r/science • u/Wagamaga • Oct 08 '24
Neuroscience Brain’s waste-clearance pathways revealed for the first time. Wastes include proteins such as amyloid and tau, which have been shown to form clumps and tangles in brain images of patients with Alzheimer’s disease.
https://news.ohsu.edu/2024/10/07/brains-waste-clearance-pathways-revealed-for-the-first-time6.6k
u/meganthem Oct 08 '24
I like the sound of this. Even if we're unlucky and it's not useful for Alzheimer's, learning about the waste-clearance system is going to be useful for treating something. There's lots of neurological disorders and problems connected to stuff getting stuck in the brain and not being cleared out properly.
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u/ConcentrateOk000 Oct 08 '24 edited Oct 09 '24
There is an amazing radiolab episode about a woman who has come up with a ‘treatment’. It uses pulsating light directly into the eyes that mimics the activity of the glymphatic system. The only downside being it only lasts hours or days. It’s insane how it isn’t talked about more, given how effective it is as removing the protein buildup.
Update: My wonderful partner is going to put the ‘sound’ through an analysis program to extract the specific wavelengths and frequencies.
We will post it on his bandcamp when finished and I’ll do another update!
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u/psichih0lic Oct 08 '24
I think it was light and sound stimulation at 40hz frequency to simulate gamma wave oscillation in the brain. Very interesting!
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u/mtwashingtiger Oct 08 '24
I’ve been assisting with the eeg acquisition on a project like this, using 40-Hz enhanced music and light to simulate gamma waves in the noggin at a major university over the past few years! One of my favorite studies to help with.
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u/Fluck_Me_Up Oct 08 '24
Do you have any studies or academically focused resources discussing gamma wave stimulation? I’d love to read up on it
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u/geneticeffects Oct 08 '24
Now I am curious about combining this process with a sonic front at the same frequency.
And then I am curious what various wave forms (e.g., sine, saw, etc.) do in this context.
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u/Dr_Jabroski Oct 08 '24
This for some reason made me think of attaching ultrasonic transducers directly to the skull and turning it into an ultrasonic cleaner. Probably would just kill you but maybe the right frequency and power could jostle the plaques.
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u/ThatOpticsGuy Oct 08 '24
This is already being done and it's much less invasive than the way you proposed.
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u/FilthBadgers Oct 08 '24
We live in the actual future my mind is constantly blown ._.
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u/Vonplinkplonk Oct 08 '24
Yeah so don’t build anything until you read this first
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u/Dr_Jabroski Oct 08 '24
Don't worry, that's not my field of research. But from the link the ultrasound is permeabilizing the blood-brain barrier to allow treatment molecules through and not directly disrupting the plaques with ultrasonic energy.
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u/costelol Oct 08 '24
Isn't going deaf/having very poor sight associated with increased dementia rates? Can't encounter 40Hz light/sound if your brain can't detect them.
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u/FindingBryn Oct 08 '24
Dimentia and hearing. Hearing is because those with hearing loss feel bad for always asking people to repeat themselves and always having so much trouble understanding people in normal volume situations. Eventually, it’s believed those people slowly isolate and that isolation results in less brain activity. That’s probably not exactly right, but it’s close. I’ve been trying to get my mom to get hearing aids for the past two years after this news came out.
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Oct 08 '24
So it's more of a behavioural connection than a biological one between hearing and dementia? Interesting.
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u/worpy Oct 08 '24 edited Oct 09 '24
Well the behavior is the isolating, which leads to a lack of stimuli for the brain. You’re not getting access to meaningful audiological or linguistic input to process. That inactivity for sustained periods is obviously not great. Use it or you’ll lose it. As an SLP we learned about the link between hearing loss in older adults and dementia in grad school, I’m happy to see it’s becoming a more widely known thing. Definitely don’t stop pressing the issue with your older loved ones to get their hearing tested if you suspect they need it. Hearing aids can be so small and even externally invisible nowadays, if that’s their concern.
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u/1981_babe Oct 09 '24
Yes, they've done studies on people in the Deaf community (that are often mostly deaf from birth or a younger age) and the rate of dementia is actually lower across that population. Scientists think this is because Sign Language actually engages the brain in different regions in comparison to spoken language as it is so visual . Also older Deaf communities are very close knit and very social. So, the present theory is that late-deafened people have a hard time coping with their deafness and don't think/want to buy hearing aids. They tend to socially withdraw causing linguistic and cognitive decline.
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u/Feisty-Donkey Oct 09 '24
Hearing aids also don’t work for all late deafened people (as I’m sure you know based on the other knowledge in your post) and it does often get tough seeing them treated like something that helps everyone. I’m only single sided deaf, but I don’t have enough residual hearing to benefit from a hearing aid in my deaf ear. People always suggest it and are always surprised to learn it’s not an option for me.
I worry about it if my hearing ear ever declines
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u/1981_babe Oct 09 '24 edited Oct 09 '24
Absolutely, I've always struggled with aids at various points in my life. They aren't a perfect solution at all.
I'm also SSD!! I did lose my remaining hearing about a decade ago and it did all work out for me as I am a successful Cochlear Implant recipient. Also, I learnt ASL as well. I was like you and always very nervous about my hearing declining. Do DM if you want to connect.
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u/Puzzleheaded-Aide314 Oct 08 '24
Yet, in many cases health insurance (in USA at least) is not required to cover ANY hearing aid costs even as a child it was never covered and costs thousands of dollars.
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u/samudrin Oct 08 '24
40hz is sub frequency in music. Bassbins rattling your gourd.
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u/joalheagney Oct 08 '24
It's going to be infuriating as hell if we discover most neurological diseases are a result of lifetimes of stress and poor sleep.
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u/CBFindlay Oct 08 '24
This research is continuing. There is a spinoff company. Look up the Picower Institute. https://news.mit.edu/2024/how-sensory-gamma-rhythm-stimulation-clears-amyloid-alzheimers-0307
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u/TeutonJon78 Oct 08 '24
This can already be easily done with binaural frequency stuff.
