Hydroxychloroquine lowers Alzheimer's disease and related dementias risk(pubmed.ncbi.nlm.nih.gov)
pubmed.ncbi.nlm.nih.gov
Hydroxychloroquine lowers Alzheimer's disease and related dementias risk
https://pubmed.ncbi.nlm.nih.gov/36577843/
166 comments
I think the study is somewhat more robust than you're letting on, since it compares HCQ against an alternative rheumatoid arthritis drug - Methotrexate. It's possible that the choice of prescribed drug itself is correlated with some other confounding factor, but it's certainly less likely to be so compared to HCQ vs nothing.
Also, the study itself is clear about the amount of evidence needed to validate whether HCQ actually reduces Alzheimer's risk: "This hypothesis merits testing through adequately powered clinical trials in at-risk individuals during preclinical stages of disease progression."
Also, the study itself is clear about the amount of evidence needed to validate whether HCQ actually reduces Alzheimer's risk: "This hypothesis merits testing through adequately powered clinical trials in at-risk individuals during preclinical stages of disease progression."
Methotrexate is standard of care, considered “strongly recommended” over hydroxychloroquine (source: https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.24596 ) for rheumatoid arthritis. If I read the paper right, hydroxychloroquine may be favored in “low disease” states.
So I would certainly expect some sort of difference in patient population. It would suggest those initiated on hydroxychloroquine would normally have less severe rheumatoid arthritis (or have some other difference that their doctor would choose to not use methotrexate by default), although I don’t know if that’s the case in reality.
So I would certainly expect some sort of difference in patient population. It would suggest those initiated on hydroxychloroquine would normally have less severe rheumatoid arthritis (or have some other difference that their doctor would choose to not use methotrexate by default), although I don’t know if that’s the case in reality.
Not having prescribed either since I was a PCP years ago, I would just say that I agree with this line of inquiry.
If both drugs were equally good and were pretty much used at random, then they could be good instruments. But if there is confounding by indication, then it’s harder to get value out of an analysis that compares them.
It doesn’t mean the conclusions are wrong (and nor does my comment above), it just tempers my interpretation.
If both drugs were equally good and were pretty much used at random, then they could be good instruments. But if there is confounding by indication, then it’s harder to get value out of an analysis that compares them.
It doesn’t mean the conclusions are wrong (and nor does my comment above), it just tempers my interpretation.
You could try and reduce the possible effect by controlling for disease severity. If it reduced the effect a large amount it'd strengthen the case that the effect is actually due to RA disease severity. Actually I'd be a bit surprised if the authors didn't do that for an observational study.
Agreed. I didn't see it described in their methods, although it seemed that the main focus of this paper (based on length dedicated to the material) was the biological/model data rather than the EHR data.
In that case, couldn't it be that Methotrexate makes the risk worse rather than Hydroxychloroquine reducing the risk?
This summary right here is what I would like to accompany any medical study that pop up online. Thanks for helping us stay skeptical (doesn’t mean that I’m not hopeful and that the claims is true)
It might be that among the causes of dementia, inflammation plays a decent role, which is also the cause of rheumatoid arthritis
Yes, I think the hypothesis is conceptually interesting. But rather than thinking about how it could be true, I try to think about how the data could be misleading. I do this to try to avoid making broader claims in my own work than I should.
I post this comment quite frequently on HN, but yet again this is not a randomized controlled trial, but rather an observational study. On top of that, they state several insignificant statistics using the point estimate (e.g. "Hydroxychloroquine initiators had an 8% lower rate of Alzheimer's disease and related dementias compared to methotrexate initiators (95% confidence interval 17% to 0%)" (paraphrased).
In this case at least the sample is good. 100k people with rheumatoid arthritis, who are likely taking HCQ for the rest of their lives.
Hydroxychloroquine is used to treat Lupus by interfering with the communication between cells (not exactly clear in the research tbh). Lupus, Rheumatoid arthritis, and other uses for Hydroxychloroquine appear to be autoimmune responses where the body attacks connective tissue.
