This Lithium hypothesis will almost certainly turn out to be wrong as well. I don't have a specific objection to it. It's just that there are a million ways to be wrong for every way there is to be right. Consequently, whenever you question medical orthodoxy, however transient the orthodoxy (e.g. during the recent pandemic) you will be treated like all heretics, but more smugly. Why? Because you had the gall to question the experts and so you are wrong.
You probably are wrong if you offer a specific position like Ivermectin cures COVID. Haha dumbass! But that's just because it's easier to be wrong probabilistically. The experts who thought masks were effective were also wrong.
Every five years or so I read the current literature on cholesterol causing heart disease and I always come away unimpressed. For this everyone is taking a statin, a drug that blocks a key early step in an important pathway? Madness--but I don't dare share that with most of my medical colleagues.
All of which is a long way of saying that this is hardly limited to Alzheimers research.
Other thoughts: by the time you are demented, it's probably irreversible. 7-UP originally contained lithium (like Coca Cola contained cocaine).
"You probably are wrong if you offer a specific position like Ivermectin cures COVID. Haha dumbass!"
One theory that couldn't get any funding to test was that hydroxychloroquine, which was going to cure covid before ivermectin, might work against Alzheimer's.
Did they have a reason to think hydroxychloroquine would work, even from a basic science bottom up reasoning POV? I can't immediately see why they would think it would work.
WRT COVID, given how poorly our specific, purpose made antivirals work relative to our antibacterials, it was always a bad bet that a random nonspecific antiviral drug like ivermectin or hydroxychloroquine, was going to be a miracle cure.
Of course nowadays the antivaxers have convinced themselves that not only did the COVID vaccine not work, it actually harmed people near universally and there is something specific about mRNA that made it especially harmful. They too are almost definitely wrong.
From another NYT op ed by Charles Piller, that lists various drugs that somebody or other thinks should be tested against Alzheimer's:
All the Alzheimer’s Research We Didn’t Do
July 7, 2024
What if a preposterous failed treatment for Covid-19 — the arthritis drug hydroxychloroquine — could successfully treat another dreaded disease, Alzheimer’s?
Dr. Madhav Thambisetty, a neurologist at the National Institute on Aging, thinks the drug’s suppression of inflammation, commonly associated with neurodegenerative disorders, might provide surprising benefits for dementia.
It’s an intriguing idea. Unfortunately, we won’t know for quite a while, if ever, whether Dr. Thambisetty is right. That’s because unconventional ideas that do not offer fealty to the dominant approach to study and treat Alzheimer’s — what’s known as the amyloid hypothesis — often find themselves starved for funds and scientific mind share.
I can't tell the background of the author (I don't subscribe) but IMO he has a pretty low bar for "intriguing". Inflammation might be involved in a disease process? So what if some random drug that has some anti-inflammatory effects turned out to be the cure? My first question is: then why not corticosteroids? Why jump to hydroxychloroquine of all things?
Also--and I admit I haven't looked into it deeply--the hypothesis that amyloid might cause Alzheimer's isn't exactly stupid and the fact that destroying the plaques doesn't reverse it, doesn't mean the hypothesis is wrong. Nor does falsified data.
As I recall, millions of people were already taking daily HCQ for malaria prevention. How did they fare with COVID? The one HCQ study I heard about in 2020, they waited until the patients were hospitalized. Governments around the world seriously overplayed their hand, and of course, it's all been swept under the rug since.
For whatever reason, people who were HCQ-Curious tended to get bored with HCQ and really get into Ivermectin instead.
In general, HCQ and Ivermectin are good drugs against tropical diseases. (Ivermectin is a Nobel-winning miracle cure for the horrible disease of river blindness.)
Not surprisingly, though, Third World medical studies aren't utterly reliable.
I have a relative who is a pediatrician who is convinced that Ivermectin saved the lives of his otherwise healthy family. None of them died of COVID. How can you argue with that? Well, except, I too, failed repeatedly to die of COVID despite my lack of Ivermectin access.
HCQ-Curious is hilarious. I bet we could get that appended to LBTQWERTY if we tried real hard.
Correction: ivermectin and hydroxichloroquin are not anti-viral drugs, they are broad spectrum anti-parasitic treatments with a long history of effective use against bacterial pathogens. That they seem to show some effectiveness just shows how little we understand about viral disease.
Correct. I didn't mean to say that those are primarily antiviral or even proven antiviral. My point was that even the drugs we create against specific viruses don't work especially well, so why would we think there is some non specific drug that randomly works great on this specific virus?
I didn't expand but our understanding of viruses is quite flawed. The Oral Polio vaccine did not defeat poliomyelitus but may well have introduced HIV into the human population. We still have no vaccines against cancer or the common cold. The known problems associated with multiple vaccinations have been hidden from us by Big Pharma with government complicity. There is a growing consensus that vaccine acquired immunity is not the same as naturally acquired immunity and inferior to it. Astonishingly, most vaccines are not even tested against placebos, only the existing vaccine that Big Pharma wants to replace with one more profitable. I think it is no accident that HS students in America are not taught nutrition or financial literacy.
"The Oral Polio vaccine did not defeat poliomyelitus but may well have introduced HIV into the human population."
Um-what?
My mom tells stories of people she knew getting polio and society being shut down COVID style over the summer because of it. I've never heard of anyone getting polio. The transition occurred after the introduction of the polio vaccine.
Coincidence?
I would also love to know how the polio vaccine managed to give AIDS almost exclusively to male homosexuals.
We used to say, Google exists, but now we can say Grok exists but with a grain of salt:
Clinical Trials for COVID-19:
• COPCOV Trial (2020–2022): The largest randomized controlled trial (RCT) for HCQ/CQ chemoprevention, involving 4,652 participants across 11 countries, found a 15% reduction in symptomatic COVID-19 (risk ratio [RR] 0.85, 95% CI 0.72–1.00, p=0.05) compared to placebo. It also reported fewer PCR-confirmed respiratory infections (RR 0.61, 95% CI 0.42–0.88) and fewer workdays lost. A meta-analysis including this trial suggested a moderate protective benefit (RR 0.80, 95% CI 0.71–0.91) for HCQ/CQ prophylaxis.
• Chen et al. (2020) conducted a small trial (n=62) showing that HCQ-treated COVID-19 patients had a shorter recovery time from fever and cough compared to placebo.
• Some studies combining HCQ with azithromycin reported reduced viral shedding in COVID-19 patients, though results were inconsistent.
Given the ideological derangement and perverse incentives of modern medicine, I'm going to assume the doctors were wrong, or at least not very right, about the mRNA vaccines as well.
I remember seeing the "97-point-three-decimal-places percent effective" number at Marginal Revolution--HQ for the War On Covid--but could never get an answer on effective at what, exactly. The "what" was apparently quite ephemeral, and recommended dosage was a continual shell game of boosters, one-two shot schedules, "first-dose-first" etc. At one point I recall the CDC recommending at least three shots a year (I could never figure out if this actually meant six shots). Other commenters were bragging about how they arranged to get a mix of the various manufacturers' vaccines, a Covid "cocktail."