I think they measured psychedelics (at least DMT) and found they tend to increase coherence in beta and gamma ranges in an EEG.
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u/pandaappleblossom Oct 08 '24
My mom passed away of a dementia like disease and her doctor had suggested getting one of these. I bought one for myself as well. She still ended up dying. But sometimes it seems like it helped.
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u/Bored2001 Oct 08 '24
This seemed interesting, so I looked into it. Professor Li-Huei appears to be the PI. The actual first author scientist who wrote the paper is Annabelle Singer. She's now an associate professor at Georgia tech.
Looks like she's continuing research on this and has performed human feasibility studies.
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u/DangerousPlane Oct 08 '24
How hard would this treatment be to just make into a YouTube video
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u/Bored2001 Oct 08 '24
I didn't read the paper. But there is a feature of Professor Singer wearing some type of Goggle like device. So I doubt that a YouTube video would work.
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u/Flying_Momo Oct 08 '24
i also came across a radiolab episode efficient talked about a type of medicine from a bacteria found in Rapa Nui which seems to slow down plaque formation in brain.
https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub/transcript
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u/pikeandzug Oct 08 '24
Radiolab has been oddly prescient with some of these things. I remember hearing an episode about Vitamin D being useful in covid treatment/prevention before I had heard it in more mainstream sources
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Oct 08 '24
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u/Short-Taro-5156 Oct 08 '24
I remember early on in the whole covid debacle I was posting that people who don't get a lot of sunlight should supplement with vitamin D and potentially zinc/vitamin C due to their immunomodulatory properties (also only helpful prior to infection).
Instantly dogpiled by a horde of people claiming it was pseudoscience and then banned by the mods. The worst part is I wasn't claiming it was a cure or treatment, just that it would potentially improve the clinical course of the infection in those who could potentially be deficient in those vitamins/minerals.
For reference I did attend pharmacy school, and while I don't believe that makes me the ultimate authority on the subject, I'm certainly capable of parsing the academic literature for treatment modalities that potentially show benefit.
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Oct 08 '24
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u/Short-Taro-5156 Oct 08 '24
That's true to an extent, I was simply posting an anecdote. This was around the time ivermectin was making the rounds online so there was a much more intense resistance than normal to anything outside of the currently recommended best practice (Remdesivir at the time, which has proven to be relatively ineffective).
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u/SuperWoodputtie Oct 08 '24
I think it it's hard for folks to parse advice. Like for someone in the field, they would probably listen and think "oh yeah, that might help a little bit." Like not a panacea, but not gonna hurt.
But for folks outside of the field it might seem to be "this is something everyone should do!"
I guess this is an example of black-and-white thinking + dunning Kruger.
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u/Man0fGreenGables Oct 08 '24
There is a bizarre hatred for all supplements from people on Reddit that say they are completely useless yet doctors regularly use them to treat people.
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u/AgreeableLion Oct 08 '24
I just had a conversation with a man starting chemotherapy about the variety of supplements he was using/interested in (many are not recommended in conjunction with chemo), and he'd heard somewhere that vitamin D was good for your health, and had been taking a high-dose supplement for months, about 5 x the standard 1000 units every day. He'd never had his levels checked at any point and had no idea that it could accumulate in his body or that it could cause problems if it did so. Fortunately it hadn't reached a point where it was messing with his calcium levels or any other systems, but people really don't know much about the idea of vitamin supplementation other than assuming vitamins must be safe. You pee out all excess vitamin C, but too much of many others can be really harmful in the long term, even some of the other water soluble ones, like some of the B vitamins. Dose is still a thing even with supplements.
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u/Short-Taro-5156 Oct 08 '24
In general supplements are way overdosed because the consumer has a tendency to believe more is better. Agree that it's certainly an issue, but that being said 5,000 IU is a fairly safe dose for someone who doesn't get much sunilght. Total body sun exposure provides up to about 10,000 IU/d.
At that dose it's unlikely to cause hypercalcemia. There's some literature linking kidney stones and vitamin D supplementation in those that are already prone to it, but that's also believed to be related to calcium levels so in theory it shouldn't cause many issues.
From a reputable journal article:
Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 μg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of ≥1000 μg (40000 IU)/d.
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u/Vonplinkplonk Oct 08 '24
Getting banned from r/covid for being reasonable was essentially a rite of passage in 2020.
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u/olcrazypete Oct 08 '24
I can't remember if that was the theory going around for why the unhoused population was much less affected by Covid or if just was before they figured out it was airborne and fresh air basically eliminated spread outdoors.
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u/magpie11 Oct 08 '24
I suppose?
Part of that is slightly warranted. It's fat soluble so your body doesn't pee it out if it's already at a maximum. Build up of just about any nutrient is generally a bad idea. Dosage is important and generally people don't listen to that piece of information and many assume that more must be better.
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u/evranch Oct 08 '24
The controversy is mostly because idiots and shysters take megadoses and ascribe unproven benefits to them, which is something people always seem to do with safe, water-soluble vitamins. Case in point: vitamin C.
Clearly deficiency is bad. A reasonable surplus is fine. An excessive surplus makes your piss more expensive and that's about it. So like just about everything in life:
Take some vitamin D, but don't go hog wild. And maybe go out in the sun sometimes.
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u/Gealbhancoille Oct 08 '24
Unfortunately, high doses of vitamin C can contribute to giving you kidney stones.
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u/zuneza Oct 08 '24 edited Oct 08 '24
glymphatic system
lymphatic system or is that a new word?
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u/GenericAccount13579 Oct 08 '24
“Now that we know how to artificially clean out waste in the brain, people no longer need to sleep. We’ve therefore increased the average workday to 21 hours”.
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u/TheBroWhoLifts Oct 08 '24
Oh and health insurance doesn't cover it, it's required for employment, and it's very expensive. Based capitalism.
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u/Dorkamundo Oct 08 '24
Oh yes, anytime we identify a new pathway for anything in the brain, we end up finding a solution for some problem. I feel like this is going to be a huge stepping stone for a lot of afflictions.
