't have a supportive family who insisted it wasn't "all in my head" and that I needed to keep searching for answers. It's very easy to start believing what the doctors say, no matter how loudly your body is screaming otherwise.
And then there's the opinions of general people... It's surprising how ignorant highly-educated engineers can be about medical issues. Again, I credit my family and friends for having kept my sanity all these years.
They don't just memorize information about one species, they need to know how to treat 5+. They do all their work without the patient giving verbal clues/feedback. And they often have limited resources/tests/treatments they can use to save a life.
They are some of the most creative, intelligent, and passionate minds in society. Although I may be a bit biased, based on my experiences. ;)
For anyone going through this fresh hell currently, I'd estimate my hit rate at about one out of 6 or 7 for doctors who'll actually look in depth versus those who were apparently just good at memorizing things for tests and can't diagnose their way out of a wet paper bag. If you haven't gotten at least that many opinions and are still suffering, keep trying.
Also, quacks are a problem too. Too many of those promising cure-alls.
I basically quiz doctors until I find one that knows the basics. I have a rheumatologist. But if I need forms filled out only a PCP will unusually do that. Unless they don’t, then your screwed royal.
This is so painfully true. My lupus was repeatedly treated with prozac despite my insistence that I didn't feel at all depressed.
Best I can tell its from Sjogrens Or neuropathy problems from Sjogrens.
Also dysatonomia is often caused by IIH. Treating IIH, drastically improved symptoms. Literally draining off spinal fluid.
Oddly salt can at times improve IIH. But it’s not something to mess around with.
Basically too much water causes organs to swell. Most organs handle this well enough. Brain will swell, but has no room to do so.
A big dose of salt will draw water out of organs, including brains.
Very good medical case I read up on, but can’t find now.
A lot of Sjogrens people recommend adding pink salt to water or other hydration packs.
Pure water seems to worsen dehydration. I have found this to true.
Be careful as this is a complicated thing, and can hurt yourself by having too much or too little.
edit to add: You said 'diagnose and fix me' ... even if they can diagnose you, they won't be able to fix you. Just a warning. Best you can do is to manage the condition.
> Cognitive decline is a real issue for me.
How do you track this? Do you have any self tests to keep the cognitive state in check or are they standard medical tests?
“You just saw that image 3 times in the last 60 seconds” Me: I have never seen that image before. At my best I could outscore most anyone in the office.
Second is more arbitrary, but more important.
Been programming for decades. Since I was a kid. A task that normally would take me a few minutes might take me a week. Harder concepts were beyond me, felt like I was trying to tackle calculus after learning fractions. I “knew” I could do it, except I couldn’t anymore.
Then I would have some good days, and I would go around the office solving all the really hard problems for people.
Do you feel there's anything missing with memtrax or any other tool which can make your life easier i.e. help track your cognitive health or help your current lifestyle?
I had symptoms 20 years ago, serious problems 10 years that were warning signs of autoimmune.
When it got really bad it was 20-40 doctor visits to get a diagnosis.
It’s the Second most common autoimmune condition, behind lupus.
Also getting ride of American diet. A lot of people are predisposed to autoimmune, but need a trigger.
You're welcomed to join the discussion, hopefully one day we'll be able to find a solution.
[1]https://needgap.com/problems/186-reduce-time-to-diagnose-aut...
Similarly to the sibling comment, I spent years struggling. There were points where I sat down to write a super simple Craigslist scraper and couldn't do it, my working memory was so poor that it was like I couldn't hold more than 2 or 3 concepts or ideas/variables in my head at the same time. This task is something that I knew just a few years before I could have whipped up in 30 minutes or less.
Do you use any tools like OP to help with your lifestyle? I know memory is a complex problem even for those who don't usually face explicit issues like you do; but does common memory retention practices like 'spaced repetition' made any positive improvements for you?
Since I know that my symptoms are almost entirely caused by diet, I have written down everything that I've eaten, every supplement that I've taken, every hour that I've slept, every noise or pain I feel in my stomach, and information about all of my bowel movements since 2017.