Then of course it turned out you can be vaccinated and still get Covid, spread Covid, and be hospitalized or even die of Covid. The statistics started breaking out "fully vaccinated," and this became another moving target. So, this is a "leaky" vaccine. Like the flu shot, it's perenially pulling the bug forward and chasing it from behind. Of course, nobody gets the vaccine any more.
My impression from all the statistics was nobody could ever point to a stack of unvaccinated corpses in contrast to the robust vaccinated. Florida should have been like that scene in Holy Grail but it ended up looking like everywhere else with a bunch of old, fat, and old and fat people. Maybe the shot provided a heads-up to the immune systems of a certain at-risk tranche and kept them out of the morgue for another year or so.
Anecdotally, my firm decided to have a Christmas party in December 2021, "fully vaccinated" only (so I didn't go). Every single attendee came down with Covid. ADE effect? I don't know.
Then there's the whole "masking" charade. And the lab leak, which went from tinfoil, grassy knoll territory to yeah, that's probably what happened.
I could go on, but at this point my default is what are they NOT lying about?
The 97% very clearly referred to its ability to reduce death over the study period in vaccinated vs unvaccinated patients. That number went down as later variants emerged. I have another relative who is an ED doc in Florida and he tells me it's so obvious to him that the vaccine reduced the chance of dying that it's silly to even debate it. From what he said, I take it the real world experience of physicians in this regard is on the level of "smoking causes vascular disease"
The idea that the vaccine would slow the spread made a certain amount of sense. The idea that it would provide "herd immunity" was extremely dubious from the beginning. I got called "crazy' by an internist for suggesting that it didn't make sense to force people to get the shot in order to get to herd immunity.
People who admit that masks didn't do much keep telling me that we didn't know that at the time. Yet at the beginning of the pandemic I was able to read multiple review articles about masking effectiveness in Asia during flu seasons. The results were mixed/unimpressive. So we had a pretty good idea.
I still think mRNA vaccines are amazing cool technology and based on their mechanism, I serious doubt they are secretly super duper harmful. We are already seeing good results from exploiting the immune system to fight cancer. I don't know why we would shut down such research for mRNA vaccines.
To toss that kind of figure around you need to show that 97 out of 100 members of the non-vaccinated, unconfounded control group died. Nobody's ever been able to come up with that pile of corpses.
I and most others in my conservative crackpot family did not get the vaccine and nobody died, including two decrepit old people in my Dunbar number who are still around.
Frankly, the mortality for Covid--almost all old, fat, old and fat, substance-abusing, or otherwise immunocompromised--is so low that it's hard to tell anything. And, what else, there were secondary gain factors for Covid reporting.
Most appallingly, it appears the liberal use of ventilation may have been motivated by secondary gain.
Masking went from, “Use these to avoid spraying your infected mucus over other people, if you absolutely must leave your couch,” to, “The masks protect you from the viral miasma,” in one of the most truly stupid beliefs by smart people I have ever seen.
The lab leak hypothesis was for the Certifiably KA-RAAZY. I also remember when people were actively encouraged to visit Chinatown with the planeloads of everybody's relatives from the Old Country to celebrate the Chinese New Year because this virus did not, not I tell you, originate in the Wuhan Institute of Virology.
There have been some other big reversals in non-medical contexts, which I'll pass over. Are mRNA vaccines the one thing out of all the things they're getting right? I'm skeptical.
We have already had one instance of a government scientist waging biological warfare against the population to advance his ideological agenda. Would you be willing to bet everything that not a single transgender-EA freak is working on a 12 Monkeys scenario to save humanity from the awful MAGATs?
> To toss that kind of figure around you need to show that 97 out of 100 members of the non-vaccinated, unconfounded control group died.
My understanding is that "97%" referred to the vaccine's ability to reduce death over the study period (when an early variant of Covid-19 was circulating) in vaccinated vs unvaccinated patients.
In those early days, the mortality rate for Americans aged 70 to 80 who caught Covid-19 was in the neighborhood of 16%. (From memory, I didn't look it up to confirm.) So for 1,000 of these senior citizens who became infected, about 160 would die and 840 would survive.
The "97%" claim means that of a comparable group of 1,000 vaccinated senior citizens, about 5 would die and 995 would survive. 5/160 = 3%.
On the other hand, healthy young Americans had relatively little to fear from Covid-19. The mortality for ages 18 to 30 might have been something like 0.05% (a SWAG, it's probably lower). So 0 to 1 of a cohort of 1,000 might have died, reduced to 0 by vaccination. If the vaccine had a rate of inducing Severe Adverse Effects of 1% (another SWAG), then a little arithmetic shows that vaccination with a "97%" vaccine is a much less attractive proposition for healthy young people, then it is for the elderly.
My views on this subject (I am a scientist, not a physician) generally track with Erik's.
I, too, have a close relative who is an ED doc (in the Northeast). He, too, tells me it's so obvious to him that the vaccine reduced the chance of dying that it's silly to debate it.
HEAVY METALS and their effects on brains in males and the shocking coincidence of serial killers growing up within miles of smelters. Have any of you read Murderland by Caroline Frasier? Pullitzer Prize winner whose excellent 2nd book has, as its center, the unstable correlation between the massive amounts of arsenic, lead, and other heavy metals that were spewing out of smelters in the Pacific Northwest since early 1900s.
Tacoma/Ruston, WA —ASARCO copper smelter; arsenic/lead plume over ~1,000 sq mi)
• Ted Bundy — moved to and grew up in Tacoma, WA; Tacoma’s North End sits inside the ASARCO plume footprint. 30-51 young females brutally killed.
• Gary Ridgway (Green River Killer) — raised in SeaTac (south King County). Ecology says the Tacoma Smelter plume extended from East Olympia up to north Seattle, which includes SeaTac. Brutally killed confirmed 71, mostly young women.
• Joseph Edward Duncan III — family settled in Tacoma when he was ~12. Again, inside the ASARCO plume area.
Upper Columbia River (cross-border smelter impacts)
• Israel Keyes — raised near Colville, WA; that region is included in Washington’s “Upper Columbia River/Lake Roosevelt” cleanup area linked to Canadian smelter emissions (Trail, B.C.). (Keyes later offended across the U.S.; this is about childhood geography/exposure potential.)
Bunker Hill (Kellogg/Smelterville, ID)
• The Bunker Hill Mining & Metallurgical Complex (lead/zinc) contaminated the Coeur d’Alene Basin for decades; heavy metals persist and are actively managed. (This is context—no widely documented serial killer grew up right in Kellogg that I can point to.)
Charles Manson served time at McNeil
University of Idaho case (Moscow, ID). The suspect Bryan Kohberger, grew up in Albrightsville, PA. Carbon County was the Palmerton Zinc Pile Superfund Site (massive zinc-smelter contamination of soil and air through 1980).