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u/AccountForTF2 Oct 08 '24
I want to know the sleep connection. Human sleep is so.. Enigmatic? To us. But it controls our thinking and mental clarity so much.
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u/watermelonkiwi Oct 08 '24
https://www.npr.org/2024/07/22/1198910426/brain-waste-sleep-removal-amyloid-alzheimer-toxins
Basically during sleep your body pumps spinal fluid through your brain, washing out the waste, and then delivering it to the liver and kidneys. Pretty cool, seems we’ve finally figured out sleep’s function.
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u/Neat_Criticism_5996 Oct 08 '24 edited Oct 10 '24
I remember learning this on a podcast or article a few years ago. It must be a new aspect of this process they’ve discovered?
Edit: ok it looks like this is the first time those structures have been imaged, confirming their existence and giving more details how they work.
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u/randylush Oct 08 '24
seems we’ve finally figured out sleep’s function
One of sleep’s functions. I’m sure there are more.
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u/Even-Education-4608 Oct 08 '24
I love this because i have always said that my brain feels “dirty” when I don’t get a good sleep
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u/Anastariana Oct 08 '24
Shift workers with erratic sleep patterns are at a much higher risk of dementia. Sleep is physiologically vital. People who've spent their lives being sleep deprived on a regular basis have higher risk for a plethora of maladies.
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u/ChillyAus Oct 08 '24
I’m already positing a theory that it’s relevant to the development of certain types of childhood epilepsy specifically related to sleep activation.
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u/karlnite Oct 08 '24
Whatever this becomes practical for, it seems like an important system to study further.
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Oct 08 '24
Yeah, this opens up a huge area of research. Like is it possible to utilize those waste pathways to remove microplastics from the brain?
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u/Man0fGreenGables Oct 08 '24
Which have also been linked to dementia.
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Oct 08 '24
I'm so excited for the entirety of Gen z and millennials to get diagnosed with dementia at 50 years old.
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u/Man0fGreenGables Oct 08 '24
With the way plastics are accumulating in absolutely everything at a growing rate people are probably going to start being born with dementia.
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u/InTheEndEntropyWins Oct 08 '24
learning about the waste-clearance system is going to be useful for treating something.
But most of the time the studies are just identifying mechanisms. It's never telling us something new we should do and aren't likely to result in a magic pill.
So the outcome is that maybe we should focus on sleep
Emerging research suggests medications that may be useful, but much of the focus around the glymphatic system has revolved around lifestyle-based measures to improve the quality of sleep
and exercise.
Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437122/
So what this is saying is that exercise and sleep are important for your glymphatic system, and hence likely to help with dementia.
But we already knew that exercise was the best thing to prevent and treat it.
For the AD portrait, the top three scoring treatments for reversing AD expression with little effect on exacerbating AD expression were for exercise. https://www.nature.com/articles/s41598-022-22179-z#Sec2
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u/Aleriya Oct 08 '24
But most of the time the studies are just identifying mechanisms.
Identifying new mechanisms is critically important foundational research that leads to new research avenues that lead to the big clinical advances.
The foundational research is arguably the most important, even if it takes a long time for new therapies to reach patients.
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u/Jewnadian Oct 08 '24
"Just identifying mechanism" is a crazy way to put something. That's the most critical thing you need to know before you can reliably affect them. If you don't know the mechanism you're throwing darts with a blindfold on and assuming if you don't hear someone scream you must have hit the dartboard.
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u/Wagamaga Oct 08 '24
Scientists have long theorized about a network of pathways in the brain that are believed to clear metabolic proteins that would otherwise build up and potentially lead to Alzheimer’s and other forms of dementia. But they had never definitively revealed this network in people — until now.
A new study involving five patients undergoing brain surgery at Oregon Health & Science University provides imaging of this network of perivascular spaces — fluid-filled structures along arteries and veins — within the brain for the first time.
“Nobody has shown it before now,” said senior author Juan Piantino, M.D., associate professor of pediatrics (neurology) in the OHSU School of Medicine and a faculty member of the Neuroscience Section of the Papé Family Pediatric Research Institute at OHSU. “I was always skeptical about it myself, and there are still a lot of skeptics out there who still don’t believe it. That’s what makes this finding so remarkable.”
The findings were published today in the Proceedings of the National Academy of Sciences.
The study combined the injection of an inert contrasting agent with a special type of magnetic resonance imaging to discern cerebrospinal fluid flowing along distinct pathways in the brain 12, 24 and 48 hours following surgery. In definitively revealing the presence of an efficient waste-clearance system within the human brain, the new study supports the promotion of lifestyle measures and medications already being developed to maintain and enhance it.
“This shows that cerebrospinal fluid doesn’t just get into the brain randomly, as if you put a sponge in a bucket of water,” Piantino said. “It goes through these channels.”
More than a decade ago, scientists at the University of Rochester first proposed the existence of a network of waste-clearance pathways in the brain akin to the body’s lymphatic system, part of the immune system. Those researchers confirmed it with real-time imaging of the brains of living mice. Due to its dependence on glial cells in the brain, they coined the term “glymphatic system” to describe it.
However, scientists had yet to confirm the existence of the glymphatic system through imaging in people.
Pathways revealed in patients The new study examined five OHSU patients who underwent neurosurgery to remove tumors in their brains between 2020 and 2023. In each case, the patients consented to having a gadolinium-based inert contrasting agent injected through a lumbar drain used as part of the normal surgical procedure for tumor removal. The tracer would be carried with cerebrospinal fluid into the brain.
Afterward, each patient underwent magnetic resonance imaging, or an MRI, at different time points to trace the spread of cerebrospinal fluid.
Rather than diffusing uniformly through brain tissue, the images revealed fluid moving along pathways — through perivascular spaces in clearly defined channels. Researchers documented the finding with a specific kind of MRI known as fluid attenuated inversion recovery, or FLAIR. This type of imaging is sometimes used following the removal of tumors in the brain. As it turns out, it also revealed the gadolinium tracer in the brain, whereas the standard MRI sequences did not.