If Hydroxychloroquine reduces inflammation and reduces immune responses damaging connective tissue I could see it generally useful for incidents where the body damages itself (such as Alzheimer or dementia)
If Hydroxychloroquine reduces inflammation and reduces immune responses damaging connective tissue I could see it generally useful for incidents where the body damages itself (such as Alzheimer or dementia)
The main concern here (and most observational studies) is confounding by indication. Specifically, the same reason some people got hydroxychloroquine as opposed methotrexate is the same reason you see differences in the outcome. In this case there’s plausible confounding that needs to be addressed before any conclusion like the title could be drawn.
Generally hydroxychloroquine is used in mild rheumatoid, whereas methotrexate is used in moderate-severe disease.
Inflammation in rheumatoid (and other inflammatory diseases) contribute to atherosclerosis and plaque buildup. Rheumatoid increases the risk of coronary disease by 1.5-2x.
That difference alone could account for the difference in dementia, particularly vascular dementia.
Generally hydroxychloroquine is used in mild rheumatoid, whereas methotrexate is used in moderate-severe disease.
Inflammation in rheumatoid (and other inflammatory diseases) contribute to atherosclerosis and plaque buildup. Rheumatoid increases the risk of coronary disease by 1.5-2x.
That difference alone could account for the difference in dementia, particularly vascular dementia.
If this is true they already have several big patient groups taking it on a daily basis for the rest of their life so should be possible to look at if the prevalence of Alzheimers is lower in those groups.
From reading the abstract, it looks like they picked up on this association from arthritis patients.
That makes me instantly sceptical that the arthritis and/or associated conditions might have played a role. I'm sure they've controlled for that as much as possible, but it's easy to miss some confounding factor since the cause and mechanism of AD is poorly understood. That makes it harder to tease out what confounders to look for.
It seems like researchers would be able to gather data from the natural experiment due to some places in the world where this drug is routinely used against malaria.
I can see an awful lot of potential confounding factors there, though. Life expectancy in most countries in Africa, for instance, isn't even long enough for non-early onset AD to develop. You'd expect less AD just because half or more of the population is going to die from other stuff at 65 or earlier.
https://www.statista.com/statistics/1218173/life-expectancy-...
https://www.statista.com/statistics/1218173/life-expectancy-...
HCQ associated with a 12% reduced risk of getting Alzheimer's disease.
Yeah, it's interesting that they mention it as a "neuroprotective therapy" rather than any kind of treatment. That suggests that it doesn't do anything to reverse damage, but can only slow (perhaps halt?) the progression of the disease.
"In mice". And, the effect size is pretty small.
The largest effect size I know of, predicting incidence of real dementia in real people (46,000 people over 70), is that a recent Tdap booster predicts a 40% reduction. Nobody knows how or why, or isn't saying. Apparently treatment for herpes has a large effect size, too.
It is easy and safe to get both.
The largest effect size I know of, predicting incidence of real dementia in real people (46,000 people over 70), is that a recent Tdap booster predicts a 40% reduction. Nobody knows how or why, or isn't saying. Apparently treatment for herpes has a large effect size, too.
It is easy and safe to get both.
Looks like we're running through the same playbook we saw with COVID, and the obesity comorbidities.
Being obese in your 30s-50s increases your chance of developing dementia or Parkinson's later in life by somewhere between 500 and 800 percent.
Losing the weight is such an OBVIOUS intervention for things like diabetes and CVD risk, but it affects risk factors for nearly every other chronic disease on the list, including something like half of all cancers.
And yet, we're researching the type of micro-optimizations indicated in this article.
Don't be fat from 30 to 60. That's it. That's the solution. And yet, all I see is:
Medically: Masking the symptoms with medication, with not even a cursory nod to improving lifestyle factors.
Societally: Wild adoration of Lizzo and "Health At Any Size" ridiculousness.
Being obese in your 30s-50s increases your chance of developing dementia or Parkinson's later in life by somewhere between 500 and 800 percent.
