This story makes a compelling case that pharma profits by overdiagnosis, with a current 600,000 early Alzheimer's patients receiving anti-amyloid drugs set to become 47 million "pre-clinical"...
This story makes a compelling case that pharma profits by overdiagnosis, with a current 600,000 early Alzheimer's patients receiving anti-amyloid drugs set to become 47 million "pre-clinical" healthy people who receive dangerous treatments because they test positive for amyloid buildup that is less than 20% likely to cause clinical symptoms.
This article is U.S.-centric, and American systemic incentives for care of elderly people through Medicare are closely aligned with drugmakers' priorities. However, it's my impression that other countries with national health systems are vulnerable to the same manipulative marketing for "preventative" Alzheimer's testing and treatment.
The "amyloid hypothesis" for Alzheimer's and related dementias has been called into question due to research misconduct, narrowly based research, and drug company biases. As the article illustrates, the risk/benefit ratio for the eye-wateringly expensive amyloid-busting drugs is very questionable.
There's growing evidence that herpesviruses, autoimmunity, and nutritional deficiency contribute to the development of symptomatic Alzheimer's dementia.
Disclosure: I have a personal stake in Alzheimer's research and prevention. I have rheumatoid arthritis, which used to carry a 40% increased risk of early dementia. I'm on a TNF-alpha inhibitor, and current research says this means I now have a 20% reduced risk of Alzheimer's compared to the general population. I've gotten my shingles vaccination. I've also started taking 1 mg lithium orotate daily, in part because I'm in a region with naturally low lithium content in water and soils. So yes, I'm biased against the single-cause amyloid hypothesis.
Apparently, the beta amyloid hypothesis is false: Also, saunas. Apparently, the key to dodging Alzheimer's is to spend more time in a sauna. Or out in the sun in hot weather. It is less convenient...
Apparently, the beta amyloid hypothesis is false:
The interesting thing about him is that Alzheimer's disease, not only the rare kind, but the kind that, you know, is much more widespread, has sort of two proteins that are hallmarks of the disease. One is called amyloid. That's the protein that clumps into plaques in brains of people with Alzheimer's, usually forms about 20 years before symptoms emerge. And the second protein is called Tau. And that's the thing that forms these kind of sticky tangles. And that's much more connected to kind of symptoms of cognitive decline.
So what they've learned about Doug Whitney is that he has a whole lot of amyloid in his brain. He has amyloid levels that should suggest that he would have Alzheimer's many years ago even, but he has very little tau. So something in his biology has interrupted that progression from amyloid protein to tau protein. And that's what they want to zero in on. From PBS
Also, saunas. Apparently, the key to dodging Alzheimer's is to spend more time in a sauna. Or out in the sun in hot weather. It is less convenient than a pill, but also far less expensive.
I am so looking forward to this. My parents are very well cared for and comfortable at their nursing home, but the TV is always on when I visit. What a waste! I'm sure I could get a good game of...
I am so looking forward to this. My parents are very well cared for and comfortable at their nursing home, but the TV is always on when I visit. What a waste! I'm sure I could get a good game of Noita going. I might not be able to do to well in Dwarf Fortress, but I didn't do to well when I used to play it in those happy care-free days of yore. Maybe Nethack will be too much for me to be able to ascend, but it's too much right now, so what's the difference? Maybe I'll finally be able to get an ascended play before... I... ascend for real.
Assuming we can remember how to connect the ethernet ports with our Alzheimer ridden brains. But assuming we can, UT2004, Quake 3, Battlefield 1942 and Command & Conquer (Never was big on...
Assuming we can remember how to connect the ethernet ports with our Alzheimer ridden brains.
But assuming we can, UT2004, Quake 3, Battlefield 1942 and Command & Conquer (Never was big on Starcraft) all the way.
It doesn’t sound like that article disproves the hypothesis. It sounds like the patient is unusual.
It doesn’t sound like that article disproves the hypothesis. It sounds like the patient is unusual.
Nearly 7 million Americans currently live with Alzheimer’s and by 2060, experts say that number could be as high as 14 million. Scientists are trying to find out how one man has been able to stave off Alzheimer's for 25 years, despite having a rare genetic mutation that, doctors say, essentially guaranteed he’d develop the disease. Pam Belluck of The New York Times joins Ali Rogin to discuss.