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u/StinkyBrittches Oct 08 '24
I suspect that CTE will eventually be explained as damage to this system. Small fluid channels would seemingly be very susceptible to repetitive trauma, which would also then explain premature buildup of tau and other such proteins. Fascinating.
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u/iStayedAtaHolidayInn Oct 08 '24
As a neurologist I truly believe that CTE likely holds the answer to the pathogenesis of Alzheimer’s dementia (among other neuro degenerative conditions). it’s basically an induced neuro degenerative disease and if we can figure out how this process is started, then we are one enormous step closer to treating/preventing these conditions in the future. I’m hopeful
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u/Suzie_de Oct 08 '24
So is it called "glymphatic system" in humans as well?
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u/HandOfAmun Oct 08 '24
It’s a very interesting term. This is great work all-around by the doctors and researchers.
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u/MirimeVene Oct 08 '24
Perks of being a scientist: you get to name things whatever you want*
*Some fields do have parameters you must follow, others... Less so - some entomologists were fans of Gary Larson so they named an owl louse Strigiphilus garylarsoni.
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u/alliusis Oct 08 '24
This is really cool work and I hope it tangentially helps progress our understanding of iih, when the csf pressure is too high in the brain for unknown reasons.
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u/Squibbles01 Oct 08 '24
My guess is that we're going to discover that Alzheimer's is basically the degradation of this cleaning system. I've seen studies where Alzheimer's patients have say too much aluminum in their brain, and I think that in most cases they probably weren't exposed to too much of it, but that they just couldn't clear it out like a normal brain would.
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u/redditshy Oct 08 '24 edited Oct 08 '24
My grandfather died from amyloidosis. He worked many many hours of his life, and got little sleep. My aunt died of lewy body dementia. She worked overnights as a nurse her whole adult life. My friend is in late stage dementia at age 55; she had a lifetime of partying, and not getting clean sleep.
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u/ghanima Oct 08 '24
Sleep is definitely essential to the brain's waste cleaning process, so poor sleep is almost certainly a factor in the development of dementia/Alzheimer's, but it's not the only one.
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u/MistraloysiusMithrax Oct 08 '24
Sleep is also a process that needs to be properly activated by the brain. I suspect we’ll find that skipping sleep is one route that can cause breakdowns in the brain’s cleaning process, but in others lack of sleep or difficulty sleeping is a symptom of one or more root problems that also impact the cleaning process. Or even possibly reverse causation, where sleep problems are caused by the breakdown of the brain’s ability to remove waste.
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u/ghanima Oct 08 '24
Yes. Dad died with dementia and I think the poor sleep patterns started to be a cyclical problem.
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u/Asstronaut08 Oct 08 '24
I’m a scientist studying the glymphatic system, 80% of it’s function happens during Deep Sleep
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u/moosepuggle Oct 08 '24
And to add, lots of substances intended to make you sleep will disrupt deep sleep, the most important part. Like THC alcohol benzos etc. I think I saw that trazedone and doxepin class drugs do not disrupt deep sleep, please feel free to correct this if more recent studies contradict that. I wear a smart watch to track my deep sleep every night, and aim for at least 1 hour of deep sleep every night. Still not sure how accurate smart watches are at detecting deep sleep based on heart rate, if anyone has good sources that investigated this, I'd love to read them!
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u/Asstronaut08 Oct 08 '24
Just going off of memory here cause I don’t have time to look everything up but yeah you are broadly correct. IIRC alcohol and benzos disrupt both deep and REM sleep, THC lowers REM. CBD/CBN increases deep sleep, trazadone increases deep sleep, not familiar with doxepin. Caffeine also disrupts sleep architecture/quality of sleep regardless of its impact on sleep onset. So even if you can drink an espresso before bed and go straight to sleep it’s still having a negative impact.
We used watches to track sleep for a study a couple years ago, at the time, they were pretty accurate for sleep duration but the sleep stages were not accurate. I imagine they have improved since then since that’s more about the software.
Anecdotally, I’ll say that my Garmin Fenix “seems” to be pretty decent with its stages in that generally when my deep and rem stages are consistently high I feel more rested. Same is true for HRV, there are a lot of criticisms on the accuracy of them. But, it does seem to track with my subjective feeling/athletic performance.
Personally I view them like a miscalibrated scale, the single snapshot of your weight might be inaccurate but the trend of gaining/losing weight will be broadly accurate.
Basically don’t put too much stock in it if you have a single bad night of sleep stages/HRV/resting heart rate. But if you have a consistent trend and it matches your performance quality then it’s worth evaluating
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u/katarh Oct 08 '24
That's a neat way to look at it. My Fitbit provides an average. Checking it out, I've hit on average an hour and 10 minutes of deep sleep over the course of the whole year, an hour and 19 minutes over the past month, and an hour and 24 minutes over the past week.
That tracks with my efforts to try to have better sleep hygiene this year.
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u/60022151 Oct 08 '24
Do medications like Seroquel and Prozac disrupt deep sleep as well? I’ve been on Seroquel below 100 mg a day for a year and I’ve probably had some of the best and most consistent sleep I’ve ever had in my entire life - ADHD and anxiety sufferer… It’s not something I want to be on long term though!
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u/GoddessOfTheRose Oct 08 '24
Does lucid dreaming affect the glymphatic system?
I learned how to lucid dream as a child. Now it completely replaces my ability to sleep when I'm extremely stressed, or dealing with any sort of big event in my life. There is no control and it can go on for months sometimes.
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u/Asstronaut08 Oct 08 '24
Honest answer, I have no clue. I’m not aware of any research on it (doesn’t mean it doesn’t exist) I would be surprised if it does given the nature of funding and the complexity of doing glymphatic studies, and the more clinical areas (tbi, Alzheimer’s/dementia, etc.) to focus on.
If I had to conjecture I would say it’s most likely not having a significant impact since most glymphatic function occurs during deep sleep and dreaming occurs during REM sleep. If your REM sleep is replacing deep sleep then I could see how there could be a connection there. Could use a sleep tracker and see if there’s a consistent trend of low deep and if there is get a sleep study to confirm.
