Worth reading the "Limitations" section of the original paper:
> The main limitation of the present study, as with most open-label studies, is that all subjects received treatment (single-arm) without inclusion of an untreated/placebo group. However, the improvements in multiple cognitive measures observed with TEMT would have been highly unlikely to occur spontaneously in AD subjects, even with repeated testing (as discussed above). Moreover, it is difficult to explain away the CSF/plasma changes and DTI/FA localized enhancements, which are consistent with TEMT’s primary mechanisms of action to disaggregate toxic brain oligomers and enhance mitochondrial function.
> Eight mild/moderate AD patients were treated with TEMT in-home by their caregivers for 2 months utilizing a unique head device.
Call me skeptical. Mild/moderate AD patients are basically still functional human beings (and pretty hard to diagnose with good accuracy unless you go for expensive brain imaging) that is nothing like "severe" AZ patients. The fact that they knew they were treated by such an invasive device surely has an impact on how they "felt".
Of course, they did not use brain imaging (with tau PET tracers) to diagnose such patients:
> Subjects had to be diagnosed with mild or moderate AD, according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
> Tau PET tracers have enabled in vivo quantification of PHF-tau burden in human brains. Tau PET can help in understanding the underlying cause of dementia symptoms, and in patient selection for clinical trials of anti-dementia therapies.
Add to the potential for unreliable patient selection the very limited sample size, and you could end up with results that look much better than they actually are.
I worked in dementia care for a number of years. When we would get a new admission we would do mini mental state exams to determine a sort of baseline as to where they were mentally such as seen here : https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/GetPdf.cgi...
You would ask things like can you tell me today's date. Do you know what season July is in? I will name 3 items have them repeat them and tell them they need to remember them in a little bit. Then you ask again about those objects and see if they can recall. The test goes on and has a bunch of questions which at the end you score. So I could see them doing something similar in this situation where they test cognitive ability and then retest it a month later. These exams I think would be a pretty good baseline to mark improvement.
I'm not even thirty and I'd have to stop and think about both of those questions for at least a second.
I actually don't know exactly the official boundaries of the seasons (I suppose because they never mattered to me?) I know autumn bleeds into winter into spring, and I know December is in Summer, though where it is in the "official" demarcation of Summer I don't actually know off the top of my head.
Now I just feel like I'm mentally deficient in someway
Lol if you look at the link I provide and scroll down you can take the full test. I can assure you it is pretty straight forward to someone of sound mind. It isn't really meant to trick and some times you have to adjust it a little. Like if I hear you lived along the equator you whole life I probably would ignore the fact that you don't know the seasons well. I guess these tests are not perfect but do shed some light.
Hah, I'm sure I actually am of sound mind. I know with the seasons thing I'm weird, and like I said I could probably figure it out if I actually thought about it.
Knowing today's date though is something I pretty much can never do unless I've had a reason to be aware of the date recently (some important event either happening soon or having just happened). I actually find it a little odd that other people seem to be so aware of it.
I could tell you the day of the week though, because that has more day to day relevance
I would fail the two example questions: can you tell me today's date. No. Do you know what season July is in? No: I'm from the southern hemisphere (additionally we don't have Fall down under).
I couldn't remember my own name when I went to the emergency clinic a while back (kidney stones, very hurt, going into shock), which at least got me immediate attention (I wonder whether it would if I looked elderly?)
I don't know about the funny hats, but getting attention and interaction from professionals twice a day I would expect to be.
The sad thing is that a study "Attention and interaction twice a day with professionals (or anyone else) who show an interest in you and your recovery reverses a year of alzeheimer's" -- would go nowhere. Because that is enormously expensive/inconvenient, and won't make any pharmaceutical or medical device company any money.
This seems wrong because anecdotally there are people who become full-time care-takers of their Alzheimer afflicted family members and have no luck in change. If wearing a funny hate is all that's needed, sign me up.
Do they believe they are also getting a new treatment that is going to work (we all want to believe, cute snake oil sales) or are they just depressed about their decline, but in company? Placebos ain't placebos.
There are studies that seem to show placebos 'working' even when you _tell_ people they are placebos. Placebos are weird.
