There is significant overlap in the distributions of prodromal and control Parkinson’s patients even for the measure with the strongest signal. While some values for that measure seem to be almost conclusive markets of Parkinson’s, there are ranges in which the overlap is enough to make it not useful as a sole measure without having a high false positive rate.
Seems promising at catching a decent proportion of Parkinson’s super early, but I don’t think by itself this could yield both a good false positive and false negative rate. Keep in mind this is an ebullient press release summarizing a more conservative publication
>Seems promising at catching a decent proportion of Parkinson’s super early
What does early intervention look like for Parkinson’s (besides lifestyle changes)?
As far as I know the treatment for Parkinson’s is basically lifelong dopamine pills, which of course you build a tolerance to and which lose effectiveness over time, requiring ever higher doses. Meaning once you start on them, the ticking countdown of your brain’s lifespan starts as well.
DBS is very much a late-stage treatment - it can stop your uncontrollable shaking once you're at that point, but it does nothing as far as reversal is concerned
While I agree that is the common sentiment, I have read numerous studies that are starting to question this...
"There is evidence to support the use of DBS in less advanced PD and that it may be appropriate for earlier stages of the disease than for which it is currently used. The improving short and long-term safety profile of DBS makes early application a realistic possibility. "
Dopamine is to help control symptoms, not to slow development of the disease. There is no use for dopamine treatment in an early diagnosis that precedes meaningful symptoms.
Lifestyle changes, on the other hand, mostly meaning exercise, significantly and reliably slow the onset and development of symptoms.
My mom has Parkinson's and was in the medical industry for many years (so is a reasonably savvy person). So I trust her opinion, and have been helping her manage the disease. There is effectively nothing at this point that appears to stop the progression of the disease besides lifestyle changes. My mother at 70 goes to the gym for about 2 hours a day on average. This is the most obviously helpful. She has tried fecal transplant (limited evidence this helps in studies, dindn't help her biomarkers), tested going gluten free/dairy free (also some limited evidence it works, didn't help her biomarkers). There are multiple things for brain stimulation, including vibrating tactile glove/boards, but these help symptoms.
We have talked to many different Parkinson's experts around the world, and I think at this point the only thing she seems to think really makes a difference is lots of exercise. She completed halting any evidence of the progression of the disease for about 5 years with exercise, but it will not last forever.
So completely serious, if you get flagged for Parkinsons, and start getting in amazing shape, you have a good chance of really helping yourself get more good years.
Fingers crossed for ongoing research to finally find some way to stop or reverse the damage in another way!
(not medical advice)
That's awesome. It's not easy to get seniors to spend that much time in the gym, so well done if you contributed to motivate her! Physical exercise is indeed one of the few Parkinson's treatments that there's little doubt about.
In terms of reversing the damage, look into photobiomodulation (PBM) aka red light therapy. In "Improvements in clinical signs of Parkinson's disease", Liebert et al in 2021, she shows improvement in all symptoms including cognition, which is one of preciously few such results I've found in my extensive search of the literature[1]. Caveats are that this was a proof-of-concept study with n=6 only and that the red light helmet is somewhat expensive if you want to try it. There's a Canadian company that makes one for above $2000 (modern, very sci-fi thing), and a more hackerish version from an Australian company for ~$700 (pairs of diodes on aluminum bands you have to finish assembling yourself).
[1]: At least which are actionable for the public. There are tons of trials but good luck getting in early unless you can donate a new library to the university! Gene therapy, stem cell therapy, GDNF, drugs that target alpha-synuclein are all promising but not yet accessible. PBM is something you can do today and since mitochondrial dysfunction is a leading hypothesis in the pathogenesis of PD, the treatment fits.
Not to discount the correlation that matches her progression history, but Parkinson's can progress in fits and starts...a stable plateau can suddenly turn into a cliff with accompanying severe decline in health.