I thought I had things under control last year, and didn't take any notes for 2 months. Now I have an issue with H2S bacterial overgrowth, essentially a sulfur sensitivity. "If it can be measured, it can be managed."
The fact that I moved to Europe in October to avoid the pandemic and election nonsense, hasn't helped me. There are tons of supplements and tests that I would be able to get in the states that are simply unavailable in the country that I'm residing in. Pretty frustrating, and tbh, I can't wait to get back, hopefully late spring/summer.
Unfortunately, I have terrible brain fog, which mostly affects my working memory. This has plagued me for over a decade. As you noted, programming interviews are a nightmare.
Through the autoimmune protocol diet I discovered caffeine has a negative impact on me. I've noticed a small, but not insignificant improvement through cutting out all caffeine. Previously, I drank several cups of coffee a day.
I also took genetic testing and found I have some MTHFR mutations plus some other things, including a supposed indicator that I'm sensitive to caffeine, reaffirming my earlier findings. I've also cut out folic acid completely. However, I take these test results with a grain of salt, since there is mixed evidence of SNPs actual being of importance.
I've also experimented with probably 30+ supplements. I'd say more than half the time, my brain fog worsens when supplementing. I've finally settled on just melatonin and glycine at night. With these, I actually remember my dreams, which I take as a good sign.
Anyway, I've done very little blood testing recently, but in the past, a standard blood panel came back normal. Again, would love to hear what testing you had in mind.
In your case, I would recommend getting some L Glutamine power and taking a bunch of that in the morning and at night. That would likely fix your brain fog or at least go a long way. Best resource I've found is brainhealthbook.com . What is your email? I'll reach out and we can discuss ideas, theories and strategies further.
Hopefully we would be able to find some solutions. You're welcomed to join the discussions.
[1]https://needgap.com/problems/187-easy-way-to-record-diet-lif...
Theme is few carbs, but not exactly. Chicken, green vegetables and sweet potatoes are my life.
I always regret cheating.
I too regret cheating most of the time.
Good luck anyhow
> Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.
I fast semi-regularly (I'm just finishing up a four-day fast), and it amazes me how often we by default reach for something (e.g. pills) to put into our bodies to solve or improve something, when sometimes the answer is to _not_ put something (i.e. food) in it (at least for a little bit). It's also a great exercise in self-control and discipline.
When I went back to the basics done right, and stopped doing experiments on myself like fasting or energy drinks at certain times, everything slowly went back into place, it only took about 3 weeks and compounding effects after a few months. Basically, consistency was key:
Start the day with aminoacids + b-complex, water soluble vitamins on empty stomach work better.
Then a protein breakfast, like 4 eggs and some greens. Eggs are a good source of choline. Only now I'd pop a vyvanse, less aggressive/spiky effect but also less anxiety and lasts longer on a neutral stomach.
Replace coffee with matcha. Has the caffeine + theanine for relaxation, and slower release. Happier gut as well.
Extended lunch break: small meal but time for a walk with my gf, light exercise, call a friend or errands, then slowly transition back to work and finish the day.
For dinner get your Omegas and Vitamin E (lowers inflammation), fat soluble vitamins do better on a full stomach.
Before bed maybe some Melatonin and Magnesium.
About supplements for brain fog, maybe try some extra B1 (Thiamine, there's also Sulbuthiamine), Ginseng.
Get tested for anemia, even if the basic blood panel looks OK, just get a video doctor to hand you out an exam order for the usual suspects like ferritin, serum iron, plasma electrolytes, b6/b12, d, c, folate. If it's low but not anemia-level low, you could supplement, it seems pretty common with iron. Low Vitamin D won't really change with those 800 IU pills, get those salts that have 50.000 IU once per week then retest after a month.
> If their findings in old mice and in human cell cultures apply to actual humans, they could presage the pharmaceutically managed recovery of older people’s mental abilities.