
Small Trial Reverses a Year of Alzheimer's Cognitive Decline in Just Two Months - lelf
https://www.sciencealert.com/small-trial-reverses-a-year-of-alzheimer-s-in-just-two-months-in-seven-patients
======
aazaa
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.

[https://content.iospress.com/articles/journal-of-
alzheimers-...](https://content.iospress.com/articles/journal-of-alzheimers-
disease/jad190367)

Clearly very preliminary but intriguing work.

~~~
ekianjo
> 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.

This is the current state of imaging with tau PET tracers:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096533/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096533/)

> 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.

~~~
14
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...](https://www.ncbi.nlm.nih.gov/projects/gap/cgi-
bin/GetPdf.cgi?id=phd001525.1)

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.

~~~
dragonsngoblins
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

~~~
14
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.

~~~
dragonsngoblins
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

------
bencollier49
There doesn't appear to have been a control group? Perhaps wearing funny hats
is good for cognition.

~~~
jrochkind1
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.

~~~
lighthazard
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.

~~~
harry8
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.

~~~
jrochkind1
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.

~~~
Filligree
No need for the scare quotes. Placebos _work_ ; they're statistically
significantly above "no action taken".

One can argue about why that is, but it seems obvious that there's something
exploitable there.

~~~
dTal
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.

~~~
tacon
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].

[0]
[https://www.wnycstudios.org/podcasts/onlyhuman/episodes/real...](https://www.wnycstudios.org/podcasts/onlyhuman/episodes/real-
doctors-fake-medicine-placebos)

[1]
[https://en.wikipedia.org/wiki/Nocebo](https://en.wikipedia.org/wiki/Nocebo)

[2]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099043/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099043/)

~~~
copperx
However, there are fields where placebos don't work. For example, in oncology.

------
tim333
>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.

~~~
WhompingWindows
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.

~~~
dTal
>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.

------
dvfjsdhgfv
> 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.

------
andy_ppp
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.

~~~
AlexCoventry
Wasn't the amyloid-plaque etiology debunked recently?

~~~
jcranmer
I'll let Derek Lowe (of Things I Won't Work With/In the Pipeline fame)
summarize it:
[https://blogs.sciencemag.org/pipeline/archives/2019/03/21/a-...](https://blogs.sciencemag.org/pipeline/archives/2019/03/21/a-brief-
note-about-alzheimers)

> 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._

~~~
lonelappde
From that summary it seems that amyloid may be an effect, not a cause, of
Alzheimer's.

------
nootropicat
>at a frequency of 918 MHz

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.

~~~
donquichotte
This is different though.

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.

[1]
[http://www.sgoc.de/Download/skin_effect.pdf](http://www.sgoc.de/Download/skin_effect.pdf)

~~~
Symmetry
They seem to have also been right up against the FCC limit for radio energy
exposure at 1.6 W/kg.

------
longtom
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.

~~~
_Microft
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, ...).

~~~
danieltillett
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.

~~~
gus_massa
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.

------
solveit
Tested on 8 people. Sounds wonderful but get back to us when it replicates.

------
graham1776
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.

------
benogorek
Apparently this works on healthy people as well
([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592297/](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?

~~~
ItsMattyG
I wouldn't be surprised if, like TES, this causes neurological tradeoffs.

[https://www.jneurosci.org/content/33/10/4482.abstract](https://www.jneurosci.org/content/33/10/4482.abstract)

~~~
benogorek
"Stimulation to the the posterior parietal cortex facilitated numerical
learning, whereas automaticity for the learned material was impaired."
Fascinating.

------
randcraw
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."

Science Alert clearly hyped the story's lead.

------
ilamont
Unfortunately, many promising studies and early trials don't pan out once
large-scale trials get underway.

------
rpmisms
It seems like anti-aging science is making leaps and bounds lately. First the
reversed biological clock study, and now this.

------
Beltiras
Repeat with larger n and a control group. Till then there's no data to
validate the effect.

------
cbeach
Was it a double blind study?

~~~
yxhuvud
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.

------
ptah
i wonder what the actual treatment feels like and what else the tech can be
applied to.

------
throwaway66920
Is it suggesting that the current itself breaks down the amyloid plaque? Does
this destroy prions?

------
codesushi42
Can this enhance memory for the unimpaired?