> "In our report, thinner INL and GCIPL were also associated with a higher risk of developing Parkinson disease. However, it should be noted that the effect sizes, especially for the INL, are small, so the practical value for an individual as a marker of early Parkinson disease is currently limited."
Looking around a bit it seems that individual GCIPL thickness varies quite a bit even in healthy young adults, with the range exceeding the effect detected in the study. Practically this might mean you'd have to have lifelong GCIPL monitoring to detect the early onset of disease (and GCIPL thinning doesn't seem sufficient to diagnose Parkinson's, it occurs in other diseases like Alzheimer's and perhaps even as a natural outcome of aging).
Probably there are more by now. As I recall this data is great for essentially saying "you should go get a real test." No one is diagnosing - just saying that a certain, say, eye movement slowness is correlated and you can detect it much earlier than a hand tremor or other more prominent symptoms.
That anecdote is not necessarily true. The combination world be very rare even if blindness offers no protection, and it seems to simply not have been studied enough to be confident those rare individuals have been identified as such and published as case reports.
You could posit that a necessary trigger for developing schizophrenia is (over)stimulation of the visual cortex. If that can't happen in blind people (I don't know if all blindness is the same), they'd be naturally protected without even having to consider a genetic component.
But to me, very low incidence rate for both seems like a sufficient rationale. Given that there's both viral and genetic causes for congenital blindness, it just doesn't make sense to imply the protection is genetic: even if true, there would still be cases of schizophrenia among the people that were blinded by a viral infection in-utero.
If nothing else, it could allow you to make different decisions in your life. If my mind is going to be gone in 10 years, I'm sure as shit not saving for long term retirement anymore.
Parkinsons affects motor control, not mental functioning. The point still stands -- if I got a diagnosis I would be less likely to embark on learning to play the piano, and I'd start educating myself on the disease.
EDIT: I'll correct myself. It primarily affects motor control, but late in the disease it can affect cognition.
"if I got a diagnosis I would be less likely to embark on learning to play the piano"
Perhaps counterintuitively, doing something like learning to play the piano could potentially slow the progression of fine motor skill impairment. Same with things like Tai Chi, dancing, exercise in general...
Every case is different , but Parkinson’s is often associated with severe dementia that can manifest fairly quickly. I saw this happen to a close family member unfortunately.
My friend's grandmother's hand started shaking badly eating soup and she got bedridden due to a fall in their home, 1 year later she started calling her daughter "nurse" because she didn't recognize her and passed away not too long after due to heart failure.
I really hope they will find a treatment to this disease eventually.
> If my mind is going to be gone in 10 years, I'm sure as shit not saving for long term retirement anymore.
But hopefully if you could get a Parkinson's diagnosis seven years prior to symptoms, you'd be able to save some money to keep from becoming a burden on your family later on.
I can't really think of any significant short-term interests I have, I think if I (relatively young) was told I was going to die in a year, or otherwise decided I should heed this advice and live that way, I'd spend the year in depression. Or at best just closing out investments, selling things, etc. to make it easier for family to deal with. I just can't imagine thinking Oh right now's the time for that (quick) 'experience' I always wanted (because what?) - I could travel and eat & drink very well perhaps, but I think I'd just find it futile.
And yes I'm well aware this applies inductively to all of life, it's just somehow better if you don't know the value of N.
> I could travel and eat & drink very well perhaps, but I think I'd just find it futile.
I tried that and found it absolutely depressing and futile. Quick experiences never did anything for me or my family. But just doing what I like/want to do only (which not everyone can; some people seem to like/want things that cost a lot of money) is what I should've done for the past 40, not only the past 20 years is what I mean. Maybe dying next year is stressful for most, so make it 5 years; is that better? Or 7 as the article says?
If we could diagnose before actual Parkinsonian symptoms emerge, studying and developing preventative strategies and pharma will be a lot easier.
Parkinson's is funny in that sometimes what initially presents as Parkinsonian symptoms could develop into something like MSA over a span of 5 or more years. If this person were in a clinical trial for pure Parkinson's, it would sort of mess things up...