Losing the weight is such an OBVIOUS intervention for things like diabetes and CVD risk, but it affects risk factors for nearly every other chronic disease on the list, including something like half of all cancers.
And yet, we're researching the type of micro-optimizations indicated in this article.
Don't be fat from 30 to 60. That's it. That's the solution. And yet, all I see is:
Medically: Masking the symptoms with medication, with not even a cursory nod to improving lifestyle factors.
Societally: Wild adoration of Lizzo and "Health At Any Size" ridiculousness.
Alzheimer's and dementia : Diabetes type III.
So is my evening G&T good for me, or will quinine not work?
I attribute never having contracted Covid-19, Malaria, and scurvy to my daily G&T therapy.
Modern tonics contain far less quinine than the “real” stuff. Like 95% less
so i need to have 20 G&Ts then?
like, two quarts of (sugar free) strong tonic water a day.
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That's great news. Alzheimer's and dementia are so such terrifyingly difficult conditions to try and help someone with. Glad we're finding atleast some possibilities to help. Does anyone know of anything others like this?
Really going all-in on trying to find an off-label use that'll allow them to repatent this, aren't they?
I don't think you re-patent an off-label use, you re-patent a minor modification. See for example ketamine to eskatamine; or citalopram to escitalopram.
Once you have the new med you use the courts to prevent the off-label use. See eg lucentis or avastin for Wet AMD.
Once you have the new med you use the courts to prevent the off-label use. See eg lucentis or avastin for Wet AMD.
Or someone has a lot in stock and wants to offload it ;)
"Re-patent"?
It's... complicated but I assume the GP meant new drug product exclusivity [1] which is a process by which a pharmaceutical manufacturer can get a short window of exclusivity for a new approved use without rights over the original patent. That exclusivity is largely for generic manufacturers [2] though and it's separate from the patent patent term restoration [3] the FDA grants to patent holders to help with the time it takes to get to market.
"Re-patent" would mean something different like Shire patenting Vyvanse by adding an amino acid cap to amphetamines, changing it enough that it becomes a new drug with a new patent. That would require clinical trials and all the expense that goes with them.
[1] https://www.fda.gov/drugs/cder-small-business-industry-assis...
[2] https://www.fda.gov/drugs/development-approval-process-drugs...
[3] https://www.fda.gov/drugs/cder-small-business-industry-assis...
"Re-patent" would mean something different like Shire patenting Vyvanse by adding an amino acid cap to amphetamines, changing it enough that it becomes a new drug with a new patent. That would require clinical trials and all the expense that goes with them.
[1] https://www.fda.gov/drugs/cder-small-business-industry-assis...
[2] https://www.fda.gov/drugs/development-approval-process-drugs...
[3] https://www.fda.gov/drugs/cder-small-business-industry-assis...
Love when people take the time to know what they are talking about.. Vyvanse is a perfect example, they took a drug and made a prodrug.
Modifying HCQ to HCQ' would also do nothing to establish exclusivity over HCQ. It's a weird argument.
I think the OP just made a fly-by comment using very imprecise language. Most people assume drug exclusivity works through patents without giving generics with expired patents (like HCQ) much thought.
They wouldn't need to modify it for exclusivity via Abbreviated New Drug Application - I just don't see the FDA accepting any evidence short of a phase III clinical trial that HCQ helps with Alzheimers to fulfill the new use requirements. At best they'd be able to run a proper clinical trial for some cocktail of generic drugs and use ANDAs to prevent competitors from using those generics in their own cocktail for a few years.
They wouldn't need to modify it for exclusivity via Abbreviated New Drug Application - I just don't see the FDA accepting any evidence short of a phase III clinical trial that HCQ helps with Alzheimers to fulfill the new use requirements. At best they'd be able to run a proper clinical trial for some cocktail of generic drugs and use ANDAs to prevent competitors from using those generics in their own cocktail for a few years.
It would if you sued to prevent the off-label use, which is something that happened with avastin and lucentis for wet AMD.
