Unfortunately, reversing hippocampal grey matter loss, myelin sheath loss, p-tau build is not possible, so it’s all about prevention.
But other than that, Dr G, like the rest of us, has NO idea the upstream causation pathway. It’s quite possible it’s multiple genes and pathways (plethora of studies showing this smoking gun) at play.
No two ways about, we will need human RCT clinical trials.
The knives are out.
Someone ask Dr B which “correct animal models, rapamycin prevents AD”?
Which itself is a dysfunctional comment??
Since in which “CORRECT animal models” do we see “AMYLOID DEMENTIA” = definition of Alzheimer Dementia = HUMAN trait?
Wonder how they evaluate cognitive function in a mouse. Some kind of running through a maze I guess.
In humans we ask questions having to do with memory and cognition.
Alan G has hundreds of very elderly that he’s been treating. Some of them must have some degree of plaque formation. Have any of them experienced sudden symptoms of AD? Even some increase in recent memory loss?
Yes Dr Green likely has the largest and best uncontrolled Rapamycin random trial. You’d think he would be seeing some type of signal either way?
I am going to pursue the cancer/transplant angle to see if I can find something meaningful. Nothing yet.
This comes back to the issue of tracking brain / cognition / memory over time… still looking for a standard measure that is cheap, easily done, and verified by academic studies:
At this point, this study has raised my RHR to 54.5.
I have been around long enough to see the publication of medical findings from major research groups only to be discredited in later years.
Since I am 81 yrs. old, I can be the canary in the coal mine. People I have known personally were well aware of their increasing signs of dementia and onset of Alzheimer’s long before they became non-functional. My family history has had zero Alzheimers or dementia, at least in recent generations. So, if I see signs I am getting Alzheimer’s or dementia and haven’t died from other causes, I will let you know because it may be from taking high doses of rapamycin.
https://journals.plos.org/plosmedicine/article/file?type=printable&id=10.1371/journal.pmed.0020124
P.S,: I am a retired engineer and we are not noted for our great English skills, so please discount English errors as a sign I am losing it.
We used to use the mini mental exam as a screening tool in a very large independent living facility. You could administer it every year or so and check for lower scores.
The test isn’t perfect but it’s easy to do and follow.
There’s a max score of 30 . Most of it is easy but serial 7’s can be a challenge.
I reached out to one of the oncologists in the rapamycin/cancer/GFJ trial asking about Sirolimus/mTOR inhibitors and reports on cognition.
He sent me this paper:
https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.12927
https://sci-hub.se/https://doi.org/10.1111/ctr.12927
The study found NO difference between everolimus or CNI groups.
Within this paper, others were referenced.
https://sci-hub.se/10.1016/j.transproceed.2009.08.050
“This report describes favorable psychiatric outcome variables using everolimus in maintenance heart transplant recipients”
https://sci-hub.se/https://doi.org/10.1080/13803395.2011.595396
“Planned comparisons revealed that groups treated with sirolimus or tacrolimus resolved cognitive tasks worse than those treated with cyclosporine and controls. More specifically, performance of sirolimus and tacrolimus groups was significantly impaired in comparison with that of controls in the direct and time arithmetic tasks and numbers key test. In sum, we observed impairment in the resolution of various cognitive tasks in those patients treated with sirolimus or tacrolimus”
High incidence of cognitive impairment in renal transplant patients I believe. Rapamycin may well exacerbate it. And prevent it if early enough.
Not probably: definitely. It’s a model of early-onset Alzheimer’s. EOAD actually is driven by amyloid beta.
170 ng/ml would be a gargantuan dose in humans. Is that avg. levels? That would be like taking 100 mg every four or days for a 70 kg person.
Thanks. Seemed like it would take a very hefty dose.
In the meantime fish consumption over 1 serving per week lowers AD risk by 60 % and viagra lowers it by 70%. Exercise also lowers it.
Certainly wouldn’t stop rapamycin over this study.
And a thread response to Matt K’s comments
And - because I like all points of view when they are well-informed, here is the response from one of the researchers on the paper:
Thanks for sharing, was waiting for the rebuttal.
5XFAD mice? C’mon, and he talks about cherry-picking?
“These 5XFAD transgenic mice overexpress both mutant human amyloid beta (A4) precursor protein 695”
5XFAD mice recapitulate major features of Alzheimer’s Disease amyloid pathology