
PET scans show many Alzheimer’s patients may not actually have the disease - DrScump
https://www.washingtonpost.com/national/health-science/brain-scans-show-many-alzheimers-patients-may-not-actually-have-the-disease/2017/07/18/52013620-6bf2-11e7-9c15-177740635e83_story.html
======
trimble
Pet scan: $3000 - $4000 Peanut butter: $3 - $10

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823377/pdf/nih...](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823377/pdf/nihms514234.pdf)

~~~
miguelrochefort
> Methods: Participants with probable AD (N=18), mild cognitive impairment
> (MCI, N=24), other causes of dementia (OD, N=26) and matched controls (OC,
> N=26) were tested, with closed eyes, for their ability to detect an odor,
> one nostril at a time. A container of 14g of peanut butter was opened, held
> medially at the bottom of a 30 cm ruler, and moved up 1cm at a time during
> the participants’ exhale. Upon odor detection, the distance between the
> subject’s nostril and container was measured.

> Results: The mean odor detection distance of AD patients’ left nostril (5.1
> cm), and not their right (17.4 cm), was significantly less (F(3,90) = 22.28,
> p < 0.0001) than the other groups. The mean, standard error, and 95%
> Confidence Interval of the L R nostril odor detection difference (cm) for AD
> was −12.4 ±0.5, (−15.0, −9.8); for MCI was −1.9 ±1.2, (−4.2,0.4); for OD was
> 4.8 ±1.0, (2.6,6.9); and for OC was 0.0 ±1.4 (−2.2,2.1).

~~~
AstralStorm
Tiny pilot study. Where are odds ratios? Where are the multiple measurements
per patient?

------
PeterisP
Historically, a bunch of symptom-defined diseases (e.g. hepatitis, diabetes,
etc) have turned out to actually be a set of _different_ diseases with
different causes, different treatments but similar symptoms - and
understanding that split has been a big milestone in treating them. This now
might be the case for Alzheimer's as well.

~~~
std_throwaway
It's not much better than searching for the cure for all illness.

Drink enough, sleep enough, eat well, do some sports, meditate. If that
doesn't help, good luck with going to the doctors.

~~~
ekianjo
> meditate

Any clinically proven benefit of meditation though? Don't throw it together
with sleep and exercising...

~~~
nefitty
It's been thoroughly proven to be beneficial, in many ways.
[https://nccih.nih.gov/health/meditation/overview.htm](https://nccih.nih.gov/health/meditation/overview.htm)

~~~
tallanvor
Sorry, what? From the site: "Some research suggests that practicing meditation
may reduce blood pressure, symptoms of irritable bowel syndrome, anxiety and
depression, and insomnia. Evidence about its effectiveness for pain and as a
smoking-cessation treatment is uncertain."

I see "may" for some things, and "uncertain" for others. Nothing on that page
says that it's been "thoroughly proven to be beneficial".

~~~
danielbln
How about this:
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203918/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203918/)

(mindfulness being a form of meditation)

~~~
tallanvor
No, I wouldn't consider that at all definitive as a study, and the authors
specifically note the following:

"This study is limited by the lack of a control group or active comparison
clinical intervention that would provide a basis for making a stronger
inference about how MBSR might modify the behavioral and neural bases of
different types of emotion regulation."

So while MBSR may help some people, this tested one specific method and did
not include a control group or test against any other treatment methods.

Now, I'm not suggesting that meditation - MBSR or other - can't be helpful for
some people (possibly even the majority of people under certain conditions),
but it certainly has not been studied enough to show clear benefits compared
to other treatment methods.

------
saint_fiasco
Does that invalidate any studies on treatments for Alzheimer? If it turns out
many people who show symptoms don't actually have it, it's no wonder that a
treatment is so hard to find.

~~~
carbocation
It reduces these studies' power to detect results. If you thought you had 100
cases and 100 controls, it turns out perhaps you really had 30 cases and 100
controls, and 70 controls misclassified as cases. Power is going to be
substantially hurt.

~~~
gwern
I could see it having more implications than just measurement error reducing
power. It's entirely plausible that a drug which has an effect on Alzheimers
would come with side-effects that would damage those who just have senile
dementia; imagine a drug which dissolves amyloid plaques while doing some
moderate damage, in a trial with a mix of dementia and Alzheimers, the
Alzheimers getting better is masked by the dementia ones getting worse, for a
net average zero compared to the placebo group.

------
Spooky23
Not surprising to me.

A family member just had a stroke... the entire system is designed around
maximizing billing. If someone is in a longer term situation and a Alzheimer's
diagnosis makes a buck, you'll get that diagnosis.

Never mind the mental condition is probably a result of the institutional
environment and drugs.

~~~
gnaritas
> the entire system is designed around maximizing billing

Our entire world is built that way, it isn't unique to medicine.

~~~
mulmen
Except for businesses that compete on price.

~~~
gnaritas
And every business does everything it can to not have to do that, it works
when there's choice and price transparency, markets fail without the right
ingredients and healthcare is certainly one of the markets the free market has
failed.

------
philovivero
This is amazing news. I love the advances we're making as a society.

In that $3-5k cost of running a PET scan, I wonder how much of that is paying
professional operators and physicians to interpret the results?

Could ML be applied to this problem to reduce the cost of a PET scan?