Yes, HN has something of a COVID-19 denialism streak.
HN is divided on topics where society at large is divided. It would be strange if it weren't.
It's also a highly international forum and divisive topics play very differently in different places. Readers often mistake a comment for something weird and radical coming from a person nearby, when in fact it's an unremarkable comment coming from a person far away. It's unfortunate that this leads to so many brutal online arguments. In person, people instinctively modulate their communication with respect to such variables; online they don't, because the information isn't available and we can't make it available.
https://news.ycombinator.com/item?id=23308098
It's also a highly international forum and divisive topics play very differently in different places. Readers often mistake a comment for something weird and radical coming from a person nearby, when in fact it's an unremarkable comment coming from a person far away. It's unfortunate that this leads to so many brutal online arguments. In person, people instinctively modulate their communication with respect to such variables; online they don't, because the information isn't available and we can't make it available.
https://news.ycombinator.com/item?id=23308098
HCQ is a much misunderstood substance as a result of the political furor around it.
It is not a miracle drug and it is not useless for all medical purposes. It is a relatively mild anti-malarial drug with some anti-inflammatory properties. It is prescribed for autoimmune disorders in addition to malaria. Its anti-inflammatory/immune regulation effects are probably not that strong but its safety profile is well understood.
It is not a miracle drug and it is not useless for all medical purposes. It is a relatively mild anti-malarial drug with some anti-inflammatory properties. It is prescribed for autoimmune disorders in addition to malaria. Its anti-inflammatory/immune regulation effects are probably not that strong but its safety profile is well understood.
How is HCQ misunderstood due to the recent political furor? It's been used since the 1950s.
It was promoted by a politically-homogenous group of people as a COVID-19 cure
https://theintercept.com/2021/09/28/covid-telehealth-hydroxy...
https://theintercept.com/2021/09/28/covid-telehealth-hydroxy...
I don't think that's accurate. It's mechanism is well known and to my knowledge the only ones saying that it was a cure were those trying to prevent it's use by misrepresenting it and those promoting it by saying THEY said it was a cure. It doesn't work by itself, and all of the research since before covid says as much. I know of no doctors who said by itself it was a cure for anything, only the press made that claim.
It's an ion transport channel facilitator. It's never been alleged to work by itself to my knowledge. It allows the immune system to work better especially when used in conjunction with other agents (z-pack and ivermectin for example). It's effectiveness and molecular mechanism was well documented from the beginning. I learned about it in March 2020 and was able to read up on it and it's use in treating covid before social media started banning anything that referenced it. But it, like ivermectin (an equally well documented DNA replication inhibitor) were demonized and mocked despite the vast body of research on it and it's use.
Australia had great research (though small sample size, it was thorough) on it's use and effectiveness at the beginning of the pandemic and it was shut down despite it being clearly explained the strict conditions under which it was effective (treatment within the first 8 days of showing symptoms, used with z-pack, etc). They even had research quantifying how it's effectiveness dropped without the z-pack components or as those treated didn't start treatment until 8 or more days. Not a controlled study but even Idris Elba was treated with it and raved about it's effectiveness in conjunction with the z-pack. It was all over the news before Trump mentioned it and then BAM! Censorship and propaganda campaign against it.
It's an ion transport channel facilitator. It's never been alleged to work by itself to my knowledge. It allows the immune system to work better especially when used in conjunction with other agents (z-pack and ivermectin for example). It's effectiveness and molecular mechanism was well documented from the beginning. I learned about it in March 2020 and was able to read up on it and it's use in treating covid before social media started banning anything that referenced it. But it, like ivermectin (an equally well documented DNA replication inhibitor) were demonized and mocked despite the vast body of research on it and it's use.
