Alzheimer’s plaque theory and possible research misconduct

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DynamicDidactic

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Looks like in this case they could forensically analyze the image to detect outright image tampering.

What is really disturbing is all of the 'sleight-of-hand' that goes on (we know it does) behind the scenes all the time that will never be detected. And that doesn't even touch on the inadvertent (non-conscious/ automatic processing-related) biases that even well-meaning and ethical researchers may be prone to even if they are not at all trying to be fraudulent. Anecdotes like these are good reminders of the age old wisdom of fallibility being the hallmark of science and the fact that we should always be open to critiquing or questioning 'established science' when multiple lines of logic and evidence suggest that we should do so.
 
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Thanks for this. Great read. Interesting that after Shrag reported the concerns to NIH they still awarded another grant to the guy being accused of tampering with the data. The amyloid hypothesis kind of reminds me of the serotonin hypothesis and the dopamine hypothesis. What is funny is how often people question the science of of psychotherapy. Our theories on behavior and social dynamics and attachment and emotions and cognition and a variety of evidence based psychotherapies are all pretty damn solid and backed by lots of replicable research. Meanwhile we can’t seem to find any magic pills to fix the brain or even diagnostics to improve over a good interview and psychological testing. Maybe the neuropsychologists have seen where imaging or an eeg has been useful, but I have yet to run into a case where it helped. Maybe I’ve just seen too many Amen clinic patients.
 
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Thanks for this. Great read. Interesting that after Shrag reported the concerns to NIH they still awarded another grant to the guy being accused of tampering with the data. The amyloid hypothesis kind of reminds me of the serotonin hypothesis and the dopamine hypothesis. What is funny is how often people question the science of of psychotherapy. Our theories on behavior and social dynamics and attachment and emotions and cognition and a variety of evidence based psychotherapies are all pretty damn solid and backed by lots of replicable research. Meanwhile we can’t seem to find any magic pills to fix the brain or even diagnostics to improve over a good interview and psychological testing. Maybe the neuropsychologists have seen where imaging or an eeg has been useful, but I have yet to run into a case where it helped. Maybe I’ve just seen too many Amen clinic patients.
It's a common thing to see people conflating the *phenomena under study* with *a scientific approach* to studying said phenomena.

For instance, I've seen a lot of really atrocious (from a methodological design and sound conclusion perspective) biological research that--if the phenomenon under study had been, say, 'behavior' or 'cognition' (as variables), it would NEVER have been published. I'm talking multiple t-tests without error correction type of stuff.

It's a common fallacy for most of the lay public (and many practitioners) to consider anything 'biological' in nature to be--a priori--'scientific' and even 'evidence-based,' and solid regardless of the actual quality and validity of the scientific literature in the area while automatically pre-judging any of the science around understanding behavior/affect/cognition/(biology) to be 'fluff,' or 'soft' science. Maybe we should call it the 'bio-woowoo / psycho-poopoo' fallacy or something. Slap on a label such as 'approved by VA Central office,' or 'approved by APA' or 'approved by NIMH,' then you really have a whopper that can persist for decades.
 
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Definitely an issue, but, similar to the recent "breaking news" that depression isn't a "chemical imbalance", the idea that amyloid plaques aren't the main driving force behind cognitive impairment in AD isn't a new thing. We've also known that AB clearing drugs have been duds in clinical trials for some time. Adulheim only got approved due to a full-court press lobbying campaign, and there is a reason that many of the advisory panel resigned after the approval.
 
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*sigh* This doesn't surprise me. It does sadden me.

I'm also increasingly coming to accept that this is a societal issue and not a scientific one. "Look busy" productivity churn with deception impacts most industries. I feel like our entire IT sector is built on it. OSF folks are missing the forest for the trees.
 
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Most of you are probably to young to remember the 70s but I swear this is like deja vu. Everything was kind of falling apart: stupid wars, Nixon, crappy cars, Japanese economy threatening our floundering economy, inflation, economic malaise, lack of faith in the institutions, thalidomide. My parents who were babyboomers grew up in a time when science was going to solve everything and they believed it. I was amazed at how naive and gullible they were since I knew that the powers that be were lying to us all the time. I wonder if the children of the millennials are going to feel the same way. In other words, maybe the millennials saw revolutionary technology such as internet and smartphones change the world pretty dramatically and got a little too optimistic. Just musings of an older gen X’er. By the way what ever happened to our generation? It’s all millennials or boomers or gen z these days. Aren’t we sort of the ones running things right now and doing a pretty bad job of it I might add.
 