But yeah, there could totally be a difference between twice-a-day intervention by a researcher who is in a good mood and optimistic about your recovery (and well-rested from going home every night from their prestigious and well-paid job), and a live-in relative who is exhausted and depressed from your state and from having had to leave much of their life to become a full-time live-in caretaker. Depressed about decline with company, indeed.
Genuine question, do placebos "work" for any non-subjective effect? Obviously if I give you a placebo painkiller you might venture "I guess it hurts a little less", but if I give you placebo blood pressure medication does your blood pressure actually go down, even a little? Do placebo antibiotics fight infection?
If not, it sounds like a reporting issue and not any kind of exploitable effect distinct from convincing someone to cheer up a bit.
This rabbit hole of placebos goes very deep. They very much do work, and they work way too well, too often. For example, [0] might really surprise you. And just to really complicate our model of placebos, you should realize there are the opposite of placebos, called nocebos[1].
This does not make /all/ placebos equal and obviously so.
Also, please understand if you haven't been anywhere near there yourself, the ONLY thing you can be 100% sure of when being used for scientific trials is that they are lying to you. Says so right there on the tin. Anything else would be unethical, right? Bad science! "Take this, this is a placebo" But is it? Or is this a sciency adjustment to show that it's the medicine working on me not any belief I have in it. Is there another reason they can't tell me why they're lying about it being a placebo? What are you trying to treat. A 1000 ft vertical fall? Whether you know it's a placebo or not makes zero difference. Described feelings of wellness? Yeah. There's a huge amount between those extremes. All those things are not equal, nor is it even approximately continuous between them.
Don't laugh when people disbelieve "this is placebo". Have some respect for the people who are in these trials because you know the scientists and doctors they're forced to deal with for their one shot at treatment have basically have none at all that is remotely visible to the poor fool staring down some hideous, heinous, vicious, rapacious monster. Don't believe me, got to hospital, try it. The drowning person will clutch the point of a sword but that's not something you'll see in scientific litterature built on data from these people with human hopes, dreams and utter desperation.
"Take a teaspoon of sugar, get it yourself from the hospital canteen then open the sachet and consume in front of a nurse at 15:00 daily just so you can be 100% sure it's not medicine and is a placebo" - no placebo verifying trial ever. Or maybe I stopped reading too early and the experimental design wasn't as flawed as it looks. Maybe you can confirm with a link to the paper because your expertise outstrips my own?
Here's something that is not a placebo: "Promising treatment found for $disease_monster affect millions directly and indirectly" as a story worth money to tell whether fact or fiction. It got viewers on tv before the web, sold magazines and papers and now gets clicks and advertising impressions. It's difficult to be cynnical enough, isn't it? Cancer, Alzheimers are very high on the qty of cure stories that go nowhere we see. Because you know people, you probably loved some of them or love people who did. It catches your eye.
Interestingly, while I'm on this ramble, medicine is where the rubber meets the road in most people's life, even highly educated people, when it comes to science. What they see are not the ideals science has for itself. This in turn undermines belief in science because there really is /so/ much scientific bullshit to wade through. YES it's better than crystals and chakras or other crap and that's an insanely low bar. If that's the best we have we are an utter disgrace as a civilization. This is not an anti-science comment. Science really could be being practised a hell of a lot better in and around medicine, including its reporting. If you love science and what it has done for the human race (who doesn't), stare at the ugliness on display. Decide if you're ok with it or not.
Here is a picture of a random person identified as a scientist who has a teaching position at a university. Do you trust them absolutely without question or are you rather more circumspect. I'll finish with the words funding and replication crisis.
I mean, people have tried several promising new Alzheimer's medications which failed, along with a host of snake oil nonsense.
I'd have to go and dig up studies, but my memory is that even the control groups don't see particularly good results; neurodegenerative disorders are just too fundamental. Most of the promising results for brain activity and dementia seem to represent either keeping information "active" so that it's not consolidated away by normal aging, or keeping patients engaged so that they have better cognitive performance despite unchecked biological losses.
I agree that if this only saw improvement on cognitive scores, a placebo delaying decline would be pretty concerning. But the biological improvements are better than drug or placebo for any other Alzheimer's medicine I've seen, which is very promising.
My father interacted with my mothers 4-8 hours a day for the years she had Alzheimer's. Can't say whether it helped. She progressively got worse but who knows, she might have declined even faster if he hadn't spent so much time with her.