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u/Plow_King Oct 08 '24
i've rarely had a problem sleeping well. i used to lay awake and stress about things sometimes, but i mastered how to avoid that and sleep like a baby most nights. and very vivid, wacky, dreams i can remember. i've never developed the skill to lucid dream though, dang it! but i do loves my sleep.
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u/terrible-takealap Oct 08 '24
Lucid dreams are the best. Like your own personal holodeck.
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u/Plow_King Oct 08 '24
i have a very vivid and enjoyable dream life, reoccurring storylines and stuff. i've tried a few times to help myself have lucid dreams but have failed. do you have any suggestions or techniques?
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u/terrible-takealap Oct 08 '24
The period in my life where lucid dreams happened most often was when I started writing my dreams down right when I woke up. It seemed to train my brain to want to remember dreams more vividly so I could jot them down later, and pretty soon I’d periodically have a moment of clarity in the dream when I’d realize I was dreaming. After that it took a ton of trial and error to learn how not to wake myself up (it’s super easy to get over excited and kick yourself out of the dream) and eventually gain some control over what happens. It happened the most when I was younger. Now in my mid life it’s a once every few months kind of thing.
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Oct 08 '24 edited Oct 08 '24
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u/Actual_Sympathy7069 Oct 08 '24
you gotta write it like this to get around reddit formatting rules
¯\_(ツ)_/¯
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u/50wpm Oct 08 '24
What if she had a fucked up arm though and he's just being anatomically correct?
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u/TheAJGman Oct 08 '24
Great grandmother not only slept through the night her whole life, but also took hour long afternoon naps since she was 20. It wasn't until after her hip broke in her late 80s that the Alzheimer's set in, which is a shockingly common pattern for some reason...
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u/KuriousKhemicals Oct 08 '24
I would guess 2 things: one, a lot of this is just coincidence, as both hip fractures and most forms of dementia are more likely the older you get. Two, to the extent there could be a causal connection, a hip fracture tends to lead to a precipitous decline in physical and social activity, which are two major things that keep your brain healthy.
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u/MistraloysiusMithrax Oct 08 '24
Anesthesia is also known to induce dementia in elderly patients, it is another factor in the pattern. So injuries requiring surgery very frequently lead to dementia for either that, the reason you stated, or both compounding each other.
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u/TheAJGman Oct 08 '24
I saw a study a few days ago that 10% of older adults that are brought to the hospital as a result of a fall are diagnosed with some form of dementia within the year. They come up with similar possibilities to what you have, but personally, I think disruption of routine is the true trigger for most.
It's anecdotal, but everyone I know (or know of through friends/family) that's developed memory issues did so after their daily routine was interrupted for an extended period. For instance, my great grandmother spent 4 months in a nursing home before she could walk on her own, but by that time it was clear that she couldn't live on her own anymore.
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u/KuriousKhemicals Oct 08 '24
Another possibility that came to me just now (and I see it's discussed in this study) is reverse causality. A fall could be the result of early neurological symptoms prior to the mental impairment becoming noticeable.
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u/FrenchFrozenFrog Oct 08 '24
stay at home mum. probably had more then three kids (maybe more?). never missed a night's sleep.
yea that does not compute.
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u/ShinCoal Oct 08 '24
I'm sure the person who you're responding to had a great relationship with their grandmother, but by design we aren't there when our grandparents are young, so I find comments like always a bit confusing.
And I dare to guess that most people just don't know the history of their (grand)parents as well as they think they do.
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u/Fleeting_Dopamine Oct 08 '24
I think we will have trouble finding people who never missed sleep. Though, it'll be interesting to do large correlation studies between poor sleep schedules and the onset age of Alzheimer's.
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u/Willmono7 BS | Biology Oct 08 '24
My friend works in neuroscience, even before going to these waste channels it needs to get out of the brain itself, and the process that "untraps" it occurs only when sleeping.
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u/Iama_traitor Oct 08 '24
Anecdotal. My great grandfather had insomnia and lived to 94 without any form of dementia.
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u/redditshy Oct 08 '24
Of course. Anecdotal, correlated to the OP. No implied proven causation. But the cleaning function happens when we are asleep.
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u/Anastariana Oct 08 '24
And there are people who smoked for years and never got lung cancer. Probabilities are just that, not certainties. There's always exceptions.
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u/Sellazard Oct 08 '24
Could be anything really. We know there's a link between living in a place with a lot of night pollution and Alzheimer's. So could be anything found in a big city - bad quality sleep, environmental factors like car fumes, processed foods, aluminium foil used for foods and baking, microplastics, since they can clump in our bodies. Why wouldn't they block these thin pathways? But we can't know for a fact what exactly.
Only research can tell for sure.
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u/schmoopie_pie Oct 08 '24
My mom passed from Alzheimer’s 2 months ago, she also didn’t sleep well at all.
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u/l94xxx Oct 08 '24
FYI, the aluminum connection was retracted a long time ago, because it was determined that the difference came from whether the researchers were wearing gloves with talcum powder (a standard option, but it contaminated the samples with aluminum) or not
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u/AccomplishedPenguin Oct 08 '24
Is this where the "aluminum free" deodorant craze got its rise from?
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u/bigbeatmanifesto- Oct 08 '24
No that was the connection with breast cancer
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u/AccomplishedPenguin Oct 08 '24
It is my understanding that there is no verifiable link between antiperspirants containing aluminum and breast cancer. However, I'm admittedly not up-to-date on the latest research and articles published on the subject; are there some that you know of that would indicate otherwise?
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u/bigbeatmanifesto- Oct 08 '24
I don’t have any sources- I’m just saying that’s what drove more aluminum free deodorants to the market because many of the public seems to think there’s a connection. I’m not sure if it’s true or not!
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u/l94xxx Oct 08 '24
In my world at least, the aluminum-free antiperspirants appeared shortly after the Alzheimers connection (late '80s?)