The recent ambush of firefighters in North Idaho
Coeur d’Alene/Canfield Mountain attack. On June 29, 2025, two firefighters were killed and another wounded. That is well within the plume of Bunker Hill Smelter in Kellog, ID.
—Charles Manson was incarcerated at McNeil Island Federal Penitentiary from 1961 to 1966 for check forgery and parole violations.
• Location: McNeil Island sits in southern Puget Sound, just across the water from Ruston/Tacoma, where the ASARCO copper smelter operated from 1890 to 1985.
• Proximity: From the prison grounds, you could literally see the ASARCO smokestack — the two are only about 6–7 miles apart in a straight line across Puget Sound.
• The Tacoma Smelter plume didn’t just spread eastward — arsenic and lead particles traveled in all directions, including across the water toward McNeil Island. Although not exposed as a child, Manson, during his entire 5-year stint there, was likely breathing air and eating food from a region within the contaminated fallout zone.
Please see the long comment I just made at 9 AM PST. I talk about HEAVY METALS —particularly arsenic and lead and what it seems to do to males growing up nearby. After reading Caroline Fraser's book on serial killers (Murderland) I did my own research to find that those same heavy metals work differently females but are just as horrible and often deadly. I have recently lost four low to middle-aged female cousins to Lewy Body Dementia. They grew up near the smelters. My mother was from there and died of that kind of dementia. Looks just like Alzheimer's but it is not. I now think my mother's parents died of it as well. Crazy. They all lived within the plume of the ARASCO Smelter in Tacoma WA. "Plumes" from smelters consist of arsenic, lead, mercury and all sorts of other heavy metals that never degrade. (Pesticides were just a side hustle for the companies to put their arsenic since there was no other use they could find for it.) They had to make money from every last bit of the deadly ore. There is a strong correlation between savage "heartless" brutal behavior in men from these heavy metals. Women seem to have other deadly reactions. Correlation —but pretty glaring.
Why can't research this for Alzheimer's and other neurological issues? Most smelters in this country were the first source of the vast fortunes of the Guggenheims and Rothchilds. They tried to hide it later with museums and so forth. These families knew what was going on yet had Power and found ways to change the "rules" and guidelines of what was "safe" for children. When these familys' companies learned, after the EPA came out, that they had to build the settlements from lawsuits and their profit margin. It is literally on record that they built into the books the "price" of children inside these lawsuits. It was $12000 per child in the mid 70s. These heavy metals still pollute Puget Sound and Coeur d'Alene lake in Idaho. Willamette River in Oregon. It is in the soil and food and all of that. It does not decompose! These were some of the largest Super fund sites anywhere. I guess it's kind of hard for the EPA to clean theSE metals out of human beings since they stay in your bones until you die.
Terrific comment Erik. Odd are your theory is wrong.
> Every five years or so I read the current literature on cholesterol causing heart disease and I always come away unimpressed. For this everyone is taking a statin, a drug that blocks a key early step in an important pathway? Madness--but I don't dare share that with most of my medical colleagues.<
I have no particular knowledge, but some little reading i've done the cholesterol jihard originally came off one study which was probably bogus. For this the "authorities" made war on eggs and fat and effectively told everyone "go eat grain"--i.e. don't eat the stuff that makes you feel full, eat the stuff that yo-yos your blood sugar and makes you hungry again in a few hours. Almost like the medical "experts" had stock in insulin manufacturers.
BTW, another theory I've heard on the Alzheimers is metabolic. Lots of yo-yoing of insulin production and flicking on and off mtor is sub-optimal. (Alzheimers does seem to be more common in the fatties, but that can obviously be for all sorts of other reasons.)
Thanks. Yes the cholesterol hypothesis comes from a small number of studies in the 1970s(?). The association between high total cholesterol and heart disease was disproven long ago. That's why laymen have heard of Low Density Lipoprotein. When that ultimately showed poor (or no) correlation, they found some new fraction of a cholesterol number to harp on. Don't get me started. Cholesterol research is a goldmine for anyone interested in cognitive bias in healthcare.
Sure Alzheimer's could be related to insulin. We definitely know that high blood sugar is bad for you. I doubt it will be that simple. It's difficult to trust anecdotal correlation because (even today I'm pretty sure) the overwhelming majority of people diagnosed with Alzheimers don't have definitive tests done.
The two people in my family who ended up with Alzheimer's were teetotalers who kept themselves in excellent physical condition. Bruce Willis probably had his share of tobacco and ethanol when he was younger but as an aging action star he stayed in excellent physical shape. As did the wife of a neighbor down the street who succumbed to Alzheimer's.
My prayer is I have enough agency left to end things in the event my brain starts going first.
My dad always said that after watching his dad in a nursing home with dementia. When Dad went in the home and was offered a DNR, he was pretty sure he wanted to keep on living. He wanted out of the home. But wanted to keep on living.
The problem with dementia patients is they don't really "want" to keep on living. They don't actually "want" anything; they can't conceive anything. They have already lost all their cognitive anchors so they're basically just panicked, hallucinatory vegetables watching their incomprehensible existences play out. They become constantly agitated so we tranquilize them and wait for their brains to forget how to run their bodies. Then the tissue breakdown starts. Then the autonomic functions start failing. Then they die. It's the worst way to go, like a lab animal.
If I still have my sense of time, place and self but I'm bedbound, that's when it will be time to go. I don't intend to wait for the creeping pneumonia, system failure, sepsis and bedsores, and I will be costing people many thousands of dollars.
My dad's dementia was mostly progressive memory loss. His last years were spent in the moment or in his teens. He usually remembered my name but couldn't believe he had a son--with a white beard, no less. He played HS and small time college football in the 40s.
Please tell me Fauci had no role in dementia research funding.
I've probably written here before about an interview of Bill Bennett after he was GHWB's Drug Czar. He had discovered no federal funding then went to research pharma treatment for drug addiction. What are the odds that's still true?
Lithium orotate or lithium carbonate are easy to get in a pharmacy. The main problem is their relatively narrow therapeutic window. Carbamazepine is therefore simpler to dose in manic depression.
The main target of Li+ seems to be the GSK3beta enzyme.
Steve, the key give-away is that the Lithium deficiency study also uses the same animal models based on the amyloid hypothesis. Maybe it will work, but my hopes are not too high. The effects of Li on AD have been tested for 15 years and, as quite usual - some see improvements, others don't:
Other divalent cations - like Zinc - might have a similar role too.
The key features of Alzheimer's dementia - from the first cases analysed by Dr Alois Alzheimer himself at the turn of 19th/20th century - were the loss of neural substance, later shown to be loss of synapses, loss of neurons, and particularly, loss of cholinergic innervation. Amyloid plaques and neurofibrillary tangles were remarked on very early, but definition of their causal role is still outstanding.