Australia had great research (though small sample size, it was thorough) on it's use and effectiveness at the beginning of the pandemic and it was shut down despite it being clearly explained the strict conditions under which it was effective (treatment within the first 8 days of showing symptoms, used with z-pack, etc). They even had research quantifying how it's effectiveness dropped without the z-pack components or as those treated didn't start treatment until 8 or more days. Not a controlled study but even Idris Elba was treated with it and raved about it's effectiveness in conjunction with the z-pack. It was all over the news before Trump mentioned it and then BAM! Censorship and propaganda campaign against it.
treeman79(2)
It's a little weird that this pilot research* made the front page of HN, in that respect there probably is a political factor.
But for the research itself I agree, there's no indication this article was in any way motivated by COVID or contains any misunderstandings of HCQ.
(* the sample is large but since it's purely observational in a very specific population it obviously requires follow-up work)
But for the research itself I agree, there's no indication this article was in any way motivated by COVID or contains any misunderstandings of HCQ.
(* the sample is large but since it's purely observational in a very specific population it obviously requires follow-up work)
It's not at all weird that new research about Alzheimers hit the HN front page; Alzheimers is a recurring fascination for the site. Unfortunately, so are political debates, which, unlike neurodegenerative illnesses, are generally off-topic for the site.
Now explain how it could affect Alzheimers
>We additionally show that HCQ exerts dose-dependent effects on late long-term potentiation (LTP) and rescues impaired hippocampal synaptic plasticity prior to significant accumulation of amyloid plaques and neurodegeneration in APP/PS1 mice.
iirc (I am not qualified!!) Alzheimers relates to plaques in our brain, and this sounds to me like it fixes a precursor to the plaque accumulation (the loss of plasticity?)
iirc (I am not qualified!!) Alzheimers relates to plaques in our brain, and this sounds to me like it fixes a precursor to the plaque accumulation (the loss of plasticity?)
The plaques are a side effect of something we don't understand yet. Treating the plaque or slowing it is not a solution, we need to find and fix the cause.
Quite apart from the validity of this study, isn’t a purely palliative measure still valuable?
Literally billions of dollars has been spent, futilely, on the idea that removing plaques would stop/reverse the symptoms of Alzheimer's Disease.
This "amyloid hypothesis" has not been a smashing success, to put in mildly.
This "amyloid hypothesis" has not been a smashing success, to put in mildly.
It's not clear that treating amyloid plaque is actually palliative for Alzheimer's patients.
> some anti-inflammatory properties
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/
Lots of literature 1 google/ddg search away for you, but there's an example.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214864/
Lots of literature 1 google/ddg search away for you, but there's an example.
[deleted]
Being anti-inflammatory?
kybernetyk(2)
I thought I read somewhere that it's easy to overdose on hydroxychloroquine? If so I'd be worried about a forgetful senior accidentally taking a double or triple dose.
THis is true of most medications and as a result there are a lot of solutions that have been developed to help people ensure they get their drug regime right. Firstly, a lot of people in altzheimer’s care will have full or part-time carers to help[1].
Secondly there are things like “pill organizers”/dossette boxes[2] where the pharmacy will actually dispense the drugs into a container which is designed to make it simple to ensure people take their correct daily dosage of drugs.
[1] Here in the UK the national health provides some community care and there are also voluntary organisations. Obviously individuals can also pay privately to have enhanced levels of support.
[2] https://en.wikipedia.org/wiki/Pill_organizer
Secondly there are things like “pill organizers”/dossette boxes[2] where the pharmacy will actually dispense the drugs into a container which is designed to make it simple to ensure people take their correct daily dosage of drugs.
[1] Here in the UK the national health provides some community care and there are also voluntary organisations. Obviously individuals can also pay privately to have enhanced levels of support.
[2] https://en.wikipedia.org/wiki/Pill_organizer
I'm not a doctor but it doesn't look highly risky. The usual adult dose for malaria is 2000 mg over the course of two days. Long term usage may be a different matter.
I suspect that concerns about safety were because people were using it off brand without medical supervision these last couple of years, which is less safe.
I suspect that concerns about safety were because people were using it off brand without medical supervision these last couple of years, which is less safe.
Wouldn't this be true for almost any medication? I'm not aware of anything unique about this one.