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Most of you are probably to young to remember the 70s but I swear this is like deja vu. Everything was kind of falling apart: stupid wars, Nixon, crappy cars, Japanese economy threatening our floundering economy, inflation, economic malaise, lack of faith in the institutions, thalidomide. My parents who were babyboomers grew up in a time when science was going to solve everything and they believed it. I was amazed at how naive and gullible they were since I knew that the powers that be were lying to us all the time. I wonder if the children of the millennials are going to feel the same way. In other words, maybe the millennials saw revolutionary technology such as internet and smartphones change the world pretty dramatically and got a little too optimistic. Just musings of an older gen X’er. By the way what ever happened to our generation? It’s all millennials or boomers or gen z these days. Aren’t we sort of the ones running things right now and doing a pretty bad job of it I might add.


Not really. Most of the power players in this country are the boomers. This includes the last two presidents, the speaker of the house, and the majority leader of the senate. All above the minimum retirement age. My guess is they will leave and the power will swing to older millennials as the largest generation.
 
As an older millennial, the idea of being in power or being seen as an authority on anything is terrifying.

I just want to play with my tamagotchi angel and collect Lisa Frank stickers.
 
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As an older millennial, the idea of being in power or being seen as an authority on anything is terrifying.

I just want to play with my tamagotchi angel and collect Lisa Frank stickers.

As a fellow older millennial, you play with the Tamagotchi and I am happy to run things. Having participated in running things, it cannot happen fast enough. I am tired of explaining why we don't need to do things manually that can be automated much more cheaply through the use of technology.
 
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As a fellow older millennial, you play with the Tamagotchi and I am happy to run things. Having participated in running things, it cannot happen fast enough. I am tired of explaining why we don't need to do things manually that can be automated much more cheaply through the use of technology.
I just lovingly bulldoze people into modernity. There is a fun story that at a VA (who knows if it's true), that the staff were super resistant to electronic medical records. Over a weekend, everything at the site was scanned and shredded. The staff were very unhappy, but the fight was over.
 
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I just lovingly bulldoze people into modernity. There is a fun story that at a VA (who knows if it's true), that the staff were super resistant to electronic medical records. Over a weekend, everything at the site was scanned and shredded. The staff were very unhappy, but the fight was over.

Something at a government facility was done quickly and over a weekend, that must be a wives tale!
 
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*sigh* This doesn't surprise me. It does sadden me.

I'm also increasingly coming to accept that this is a societal issue and not a scientific one. "Look busy" productivity churn with deception impacts most industries. I feel like our entire IT sector is built on it. OSF folks are missing the forest for the trees.
Agreed. This is a trans-system dysfunctional process at work. The glorification of APPEARING busy rather than actually doing productive work; glorification of PROCLAIMING publicly to care rather than simply quietly engaging in caring actions, etc., etc....almost as if superficiality and counterfeit displays have been elevated over virtuous behavior and substance. Happening all over the place. It's weird.
 
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Something at a government facility was done quickly and over a weekend, that must be a wives tale!
Yeah, the rapidity of implementation part sounds suspect (poetic license, maybe?), but the absolutely authoritarian brute force mentality of 'solving' problems and overcoming resistance DEFINITELY checks out as 'VA all the way.'
 
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Agreed. This is a trans-system dysfunctional process at work. The glorification of APPEARING busy rather than actually doing productive work; glorification of PROCLAIMING publicly to care rather than simply quietly engaging in caring actions, etc., etc....almost as if superficiality and counterfeit displays have been elevated over virtuous behavior and substance. Happening all over the place. It's weird.

That is what happens when you start removing things like adequate working conditions, decent wages, and tenure from the equation. Academia became more about grant funding and promotion than the science. As a result, bad actors will bend the truth to get ahead and provide for themselves. I've seen it happen on a smaller scale and work.
 
