Ezetimibe Reduces Alzheimer's Disease Risk (study)

No.
I am not currently taking memantine or galantamine.
I was experiencing unexplained brain fog and loss of short-term memory.
Memantine and galantamine really helped. Since I was taking both, I really didn’t know which one was the most effective.
It took about two months to get results. After four months, everything seemed to return to normal, so I quit taking them. One reason I don’t take galantamine is the effect it has on my sleep, excessive dreaming mainly.
At ~84, my mind is mostly normal. The main thing I notice is a slowing of processing speed. This manifests in my inability to find objects in a clutter as fast as a normal brain would.
My ability to do things like crossword puzzles and sudoku puzzles has never been better.
The main supplements I take for maintaining brain functioning are:
Vinpocetine, Huperzine A, and Ginkgo Biloba.

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@desertshores Curious if you’ve tried HMB.

I have a container of powdered HMB. Unfortunately, I should have bought the capsules. It ruins the flavor of everything I put it in, so I have not really taken very much of it.

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Yeah I’d been warned so I got capsules but only take them once in a while. Need to put them in pill organizers so I actually take them.

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Random Chinese university and journal but bad news: Mendelian randomization analysis of lipids traits and lipid-lowering drug-targets in relation to cognitive status 2025

Mendelian randomization reveals no causal link between lipid traits and cognition;
NPC1L1 inhibition genetically linked to higher cognitive impairment risk;
Ezetimibe’s cognitive effects may be independent of lipid-lowering action;
Findings highlight caution when prescribing ezetimibe to cognitively impaired patients.

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That looks like p-hacking to me if they used 9 drug targets + lipids, and on top of that multiple different outcomes and six different datasets (and found a genetic correlation in three):

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I wonder how much care we need to put into interpreting Mendelian randomization studies due to linkage disequilibrium types of effects. The rarer is any given mutation that drives the result, the more likely it would tend to be packaged with some other mutations that impact things we care about. If mutation A that causes lower LDL-C comes along with mutation B that causes X, should we conclude that lowering LDL-C also lowers X? We should not unless there is a sensible mechanistic story and observational evidence showing some relationship between LDL-C and X independent of the MR study.

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It’s possible. Might explain why it’s published by the “Department of Anesthesiology” (lol) of a university in the random “Journal of Affective Disorders”. If it was of higher quality it would be published in Brain by a Stanford team. I’m sure other teams looked at ezetimibe MR and dementia and found nothing and didn’t publish anything.

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Null results are still valuable results. They should be published. If they have them, but didn’t publish, that’s a pity. I am not aware of it either way.

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Actually I was wrong, some good researchers published this null result in a good journal: Lipid lowering and Alzheimer disease risk: A mendelian randomization study 2019

University College London + Cambridge + Karolinska + Utrecht so Tier 1. In Annals of Neurology, Tier 1 as well.

Results:

NPC1L1 (encoding the target for ezetimibe)
Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23–1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.

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That’s fantastic, and very encouraging. Great harm is done when null findings are suppressed, as it distorts what we know and obstructs hypothesis generation. Unfortunately publishing incentives don’t always align.

Concerning about PCSK9i and AD though.

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Huge sigh :frowning:
I have one apoe4 and I take repatha
Oh well, I guess my chances of an MI are greater than AD, so….

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On first pass, I was disappointed that the genetic deficiency of NPC1L1 does not protect against Alzheimer’s disease. The NPC1L1 protein in question is central to cholesterol absorption in the bowel and that function is blocked by the drug ezetimibe. So the implication is, in Mendelian Randomization, if that protein is absent due to an allele being disrupted/absent, then that should somehow represent taking ezetimibe in terms of lowering Alzheimer’s risk. My earlier hope was based on prior research that showed ezetimibe lowers the risk of Alzheimer’s and related dementias by > sevenfold. So Mendelian Randomization suggests that is not so, but we are in fact talking about two different mechanisms of action. I really comes down to this: not producing enough NPC1L1 does not increase Alzheimer’s risk, but taking ezetimibe has a different (non-cholesterol) mechanism of action in the brain by presumably lowering the binding of hexokinase-1::14-3-3G protein. That is, ezetimibe has a stronger affinity for that binding site and replacing hexokinase-1 with ezetimibe at that site lowers the risk of AD. My hope in ezetimibe is restored for now.

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Where do you get prescriptions for ezetimibe in the USA these days? Or which pharmacies do you order from?

I’ve just used the sources we have listed on this page: How to Get Rapamycin, Where to get a Prescription

But if you’re looking for India-based resellers, there is this whole issue which is a quickly evolving situation (we’re hearing some people may be getting orders through)… Disturbing news regarding Medications Ordering from India, Price Increases, Parcels Stopped

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Just ask your family doc for an rx. I printed out the study and handed it to my family doc. And who does not benefit by lowering cholesterol? It costs $45 for a 90 day supply here in the USA, but cheaper in India when I could get it there.

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To add to your post…

PRO TIP:
Always check goodrx (cost plus is also an option). And ALWAYS put in custom amounts

For example, cash pay on good rx for:
90 pills is $38
180 pills is $41
365 pills is $45

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Very good point - Thanks! Definitely worth it to ask your doctor if he/she will prescribe it for us. I’ll do that now, as I was just thinking of ordering more. Though I do like the combo Ezetimibe/Bempadoic Acid pill that is available from India (that I don’t think we have here in the US).

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FWIW, incase you have not seen US sourced ezetimibe, it’s a tiny pill.

I loved the idea of a combo pill, so I bought that from India, too, but then I saw they were fairly large.

My next order from India was only for BA, and I will get EZ from a US pharmacy (the volume of the two pills won’t be larger than the one BZ/EZ pill). My thought was after seeing the poor quality incident with Sun Pharma, I figured there would be slightly less risk in quality with buying US drugs. If the combo pill was actually smaller, then I would throw risk out the window :slight_smile:

PS, not all BA is smaller, I specified brand after some great people here showed me their various sizes

Ah - the combo pill is available in the US, just probably expensive unless covered by insurance:

https://www.goodrx.com/nexlizet/what-is#cost

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