#327

Exercise is undoubtedly number one in prevention (or have lucky genes)

Keywords: donepezil, galantamine, memantine, rivastigmine, sodium oligomannate

There is no drug or supplement that I can find that has any proof of delaying or reversing Alzheimer’s or dementia. However, every one of the above drugs helps with age-related cognitive decline.

I take donepezil/memantine and galantamine.
Subjectively, they work great in clearing brain fog and helping short-term memory.
The donepezil/memantine took a week or two to really feel the effect.
Galantamine works immediately if you take 8 mg or more.
Galantamine has several nootropic and synergistic properties.

I definitely would not recommend donepezil/memantine to younger people.

Galatamine: Read some of the threads mentioning galantamine.

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#328

Components of ashwagandha did show the unique ability to halt dementia in a mouse model and even promote reconstruction of the damaged neuronal networks themselves, effectively reversing the condition. It’s unknown whether it would similarly benefit humans with Alzheimer’s.

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#329

Since humans have taken ashwagandha for millennia, I think any benefits for Alzheimer’s would have been noticed. “The history of its use in traditional Indian medicine dates back nearly 3000 years.”

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#330

But with all that has been said… what if it is the immune system that causes Alzheimer’s and what better to help the immune system than rapamycin.

Rapamycin is an immune modulator it improves the immune system against flu, allergies, inflamm-aging.

Here’s a link: Alzheimer’s may not actually be a "brain disease" - Earth.com

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#331

Look up intranasal rifampicin. Also klotho seems to be protective but obviously not at the clinical stage yet so high uncertainty re: dosing.

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#332

More reasons to lose any visceral fat we have…

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#333

Ketone Bodies Clear Damaged Proteins in the Brain

New research reveals that ketone bodies, beyond their role in energy production, are crucial in maintaining brain health by regulating protein quality control.

Ketone bodies, such as β-hydroxybutyrate, interact directly with misfolded proteins, making them insoluble and aiding in their clearance via autophagy.

This process helps prevent protein aggregation, which is linked to aging and neurodegenerative diseases like Alzheimer’s.

Animal studies demonstrated that increasing ketone levels through diet or supplementation reduces protein buildup in the brain and restores cellular function.

The findings connect metabolism with proteome health, offering new avenues for treatments targeting brain aging and diseases.

Researchers are now exploring how ketone-based therapies can be applied beyond the brain, including the gut and other systems.

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#334

BTW does anybody know what the minimum to target is? Are there any downside to 0 if that’s even possible?
Thanks to low carbs and running, my latest DEXA says my visceral fat is 190g (6.7 oz) which is probably OK but there is still room for improvement if the target is 0.

BTW that also puts me all the time in mild ketosis so the following is another good news:

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#335

Source article for a deep dive:

https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(24)00459-8

This is why I’d put ketogenic diet in my bullet list of promising interventions for Alzheimer’s but truly it could be ketone esters alone.

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#336

More on the nitty gritty. Also seems to work on APOE4 carriers. Might also explain part of the neuroprotective effect of SGLT2i drugs, since they put the patient in mild ketosis.

https://www.sciencedirect.com/science/article/pii/S1471489221001582

I have ordered the ketone esters but can’t take them while I nurse as they can be dangerous to the baby.

Also @John_Hemming thought you’d find this interesting:

βOHB improves memory by increasing histone acetylation

βOHB is an inhibitor of endogenous HDACs that lead to the upregulation of genes involved in protection against oxidative stress. βOHB-induced inhibition of HDAC is associated with full transcriptional changes, including those of genes encoding oxidative stress resistance factors FOXO3A and MT2. Treatment of cells with βOHB increased histone acetylation on the FOXO3A and MT2 promoters, both of which were selectively depleted upon HDAC1 and HDAC2activation. Consistent with the increase in FOXO3A and MT2 activity, substantial protection against oxidative stress was observed in mice treated with βOHB [18]. BDNF is a neurotrophic protein with properties that promote neuronal survival and synaptic integrity. Studies in animal models have suggested that BDNFcan inhibit HDAC expression, which leads to the epigenetic downregulation of BDNF by inhibiting the transcription of BDNF promoter I [19]. The overexpression of HDACs increased the amyloid load in AD mice. Inhibiting HDACs can improve spatial memory disorder in mice, suggesting that it could be an effective way of improving the cognitive function of AD patients [20]. Animal studies have shown that βOHB therapy not only improves the acetylation levels of histones H3 and H4 but also antagonizes the reduction of acetylated histones H3 and H4 under low-pressure hypoxia. Moreover, βOHB therapy also promotes PKA/CREB activation and BDNF protein expression. The role of βOHB in improving memory is also due to an increase in the modification of histone acetylation [21]. The tyrosine kinase receptor A (Trk A) signaling pathway is also a key point in protecting cholinergic neurons, which are the most vulnerable in AD. Some animal studies have suggested that βOHB improves TrkA expression by inhibiting HDAC1/3 expression in SH-SY5Y cells; thus, βOHB protects neurons from Aβ-induced neurotoxicity [22].

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#337

Peter attia has zero as a target for his clients, so that is my target

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#338
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#339

Interesting. I wonder if that is why Galantamine, which treats dementia may also be used to treat Sarcopenia along with Metformin. Maybe the two diseases are truly linked.

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#340

I’m around 0.5 lbs visceral fat and 15% body fat. What’s the best way to drop the last 0.5?

I get very hungry if I go below 14% body fat.

#341

I’m doing the things in the videos, etc. in this thread (scroll down) - calorie reduction, exercise, some diet changes: Amount of Central Fat Predicts Mortality Risk in Non-Obese Individuals

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#342

I, too, am trying to lose that last bit of visceral fat. I am trying the GLP-1 inhibiter tirzepatide.
This is my first week of taking it at a low dose of 2.5mg. I have noticed no negative side effects so far, but it will probably take a few months to see any positive results. My current BMI is ~22, and my body fat is ~10-15%. I have been exercising regularly for decades, but getting rid of that last bit of visceral fat has been challenging.

“Multiple studies have shown that tirzepatide can significantly reduce visceral adipose tissue (VAT) in people with type 2 diabetes (T2D):
A study published in Diabetes, Obesity and Metabolism found that tirzepatide treatment resulted in a significant reduction in VAT and liver fat.”

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#343
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#344

This is an interesting story, showing just how much we may be able to influence the course of Alzheimers…

Preventive neurologist Dr Richard Isaacson stared at the numbers on the fax in astonishment. Blood biomarkers of telltale signs of early Alzheimer’s disease in the brain of his patient, 55-year-old entrepreneur Simon Nicholls, had all but disappeared in a mere 14 months.

“I had to catch my breath. It was a complete shock: The blood tests on his brain had normalized,” said Isaacson, director of research at the Institute for Neurodegenerative Diseases in Boca Raton, Florida.

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#345

Yeah, truly is - this case and others are discussed here and in the following posts

Did anyone end up seeing the documentary that they did?

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#346

I did not - but here is more info on it:

Its available on Amazon / Peacock to stream:
https://www.amazon.com/Dr-Sanjay-Gupta-Reports-Alzheimers/dp/B0CVDP5MS5

More details:

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