You don't have to take my word for it: I was speaking to the point in the article, that pharmaceutical treatments, mostly based around amyloid targets, have been dubious. Conversely, I was...
You don't have to take my word for it:
“You can’t look at brain tissue and believe beta amyloid has nothing to do with it. It’s absolutely everywhere. But we’ve got lots and lots of patients who have tons of amyloid … with normal cognition,” said Matthew Schrag, a Vanderbilt University neuroscientist who discovered the doctored images in the 2006 Nature paper while working independently of his employer. “Biology is trying to tell you that there’s clearly more to the story.” Stat News
I was speaking to the point in the article, that pharmaceutical treatments, mostly based around amyloid targets, have been dubious. Conversely, I was surprised to learn that the production of heat shock proteins from high temperature exposure is correlated with lowered Alzheimer's incidence.
But where would the profit motive be in generating an Alzheimer's epidemic if the treatment were just several sessions a sauna each week?
Multicenter (277 medical research centers/hospitals in 8 countries), randomized, double-blind, placebo-controlled, 18-month phase 3 trial that enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 (last patient visit for primary outcome in April 2023).
Sounds pretty legit, and
Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population.
Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit It is clear that there isn't consensus here: Efficacy, safety, and ARIA risk of anti–β-amyloid antibodies in early...
We believe that these findings are subject to misinterpretation and statistical bias. Donanemab is claimed to cause removal of up to 86 % of cerebral amyloid and 36 % delay in cognitive decline compared to placebo. In reality, these are very small changes on an absolute scale and arguably less than what can be achieved with cholinesterase inhibitor/memantine therapy. Moreover, the "removal" of amyloid, based on the reduced accumulation of amyloid-PET tracer, most likely also reflects therapy-related tissue damage. This would also correlate with the minimal clinical effect, the increased frequency of amyloid-related imaging abnormalities, and the accelerated loss of brain volume in treated compared to placebo patients observed with these antibodies.
In early AD, anti–β-amyloid monoclonal antibodies are associated with modest slowing of decline accompanied by increased ARIA risk and unfavorable structural brain changes, limiting clinical applicability.
I think a lot of people are conflating "there's more to the story than just B amyloid" (certainly true) with "the amyloid hypothesis is debunked!" (probably overstated). More specifically, that's...
I think a lot of people are conflating "there's more to the story than just B amyloid" (certainly true) with "the amyloid hypothesis is debunked!" (probably overstated).
Conversely, I was surprised to learn that the production of heat shock proteins from high temperature exposure is correlated with lowered Alzheimer's incidence.
More specifically, that's a theoretical mechanism. What we can actually say is that saunaing (among certain populations, etc etc) is correlated with lower AD incidence, and HSP is a reasonably plausible theory suggesting why. But exercise is also linked to lower AD incidence, and so the benefit of sauna might just be the elevated heart rate and have nothing to do with HSP at all. The evidence supporting the B amyloid hypothesis - even accounting for the questionable stuff - is much, much stronger than the evidence supporting the "it's all HSP!" hypothesis.
I know you were being a bit glib, but if the treatment for AD was just "sauna!" we would've already figured it out, because nobody in all of Finland would have AD. And they do. Ironically, in fact, Finns suffer from AD at disproportionately high rates - the highest mortality rate from AD in the world.
So I've gotten into Nordic saunas, too - it's an easy way to get some of the benefits of cardiovascular exercise without the joint pounding, raises body temperature enough to reduce infectious...
So I've gotten into Nordic saunas, too - it's an easy way to get some of the benefits of cardiovascular exercise without the joint pounding, raises body temperature enough to reduce infectious disease risk, and you've just provided evidence of yet another benefit. Plus a sauna just feels ecstatically good when it's January, -20 °C outside, and the sun has been invisible for months.
This story makes a compelling case that pharma profits by overdiagnosis, with a current 600,000 early Alzheimer's patients receiving anti-amyloid drugs set to become 47 million "pre-clinical" healthy people who receive dangerous treatments because they test positive for amyloid buildup that is less than 20% likely to cause clinical symptoms.