I don't believe any disease modifying interventions exist which would suggest no, from a purely medical patient perspective at least.
There are some candidates advertised as promising but I'm not sure how much stock I have in this. This isn't my area of expertise but disease modifying therapies for neurodegenerative diseases have been touted as being "around the corner" since I was a first year medical student.
I expect people will look into why eye scans work and how to make them work better.
I also expect them to use this to catch potential Parkinson's patients early and see if they can find out more about early stages of the disease. Maybe they'll find something that works even earlier than eye scans.
To medicine, generally? Yes, because we could enroll patients in trials to look at prevention/delay of symptom onset. To patients right now? No, and probably a net negative, because the psychological harms from knowing what's coming would cause greater harm than the benefit of planning.
I don't hate your comment because you're against VC or business or because you're a cynic, I hate it because it's not going to create good or interesting discussion because its a generic outrage rant with nothing new brought to the table that literally every one on this site hasn't heard before.
That's not necessarily true. Major US corporations like DICK's are all aboard the woke train despite hemorrhaging customers massively from the second and third order consequences of banning scary things from their stores several years ago. To the tune of $250 million. And the CEO kept his job!
In the UK, Wilko has gone into receivership because it's been borrowing at cheap rates, and the bill's just come due. It's widely believed that it's just the first of many.
No idea if that's what is happening with this company or not, I haven't chased any further than a revenue graph (and even that isn't from a source I trust much).
The idea of knowing you're going to get dementia sometime in the next decade is interesting. But I don't think it's straight-forward as to whether or not knowing is a good idea.
It's also a little amusing to take the idea to its logical extreme: What if it becomes a societal norm to know? Would public venues allow soon-to-be dementia patients line cutting priority etc? Think amusement parks, transit reservations, hotel booking, bars, movie theaters -- all of it. There could be a whole industry built overnight of catering to this specific demographic.
> The idea of knowing you're going to get dementia sometime in the next decade is interesting. But I don't think it's straight-forward as to whether or not knowing is a good idea.
It's not fun, but being able to do long-term planning around challenging medical conditions is without a doubt better than not knowing. This includes everything from financial planning to finding a house that is ideal for your condition (no stairs, single level, etc.)
Ideally we'll have a better understanding of disease-modifying drugs in the near future that can slow progression of Parkinson's. If we get confirmation that drugs like Exenatide actually do slow the progression of Parkinson's (trials ongoing) then you'd definitely want to know as early as possible.
I've known several folks over the years that found peace with their diagnosis, and were able to live their remaining good time with joy and grace. I know I would want to know. FWIW.
It depends on the person, but I'd wager that that perspective isn't even close to the majority one. Death is waiting for everyone, having an actual date range for it doesn't really change _that_ much.
"Would public venues allow soon-to-be dementia patients line cutting priority etc? Think amusement parks, transit reservations, hotel booking, bars, movie theaters -- all of it. There could be a whole industry built overnight of catering to this specific demographic."
IME, the prognoses there are on the order of months, generally. Although not likely always formalized and treated with a blanket policy, you can probably get priority service in at least some circumstances.
This situation is unique because of the time span. I'm sure there would be an increased sustained and consistent demand for nostalgia-focused apps. And probably for many other products I haven't considered.
Most developed countries (and many less developed countries) have some government coverage for cancer or dementia.
In New Zealand we can also pay for premium private insurance - although I don't think that helps much for chronic conditions.
Dementia will often still drain your bank account in New Zealand because the government here will take all your equity to pay for nursing home fees. But you do get looked after a bit when you have nothing, so there is that. You can avoid having all your equity taken but it does take some planning, some costs and some effort (e.g. give equity to children more than 7 years before you lose your marbles, e.g. use a family trust, e.g. if married it is very important to ensure your will limits equity damage to one if the other falls ill).