It looks like they considered the "control" to be each patient's baseline measurements before beginning treatment.[1] I would imagine it's also difficult to recruit a healthy control group for these sorts of tests where someone with Alzheimers is probably more willing to accept the risk.
Is it needed and / or ethical in this case? Alzheimers patients don't spontaneously recover, seems immoral to deny them treatment via a placebo when there is no possibility of improvement from their current state. I'm not a scientist or anything, just curious what normal procedure is here
Needed, I would say yes, definitely. Having controls is really a core tenet of science.
I wouldn't really think it's any more unethical than any other clinical trial for any other disease. The whole point is you don't know if the drug/treatment works, so I don't think it's unethical to withhold it. All participants are informed that there is a chance they'll receive placebo treatment as well, no one is being tricked. The point of the trial is to test the treatment, not to just fix a small group of people before the big roll-out.
We know what Alzheimer will do to a person. Don't we have enough data to determine if a new treatment works. I lasted 10 months in clinical trials, and still think it is unethical in the extreme to put in control groups for things we know will kill you. Having watched a control group lose 70% of the people while the people getting the real drug survived is just inhuman.
> Having watched a control group lose 70% of the people while the people getting the real drug survived is just inhuman.
Again, at this stage you're just assessing if the treatment even works. The point isn't to fix one group and screw over another, the whole point is that you don't know if the drug is going to do anything. It's much easier to tell if a treatment is worth giving to everyone if you first do the correctly controlled trials.
It seems like you're coming at this from a place of assuming the treatment is going to work from the get go, which is not true for the majority of treatments that undergo this kind of trial. Moreover, many treatments have side effects that, again, are much easier to look at if you can compared them to a group that went through the exact same handling. Even small, seemingly innocuous things like going to a hospital to talk to an interested person about how you're doing can have an effect on health readouts that may be relevant to a study. Or maybe the stress of sitting down having this weird hat put on your head affects something. Or maybe some much less obvious aspect of the study. The point of the control is that you cancel out all of these kinds of effects, obvious or otherwise, so that the ONLY difference is the treatment.
Controls also help with allowing double blinded studies. If the researchers know who is receiving treatment and who is receiving placebo, they can unconsciously influence the results, especially for things like behavioral surveys that aren't as objective as, say, taking blood and seeing if you have more or less cancer cells. Obviously you can't have this kind of blinding if the researchers know every single person is getting the real treatment.
In certain fields, such as oncology, the control group receives the "standard of care," that is, the standard drug of choice. Even for terminal stage cancer, I believe such trials are ethical because there is no guarantee that the new drug is going to be more effective or even not kill you.
The control group doesn't need to be treatment-free.
So, you can't have enough data to know if a new treatment works without doing a study with a proper control. You need to control to know if the new treatment works, generally.
But, you are right that sometimes the 'control' portion of a study is halted and the control people are given the treatment if a study seems to be going especially obviously well, on ethical grounds.
It can be some difficult ethical decisions. But whether you have 40 people in the experimental group and no control group, or 40 people in the experimental group and 40 people in a control group, you still only have 40 people in the experimental group.
Not having a control group doesn't somehow get the treatment to all effected people in the world. And it would be unethical to give the experimental treatment to everyone in the world _before you have evidence of it's efficacy_ anyway. It might be ineffective, it might even make the condition _worse_ or have other dangerous side effects in addition to being ineffective. You don't know this until you study it properly. Studying it properly means using proper valid statistical techniques, and may mean having a control group. I think it is unethical to give a treatment to people widely _without_ having done a study with a control. Being a part of a research study can be _dangerous_.
Anyone that participates in a research study, knowing the risks, is providing a valuable service to everyone else that may later benefit from what is discovered, whether they end up in the experimental group or the control group. They are taking on risks of a still experimental treatment to help get knowledge to help others.
I'm not saying it's simple. I'm just saying that it is definitely not as simple as thinking having no control group is somehow more ethical than having a control group, or that it's good idea to widely distribute experimental treatments which haven't yet been properly studied. You will harm people by doing so.
You need to control to know if the new treatment works, generally.
That's my dispute. We know X will kill you in a certain time frame. We have thousands if not millions of data points. I fail to see how the control group is really telling you anything you do not already know. Ignoring what we already know is unethical.