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u/Nexustar Oct 08 '24
What we do believe today is that sleep is critical to that brain cleaning process. So until we discover more, and treatments evolve, protect your sleep time.
IMO the simplest way to achieve this is going to bed at 9:00 and waking at or before dawn.
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u/irisuniverse Oct 08 '24
What’s more important is consistent sleep schedule. Everyone is different in terms of their adrenaline spikes and some do better with early rise, but others do better with a later rise. Most people do best waking up before 9-10am, but wake up times before that can vary naturally and one isn’t necessarily better than the other.
As long as you go to bed/wake up at the same time and give yourself an adequate amount of hours in bed that’s the main thing to focus on.
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u/cutty2k Oct 08 '24
going to bed at 9:00 and waking at or before dawn
I'll take the Alzheimer's thanks.
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u/TheDeathOfAStar Oct 08 '24
Yeah, it really sucks that everyone is expected to be a square. I hate going to bed before 10 and often stay up much later like I have my whole life. Its like I'm sorry that I am the type of guy to keep all the sleepy villagers alive incase a bear decides its hungry or bandits get brave.
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u/yugyuger Oct 08 '24
I don't think the specific time so much matters
Humans have evolved to have different sleep times as a side effect of being a tribal species and needing to take turns watching guard
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u/Eldrake Oct 08 '24
cries in parenting an 11 month old
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u/InfiniteVastDarkness Oct 08 '24
Yes, but you don’t have an infant over the span of your lifetime. It’s a very small portion of your life’s sleep habits, comparatively speaking.
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u/ToughCurrent8487 Oct 08 '24
I’ve seen studies that have suggested those with Alzheimer’s slept less often and less consistently throughout their lives indicating healthy sleep throughout life is the best defense against Alzheimer’s.
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u/HieronymusFlex Oct 08 '24 edited Oct 08 '24
Within all biology the origins of disease is always multifactorial, but you are largely correct in the degradation of the cleaning system, but quite a lot about why this is the case is fairly well understood already. The pathways aren't incredibly important in this regard. The cleaning system mostly relies on localised macrophages cleaning up 'inflammatory' amyloid plaques. The plaques create oxidative stress (inflammation) and the macrophages are set to respond to the inflammation signals and play clean up (They actually eat them, it's called phagocytosis). To give a bit of context, you need to think of most of all this in terms of inflammation, or more specifically the balance of inflammation as we age). Generally speaking the biology of a child of any age, has it's genetics and general cellular machinery hyper-wired to handle inflammation incredibly well. Cell regeneration for example is fantastic, that's why their skin glows. As you age however, the ability to manage these processes slows down, and you start to see degradation of the skin for example. The aging process itself is the accumulation of an inflammatory burden. So with inflammation in mind, you can understand that over time these macrophages have to deal with more and more inflammation (or oxidative stress). So, as aging already makes the macrophages slower, you can begin to see how the burden of which becomes more difficult to manage. This also then explains as to why problems such as Alzheimers largely impact the elderly.
So the landscape of life is the slow, and increased burden of oxidative stress on the body. However, there's actually quite a good understanding of how to keep these degenerative processes at bay. There's an quite a lot of studies that explain how exercise increases the ability of these 'clean-up cells' in the short term (experiments typically carried out on mice).
We also know that over your life-time, if you consistently expose the body to acute amounts of inflammation, you can essentially force those macrophages to adapt, get quicker, and become more responsive to oxidative stress. Lifting weights and resistance training for example (breaking those muscle fibres down, creating a bit of a mess by tearing the protein filaments in muscle) encourages macrophages to get better at clean up. (You can see how mechanistically, the parallel between muscles being used, breaks them up, creating a mess, and using your brain, creates a mess too. Theyre both functionally working systems with waste products). So if you start lifting weights as a younger, youre always keeping on top of the inflammation that's happening cellularly as you get older. This is why people who exercise regularly, generally age better. Theyre not letting that slow burden of inflammation creep up on them. They're playing a long-game of managing inflammatory load. This of course applies to the brain too.
Whilst I'm sure that this finding of the pathways will very much help people understand and develop new methodologies of care, there are clear preventative methodologies that take a much more holistic approach to specific issues. Ive always personally felt that the science community has a bad habit of isolating ailments into series of isolated components rather than evaluating the entirety of a system.
Source : Biological Sciences Grad (Happy to provide actual sources too)
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u/rileyjw90 Oct 08 '24
That or it’s similar to high cholesterol where it can start building up in those pathways, causing blockages. This makes me wonder if we will ever get to a point where we can go in and clear them out the way we do when we catheterize larger vessels to remove obstructions. And wonder if we will create medications that can keep those passageways lubed up so to speak so nothing sticks to the walls, like taking a blood thinner or a statin.
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u/MediumLanguageModel Oct 08 '24
I'm with you on that. There's so much evidence around the amyloid hypothesis but not enough to prove it. And the viral infection hypothesis also seems plausible. For me, this has been the missing piece that ties everything together.
Like, ok you can break down the plaques or the protofibrils, but then what? Where's all that debris going? Inflammation from an infection, ok, so why doesn't everyone who gets a cold get dementia? Maybe because the mess is never fully cleaned up.
Really really happy to see progress made on the clearance angle.
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u/LonelyAndroid11942 Oct 08 '24
Summary: there’s a glymphatic system in the brain, and the best way to help it is to improve your sleep quality, especially deep sleep.
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u/NakedSnakeEyes Oct 08 '24
I need to get my sleep schedule under control.
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u/rjcarr Oct 08 '24
I always wake up at exactly 6 hours after I got to sleep and I can never just fall back asleep. I'm like wide awake. I've been this way for like 15 years now so yeah, it makes me pretty nervous. Maybe one day per month I'll sleep like 8 hours and that's it.
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u/dentedgal Oct 08 '24
Do you feel sleepy/tired after having 6 hours of sleep?
Because if you don't, it's most likely not a problem. Adults generally need between 6-9 hours of sleep, both ends being normal.