If insurances dont cover you for future risks its not worth calling it this way. Insurance's only purpose is to help the minority of us who will get serious problems throughout their lives, not that exclude them.
Insurance is absolutely not here with "the purpose of helping the minority of us."
Insurance is a business built on exploiting information asymmetries to make money from groups who they try to show empirically can't actually cost more than they pay. If they can find a way to exploit extra information in order to show you're in a riskier group and hence exclude you from coverage, they will. They have absolutely no reason not to.
Insurance companies and you absolutely have an oppositional relationship; they love when we collectively ignore this.
There is probably a difference between someone losing their health insurance after the insurance company finds out about their upcoming Parkinson disease, or their car's insurance sending an SMS about tripling the premium, and someone creating a life insurance contract for a million bucks one day after their diagnosis with a quickly killing unstoppable cancer type.
We could spend our remaining days living it up, but after we're dead all those experiences won't make one whit of difference to us. What will live on is our legacy, in the minds of those still living. I'd rather not be remembered as someone who pushed others aside and spent their inheritances.
Odd statement, as it is of course always the thinker that gets the attribution, i.e. the manipulator of tools and the interpreter of results.
E.g.1: Galileo saw Jupiter, not The telescope saw Jupiter.
E.g.2: Joe built the wall, not The crane built the wall.
In this case, AI is the thinker, not a human, hence the phrasing.
A human creating the AI does not remove the attribution either, just as we never say Joe's mother built the wall just because Joe was created by his mother.
AI does not think. It filters data to identify patterns (ML) or accomplish objectives (AI generally), or generates output based on prior patterns or rulesets under nondeterminism.
Sounds like the ideal employee - does what it's told, generates output based on prior examples and patterns.
the average code monkey cranking out web microservices is not exactly plato either here, after all. look at the existing codebase, try to mimic the style, can you have the PR by friday?
As an AI specialist, I strongly object that statement. There's usually very little surprise in what "AI has discovered", usually we spend months of hard work to make it discover that one thing. But all the credit goes to "AI" :)
PS: I'm yet to see an AI (in any area) that's the thinker.
It's good that there's progress being made on Parkinson's, even if there's no cure.
My father had it, and he's a definite data point for it being caused by trichloroethylene, as an engineer that worked with metal and degreasers, he was exposed to it for years.
We already carry a highly sophisticated camera in our pockets.
How long before we can leverage a smart phone to become the tricorder Star Trek had always promised?
Apple Watch looks to be promising, and I imagine a world where humans won’t have to visit a doctor for a diagnosis, but rather to confirm, and walk a patient through a successful treatment plan
For the developing world, this is likely a great option [1] [2] (although you need to account for additional optics for a smartphone ["fundus camera"]). For the developed world, it's likely this gets lumped into a traditional eye exam. The benefit is from squeezing more data out of existing imaging encounters using ML; think about these as data pipeline implementations.
> High-resolution images of the retina are now a routine part of eye care – in particular, a type of 3D scan known as ‘optical coherence tomography’ (OCT), which is widely used in eye clinics and high-street opticians. In less than a minute, an OCT scan produces a cross-section of the retina (the back of the eye) in incredible detail – down to a thousandth of a millimetre.
I don’t see an iPhone or similar device getting OCT-like images anytime soon. They need special optics to image the whole retina (although I can imagine image processing hacks to work around that at the expense of exam speed), but they also require an optical system that’s quite unlike a normal camera to acquire an image at all.
I think the real issue with OCT cost is machine utilization. An OCT machine is cheap as medical devices go, but, in the usual US model, it gets extremely low utilization. It takes a minute or so to get a scan, it’s completely painless and requires neither dilation or any particular expertise, but the machines only get used a couple times a day.
A venue like Costco or a comparably busy place in a different country could probably offer walk-up OCT scanning for a couple dollars or maybe even free and encourage people to do it once per year. If the FDA played along, software could likely analyze the images and detect the progression of quite a few diseases, several of which would be treatable.