Part of the reason that I went on medical insurance when I retired was the increasingly suspect nature of medical research in this country. With the "replication crisis" where at least half of all published papers describe results that can't be replicated, their is increased skepticism that the drug companies and the studies they fund are just a scam. Add to that the absolutely atrocious failure of the media to police its own reports, to insure that what they report has some grounding of truth and you have a perfect storm of mistrust that seems more correct every day. But these are just the unintended consequences of a culture that has corrupted itself. Irreligious people are so afraid of aging and death that they will do anything and pay any price in a vain attempt to stave them off. Too many of us never question our physicians' assurance that every condition is treatable by throwing enough money at it. In the past, only wealthy people could afford to line a doctor's pockets for dubious treatments. But with the post-war shift to an insurance model the unscrupulous behavior of "physicians to the overfed elites" has become standard practice for all patients. No longer can you have a frank discussion with doctor(s) of the costs and benefits of treatment over inaction. Prices creep up at multiples of the inflation rate every year and no one protests. "It's not my money" and "Thank the Lord I have insurance" is what goes through most peoples mind when they need treatment. All while even the most minimal treatment unaffordable without insurance. Go to the doctor for something minor and even the co-pay will get expensive. As a result, people without insurace go to the Emergency Room for everything. Sure, that is insanely expensive but those who can't pay simply won't sticking those who can with ever increasing premiums for ever shrinking results to cover the costs of the uninsured. As insurance becomes increasingly unaffordable to the poor, the rates on those that can afford it rise. Britain's NHS has certainly not covered itself in glory but at least the well-off are given no special treatment denied the poor. The horror stories
that come out of the UK are the inevitable outcome of massively unrealistic expectations but are they really so much worse than treatments we can't afford being denied because insurance companies are protecting their bottom lines?
>Or was it a lot of careerists finding themselves unable to replicate the most prestigious results, so they individually altered their studies’ images to make them look valid, not realizing that the gold standard images they were following had had a thumb on the scale too?
That’s a rather nightmarish scenario.<
This reminds me of one of the hidden stories of the telecom bubble around the end of the century. WorldCom was fraudulently capitalizing termination costs. leading to furious efforts by fellow service providers and equipment providers to keep up. At the service provider level, firms felt that they had to emulate WorldCom's level of capital expenditures, usually without regard to returns on it. Equipment providers were happy to sell all they could, but the dynamics inside Lucent, Alcatel, Cisco and others were driven by their apparent smaller share of WorldCom's equipment spend. The image of CEOs upbraiding their henchman over not selling enough gear to WorldCom never fails to crack me up, but probably explains why they were so willing to commit fraud through channel stuffing and other means during the period.
I remember reading 30 years ago that we were on the verge of curing all disease via stem cells and gene sequencing. I'm not sure whether to be discouraged at the negligible progress made in so many biomedical fields despite all the kajillions spent on research over the past quarter-century, or encouraged that at least in some areas (alzheimers, cancer) one can finally see green shoots of out-of-the-box thinking.
Am I alone in thinking that slashing federal research grants might well *accelerate* innovation, by euthanizing paper-shuffling bureaucratic fossils like Tesser-Levigne and letting a new generation rise from the ashes?
This might be a dumb question, but if the drugs developed to treat Alzheimers memory loss basically don't work, why were they allowed on the market or remain there? I understand the FDA collects a lot of user fees from pharmaceutical companies so perhaps there is some moral hazard there, and perhaps there is some concern about the financial hit to these companies of spending vast amounts of money on drug development that killing too many of these in the crib would stifle new drug exploration. Still, one has to question the integrity of our regulators when stuff like this happens.
Remember the serotonin theory for depression? Then the meta-studies came out and they couldn't exclude a placebo effect.
I suffered from chronic depression most of my life, hitting me really hard in my thirties and forties. I would take a prescribed SSRI and it would work for about two to three months. Then a psychiatrist got the idea that I should take two different SSRIs and see how that worked. After a couple of episodes of the most vivid nightmares I have ever had, I stopped seeing the psychiatrist and threw the rest of the prescriptions away.
I'd love to say diet, exercise, or meditation cured me; I could write a book and make some money. But all I can conclude is that I just aged out of it.
Glad you did! I don't want to sound flippant, but it appears to me that a lot of mood-related issues people have really cannot be addressed through medication and they will resolve themselves eventually. Some are obviously "real" in the sense they occur with no real apparent trigger and persist when there is nothing unusually wrong in a person's life, but a lot seem to be sort of self induced and/or poor coping skills of what are essentially life's travails, and no one gets to avoid those entirely.
At any rate, it seems like far too many people run for the pills and of the people I know that did I cannot say it really resolved anything.
In Americans, Alzheimer's disease is most prevalent in blacks, next most in Hispanics, less prevalent in non-Hispanic whites, and least prevalent in Asians, when comparing similar age groups (https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2018.06.3063). Of course, since it's socially unacceptable to be aware of the fact that this is also the gradient of IQs and brain sizes, I expect this has led researchers to search for various environmental effects that might not exist, when perhaps the answer is simply that people with larger brains are somewhat protected. (Weirdly, the rates in Native Americans are apparently lower than in whites; not sure if this is due to a smaller sample size or if this points to some kind of interesting environmental effect). Observational studies have led to suggestions to prevent Alzheimer's disease with "modifiable factors" like getting more education and engaging in mentally stimulating activities like reading and chess (https://pmc.ncbi.nlm.nih.gov/articles/PMC7569385/). My guess is that high-IQ people who are at lower risk for whatever reason are just more likely to do these things, rather than that forcing yourself to play chess would in some way help.
For those interested in a deep dive on this topic, on 7/11/25, Astral Codex Ten posted a Review (not authored by Scott Alexander) called "Of Mice, Mechanisms, and Dementia."
Many of the comments are well-informed. One linked a podcast episode "Where has Alzheimer’s research gone wrong?," an interview of amyloid plaque critic Karl Herrup. It's on my to-listen list.
The anti-amyloid drug lecanemab slowed cognitive decline by 25-36% over 18 months and WSJ just reported that recent studies showed that the benefits quadrupled over a 4 year period. That hardly qualifies as “minutely”
The original study was on people with mild cognitive decline. I’m currently participating in a 4 year study on people with elevated amyloids but cognitively healthy.
These results would seem to indicate that the reduction of amyloids does slow cognitive decline.
Faster please!
This Lithium hypothesis will almost certainly turn out to be wrong as well. I don't have a specific objection to it. It's just that there are a million ways to be wrong for every way there is to be right. Consequently, whenever you question medical orthodoxy, however transient the orthodoxy (e.g. during the recent pandemic) you will be treated like all heretics, but more smugly. Why? Because you had the gall to question the experts and so you are wrong.
You probably are wrong if you offer a specific position like Ivermectin cures COVID. Haha dumbass! But that's just because it's easier to be wrong probabilistically. The experts who thought masks were effective were also wrong.