It is just is insane that we set people up for false hope and watch them die in droves. I guess it looks better on the marketing material to doctors. I wonder how many actual studies are halted because of die off in the control group. It sure seemed like that wasn't going to be an option.
> That's my dispute. We know X will kill you in a certain time frame. We have thousands if not millions of data points. I fail to see how the control group is really telling you anything you do not already know.
I don't think you understand the purpose of the control group.
It is irrelevant how much we already know about what Alzheimer's disease does, because the control group is not intended to tell you anything about that at all. The justification for the control group is not that it will tell us something about what Alzheimer's does.
The purpose of the control group is to determine if the treatment works. That's it.
You seem to be suggesting that when doing a research study of a new treatment, it would be unethical not to give this treatment to everyone on the planet who has the disease. That makes no sense at all. The experimental treatment may do nothing for them, or may actually harm them. Giving an experimental unproven treatment to everyone would be unethical.
If you want to argue that it is unnecessary to have control groups in an experiment, you need to first understand what the purpose they are said to serve by those who believe they are important (which is pretty much any statisticians or methodologists).
One of the reasons for a control group is to provide opportunities for blindness and double-blindness. Placebo effects are (hopefully) very well-known, but that's not the only common cause of systematic error. Allegiance effect also exists--a doctor may score the same patient with the same symptoms differently if there is a reason to favor one interpretation over another, and it need not even be a fully conscious effect.
Obviously you can't give all Alzheimer's patients your experimental drug/treatment that isn't even shown to work yet. That would not make any sense, and would not in fact be ethical.
So, yeah, that is how controls work, generally. If there is some other standardly accepted treatment for Alzheimer's already, it might be unethical to _refrain_ from giving that, perhaps the control would be given that too. But it's not unethical not to give someone the treatment that you don't even know if it works yet.
Usually. As a general principle. These are certainly interesting things to talk about in the field of medical ethics, and you can find lots of discussion of them in article and such, it's not always totally straightforward or universally agreed upon and of course medical researchers do unethical things all the time.
But simply having a control group that does not get the treatment you are researching is not by itself considered unethical. Which seems to be what you are suggesting. Remember that you don't know if the experimental treatment works at all, that's why it's being studied -- it may even make the condition _worse_, or have negative side effects.
And yes, having a control group is normal procedure. And that's what a control group is, starting off in the same place as the experimental group, but not receiving the experimental treatment, with other conditions being normalized the same. If the control group is 'double blinded', then neither the subjects nor the research staff know if a given subject is receiving the experimental treatment or control.
Yes, because there are more factors than the treatment itself, and it is important to be able to ascribe benefit/harm to the treatment vs. the other factors.
As mentioned in another comment, the sad state of Alzheimers patient care today includes infrequent attention. It is plausible that two visits from another human each day would in itself cause the same kind of improvement seen in the study.
Without a control group, it is impossible to ascribe the results to the treatment or the other aspects of the study.
It is definitely needed and ethical. Consider that most there are many many people in the world that don't get to participate in this experiment at all, neither as active nor as control.
Being control just means you are still part of that status quo.
If we had like 99.9% confidence that the procedure would work, sure roll it out to everyone ASAP, but I don't think we are there yet.
It'll be needed eventually, if progress with the treatment continues, to quantify exactly how much of a difference it makes.
But say you've developed a treatment device for heart attacks. Untreated, let's say the death rate is 90%. With your treatment, the death rate is 20%. Even without running a controlled experiment where half the heart attack patients get the deactivated device, you can state pretty strongly that your device has better-than-placebo results.
In before "the placebo effect is real!" Well, sure it is. But it's most effective for subjective complaints, such as for pain relief, where the person's mental state is responsible for a large part of the experience. Placebos aren't so great for objective issues like "cardiac arteries are experiencing insufficient blood flow", "liver has cancer", or "patient has late stage Alzheimers".
The standard is to have a placebo/control group because then you know for sure if the treatment is responsible for any improvement. Most new treatments either fail or provide a small benefit, however if the treatment is found to be extremely effective the trial is stopped and all participants are given access. As you pointed out, it would be unethical to deny access. This happened recently with two Ebola drugs that were being tested during an outbreak.
But what if the procedure somehow makes brain functionality worse? Wouldn’t a control group of Alzheimer’s patients falsely attribute that decline to the disease rather than the treatment?