Different medications have different ratios between their effective doses and their harmful doses. The smaller the ratio, the more sensitive the results to an overdose.
https://en.wikipedia.org/wiki/Therapeutic_index
https://en.wikipedia.org/wiki/Therapeutic_index
[deleted]
[deleted]
See I believe this.
There are remarkably fewer demented people as a result of people taking Hydroxychloroquine.
There are remarkably fewer demented people as a result of people taking Hydroxychloroquine.
Please don't post unsubstantive and/or flamebait comments to HN. It's not what this site is for, and destroys what it is for.
If you wouldn't mind reviewing https://news.ycombinator.com/newsguidelines.html and taking the intended spirit of the site more to heart, we'd be grateful.
If you wouldn't mind reviewing https://news.ycombinator.com/newsguidelines.html and taking the intended spirit of the site more to heart, we'd be grateful.
Relishing in other people's actions that were driven out of fear during a crisis when our institutions (media and state) failed to keep public trust for millions. Empathy, even for those who make foolish decisions is difficult but necessary, you should try to understand rather than judge.
Why is empathy "necessary"?
Why "should" someone try to understand rather than judge?
What's the actual rationale for it?
What is the mutually agreed desired result of acting in those ways?
Why "should" someone try to understand rather than judge?
What's the actual rationale for it?
What is the mutually agreed desired result of acting in those ways?
Keeping just to the utilitarian perspective, cooperative strategies in humans overwhelmingly have better outcomes in both individual well-being and output (innovation, manufacturing, zero-sun games). Cooperation is extremely hard to achieve and sustain without some empathy for your peers. Similarly, judgement runs counter to group cohesion, except in the divergent strategy of establishing an Us/Them dynamic, sustainable in the short term but leading to homogeneity, worse outcomes.
Tossing the utilitarian perspective, being transactional and self-serving in your daily life tends to get you invited to less parties.
Tossing the utilitarian perspective, being transactional and self-serving in your daily life tends to get you invited to less parties.
>Why is empathy “necessary”
This is a philosophical question that man has sought to answer since the Stone Age. Much smarter people than us have dedicated their lives to the study of ethics and come up with wildly differing ideas, I don’t think you’re going to find an objective answer here.
This is a philosophical question that man has sought to answer since the Stone Age. Much smarter people than us have dedicated their lives to the study of ethics and come up with wildly differing ideas, I don’t think you’re going to find an objective answer here.
>why is empathy necessary?
I don't really have an objective answer for you. I do find personal value in empathy, I get less mad when I can understand why someone did something I disagree with. It doesn't change what they did nor does it excuse it.
>What is the mutually agreed desired result of acting in those ways
Harmony.
I don't really have an objective answer for you. I do find personal value in empathy, I get less mad when I can understand why someone did something I disagree with. It doesn't change what they did nor does it excuse it.
>What is the mutually agreed desired result of acting in those ways
Harmony.
mint2(5)
Note that this is an article making huge claims about Alzheimer's but is published in Molecular Psychiatry. Given that signal, I'm just going to look at the abstract and not read the full text.
Here, the study population is patients with rheumatoid arthritis. This tells you up front that we don't have a typical population, but a highly selected one.
The use of HCQ is observational, not randomly assigned.
So, how could HCQ look protective even if it had no effect on Alzheimer's biology?
1. Maybe more rheumatoid arthritis patients should be on HCQ. It's a disease-modifying drug, after all. So it may be the case that people with better care, or more wealth, are more likely to be on HCQ. And that could be associated with other lifestyle factors that are never fully accounted for in an observational analysis.
2. Or it could be the case that people with dementia are less likely to have their HCQ prescriptions renewed, so the arrow of causation could even be reversed.
Additionally, one could imagine that HCQ might actually protect against Alzheimer's disease in people with rheumatoid arthritis—but not in a general population. That would be very big news, but would require further study.
And sure, it could be the case that HCQ reduces Alzheimer's risk in everyone. But you'd need a lot more evidence to buy that.