Every five years or so I read the current literature on cholesterol causing heart disease and I always come away unimpressed. For this everyone is taking a statin, a drug that blocks a key early step in an important pathway? Madness--but I don't dare share that with most of my medical colleagues.
All of which is a long way of saying that this is hardly limited to Alzheimers research.
Other thoughts: by the time you are demented, it's probably irreversible. 7-UP originally contained lithium (like Coca Cola contained cocaine).
"You probably are wrong if you offer a specific position like Ivermectin cures COVID. Haha dumbass!"
One theory that couldn't get any funding to test was that hydroxychloroquine, which was going to cure covid before ivermectin, might work against Alzheimer's.
Did they have a reason to think hydroxychloroquine would work, even from a basic science bottom up reasoning POV? I can't immediately see why they would think it would work.
WRT COVID, given how poorly our specific, purpose made antivirals work relative to our antibacterials, it was always a bad bet that a random nonspecific antiviral drug like ivermectin or hydroxychloroquine, was going to be a miracle cure.
Of course nowadays the antivaxers have convinced themselves that not only did the COVID vaccine not work, it actually harmed people near universally and there is something specific about mRNA that made it especially harmful. They too are almost definitely wrong.
From another NYT op ed by Charles Piller, that lists various drugs that somebody or other thinks should be tested against Alzheimer's:
All the Alzheimer’s Research We Didn’t Do
July 7, 2024
What if a preposterous failed treatment for Covid-19 — the arthritis drug hydroxychloroquine — could successfully treat another dreaded disease, Alzheimer’s?
Dr. Madhav Thambisetty, a neurologist at the National Institute on Aging, thinks the drug’s suppression of inflammation, commonly associated with neurodegenerative disorders, might provide surprising benefits for dementia.
It’s an intriguing idea. Unfortunately, we won’t know for quite a while, if ever, whether Dr. Thambisetty is right. That’s because unconventional ideas that do not offer fealty to the dominant approach to study and treat Alzheimer’s — what’s known as the amyloid hypothesis — often find themselves starved for funds and scientific mind share.
https://www.nytimes.com/2024/07/07/opinion/alzheimers-missed-opportunities.html
I can't tell the background of the author (I don't subscribe) but IMO he has a pretty low bar for "intriguing". Inflammation might be involved in a disease process? So what if some random drug that has some anti-inflammatory effects turned out to be the cure? My first question is: then why not corticosteroids? Why jump to hydroxychloroquine of all things?
Also--and I admit I haven't looked into it deeply--the hypothesis that amyloid might cause Alzheimer's isn't exactly stupid and the fact that destroying the plaques doesn't reverse it, doesn't mean the hypothesis is wrong. Nor does falsified data.
Sure check other things too.
As I recall, millions of people were already taking daily HCQ for malaria prevention. How did they fare with COVID? The one HCQ study I heard about in 2020, they waited until the patients were hospitalized. Governments around the world seriously overplayed their hand, and of course, it's all been swept under the rug since.
For whatever reason, people who were HCQ-Curious tended to get bored with HCQ and really get into Ivermectin instead.
In general, HCQ and Ivermectin are good drugs against tropical diseases. (Ivermectin is a Nobel-winning miracle cure for the horrible disease of river blindness.)
Not surprisingly, though, Third World medical studies aren't utterly reliable.
I have a relative who is a pediatrician who is convinced that Ivermectin saved the lives of his otherwise healthy family. None of them died of COVID. How can you argue with that? Well, except, I too, failed repeatedly to die of COVID despite my lack of Ivermectin access.
HCQ-Curious is hilarious. I bet we could get that appended to LBTQWERTY if we tried real hard.
Correction: ivermectin and hydroxichloroquin are not anti-viral drugs, they are broad spectrum anti-parasitic treatments with a long history of effective use against bacterial pathogens. That they seem to show some effectiveness just shows how little we understand about viral disease.
Correct. I didn't mean to say that those are primarily antiviral or even proven antiviral. My point was that even the drugs we create against specific viruses don't work especially well, so why would we think there is some non specific drug that randomly works great on this specific virus?
I didn't expand but our understanding of viruses is quite flawed. The Oral Polio vaccine did not defeat poliomyelitus but may well have introduced HIV into the human population. We still have no vaccines against cancer or the common cold. The known problems associated with multiple vaccinations have been hidden from us by Big Pharma with government complicity. There is a growing consensus that vaccine acquired immunity is not the same as naturally acquired immunity and inferior to it. Astonishingly, most vaccines are not even tested against placebos, only the existing vaccine that Big Pharma wants to replace with one more profitable. I think it is no accident that HS students in America are not taught nutrition or financial literacy.
"The Oral Polio vaccine did not defeat poliomyelitus but may well have introduced HIV into the human population."
Um-what?
My mom tells stories of people she knew getting polio and society being shut down COVID style over the summer because of it. I've never heard of anyone getting polio. The transition occurred after the introduction of the polio vaccine.
Coincidence?
I would also love to know how the polio vaccine managed to give AIDS almost exclusively to male homosexuals.
We used to say, Google exists, but now we can say Grok exists but with a grain of salt:
Clinical Trials for COVID-19:
• COPCOV Trial (2020–2022): The largest randomized controlled trial (RCT) for HCQ/CQ chemoprevention, involving 4,652 participants across 11 countries, found a 15% reduction in symptomatic COVID-19 (risk ratio [RR] 0.85, 95% CI 0.72–1.00, p=0.05) compared to placebo. It also reported fewer PCR-confirmed respiratory infections (RR 0.61, 95% CI 0.42–0.88) and fewer workdays lost. A meta-analysis including this trial suggested a moderate protective benefit (RR 0.80, 95% CI 0.71–0.91) for HCQ/CQ prophylaxis.
• Chen et al. (2020) conducted a small trial (n=62) showing that HCQ-treated COVID-19 patients had a shorter recovery time from fever and cough compared to placebo.
• Some studies combining HCQ with azithromycin reported reduced viral shedding in COVID-19 patients, though results were inconsistent.
Given the ideological derangement and perverse incentives of modern medicine, I'm going to assume the doctors were wrong, or at least not very right, about the mRNA vaccines as well.
I remember seeing the "97-point-three-decimal-places percent effective" number at Marginal Revolution--HQ for the War On Covid--but could never get an answer on effective at what, exactly. The "what" was apparently quite ephemeral, and recommended dosage was a continual shell game of boosters, one-two shot schedules, "first-dose-first" etc. At one point I recall the CDC recommending at least three shots a year (I could never figure out if this actually meant six shots). Other commenters were bragging about how they arranged to get a mix of the various manufacturers' vaccines, a Covid "cocktail."
Then of course it turned out you can be vaccinated and still get Covid, spread Covid, and be hospitalized or even die of Covid. The statistics started breaking out "fully vaccinated," and this became another moving target. So, this is a "leaky" vaccine. Like the flu shot, it's perenially pulling the bug forward and chasing it from behind. Of course, nobody gets the vaccine any more.