Though I suppose you run into the same issue the other way, too. If the treatment somehow improves everyone’s cognitive function it’s difficult to measure because your “baseline” has moved.
>TEMT looks like it can break up the toxic amyloid-beta and tau proteins that have been extensively linked with Alzheimer's – the waves are apparently able to destabilise the weak hydrogen bonds that hold them together.
Is that actually a thing - that you can break up proteins by putting a fairly weak electromagnetic field on them? It sounds like the sort of thing you could test in the kitchen with a coil, oscillator and some half cooked eggs.
The brain responds to various stimuli by changing its regulatory protein environment. There are different wave patterns during sleep, waking, focus, rest, shock, fear, etc. You may see other studies involving magnetism or light stimulation or sonic stimulation, and they work by inducing brain states, not by actively targeting proteins themselves.
Think of it: how could you get a specific magnetic effect to just those beta-amyloid or tau proteins and not the 10,000 other proteins in the brain? These magnetic devices induce changes in the brain state, not in individual protein states... they nudge the brain to employ its own cleaning apparatuses.
>how could you get a specific magnetic effect to just those beta-amyloid or tau proteins and not the 10,000 other proteins in the brain?
By selecting a pattern of wavelengths and phases that causes different parts of that specific protein to resonate out of phase? I don't know how much structural specificity one could achieve with such a method, but not zero I should think.
No that's not what it said. First there s no such thing as a brain state, second yes ofc the waves can target these specific proteins, they explain why in the article: the hydrogen bond between atoms of the molecules of the proteins would be "weak enough" to be broken.
And, to be honest, they said it's hard to verify what happens inside and it s a limited study: maybe it does destroy a lot more.
In any case stop spitting nonsense brain state magic :)
No, it works because it (very likely) stimulates a very specific kind of brain activity that leads the body to break up the proteins. The article's explanation is incorrect. The experiment itself didn't verify what I just said because it is an invivo clinical study, but if you dig around you can find support for my claim.
Personal attacks and flamewar will get you banned here. Would you mind reviewing https://news.ycombinator.com/newsguidelines.html and taking the spirit of this site to heart when posting here? We'd be grateful.
> The MemorEM device is being developed by NeuroEM Therapeutics, and we should point out that two of the authors behind the new study founded the company – so there is some vested commercial interest here.
Nevertheless, the results seem promising in spite of the ridiculously small number of participants, and if other researchers are able to replicate them - that is, if the original study has enough details to build a device with identical EM function - and confirm the results, especially the lack of side-effects claimed by the team, this could be great news to all of us.
So I'm pretty skeptical, they are presumably targeting amyloid plaques in the brain with electro-magnetic stimulation. I just think how? Is it a microwave tuned to destroy the proteins or some other means? The mechanism of action seems very very sketchy to me and I just don't believe you can target proteins without hurting other parts of the brain. Anyone with more information on the mechanism of action I'd love to hear it. Until then I'll assume it's just made up.
Not debunked, just very much in question. A number of amyloid clearing drug trails have failed to achieve clinical progress on the disease in spite of clearing beta-amyloid.
> Something is wrong with the way we’re thinking about Alzheimer’s and amyloid, folks, something is wrong. It’s been wrong for a long time and that’s been clear for a long time. Do something else.
FTA, though I don't have any more detailed information about the process:
> Based on the evidence so far, TEMT looks like it can break up the toxic amyloid-beta and tau proteins that have been extensively linked with Alzheimer's – the waves are apparently able to destabilise the weak hydrogen bonds that hold them together.
Many treatments for many diseases do a lot of harm to stuff that we don't want harmed ... chemotherapy, radiotherapy, most of the thousands of drugs have side effects.
Molecular hydrogen bonding appears to have a medically-interesting effect on cell permeability in the brain, and I'm sure other things.
But most hydrogen bond effects are pretty short-lived, while amyloid plaques build up over a long time as the brain fails to remove them as waste. This is obviously hugely preliminary, but it sounds possible that whatever disruption is being caused is at least shorter-term or less destructive than the benefits of counteracting a slow-moving process like Alzheimer's.
If this works, it lends credence to people that think cell and wifi frequencies are not neutral. The fundamental assumption behind neutrality is that the only effect on the human body is thermal.
It looks like they are using transcranial stimulation, i.e. putting electrodes on both sides of your head and running a current through it, resulting in what I assume to be a quite homogeneous current distribution throughout brain tissue.
