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.
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?
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.
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.
The study found NO difference between everolimus or CNI groups.
Within this paper, others were referenced.
Immunosuppression using the mammalian target of rapamycin (mTOR) inhibitor everolimus: pilot study shows significant cognitive and affective improvement
“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”
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