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That is what happens when you start removing things like adequate working conditions, decent wages, and tenure from the equation. Academia became more about grant funding and promotion than the science. As a result, bad actors will bend the truth to get ahead and provide for themselves. I've seen it happen on a smaller scale and work.
That's the thing. I don't deny those are factors to some degree, but I'm really hesitant to blame on things like that.

I threw it out there as one of a dozen examples, but let's actually run with my mention of tech above. Software engineers make a comical ****-ton of money right now. We can debate the best way to define "good working conditions" but there is such demand in that field that companies treating SEs truly terribly generally haven't done well in recent history. From an end-user perspective, I genuinely don't know what most "new versions" of software achieve other than redecorating the GUI, adding new features that < .01% of users will ever use and marginal performance improvements to keep up with OS changes that were equally unimportant to make. Tech startups appear to be mostly about creating the illusion that you have a functional product that does something useful when you absolutely, positively do not have anything that is remotely functional or useful. In some cases this is truly nefarious but in a lot of cases I think this is some people truly believing the hype, not having the time to sit down and actually make anything really, truly, genuinely good and everyone else moving too fast to notice. Either way, it isn't just academia.
 
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Interesting article. Disappointing, though not entirely surprising. In any system, we rely on everyone to follow the rules, so the science is only as sound as the researcher (and their knowledge level and integrity). There are always those who will bend or break the rules to become the renown "X topic" expert.

This reminds me of a few years back when I finally learned about Zimbardo encouraging the guards to be meaner, which (in an already very flawed study), made his results completely useless. Yet he made an entire career out of it, and every Intro Psych class still teaches about that study--no textbook gets the facts right about how he tampered with his own study to get the results he did so he could say that social roles/roleplaying is a phenomenon. It's a bummer that so much is left out of our learning in school.

Nobody wants to be that person who takes down the psychological research "heroes." Kudos to Schrag, who called out the imaging issues in the Alzheimer's studies. That can be career-ending in some cases, so I'm glad to hear that this doesn't seem to be the case, at least not yet.

Make way for new Alzheimer's theories, perhaps?
 
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That's the thing. I don't deny those are factors to some degree, but I'm really hesitant to blame on things like that.

I threw it out there as one of a dozen examples, but let's actually run with my mention of tech above. Software engineers make a comical ****-ton of money right now. We can debate the best way to define "good working conditions" but there is such demand in that field that companies treating SEs truly terribly generally haven't done well in recent history. From an end-user perspective, I genuinely don't know what most "new versions" of software achieve other than redecorating the GUI, adding new features that < .01% of users will ever use and marginal performance improvements to keep up with OS changes that were equally unimportant to make. Tech startups appear to be mostly about creating the illusion that you have a functional product that does something useful when you absolutely, positively do not have anything that is remotely functional or useful. In some cases this is truly nefarious but in a lot of cases I think this is some people truly believing the hype, not having the time to sit down and actually make anything really, truly, genuinely good and everyone else moving too fast to notice. Either way, it isn't just academia.

It isn't just academia. However, part of the issue with tech startups is the business model has changed. With companies like Softbank around, the money starts by pitching an idea. If you can't get that initial round of startup funding, the game is acquisition. I have a friend that just sold his company for an 8 figure payout. The goal from the start is to have their work acquired by a larger company and move on. There is too much money in the sector to compete without backing from the giants. So, I am not sure they care if the software is ever completed or be market competitive.
 
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Interesting article. Disappointing, though not entirely surprising. In any system, we rely on everyone to follow the rules, so the science is only as sound as the researcher (and their knowledge level and integrity). There are always those who will bend or break the rules to become the renown "X topic" expert.

This reminds me of a few years back when I finally learned about Zimbardo playing warden in his own study and encouraging the guards to be meaner, which (in an already very flawed study), made his results completely useless. Yet he made an entire career out of it, and every Intro Psych class still teaches about that study--no textbook gets the facts right about how he tampered with his own study to get the results he did so he could say that social roles/roleplaying is a phenomenon. It's a bummer that so much is left out of our learning in school.

Nobody wants to be that person who takes down the psychological research "heroes." Kudos to Schrag, who called out the imaging issues in the Alzheimer's studies. That can be career-ending in some cases, so I'm glad to hear that this doesn't seem to be the case, at least not yet.

Make way for new Alzheimer's theories, perhaps?