RF waves' tissue penetration is stronger at the surface of a conductor, see Skin Effect.
EDIT: substituting the frequency in [1], we arrive at ~9mm skin depth for 918MHz.
Does anyone have a statistics how often awesome inventions and advances in medicine etc. in the media actually turn out true, also how long it takes on average for them to hit the market, if legit. My hunch is that it's like 2% and 10 years, respectively.
From what I read the really sad thing is how many of these failures are even not failure of the method or the underlying idea being wrong but pretty mundane things like failing to get funding for follow-up research, workgroups disbanding, PhD students finally throwing in the towel, researchers getting out of research for other reasons (family, ...).
My undergrad students did a research paper on this about 10 years ago (when I was a professor). It turns out that most promising results don’t get followed through for non-scientific reasons, mostly a lack of money. We never published the work (I left academia shortly afterwards), but it certainly was depressing.
I do realise the irony of not publishing this work.
I was going to ask for a link to the paper ... In particular "mostly lack of money" may mean "the results are not convincing enough to get more funds".
In this case they already tried something similar in mice, and they made a small business around the hat, and this is a preliminary safety trial, so I expect that they have a follow up.
For me, the results are not very convincing:
* They don't have a control group (because it is a safety trial)
* They have some improvements in difficult to compare test like the amount of words that the person can remember (it's standardized, but I guess you improve automatically the second time you try it, it's difficult to be sure without a control group)
* The blood sample test have a few changes marked as "significant" but they are using a very loose criteria to classify it as significant. The error bars overlap too much with the baseline.
So I don't expect that they get good results in a big double blind trial, but negative results are difficult to publish in journals and they almost never get press coverage.
Also (in other branches of science) it's standard to have a pipeline of papers. While one paper is published, other is been written and other is in the research part, and there are some brainstorming about what to do next. Once a group has a vein of subjects to publish about, it's much easier to continue with something similar.
Really? I doubt it. Sure, changing teams and funding may have a short term effect, but given how world-changing all the "miracle cures" that are announced would be, and that they so rarely pan out, makes me believe nearly all of these exciting breakthroughs have something fundamentally wrong.
All: Family member recently diagnosed with Early Onset Alz Disease. Articles like this excite us and we desparately want treatments to work (including the hyperbaric chamber, stem cells, dietary changes, the works, etc), but can't help but think following these rabbit trails is only confirmation bias. Does anyone here know of any treatments that actually are worth exploring (ie have actually been studied, but not gained wide-spread adoption). I know this is a shot in the dark but appreciate any new research you could point me to.
Apparently this works on healthy people as well (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592297/). "it was proposed that use of emerging brain stimulation techniques might also enhance physical and mental performance in sports." Anybody...want to try it?
"Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired." Fascinating.
I scanned the article. The authors make no claim that they reversed a year of cognitive decline. Nor did they assess the health of the subjects at any earlier date in order to compare post-treatment performance to that pre-treatment performance to quantify the treatment effect.
At most, they idly speculate that on one metric, ONLY THE RESPONDING AD PATIENTS saw as much as 15 months of disease regression (ADAS-cog):
"Since a typical decline in ADAS-cog expected for AD subjects is around 4 points over a 12- to 15-month period [48], 2 months of TEMT appears to have reversed cognitive decline (as measured by the ADAS-cog) of responding AD subjects as a group, perhaps back to the cognitive level subjects had 12 to 15 months earlier."
It was an initial pre-study where the purpose is to determine if it would even be interesting to do a proper study. They didn't even have a nonblind control group.
It is still exciting, because most studies of Alzheimers doesn't even pass this initial step from curing mice.
> The main limitation of the present study, as with most open-label studies, is that all subjects received treatment (single-arm) without inclusion of an untreated/placebo group. However, the improvements in multiple cognitive measures observed with TEMT would have been highly unlikely to occur spontaneously in AD subjects, even with repeated testing (as discussed above). Moreover, it is difficult to explain away the CSF/plasma changes and DTI/FA localized enhancements, which are consistent with TEMT’s primary mechanisms of action to disaggregate toxic brain oligomers and enhance mitochondrial function.
https://content.iospress.com/articles/journal-of-alzheimers-...
Clearly very preliminary but intriguing work.