My impression from all the statistics was nobody could ever point to a stack of unvaccinated corpses in contrast to the robust vaccinated. Florida should have been like that scene in Holy Grail but it ended up looking like everywhere else with a bunch of old, fat, and old and fat people. Maybe the shot provided a heads-up to the immune systems of a certain at-risk tranche and kept them out of the morgue for another year or so.
Anecdotally, my firm decided to have a Christmas party in December 2021, "fully vaccinated" only (so I didn't go). Every single attendee came down with Covid. ADE effect? I don't know.
Then there's the whole "masking" charade. And the lab leak, which went from tinfoil, grassy knoll territory to yeah, that's probably what happened.
I could go on, but at this point my default is what are they NOT lying about?
The 97% very clearly referred to its ability to reduce death over the study period in vaccinated vs unvaccinated patients. That number went down as later variants emerged. I have another relative who is an ED doc in Florida and he tells me it's so obvious to him that the vaccine reduced the chance of dying that it's silly to even debate it. From what he said, I take it the real world experience of physicians in this regard is on the level of "smoking causes vascular disease"
The idea that the vaccine would slow the spread made a certain amount of sense. The idea that it would provide "herd immunity" was extremely dubious from the beginning. I got called "crazy' by an internist for suggesting that it didn't make sense to force people to get the shot in order to get to herd immunity.
People who admit that masks didn't do much keep telling me that we didn't know that at the time. Yet at the beginning of the pandemic I was able to read multiple review articles about masking effectiveness in Asia during flu seasons. The results were mixed/unimpressive. So we had a pretty good idea.
I still think mRNA vaccines are amazing cool technology and based on their mechanism, I serious doubt they are secretly super duper harmful. We are already seeing good results from exploiting the immune system to fight cancer. I don't know why we would shut down such research for mRNA vaccines.
Of course--they probably won't work ;)
To toss that kind of figure around you need to show that 97 out of 100 members of the non-vaccinated, unconfounded control group died. Nobody's ever been able to come up with that pile of corpses.
I and most others in my conservative crackpot family did not get the vaccine and nobody died, including two decrepit old people in my Dunbar number who are still around.
Frankly, the mortality for Covid--almost all old, fat, old and fat, substance-abusing, or otherwise immunocompromised--is so low that it's hard to tell anything. And, what else, there were secondary gain factors for Covid reporting.
Most appallingly, it appears the liberal use of ventilation may have been motivated by secondary gain.
Masking went from, “Use these to avoid spraying your infected mucus over other people, if you absolutely must leave your couch,” to, “The masks protect you from the viral miasma,” in one of the most truly stupid beliefs by smart people I have ever seen.
The lab leak hypothesis was for the Certifiably KA-RAAZY. I also remember when people were actively encouraged to visit Chinatown with the planeloads of everybody's relatives from the Old Country to celebrate the Chinese New Year because this virus did not, not I tell you, originate in the Wuhan Institute of Virology.
There have been some other big reversals in non-medical contexts, which I'll pass over. Are mRNA vaccines the one thing out of all the things they're getting right? I'm skeptical.
We have already had one instance of a government scientist waging biological warfare against the population to advance his ideological agenda. Would you be willing to bet everything that not a single transgender-EA freak is working on a 12 Monkeys scenario to save humanity from the awful MAGATs?
> To toss that kind of figure around you need to show that 97 out of 100 members of the non-vaccinated, unconfounded control group died.
My understanding is that "97%" referred to the vaccine's ability to reduce death over the study period (when an early variant of Covid-19 was circulating) in vaccinated vs unvaccinated patients.
In those early days, the mortality rate for Americans aged 70 to 80 who caught Covid-19 was in the neighborhood of 16%. (From memory, I didn't look it up to confirm.) So for 1,000 of these senior citizens who became infected, about 160 would die and 840 would survive.
The "97%" claim means that of a comparable group of 1,000 vaccinated senior citizens, about 5 would die and 995 would survive. 5/160 = 3%.
On the other hand, healthy young Americans had relatively little to fear from Covid-19. The mortality for ages 18 to 30 might have been something like 0.05% (a SWAG, it's probably lower). So 0 to 1 of a cohort of 1,000 might have died, reduced to 0 by vaccination. If the vaccine had a rate of inducing Severe Adverse Effects of 1% (another SWAG), then a little arithmetic shows that vaccination with a "97%" vaccine is a much less attractive proposition for healthy young people, then it is for the elderly.
My views on this subject (I am a scientist, not a physician) generally track with Erik's.
I, too, have a close relative who is an ED doc (in the Northeast). He, too, tells me it's so obvious to him that the vaccine reduced the chance of dying that it's silly to debate it.
HEAVY METALS and their effects on brains in males and the shocking coincidence of serial killers growing up within miles of smelters. Have any of you read Murderland by Caroline Frasier? Pullitzer Prize winner whose excellent 2nd book has, as its center, the unstable correlation between the massive amounts of arsenic, lead, and other heavy metals that were spewing out of smelters in the Pacific Northwest since early 1900s.
Tacoma/Ruston, WA —ASARCO copper smelter; arsenic/lead plume over ~1,000 sq mi)
• Ted Bundy — moved to and grew up in Tacoma, WA; Tacoma’s North End sits inside the ASARCO plume footprint. 30-51 young females brutally killed.
• Gary Ridgway (Green River Killer) — raised in SeaTac (south King County). Ecology says the Tacoma Smelter plume extended from East Olympia up to north Seattle, which includes SeaTac. Brutally killed confirmed 71, mostly young women.
• Joseph Edward Duncan III — family settled in Tacoma when he was ~12. Again, inside the ASARCO plume area.
Upper Columbia River (cross-border smelter impacts)
• Israel Keyes — raised near Colville, WA; that region is included in Washington’s “Upper Columbia River/Lake Roosevelt” cleanup area linked to Canadian smelter emissions (Trail, B.C.). (Keyes later offended across the U.S.; this is about childhood geography/exposure potential.)
Bunker Hill (Kellogg/Smelterville, ID)
• The Bunker Hill Mining & Metallurgical Complex (lead/zinc) contaminated the Coeur d’Alene Basin for decades; heavy metals persist and are actively managed. (This is context—no widely documented serial killer grew up right in Kellogg that I can point to.)
Charles Manson served time at McNeil
University of Idaho case (Moscow, ID). The suspect Bryan Kohberger, grew up in Albrightsville, PA. Carbon County was the Palmerton Zinc Pile Superfund Site (massive zinc-smelter contamination of soil and air through 1980).
The recent ambush of firefighters in North Idaho
Coeur d’Alene/Canfield Mountain attack. On June 29, 2025, two firefighters were killed and another wounded. That is well within the plume of Bunker Hill Smelter in Kellog, ID.
—Charles Manson was incarcerated at McNeil Island Federal Penitentiary from 1961 to 1966 for check forgery and parole violations.