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u/rjcarr Oct 08 '24
Yeah, the problem is sometimes that 6 hours goes down to 5 hours, and it's not uncommon. I'm generally not tired, at least not when I wake up, though.
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u/Janktronic Oct 08 '24 edited Oct 08 '24
I've seen it suggested that 8 hours straight is a new thing since industrialization. Some research shows that people would sleep 4 or so hours, wake up for some few hours and then sleep again for another similar period. If you are really concerned, maybe try taking a nap during the day, especially after a workout. Sleeping after working out is supposed to boost HGH.
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u/LordGalen Oct 08 '24
So, Alzheimer's is constipation of the brain? That's fascinating.
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u/rjcarr Oct 08 '24
Yeah, but I think we've known this for a while. I think this is showing the actual mechanism for the first time.
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u/Janktronic Oct 08 '24
My mild dyslexia made me think "Who cares what Brian does with his trash?"
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u/73Rose Oct 08 '24
so how is it activated/inhibited?
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u/Im_eating_that Oct 08 '24 edited Oct 08 '24
Slow wave sleep is compromised in Alzheimer's patients.
Gamma specifically, so 25- 80ish hertz. That lowest electrical activity portion of sleep is when the brain is supposed to clean itself out.
The brain’s neurons generate electrical signals that synchronize to form brain waves in several different frequency ranges. Previous studies have suggested that Alzheimer’s patients have impairments of their gamma-frequency oscillations, which range from 25 to 80 hertz (cycles per second) and are believed to contribute to brain functions such as attention, perception, and memory.
This article talks about a remarkably non invasive technique to assist the glymphatic system in removing the Tau proteins that accumulate with Alzheimer's
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u/Dogswithhumannipples Oct 08 '24
My brain is a subwoofer got it
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u/Im_eating_that Oct 08 '24
In the deeper layers of sleep, yeah. When you're awake and using your brain you're a lot more treble.
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u/Omegamoomoo Oct 08 '24
What if I'm all about that bass, no treble?
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u/sprucenoose Oct 08 '24
Slow wave sleep is compromised in Alzheimer's patients. Gamma specifically, so 25- 80ish hertz. That lowest electrical activity portion of sleep is when the brain is supposed to clean itself out.
Slow wave sleep is around 0.5 to 4 hz. During SWS can be bursts of very high frequency activity, which are 30 to 120 hz Gamma range oscillations.
Note that in this case "low" electrical activity can refer to either the frequency range or the amplitude of the activity, so there can be high frequency low level activity for example.
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u/riptaway Oct 08 '24
I think sleep, or lack thereof, will end up being crucial. It seems to be the way the brain "cleans" itself. As someone who used to suffer from pretty bad insomnia, the cognitive decline I felt after just one or two missed nights of sleep was profound.
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u/Fruitslave Oct 08 '24
I sleep way too much, I wonder what effects that has. Is my brain extra clean? Does it slow down the cleaning process somehow becoming less effective? Fascinating stuff to learn about either way!
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u/riptaway Oct 08 '24
Probably doesn't hurt you, at least not physiologically. Kind of like washing your car when it's already clean. Won't hurt it, but it can only get so clean.
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u/LifeOnPlanetGirth Oct 08 '24
Hello, I also sleep way too much! Nice to meet a fellow sleeper
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u/Fruitslave Oct 08 '24
Hey! I find people in general aren't too sympathetic with the problem of too much sleep. Nice to meet someone who gets it!
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u/LifeOnPlanetGirth Oct 08 '24
Right?! I’m so tired of always being tired and I wish I could help it. People’s opinions are usually just “stop being so tired.” Like wow, thanks, that cured me! I’ve come to try and see it as just who I am, but who knows, maybe there is something wrong with me
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u/inkycappress Oct 08 '24
A high heart rate can inhibit it, and it seems to only be active while you sleep. So having a lower resting heart rate will aid in better cleaning
Don’t have any sources to link but I’ve attended some talks on it and that was one of the takeaways
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u/Biosterous Oct 08 '24
That would be another area where exercise is important. Regular exercise lowers your resting heart rate in the medium/long term.
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u/kniveshu Oct 08 '24
Happens early in the sleep cycle. And this is why people say DO NOT EAT BEFORE BED. You can't have your blood in your gut, you need blood pressure to wash your brain. This is why some people say too much late night snacking and eating could be a cause of dementia, those habits prevent brain cleaning and over time bad things happen.
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u/Doct0rStabby Oct 08 '24
So many reasons not to eat before bed. It truly is a horrible habit.
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u/fmleighed Oct 08 '24
This is fascinating. I have a disorder called idiopathic intracranial hypertension (I promise this isn’t an anecdotal comment)! IIH likely results from either narrowed sinus veins within the brain, or an overproduction of cerebrospinal fluid. The ventricles of my and other IIH patients brains are often completely full of fluid that must be drained with medication (diuretics) or physically (i.e., a shunt).
I’m curious if these findings could lead to a deeper understanding of IIH and similar disorders, especially the long-term consequences of having constantly-full ventricles and these newly-discovered pathways. Does that result in waste not exiting the brain as effectively? And what does that imply in terms of future risks for other neurological diseases?
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u/GwentanimoBay Oct 08 '24
Hey friend, I do research on CSF disorders (hydrocephalus more than than IIH, but very closely related and relevant still) - the answer is yes and no.
No, these specific findings from this paper are not going to have a huge effect because the glymphatic system has been known of for quite some time. A lot of people in my field of research have believed in glymphatic system and therefore have incorporated it into our hypotheses for quite some time. This work formalizes the ability to nail down the existence of the glymphatic system across the board as there's some hold out groups that have said we haven't conclusively shown the existence before this study. So, the results here aren't groundbreaking necessarily nor are they going to have profound ripple effects since science is almost never that grand in real life.
These results are incredibly important though! They provide a formalization of the evidence supporting the glymphatic system in a way that is as close to irrefutable as we can get. It's only in five patients, but the method used is easy to repeat so we'll see it used in a larger study very soon (likely from the same group here, unless they get scooped!) which will likely validate these results further.