Dude, that's why I can't stand Zimbardo. He got to have his cake and eat it, too. He also doesn't seem like, even a little bit remorseful?

There are stories too of when he visited my old department and apparently didn't have the best behavior...
 
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Dude, that's why I can't stand Zimbardo. He got to have his cake and eat it, too. He also doesn't seem like, even a little bit remorseful?

There are stories too of when he visited my old department and apparently didn't have the best behavior...

Never trust someone who intentionally looks like the Devil from a 1930's movie.
 
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Definitely an issue, but, similar to the recent "breaking news" that depression isn't a "chemical imbalance", the idea that amyloid plaques aren't the main driving force behind cognitive impairment in AD isn't a new thing. We've also known that AB clearing drugs have been duds in clinical trials for some time. Adulheim only got approved due to a full-court press lobbying campaign, and there is a reason that many of the advisory panel resigned after the approval.
Yeah, my understanding is that there have been drugs that reduce amyloid plaques, but it doesn't seem to slow or alter the course of AD much.
 
Yeah, my understanding is that there have been drugs that reduce amyloid plaques, but it doesn't seem to slow or alter the course of AD much.

Don't forget that these drugs also induce significant microbleeds in about a third of study participants.
 
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Dude, that's why I can't stand Zimbardo. He got to have his cake and eat it, too. He also doesn't seem like, even a little bit remorseful?

There are stories too of when he visited my old department and apparently didn't have the best behavior...
A colleague of mine was in her 20s with some fellow female grad students at an APA convention many years back and said he was creepily lecherous in their short interaction and overly touchy during photos with them. That certainly affected my view of him before I knew about the study details.

In my opinion, his study should be dropped from the textbooks altogether or discussed only in light of his tampering as an example of extreme and unethical behavior in research (and why we now have research ethics). It was absolutely useless “data” and rather sadistic of him to keep the study going as long as he did.
 
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Thanks for correcting me, it wasn't a third who got microbleeds, it was 41% :)

Yeah man, it's like less than half and it's really just like a paper cut in your brain. So, how long do you think Biogen has been working on a drug to address small vessel disease?
 
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Just some thoughts from a guy that is quite a few years away from my neuropsych rotation and experience. Also had a patient who has spouse with some significant early symptoms of neurological dysfunction that could be dementia. Wouldn’t microbleeds potentially cause vascular dementia? Also, is this medication increasing blood flow and is that what causes the bleeds and if medication is increasing blood flow is that really treating DAT or is it vascular dementia? Feel free to correct any misstatements or misconceptions. This has always been an area of interest of mine but haven’t really been keeping up on it at all.
 
A colleague of mine was in her 20s with some fellow female grad students at an APA convention many years back and said he was creepily lecherous in their short interaction and overly touchy during photos with them. That certainly affected my view of him before I knew about the study details.

In my opinion, his study should be dropped from the textbooks altogether or discussed only in light of his tampering as an example of extreme and unethical behavior in research (and why we now have research ethics). It was absolutely useless “data” and rather sadistic of him to keep the study going as long as he did.
I TAed in a class where his intro textbook was still being used. It feels like there have been no substantive consequences.
 
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Just some thoughts from a guy that is quite a few years away from my neuropsych rotation and experience. Also had a patient who has spouse with some significant early symptoms of neurological dysfunction that could be dementia. Wouldn’t microbleeds potentially cause vascular dementia? Also, is this medication increasing blood flow and is that what causes the bleeds and if medication is increasing blood flow is that really treating DAT or is it vascular dementia? Feel free to correct any misstatements or misconceptions. This has always been an area of interest of mine but haven’t really been keeping up on it at all.

The broadstrokes: Aduhelm is a monoclonal antibody that targets the beta-amyloid plaques thought to be a cause of Alzheimer's disease. Though this is in question given the unethical research. In so doing it causes microbleeds in 41% of folks. This results in small vessel disease/white matter disease (reduced blood flow to the white matter), which is implicated in vascular dementia (as you mentioned). So, the FDA approved a drug that attacks some plaques that may or may not stop Alzheimer's disease, but definitely increases the risk of vascular dementia in 41% of folks. I'll let the others chime in on anything I missed as I am not the expert on this by any means.
 