• Location: McNeil Island sits in southern Puget Sound, just across the water from Ruston/Tacoma, where the ASARCO copper smelter operated from 1890 to 1985.
• Proximity: From the prison grounds, you could literally see the ASARCO smokestack — the two are only about 6–7 miles apart in a straight line across Puget Sound.
• The Tacoma Smelter plume didn’t just spread eastward — arsenic and lead particles traveled in all directions, including across the water toward McNeil Island. Although not exposed as a child, Manson, during his entire 5-year stint there, was likely breathing air and eating food from a region within the contaminated fallout zone.
Please see the long comment I just made at 9 AM PST. I talk about HEAVY METALS —particularly arsenic and lead and what it seems to do to males growing up nearby. After reading Caroline Fraser's book on serial killers (Murderland) I did my own research to find that those same heavy metals work differently females but are just as horrible and often deadly. I have recently lost four low to middle-aged female cousins to Lewy Body Dementia. They grew up near the smelters. My mother was from there and died of that kind of dementia. Looks just like Alzheimer's but it is not. I now think my mother's parents died of it as well. Crazy. They all lived within the plume of the ARASCO Smelter in Tacoma WA. "Plumes" from smelters consist of arsenic, lead, mercury and all sorts of other heavy metals that never degrade. (Pesticides were just a side hustle for the companies to put their arsenic since there was no other use they could find for it.) They had to make money from every last bit of the deadly ore. There is a strong correlation between savage "heartless" brutal behavior in men from these heavy metals. Women seem to have other deadly reactions. Correlation —but pretty glaring.
Why can't research this for Alzheimer's and other neurological issues? Most smelters in this country were the first source of the vast fortunes of the Guggenheims and Rothchilds. They tried to hide it later with museums and so forth. These families knew what was going on yet had Power and found ways to change the "rules" and guidelines of what was "safe" for children. When these familys' companies learned, after the EPA came out, that they had to build the settlements from lawsuits and their profit margin. It is literally on record that they built into the books the "price" of children inside these lawsuits. It was $12000 per child in the mid 70s. These heavy metals still pollute Puget Sound and Coeur d'Alene lake in Idaho. Willamette River in Oregon. It is in the soil and food and all of that. It does not decompose! These were some of the largest Super fund sites anywhere. I guess it's kind of hard for the EPA to clean theSE metals out of human beings since they stay in your bones until you die.
Terrific comment Erik. Odd are your theory is wrong.
> Every five years or so I read the current literature on cholesterol causing heart disease and I always come away unimpressed. For this everyone is taking a statin, a drug that blocks a key early step in an important pathway? Madness--but I don't dare share that with most of my medical colleagues.<
I have no particular knowledge, but some little reading i've done the cholesterol jihard originally came off one study which was probably bogus. For this the "authorities" made war on eggs and fat and effectively told everyone "go eat grain"--i.e. don't eat the stuff that makes you feel full, eat the stuff that yo-yos your blood sugar and makes you hungry again in a few hours. Almost like the medical "experts" had stock in insulin manufacturers.
BTW, another theory I've heard on the Alzheimers is metabolic. Lots of yo-yoing of insulin production and flicking on and off mtor is sub-optimal. (Alzheimers does seem to be more common in the fatties, but that can obviously be for all sorts of other reasons.)
We have to remember that science is wrong over 50% of the time, but still we should trust (not corrupt) the process.
Thanks. Yes the cholesterol hypothesis comes from a small number of studies in the 1970s(?). The association between high total cholesterol and heart disease was disproven long ago. That's why laymen have heard of Low Density Lipoprotein. When that ultimately showed poor (or no) correlation, they found some new fraction of a cholesterol number to harp on. Don't get me started. Cholesterol research is a goldmine for anyone interested in cognitive bias in healthcare.
Sure Alzheimer's could be related to insulin. We definitely know that high blood sugar is bad for you. I doubt it will be that simple. It's difficult to trust anecdotal correlation because (even today I'm pretty sure) the overwhelming majority of people diagnosed with Alzheimers don't have definitive tests done.
The two people in my family who ended up with Alzheimer's were teetotalers who kept themselves in excellent physical condition. Bruce Willis probably had his share of tobacco and ethanol when he was younger but as an aging action star he stayed in excellent physical shape. As did the wife of a neighbor down the street who succumbed to Alzheimer's.
My prayer is I have enough agency left to end things in the event my brain starts going first.
My dad always said that after watching his dad in a nursing home with dementia. When Dad went in the home and was offered a DNR, he was pretty sure he wanted to keep on living. He wanted out of the home. But wanted to keep on living.
The problem with dementia patients is they don't really "want" to keep on living. They don't actually "want" anything; they can't conceive anything. They have already lost all their cognitive anchors so they're basically just panicked, hallucinatory vegetables watching their incomprehensible existences play out. They become constantly agitated so we tranquilize them and wait for their brains to forget how to run their bodies. Then the tissue breakdown starts. Then the autonomic functions start failing. Then they die. It's the worst way to go, like a lab animal.
If I still have my sense of time, place and self but I'm bedbound, that's when it will be time to go. I don't intend to wait for the creeping pneumonia, system failure, sepsis and bedsores, and I will be costing people many thousands of dollars.
What you need is to set up a computer such that it can kill you as soon as you fail your mental status exam :)
My dad's dementia was mostly progressive memory loss. His last years were spent in the moment or in his teens. He usually remembered my name but couldn't believe he had a son--with a white beard, no less. He played HS and small time college football in the 40s.
Government funding has displaced and destroyed honest, effective medical research.
Everything the government touches turns to crap.
Lick your Tesla daily!
Please tell me Fauci had no role in dementia research funding.
I've probably written here before about an interview of Bill Bennett after he was GHWB's Drug Czar. He had discovered no federal funding then went to research pharma treatment for drug addiction. What are the odds that's still true?
< "It’s easier to publish dubious science that aligns with conventional wisdom."
NEWSFLASH: It ain't just the amyloid hypothesis.
If any of you are now tempted to go gnaw on some rechargeable batteries, just make sure they are the yummy lithium ones and not NiCds.
Lithium orotate or lithium carbonate are easy to get in a pharmacy. The main problem is their relatively narrow therapeutic window. Carbamazepine is therefore simpler to dose in manic depression.
The main target of Li+ seems to be the GSK3beta enzyme.
Steve, the key give-away is that the Lithium deficiency study also uses the same animal models based on the amyloid hypothesis. Maybe it will work, but my hopes are not too high. The effects of Li on AD have been tested for 15 years and, as quite usual - some see improvements, others don't:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3204427/
Other divalent cations - like Zinc - might have a similar role too.
The key features of Alzheimer's dementia - from the first cases analysed by Dr Alois Alzheimer himself at the turn of 19th/20th century - were the loss of neural substance, later shown to be loss of synapses, loss of neurons, and particularly, loss of cholinergic innervation. Amyloid plaques and neurofibrillary tangles were remarked on very early, but definition of their causal role is still outstanding.