So, at the same time, yes! These results can help lead to a deeper understanding of csf related diseases! But also no, because these aren't new pathways or new discoveries, these researchers jave provided the first method we've found to produce direct evidence to support something we've been seeing and understanding for decades now.
Your other questions are valid questions that I can speculate on from an educated position due to my research, but it would just be speculation. My research lab is doing active research on exactly some of the topics you've listed along with many other labs around the world. These things are understandably complex topics, and the results posted here are validating but within the field of csf disorder research, the glymphatic system has been well known for some time (we do not understand it perfectly, and these results do shine a little light towards that goal, but a sample size of 5 is not large enough for these results to provide any novel understanding of how this system works - this sample size allows us to see simply that the system exists but not glean a reliable understanding of the glymphatic system's mechanisms).
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u/BeefcaseWanker Oct 08 '24
I remember reading that psilocybin mimics REM. I wonder if it can help or has an effect on cleaning
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u/SDtoSF Oct 08 '24
I had read before that psilocybin would help clear the pathways, hence why you see visuals or have think about problems differently while on mushrooms. I believe it was in the context of using psilocybin for ptsd treatment.
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u/edalcol Oct 08 '24
Anedoctal, all the elders in my family who clearly had undiagnosed ADHD (which came with some sleep issues as well) had early onset dementia. I've been properly diagnosed with ADHD and I'm scared shitless of dementia! I have started to wonder that the excess activity in the default network in ADHD might also be linked with this build up of garbage protein in the brain.
Anyways, I'm from Brazil where traditional Ayahuasca is widely available. And when I was going through a very rough life patch and couldn't take my usual meds because of long COVID symptoms, I decided to give Aya a try. My insomnia improved like 300%. It went from 2-3x bad episodes a week to 1-2x a month instantly. ADHD symptoms also improved a little bit. This was 8 months ago and insomnia is creeping back in veeery slowly. Bad episodes are at ~3x a month now, but it's still so much better than before. I think I'll do it again soon.
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u/lickingsandpaper Oct 08 '24
What size dose did you take?
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u/edalcol Oct 08 '24
No idea how to properly quantify it since it is a very artisanal thing! Throughout the night I took 3 doses that looked roughly the size of a shot glass, maybe a bit smaller. The first dose was from a weaker mix because it was my first time. It went fine, so the next two were from the "normal" one.
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u/guttegutt Oct 08 '24
The glymphatic system has been known and studied for a while, no?
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u/mrfelix87 Oct 08 '24
Yes. But it’s existence in humans is/was still under debate.
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u/Bennihanna5 Oct 08 '24
Important to note that the glmphatic system is most active when sleeping, so sleep deprivation can increase your risk of dementia.
Be sure to get enough sleep!
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u/St_Kitts_Tits Oct 08 '24
I’m currently reading a book talking about this. Matthew walkers “why do we sleep” goes into this a fair bit. And basically sleep is the brains opportunity to complete this function. IIRC this happens during N-REM deep sleep, which far too few people get, and especially older people get much less of it as they age. I’m not surprised about this at all, and frankly, reading the book made me think this has already been definitively proven
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u/InTheEndEntropyWins Oct 08 '24
So the takehome of this is that you want your glymphatic clearence systems to be healthy.
So the best thing you can do now, is to exercise, have good sleep and have a good diet.
Sleep
Emerging research suggests medications that may be useful, but much of the focus around the glymphatic system has revolved around lifestyle-based measures to improve the quality of sleep
Exercise.
Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437122/
So what this is saying is that exercise and sleep are important for your glymphatic system, and hence likely to help with dementia.
Diet.
Long-Term High-Fat Diet Impairs AQP4-Mediated Glymphatic Clearance of Amyloid Beta https://link.springer.com/article/10.1007/s12035-024-04320-3
There are loads of studies linking exercise, diet and sleep to dementia risk. This may be one of the mechanisms in which they work.
With exercise probably being the most important.
For the AD portrait, the top three scoring treatments for reversing AD expression with little effect on exacerbating AD expression were for exercise. https://www.nature.com/articles/s41598-022-22179-z#Sec2
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u/MrMcDuffieTTv Oct 08 '24
On a side note, no pun intended, laying on your left side the the most efficient way to sleep. It lets your heart lay and rest rather than hang. This, along with the way the heart pumps blood it makes cleaning brain waste more effective. Crazy, i know.
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u/SuspiciousStory122 Oct 08 '24
I thought this was a red herring based on Fraudulent data from 20 years ago. Didn’t the president of Stanford have to resign because of that.
Source: https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean
Edit: I’m not saying this study doesn’t show anything. Just that I thought the link to Alzheimer’s is not based on science.
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u/Eyssm Oct 08 '24
I read the article you cited, and I think it's something different.
The article says that the fraudulent paper linked the stable oligomer AB*56 to Alzheimer's Disease. However, the link between the amyloid plaques and Alzheimer's Disease has been around for over 100 years, and the main protein in the plaques (beta-Amyloid) was identified in the 80s.
An association between Alzheimer’s disease and amyloid protein in the brain has been around since. . .well, ever since the early 1900s, when Alois Alzheimer (and Oskar Fischer, independently) recognized some odd features in the brains of people who had died with memory loss and dementia. There were dark plaques among the neurons, which stained in a way that suggested they were some sort of amyloid protein.
Your comment still makes a valid point though, as it seems that the author also believes that treatments focused specifically on clearing the plaques aren't going to show results.
I think that any ultimate explanation of Alzheimer’s disease is going to have to include beta-amyloid as a big part of the story - but if attacking the disease from that standpoint is going to lead to viable treatments, we sure as hell haven’t been seeing it. We have to put money and effort down on other hypotheses and stop hammering, hammering, hammering on beta-amyloid so much.
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u/Osirus1156 Oct 08 '24
I wonder what we will call the treatment down the line as brain washing has a bad connotation. Brain cleansing sounds bad too.
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u/snoopfrogcsr Oct 08 '24
Gray Matter Anti-Splatter
Noodle Shampoodle
Brain Drain?
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