(A brand new machine seems to
cost something like $20k. If it gets used 60 times per day (credible for a large scale user but not for a small shop), $1 of revenue per scan gives an adequate payback.)
> I don’t see an iPhone or similar device getting OCT-like images anytime soon. They need special optics to image the whole retina (although I can imagine image processing hacks to work around that at the expense of exam speed), but they also require an optical system that’s quite unlike a normal camera to acquire an image at all.
the star trek tricorder had attachments, for example the medical tricorder had an additional module and a detachable hand scanner.
the cellphone as the basis for the processing of various sensors, delivering software and connectivity, is essentially similar to this idea. Like when you have a thermal camera that connects to your cellphone.
They already do. Any time you start talking about wanting to do exploratory analysis for preventative reasons they’ll react in some way like “Hurr hurr whoa there buddy, you don’t want to get yourself anxious over benign stuff! This will do more harm than good!”
Doctors are, in my experience, very good at justifying preventative checks they thought of and very poor at justifying ones you thought of.
In both cases, they're correct - since no intervention is risk free, even if you have a 0% false positive rate in the sense of "I found a mass in your arm", for example, you might still have a worse outcome rate if the rate of "mass in your arm causes harm" is lower than "complications from removing mass in your arm".
That's not to say that their suggestions are right and yours are wrong, just that they're right about the reasoning but tend to dismiss concerns that they didn't think of and justify ones they did, and we need a more complicated basis for justifying this than "I think".
People Googling their symptoms and treatments undoubtedly does cause anxiety and correcting mistaken impressions does cost clinical time. There is a middle road here somewhere - we just have to find it, or accept the costs that come with having more tools.
"They do zero efforts to help the public understand anything."
To be fair, with complex diseases, the experts don't even understand them fully...
Trying to explain something super complex with incomplete knowledge to most humans, who often don't have even a basic understanding of how biological systems work, seems like a bad idea...
In the United States, insurance plans are prohibited from excluding people based on pre-existing conditions since 2014.
I suppose if you tried to get certain types of long-term care insurance or life insurance and failed to disclose this you'd be at risk of losing the policy.
But nobody should be avoiding screenings or care for fear of losing health coverage for pre-existing conditions. That stopped being true almost a decade ago.
I believe Obamacare did fix this in the US, but at the trade off of requiring people to hold health insurance at all times. The thinking was otherwise people would just only get insurance when they got supper sick. The republicans chipped away at that requirement (it was one of the least popular parts of the bill) and I think removing it didn’t actually cause the insurance market to collapse which everyone thought it would, but I’m not clear on exactly why? Generally requiring insurance to not charge extra when people only buy it when they need the insurance is doomed
Do we even know if Parkinson's mechanism is the same in all people? Or, is it really a set of things that arbitrarily and uniquely go wrong and end up causing symptoms that clinicians give a loose common name?
I was reading this paper yesterday: https://www.frontiersin.org/articles/10.3389/fchem.2023.1106... . Wouldn't it be good if we could scale those tools to human organisms and to individual patients? Use ML to compensate for the fact that our CPUs and GPUs can't really simulate something that big? What if we could see into the private lives of individual diseases with more resolution than the world's best spying agencies? [^1]
[^1] I dream I could work in something like that, send me an email if you are hiring.
I must mention that I wrote the article titled “Opportunistic detection of type 2 diabetes using deep learning from frontal chest radiographs” (you can find it here: https://www.nature.com/articles/s41467-023-39631-x). While many of these models present promising advantages for population health, there are still many challenges related to bias and execution. However, it’s worth noting that early disease detection can provide benefits, not necessarily cures. The IDEAs study is a good example of this in Alzheimer’s disease.
How predictive is it really? p-values and confidence intervals of hazard ratios only tell you the probability of comparisons to null effects on hypothetically repeated data. What I really want to know is, under the prior of proportion of PD in the general population, what is confusion matrix for this method?