Part of the reason that I went on medical insurance when I retired was the increasingly suspect nature of medical research in this country. With the "replication crisis" where at least half of all published papers describe results that can't be replicated, their is increased skepticism that the drug companies and the studies they fund are just a scam. Add to that the absolutely atrocious failure of the media to police its own reports, to insure that what they report has some grounding of truth and you have a perfect storm of mistrust that seems more correct every day. But these are just the unintended consequences of a culture that has corrupted itself. Irreligious people are so afraid of aging and death that they will do anything and pay any price in a vain attempt to stave them off. Too many of us never question our physicians' assurance that every condition is treatable by throwing enough money at it. In the past, only wealthy people could afford to line a doctor's pockets for dubious treatments. But with the post-war shift to an insurance model the unscrupulous behavior of "physicians to the overfed elites" has become standard practice for all patients. No longer can you have a frank discussion with doctor(s) of the costs and benefits of treatment over inaction. Prices creep up at multiples of the inflation rate every year and no one protests. "It's not my money" and "Thank the Lord I have insurance" is what goes through most peoples mind when they need treatment. All while even the most minimal treatment unaffordable without insurance. Go to the doctor for something minor and even the co-pay will get expensive. As a result, people without insurace go to the Emergency Room for everything. Sure, that is insanely expensive but those who can't pay simply won't sticking those who can with ever increasing premiums for ever shrinking results to cover the costs of the uninsured. As insurance becomes increasingly unaffordable to the poor, the rates on those that can afford it rise. Britain's NHS has certainly not covered itself in glory but at least the well-off are given no special treatment denied the poor. The horror stories
that come out of the UK are the inevitable outcome of massively unrealistic expectations but are they really so much worse than treatments we can't afford being denied because insurance companies are protecting their bottom lines?
>Or was it a lot of careerists finding themselves unable to replicate the most prestigious results, so they individually altered their studies’ images to make them look valid, not realizing that the gold standard images they were following had had a thumb on the scale too?
That’s a rather nightmarish scenario.<
This reminds me of one of the hidden stories of the telecom bubble around the end of the century. WorldCom was fraudulently capitalizing termination costs. leading to furious efforts by fellow service providers and equipment providers to keep up. At the service provider level, firms felt that they had to emulate WorldCom's level of capital expenditures, usually without regard to returns on it. Equipment providers were happy to sell all they could, but the dynamics inside Lucent, Alcatel, Cisco and others were driven by their apparent smaller share of WorldCom's equipment spend. The image of CEOs upbraiding their henchman over not selling enough gear to WorldCom never fails to crack me up, but probably explains why they were so willing to commit fraud through channel stuffing and other means during the period.
"Some skeptics, however, wonder whether amyloid proteins are the rubble rather than the bomb.
In other words, correlation does not imply causation necessarily?
I remember reading 30 years ago that we were on the verge of curing all disease via stem cells and gene sequencing. I'm not sure whether to be discouraged at the negligible progress made in so many biomedical fields despite all the kajillions spent on research over the past quarter-century, or encouraged that at least in some areas (alzheimers, cancer) one can finally see green shoots of out-of-the-box thinking.
Am I alone in thinking that slashing federal research grants might well *accelerate* innovation, by euthanizing paper-shuffling bureaucratic fossils like Tesser-Levigne and letting a new generation rise from the ashes?
Yeah, whatever happened to the promised fetal stem cell miracles? I only thought of them when Left X was up in arms over RFK's mRNA decision.
This might be a dumb question, but if the drugs developed to treat Alzheimers memory loss basically don't work, why were they allowed on the market or remain there? I understand the FDA collects a lot of user fees from pharmaceutical companies so perhaps there is some moral hazard there, and perhaps there is some concern about the financial hit to these companies of spending vast amounts of money on drug development that killing too many of these in the crib would stifle new drug exploration. Still, one has to question the integrity of our regulators when stuff like this happens.
Remember the serotonin theory for depression? Then the meta-studies came out and they couldn't exclude a placebo effect.
I suffered from chronic depression most of my life, hitting me really hard in my thirties and forties. I would take a prescribed SSRI and it would work for about two to three months. Then a psychiatrist got the idea that I should take two different SSRIs and see how that worked. After a couple of episodes of the most vivid nightmares I have ever had, I stopped seeing the psychiatrist and threw the rest of the prescriptions away.
I'd love to say diet, exercise, or meditation cured me; I could write a book and make some money. But all I can conclude is that I just aged out of it.
Glad you did! I don't want to sound flippant, but it appears to me that a lot of mood-related issues people have really cannot be addressed through medication and they will resolve themselves eventually. Some are obviously "real" in the sense they occur with no real apparent trigger and persist when there is nothing unusually wrong in a person's life, but a lot seem to be sort of self induced and/or poor coping skills of what are essentially life's travails, and no one gets to avoid those entirely.
At any rate, it seems like far too many people run for the pills and of the people I know that did I cannot say it really resolved anything.
Regular exercise still helps my mood, but I seem to have largely aged out of sinus allergies.
In Americans, Alzheimer's disease is most prevalent in blacks, next most in Hispanics, less prevalent in non-Hispanic whites, and least prevalent in Asians, when comparing similar age groups (https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2018.06.3063). Of course, since it's socially unacceptable to be aware of the fact that this is also the gradient of IQs and brain sizes, I expect this has led researchers to search for various environmental effects that might not exist, when perhaps the answer is simply that people with larger brains are somewhat protected. (Weirdly, the rates in Native Americans are apparently lower than in whites; not sure if this is due to a smaller sample size or if this points to some kind of interesting environmental effect). Observational studies have led to suggestions to prevent Alzheimer's disease with "modifiable factors" like getting more education and engaging in mentally stimulating activities like reading and chess (https://pmc.ncbi.nlm.nih.gov/articles/PMC7569385/). My guess is that high-IQ people who are at lower risk for whatever reason are just more likely to do these things, rather than that forcing yourself to play chess would in some way help.
For those interested in a deep dive on this topic, on 7/11/25, Astral Codex Ten posted a Review (not authored by Scott Alexander) called "Of Mice, Mechanisms, and Dementia."
https://www.astralcodexten.com/p/your-review-of-mice-mechanisms-and
Many of the comments are well-informed. One linked a podcast episode "Where has Alzheimer’s research gone wrong?," an interview of amyloid plaque critic Karl Herrup. It's on my to-listen list.
https://news.uchicago.edu/where-has-alzheimers-research-gone-wrong
The anti-amyloid drug lecanemab slowed cognitive decline by 25-36% over 18 months and WSJ just reported that recent studies showed that the benefits quadrupled over a 4 year period. That hardly qualifies as “minutely”
The original study was on people with mild cognitive decline. I’m currently participating in a 4 year study on people with elevated amyloids but cognitively healthy.
These results would seem to indicate that the reduction of amyloids does slow cognitive decline.