This article is U.S.-centric, and American systemic incentives for care of elderly people through Medicare are closely aligned with drugmakers' priorities. However, it's my impression that other countries with national health systems are vulnerable to the same manipulative marketing for "preventative" Alzheimer's testing and treatment.
The "amyloid hypothesis" for Alzheimer's and related dementias has been called into question due to research misconduct, narrowly based research, and drug company biases. As the article illustrates, the risk/benefit ratio for the eye-wateringly expensive amyloid-busting drugs is very questionable.
There's growing evidence that herpesviruses, autoimmunity, and nutritional deficiency contribute to the development of symptomatic Alzheimer's dementia.
Disclosure: I have a personal stake in Alzheimer's research and prevention. I have rheumatoid arthritis, which used to carry a 40% increased risk of early dementia. I'm on a TNF-alpha inhibitor, and current research says this means I now have a 20% reduced risk of Alzheimer's compared to the general population. I've gotten my shingles vaccination. I've also started taking 1 mg lithium orotate daily, in part because I'm in a region with naturally low lithium content in water and soils. So yes, I'm biased against the single-cause amyloid hypothesis.
Apparently, the beta amyloid hypothesis is false:
Also, saunas. Apparently, the key to dodging Alzheimer's is to spend more time in a sauna. Or out in the sun in hot weather. It is less convenient than a pill, but also far less expensive.
Us millennial gamers are screwed.
On the other hand, imagine the LAN parties we can have in the group retirement homes...
I am so looking forward to this. My parents are very well cared for and comfortable at their nursing home, but the TV is always on when I visit. What a waste! I'm sure I could get a good game of Noita going. I might not be able to do to well in Dwarf Fortress, but I didn't do to well when I used to play it in those happy care-free days of yore. Maybe Nethack will be too much for me to be able to ascend, but it's too much right now, so what's the difference? Maybe I'll finally be able to get an ascended play before... I... ascend for real.
Assuming we can remember how to connect the ethernet ports with our Alzheimer ridden brains.
But assuming we can, UT2004, Quake 3, Battlefield 1942 and Command & Conquer (Never was big on Starcraft) all the way.
I yearn for UT2k4. It's an absolute shame what Epic has become.
It doesn’t sound like that article disproves the hypothesis. It sounds like the patient is unusual.
You don't have to take my word for it:
I was speaking to the point in the article, that pharmaceutical treatments, mostly based around amyloid targets, have been dubious. Conversely, I was surprised to learn that the production of heat shock proteins from high temperature exposure is correlated with lowered Alzheimer's incidence.
But where would the profit motive be in generating an Alzheimer's epidemic if the treatment were just several sessions a sauna each week?
Dubious how?
https://jamanetwork.com/journals/jama/fullarticle/2807533
Sounds pretty legit, and
Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit
It is clear that there isn't consensus here:
Efficacy, safety, and ARIA risk of anti–β-amyloid antibodies in early Alzheimer’s disease: a systematic review, meta-analysis, and meta-regression
I think a lot of people are conflating "there's more to the story than just B amyloid" (certainly true) with "the amyloid hypothesis is debunked!" (probably overstated).
More specifically, that's a theoretical mechanism. What we can actually say is that saunaing (among certain populations, etc etc) is correlated with lower AD incidence, and HSP is a reasonably plausible theory suggesting why. But exercise is also linked to lower AD incidence, and so the benefit of sauna might just be the elevated heart rate and have nothing to do with HSP at all. The evidence supporting the B amyloid hypothesis - even accounting for the questionable stuff - is much, much stronger than the evidence supporting the "it's all HSP!" hypothesis.
I know you were being a bit glib, but if the treatment for AD was just "sauna!" we would've already figured it out, because nobody in all of Finland would have AD. And they do. Ironically, in fact, Finns suffer from AD at disproportionately high rates - the highest mortality rate from AD in the world.
So I've gotten into Nordic saunas, too - it's an easy way to get some of the benefits of cardiovascular exercise without the joint pounding, raises body temperature enough to reduce infectious disease risk, and you've just provided evidence of yet another benefit. Plus a sauna just feels ecstatically good when it's January, -20 °C outside, and the sun has been invisible for months.