I went down a bit of a rabbit-hole there. Apparently, the current belief is that the meaning is "If the eye is healthy, it functions as the light of the body and indicates that the owner is sincere, generous and helpful." [0]
I find it oddly reductive, unsubstantiated, and meaningless.
I've read that because Parkinson's is caused by the death of dopaminergic neurons in the brain, the same process could be affecting dopaminergic cells in the eye, which do exist. This might be what they're seeing. Thoughts?
"I've read that because Parkinson's is caused by the death of dopaminergic neurons in the brain"
Not to nitpick, but it's my understanding that we all lose dopaminergic neurons in the Substantia Nigra as we get older. Some people lose them a a lot faster, and they develop what we call "Parkinsons". There is also presence of Alpha Synuclein in the dysfunctional dopaminergic neurons, which are not generally present in the "non-parkinsons" population...
OK, so we get the eye machine (OCT?), the woman who can sniff Parkinson's and the lab test for alpha-synuclein in one location and we can get 100% guaranteed confirmed Parkinson's detection !
So if this works then the benefits will be amazing.
I am skeptical for three reasons.
First, the article goes on about the eyes being “windows” to the body and introduces us to the new “science” of “oculomics”. That might be journalist license but it smells of pseudoscience; phrenology anyone?
Second, the idea that any image of an eye can be used to diagnose lots of different neurological conditions like schizophrenia again smells like pseudoscience; reminds me of excessive claims of what chiropractic can do.
Finally, the study seems to be “let’s dump medical records and retina images into a neural network and see what correlates”. I didn’t read the actual study but I would be extremely concerned about accuracy rates.
So I remain cautiously optimistic but still very skeptical; I would be happy to be wrong in this case.
(Disclaimer: I worked in retinal imagery AI for a few years)
I understand why this seems like pseudoscience, but I'd like to explain the assumption better.
As the article states,
> a scan of the retina is the only non-intrusive way to view layers of cells below the skin’s surface.
As an extension, you could also make the case for being able to view the nervous system via such imagery. As stated in [1],
> Despite its peripheral location, the retina or neural portion of the eye, is actually part of the central nervous system.
The theory is that such a non-invasive of visualizing crucial parts of the inner body opens up a "window" into noticing such biomarkers well before the common-but-late-stage symptoms are noticeable.
As for your gripe about:
> let’s dump medical records and retina images into a neural network and see what correlates
, I agree that this requires more careful analysis, but I assume that will happen as part of clinical trials of any such technology. The first foray, which is more experimental than anything concrete, is what this article seems to suggest.
> Finally, the study seems to be “let’s dump medical records and retina images into a neural network and see what correlates”. I didn’t read the actual study but I would be extremely concerned about accuracy rates.
I was left with exactly the same impression. This article was about a data set and the predictions being made from it without any mention of accuracy.
I would hate to get a wrong diagnosis of Parkinson's.
Yes - diet and exercise can play a significant role in slowing progression. If you become aware early you can quickly adjust these things in your life and it could slow progression.
Not a doctor but a relative of a parkinsons patient - the dopamine supplements are somewhat a dual edged blade given that external supplementation will further degrade your own production
Meh. German naturopathic healing practitioners ("heilpraktiker") have been detecting diseases early for centuries. Its called "iris analysis". The idea being, that the iris is divided into sections, each representing a part of the body and subtle but visible changes in a section suggest onset of disease in the connected area of the body. Acupuncture also recognizes such "microsystems" on the body.
There is significant overlap in the distributions of prodromal and control Parkinson’s patients even for the measure with the strongest signal. While some values for that measure seem to be almost conclusive markets of Parkinson’s, there are ranges in which the overlap is enough to make it not useful as a sole measure without having a high false positive rate.
Seems promising at catching a decent proportion of Parkinson’s super early, but I don’t think by itself this could yield both a good false positive and false negative rate. Keep in mind this is an ebullient press release summarizing a more conservative publication