~~~
jimjimjim
why does an IV bag cost $500?

I want professional operators and physicians to look at my details.

What I don't want is dozens of layers of middlemen or ticket clippers (or
healthcare driven by profit).

~~~
duozerk
> why does an IV bag cost $500?

It doesn't outside of the US.

~~~
mirimir
Indeed. In the US, it does because manufacturers have gamed the system.
Through bundled contracting with hospitals etc, for example.

~~~
maxerickson
Hospitals pay a couple dollars for IV saline.

 _In fact, manufacturers are required to report such prices annually to the
federal government, which bases Medicare payments on the average national
price plus 6 percent. The limit for one liter of normal saline (a little more
than a quart) went to $1.07 this year from 46 cents in 2010, an increase
manufacturers linked to the cost of raw materials, fuel and transportation._

[http://www.nytimes.com/2013/08/27/health/exploring-
salines-s...](http://www.nytimes.com/2013/08/27/health/exploring-salines-
secret-costs.html)

(which implies that manufacturers aren't the primary beneficiaries of the
price that the hospitals charge)

~~~
mirimir
Thanks. It does seem that, in this case, it's hospitals that are inflating
costs. But even so, this is the Medicare reimbursement price. Maybe hospitals
are "paying" cash price for saline, with a rebate on some product bundle,
which doesn't get allocated properly to their cost basis for saline.

------
mirimir
I suspect that AD diagnoses are driven largely by caregiver frustration with
unhappy old people. Just as ADHD etc diagnoses are arguably driven by
caregiver frustration with unhappy young people. The simplest solution is
drugging unhappy people to keep them manageable.

~~~
Beltiras
Spoken with the privilege of someone having never faced a diagnosis or had a
close one diagnosed. One of the best things that happened to me was an adult
diagnosis of ADD. Drugs really helped. Knowing what ailed me was a greater
relief thou.

~~~
mirimir
Not at all. My bipolar diagnosis was great for me, because it got my
depressive episodes treated properly.

But an important distinction is whether medication is a choice, or is imposed
by caregivers with legal authority, psychological influence, or whatever. I
mean, I chose to take SSRIs for many years. And it made me crazy. Which I
eventually realized.

But a ten year old kid who gets put on SSRIs inappropriately? They are
screwed, and perhaps permanently.

~~~
eigenstuff
I was put on ADHD meds as a 4 (almost 5) year old after my first violin
lesson, this was back in the mid-90s. My mom said it was the weirdest thing
she'd ever seen: I so badly wanted to sit still and listen because I wanted to
learn to play the violin but I literally physically could not do it and became
visibly frustrated with myself. And a bad change in meds in 1st grade (because
I didn't like the bitter tablets) was enough for my 1st grade teacher to
contact my mom about my change in behavior. It was only as an adult that I
realized this must have been the few days where I got in trouble and had to
sit out during recess, which was humiliating to me. I have anecdotes for days
about this kind of stuff.

I am eternally grateful my parents took me to a psychiatrist when they saw
some aspect of my behavior wasn't normal and that it was affecting my quality
of life, even if I was far too young to know or understand that. I think it
was the humane thing to do, 100%.

People talk a lot about how terrible it is that 5 year olds are put on this
shit, but extreme cases like mine are out there and they are legitimate.
Sometimes things show up early because they're severe enough. It'd be fucked
up if 10 year olds on SSRIs was the norm, but I have no doubt that there are
rare cases where it'd almost be cruel /not/ to do it. Bipolar can absolutely
be diagnosed in children. If you can diagnose it that early, why wouldn't you
start treating it? Isn't that what you SHOULD do as a parent?

~~~
mirimir
I get that it helped you. But there are concerns about misguided and
inappropriate medication of children. It's a complicated issue, I admit. And I
admit that I tend toward cynicism. Anyway, this seems like a decent overview:
[https://www.nimh.nih.gov/about/directors/thomas-
insel/blog/2...](https://www.nimh.nih.gov/about/directors/thomas-
insel/blog/2014/are-children-overmedicated.shtml)

------
ekianjo
> “If someone had a putative diagnosis of Alzheimer’s disease, they might be
> on an Alzheimer’s drug like Aricept or Namenda,” said James Hendrix,

Aricept is an expensive drug and does about nothing. I dont even know why
patients with AD are taking it.

[http://www.alzforum.org/therapeutics/donepezil](http://www.alzforum.org/therapeutics/donepezil)

> The effect size of donepezil's benefits is small and the drug does not
> modify the underlying pathophysiology of the disease

------
dm319
The term 'Alzheimer's' has been politicised. Making a diagnosis requires a
brain biopsy, usually done as part of an autopsy. I don't believe a PET scan
is capable of making the diagnosis, despite what the article says.

To understand what is going on, we have to see the problem that hit clinicians
and families around 10-20 years ago. It seemed like an epidemic of confused
elderly patients landing on wards without a specific diagnosis, very little
ability to describe what is wrong with them, and causing disruption to other
patients, either directly, or because they required a nurse to attend them
continually.

