My husband tried both donepezil (oral) and rivastigme (patch) and could not tolerate the GI sides. It has this effect on many people.
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Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17Ī±-estradiol in middle-aged male mice
Conclusions
These findings demonstrate that APOE4 promotes systemic and neural aging phenotypes linked to AD and that 17Ī±E2-mediated healthspan actions show a positive APOE4 bias. Collectively, the findings suggest that longevity-promoting interventions may be useful in mitigating deleterious age-related risks associated with the APOE4 genotype.
Open Access Paper:
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Itās pretty obvious to this groupā¦ butā¦ here you go.
I hit the gym before heading to the airport to go to San Antonio. Family reunion. A healthy long-lived tribe of siblings.
Exercise Rewires Alzheimerās-Affected Brain Cells - Neuroscience News
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@RapAdmin Has anyone discovered a way to obtain 17alpha estradiol? Seems like it should be available through India or perhaps a compounding pharmacy?
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Not that Iāve heard of. @DrFraser had mentioned some time ago that he heard of some group that may be providing it at some point in the future, but that was quite a while ago - Any updates Dr. Fraser?
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Yes the gentleman that I was talking with on this and yes, it was going to be synthesized in a for human use form, off shore. Itās been a while since Iāve had contact with him however. When I get an update, Iāll share what I can.
Of course there are multiple groups that synthesize it ā but all are selling only to verified research labs or academic institutions.
Here are examples:
Iām contacting a few of the compounding pharmacies I work with as I heard that some might be willing to synthesize it. If I get any positive response from any of them, Iāll post that.
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https://english.elpais.com/health/2025-06-22/how-to-avoid-age-related-cognitive-deterioration.htm
And a story on ozempic helping avoid dementiaā¦
lhttps://www.medicalnewstoday.com/articles/can-ozempic-weight-loss-diabetes-help-lower-risk-vascular-dementia
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My favorite PharmD at a compounding pharmacy says he might be able to get this. He wants to know what formulation (tablet, injection)ā¦ I think tablet would be most consistent with what I know, then he has asked on dosing.
Does anyone have a good source for how to dose this?
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There is this review (paywalled and I donāt have access through my institution).
Review of the effects of 17Ī±-estradiol in humans: a less feminizing estrogen with neuroprotective potential
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.20284
AI says the dose that has been tested and determined to be non-feminizing in Men is 2mg/day but this may be well below the dose for longevity. Mouse dose was ā4.8 mg 17aE2/kg (4.8 ppm) dietā.
Here is a Resus macaque study that suggests a dose of 0.20 mg/kg/day while tolerated, resulted in āsignificant feminizationā (that would be 14 mg / day for a 70 kg. human). They explain in the study that the mouse dose above equates to 0.92 -1.15 mg /kg/day which translates to a primate dose of 0.2 to 0.3 mg/kg/day. They also suggest that the feminization may be do to bolus dosing and isomerization to beta estradiol and that future studies may want to use transdermal patches to avoid the feminization effects.
Not much help and I was unaware that higher doses were feminizing as I believe the studies in mice and rats did not show feminization. It sounds like all we know is that 2mg/day was non-feminizing and tolerated in humans.
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I would guess a transdermal formulation would be best.
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Thanks @59vw and @dicarlo2 for giving input.
I think the doses being used that showed longevity benefit were potentially feminizing.
On route - does oral 17 alpha estradiol result in liver enzyme induction and cause individuals to be at increased risk of thrombosis (DVT/PE) like oral standard estradiol does? It looks like that question is probably known - and looks like it is probably safe in that regard.
Topical brings in another complexity on absorption, how to measure, and what a normal level would be? Even with known quantities of of 17 beta estradiol (the one we use now for female HRT) in patches has required a lot of work to get consistent absorption. The compounded creams that individuals use result in serum levels all over the place, depending upon how they compound it - and at least we can easily and cheaply measure this in 17 beta, but not 17 alpha.
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On route - does oral 17 alpha estradiol result in liver enzyme induction and cause individuals to be at increased risk of thrombosis (DVT/PE) like oral standard estradiol does? It looks like that question is probably known - and looks like it is probably safe in that regard.
Good question, Iām not sure it has been tested enough in humans to know.
Re route, the macaque paper hypothesizes that estrogen receptors are getting saturated with bolus dosing and unconjugated molecules are isomerizing to beta-estradiol. They found significantly higher beta-estradiol in animals that received alpha-estradiol.
On 17 alpha estradiol, my cost $3 per 2 mg tablet. Iām just not sure we know enough on this, but yes, it can be done.
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Scientists can tell how fast youāre aging from a single brain scan
New aging clock can predict risk for dementia, other age-related diseases years before symptoms appear
āThe way we age as we get older is quite distinct from how many times weāve traveled around the sun,ā said Ahmad Hariri, professor of psychology and neuroscience at Duke University.
Now, scientists at Duke, Harvard and the University of Otago in New Zealand have developed a freely available tool that can tell how fast someone is aging, and while theyāre still reasonably healthy ā by looking at a snapshot of their brain.
From a single MRI brain scan, the tool can estimate your risk in midlife for chronic diseases that typically emerge decades later. That information could help motivate lifestyle and dietary changes that improve health.
In older people, the tool can predict whether someone will develop dementia or other age-related diseases years before symptoms appear, when they might have a better shot at slowing the course of disease.
āWhatās really cool about this is that weāve captured how fast people are aging using data collected in midlife,ā Hariri said. āAnd itās helping us predict diagnosis of dementia among people who are much older.ā
The results were published July 1 in the journal Nature Aging.
https://www.eurekalert.org/news-releases/1089381
Open access paper:
DunedinPACNI estimates the longitudinal Pace of Aging from a single brain image to track health and diseas
To understand how aging affects functional decline and increases disease risk, it is necessary to develop measures of how fast a person is aging. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain magnetic resonance imaging, that is, the Dunedin Pace of Aging Calculated from NeuroImaging (DunedinPACNI). Exporting this measure to the Alzheimerās Disease Neuroimaging Initiative, UK Biobank and BrainLat datasets revealed that faster DunedinPACNI predicted cognitive impairment, accelerated brain atrophy and conversion to diagnosed dementia. Faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases and mortality in older adults. When compared to brain age gap, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a next-generation brain magnetic resonance imaging biomarker that can help researchers explore aging effects on health outcomes and evaluate the effectiveness of antiaging strategies.
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, apply this tech to our existing brain MRIās ?Iām new to the forum here, so first off hello to everyone!
I found this piece by Crissman Loomis to be quite interesting. It suggests that 45% of dementia cases could be avoided/prevented with lifestyle interventions. It includes many great suggestions around exercise, sauna, dietary patterns, coffee, alcohol, etc. What is perhaps lesser appreciated is the controversy around the protective effects of education, and how factors like air pollution, hearing, and social connections matter.
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The code is available on github with what appear to be good instructions on how to use it. I asked ChatGPT if I could somehow convert the SimonONE results to the format the algorithm expects and it sounded like it should be possible with all free software. I have not attempted yet though.
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Ok, @dicarlo2, be my canaryā¦ after you figure it out, let me know! I have the same Simon one mri. Thanks!
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