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A colleague of mine was in her 20s with some fellow female grad students at an APA convention many years back and said he was creepily lecherous in their short interaction and overly touchy during photos with them. That certainly affected my view of him before I knew about the study details.

In my opinion, his study should be dropped from the textbooks altogether or discussed only in light of his tampering as an example of extreme and unethical behavior in research (and why we now have research ethics). It was absolutely useless “data” and rather sadistic of him to keep the study going as long as he did.

Yup, the stories from my dept also involved behavior with women.

And he ONLY discontinued the study because the woman that he proudly announces later became this wife (so I am going to uncharitably label her as "the woman he wanted to nail") called him out. Why are we still even talking about the study, anyway? Methodology-wise, it's a mess. We know now that we can't really generalize from it.

Are you familiar with his grasshopper study? When I heard about that one in undergrad, I just became convinced that this guy became a research psychologist because he wants to mess with people.

Seriously, Milgram gets way more flack when imo his study and ethics violations were less egregious or at least more defendable. I mean Zimbardo wouldn't even let someone DROP OUT.

(Sorry, I have a lot of feelings on this topic)
 
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Yup, the stories from my dept also involved behavior with women.

And he ONLY discontinued the study because the woman that he proudly announces later became this wife (so I am going to uncharitably label her as "the woman he wanted to nail") called him out. Why are we still even talking about the study, anyway? Methodology-wise, it's a mess. We know now that we can't really generalize from it.

Are you familiar with his grasshopper study? When I heard about that one in undergrad, I just became convinced that this guy became a research psychologist because he wants to mess with people.

Seriously, Milgram gets way more flack when imo his study and ethics violations were less egregious or at least more defendable. I mean Zimbardo wouldn't even let someone DROP OUT.

(Sorry, I have a lot of feelings on this topic)

You know that whole era of psychology and academia kind of blow me away. Academia is now a very serious and competitive business where you need to jump through many hoops. However, whenever I speak to a psychologist from that era (even some famous ones whose books are used today) the story of how they became an academic amounts to I was bored and tried a thing or I went and hung out with a guy who tried a thing and now I am the world's leading expert on X. There were no board certifications and multiple layers of reviews and funding games. These people are who they are because of that. I am sure what will come out about the newer generation of science will be because of the environment the science was conducted in during this era. When looking back at history, we lose so much context.
 
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A colleague of mine was in her 20s with some fellow female grad students at an APA convention many years back and said he was creepily lecherous in their short interaction and overly touchy during photos with them. That certainly affected my view of him before I knew about the study details.

In my opinion, his study should be dropped from the textbooks altogether or discussed only in light of his tampering as an example of extreme and unethical behavior in research (and why we now have research ethics). It was absolutely useless “data” and rather sadistic of him to keep the study going as long as he did.
All of social psychology should be dropped from textbooks until replication with prepub can be done.
 
All of social psychology should be dropped from textbooks until replication with prepub can be done.

Add personality into the mix. Those two areas are filled with poorly done research that still permeate pop psych (e.g., Generation Me, power pose, etc).
 
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Yup, the stories from my dept also involved behavior with women.

And he ONLY discontinued the study because the woman that he proudly announces later became this wife (so I am going to uncharitably label her as "the woman he wanted to nail") called him out. Why are we still even talking about the study, anyway? Methodology-wise, it's a mess. We know now that we can't really generalize from it.

Are you familiar with his grasshopper study? When I heard about that one in undergrad, I just became convinced that this guy became a research psychologist because he wants to mess with people.

Seriously, Milgram gets way more flack when imo his study and ethics violations were less egregious or at least more defendable. I mean Zimbardo wouldn't even let someone DROP OUT.

(Sorry, I have a lot of feelings on this topic)
I just looked up the grasshopper study—yeah, that seems to reflect a pattern of research that involves forcing people to do something via manipulation.

The departmental behavior does not surprise me in the least.

But Zimbardo said the prisoners didn’t use their safe words that were supposedly listed in the consent forms (no such words were found in the records—surprise surprise)! To think that Zimbardo justified not releasing people because they didn’t use specific words to leave is completely ludicrous as an explanation. His reaction to the Medium article expose in 2018 was very defensive and doesn’t actually make him look any better as a person or researcher.

What researchers got away with (and some still get away with, as uncovered in the article in this thread) astounds.
 
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