Explaining to the family why their mother/father had gone from being someone
who was independent at home to someone confused and unable to tend for
themselves was difficult. Usually the blame would be attributed to infections
(especially urinary tract infections, which are very difficult to diagnose in
a confused patient), but doctors were reluctant to start using the term
'dementia' initially, particularly since there wasn't a good test for it.

In retrospect, what was happening was that we were seeing the success of
treatment for cardiovascular disease. Many patients who would normally have
died in their 50s and 60s of heart disease we now making it to their 70s, 80s
and 90s, albeit with arteries that were still far from ideal.

Every organ in the body degrades with age. We tolerate and compensate for it
up to a point. At the age of 20 our hearts can increase output from 5l/min to
20l/min, sometimes this is necessary to survive a particular bad infection. If
your heart is unable to do this, we say it has decompensated. At the age of
60, even without a diagnosis of heart failure, this is not possible, but
thankfully we are rarely in a position where 20L/min is necessary. The brain
is no exception. An old brain with loss of volume can handle a daily routine
in a familiar environment, but throw in a cold, or another infection, then
make it worse by starting drugs and abruptly changing their environment, and
we end up with an acute confusional state which can take weeks to resolve, if
it ever does completely.

My suspicion is that most cases of dementia (and mild cognitive impairment) is
due to a general decrease in function as we get elderly, exacerbated by
vascular insufficiencies. Alzheimer's is a specific histological diagnosis -
it doesn't give us a cause, it's more of a histological finding. Since we
don't really have any good treatments for dementia caused by Alzheimer's or
vascular causes, and we don't have a way of telling them apart, you could
argue whether this histological finding matters..

Except that Alzheimer's is a term the public are familiar with, and will
donate to.

NB I am not a neurologist nor a dementia expert. I've worked a lot in elderly
care and have had to deal with patients and their families on many occasions.
I have some amusing memories including overhearing a conversation between a
confused patient on a ward who had picked up the ward phone at around 1AM - it
was the bed manager calling to see if their were any beds, but the patient she
was still at home so was quite confused at the question.

~~~
mrfusion
Very interesting idea! I've never noticed an increased heart rate during an
infection though. That sounds kind of strange.

~~~
dm319
It's seen as fairly basic/text-book knowledge, and finding a paper on it is
pretty difficult. It was probably shown in the 19th century and isn't easily
found on google scholar! I did find one reference [1] from more recently. Part
of our sepsis warning scores depend on the heart rate to rate the severity of
the illness. I suspect even in mild colds your cardiac output goes up, but it
might be difficult to notice just from measuring the pulse (stroke volume can
change).

Heart is just one example - our kidneys get worse as we get older too (see
figure 4 of this paper - it's a straight line pretty much [2]). In practice,
it doesn't cause us problems in day to day life, but give it a really big
insult (like sepsis) and it can decompensate. The difference with kidneys is
that we can support kidney failure with dialysis or filtering (if their heart
can support that), whereas with cardiac failure this is not so simple.

Brain failure is probably one of the worst forms of failure. Most causes have
no cure, and they often require 24hr care.

[1]
[http://ajpregu.physiology.org/content/246/3/R331.short](http://ajpregu.physiology.org/content/246/3/R331.short)

[2] [https://www.spandidos-
publications.com/10.3892/mmr.2015.3292](https://www.spandidos-
publications.com/10.3892/mmr.2015.3292)

------
nabla9
Alzheimer is just the most common dementia.

Valscular dementia is also common and Dementia with Lewy bodies are also
possible. Is it possible that many of these were misdiagnosed other
dementia's?

------
jiggunjer
Anybody read the words sensitivity, specificity, or gold standard? Just
because it doesn't show up on PET doesn't mean squat if PET has a low
sensitivity.

~~~
AstralStorm
So what's the gold standard of detecting Alzheimer's? (It is a rhetorical
question.)

~~~
seesomesense
Brain cutting and histopathology See [http://www.bu.edu/alzresearch/brain-
cutting-636x433/](http://www.bu.edu/alzresearch/brain-cutting-636x433/)

"one of a variety of silver impregnation staining techniques, such as the
modified Bielschowski or Gallyas technique, or the fluorochrome dye thioflavin
S is typically employed to visualize neurofibrillary tangles

Because these techniques require either specialized equipment (the thioflavin
S stain requires the use of a fluorescence microscope with specialized
excitatory and barrier filters) or experienced histotechnologists (in the case
of silver impregnation stains), most anatomic pathologists in general practice
lack the capability to properly evaluate brain specimens submitted for the
diagnosis of Alzheimer's disease. Such specimens are best referred to
specialized neuropathology laboratories where the necessary experience and
facilities are in place."

------
seesomesense
Alzheimers is a tauprotein disorder. Alzheimers without plaques is called
Primary Age-Related Tauopathy, aka PARTS.

------
homero
So what did they have?

------
kagamine
I may have Alzheimer's but .. uh... at least I don't have Alzheimer's.

It's an old joke, but fitting for the title.

