#60

The PREVENTABLE study investigators chose atorvastatin for their trial to see if it can prevent dementia, and is expected to cost $90M over 7 years.

Because of this I’m suspecting Attia and Dayspring might be catastrophically wrong and if it works, then everyone is going to start 40 mg atorvastatin immediately.

2 Likes
#61

A trial of atorvastatin for dementia prevention has already been done and failed.

2 Likes
#62

Which study is that?

#63

NCT02913664, Risk Reduction for Alzheimer’s Disease (rrAD). They had the following arms:

  • Aerobic Exercise
  • Stretching Exercise
  • Losartan + Amlodipine + Atorvastatin 80 mg + Stretching Exercise
  • Losartan + Amlodipine + Atorvastatin 80 mg + Aerobic Exercise Training

The principal investigator, Zhang Rong, emailed me in Jan 2024:

Dear Antoine, The paper is still under preparation. The primary data analysis showed that overall there were no differences in changes in neurocognitive function over 24 months among the trial groups, a negative finding, consistent with other recently completed trials in this aspect. The team is working on the imaging and blood-based biomarkers obtained from this project.

2 Likes
#64

I’d like to see atorvastatin only personally in a double blinded trial compared to placebo pills.

#65

Of course, me too, but that doesn’t look great for atorvastatin.

On top of that, statins mess up with the gut and GLP-1 levels: x.com

image
image816×1342 118 KB

Given the millions (billions?) spent on repurposing GLP-1RAs for neurodegenerative diseases (including massive phase 3 trials sponsored by Novo Nordisk of semaglutide in AD). So, like you, I tend to “follow the money”. That trumps the $90M of PREVENTABLE. So, don’t mess with GLP-1 levels; start with non-statin lipid-lowering medications (ezetimibe, ftw), and in the last resort, take rosuvastatin 5 mg (or atorvastatin 10 mg if you’re at risk of diabetes).

4 Likes
Parkinson's disease
#66

@AnUser I wanted to create a market “Will the PREVENTABLE trial of atorvastatin in mild cognitive impairment succeed?” on Manifold but I don’t have enough Mana… Still, you can see that my market for semaglutide in AD (which is about FDA approval, so a higher burden of proof than just a successful trial): Will Ozempic / semaglutide be FDA-approved for Alzheimer's before 2030? | Manifold

1 Like
#67

I can’t see the cost of the Novo Nordisk trials anywhere, but it’s completely different studies. Atorvastatin is not done with those with AD or MCI. It’s in pretty much healthy adults over 75 years with a simple outcome of cases of dementia, and disability.

1 Like
#68

o1 estimates it at about $200m as it’s industry-sponsored, phase 3, 2k participants, 173 weeks, in AD, with 17 clinic visits and several tests and scans.

And that’s only one instance. There are various non-profit (charities and academia) and for-profit (startups and big pharma) efforts to repurpose GLP-1RAs for NDDs (mostly AD and PD) or create new GLP-1RA specifically for NDDs (for instance: https://www.kariyapharma.com ).

That’s at least 10x if not 100x more than the money invested to study statins in NDDs.

#69

Ah and if this wasn’t already convincing enough: there are also ongoing research efforts for statin CESSATION to see if that improves cognition.

Follow the money…

1 Like
#70

NDD =/= dementia prevention.

Lots of people research different things.

They expect around a 20% reduction in dementia cases in PREVENTABLE over the study period, that’s very good, at least what they’ll be able to detect…

#71

90% of money going to NDD probably goes to dementia (and especially AD). My point about the money was only an answer to your mention of $90M for PREVENTABLE: that’s nothing compared to investment in GLP-1RAs for dementia.

But don’t get me wrong: I would LOVE the PREVENTABLE trial to succeed. It might succeed: anyone above 75yo can join the trial so that will include a lot of people with very high apoB and for these people the benefits atorvastatin 40 mg surely outweigh the potential risks. So results stratified by baseline apoB will be super interesting.

1 Like
#72

This a disappointing to read. I thought I’d finally found a statin I could use without sides in atorvastatin. Rosuvastatin causes weakness for me and I’m 4/4. I’m already taking bempedoic acid and ezetimibe and that gets me down to 75. I haven’t tested again since starting the statin. I Don’t have access to Repatha. What would you think about doing in my situation? I’m 43 and have not had any heart scans yet. My dad had a heart attack at 55.

1 Like
#73

That is too complex to answer properly without actually having a chat with you - on via messaging. I’m wiling to give generic advice, but there are a lot of things to do with an E4/E4. If you don’t tolerate rosuvastatin, then the issue is do you have heart disease or not … yet? If you have the resources, getting a baseline CTCA with Cleerly is sensible. If you have disease, then get a CardiaX by Vibrant to see if you have a genetic SNP as we have specific treatments for each of the SNP’s.
If one has a clear CTCA, one would have to consider backing off of Atorvastatin, but if you have disease, then there is need to escalate therapy.
I’m almost done checking desmosterol on individuals on statin with ApoE4’s … it’s low on everyone. The statins do a great job of this.
Getting Omega 3 index to 10%, Lithium, GLP1’s, SGLT2’s, 17 alpha estradiol … all interesting areas to pursue.

5 Likes
#74

I have the same issue as you. Rosuvastatin was horrible and Atorvastatin is much better. However Atorvastatin causes muscle spasms and weakness if I take 5 mg every day. So, now I take it Monday Wednesday and Friday only. I don’t have blood work back to know how effective it is. 5 mg daily reduced LDL and ApoB by 20.

1 Like
#75

If you have a positive ApoE4 that is an issue requiring review. If not, power on. I have an E4, so I’m doing bempodoic acid and ezetimibe now. I advise my E4 positive patients to probably head down this pathway.

1 Like
#76

I do not have a positive ApoE4. I do have an ApoE3 and ApoE2.

#77

I just got my empowerdx results from 5mg crestor and ezetimibe and all 4 markers were too low for boston heart to detect, and i was worried but sounds like thats not too abnormal for e4. Im thinking of trying 2.5mg or taking 4 days a week and see if i can get a dectable amount. Any thoughts?

#78

Two things: one, at least atorvastatin didn’t make neurocognitive function worse, and two, perhaps two years is a little short for showing measurable effects (and that’s assuming the trial was adequately powered).

A frequent line of attack against statins for CV benefits is that those benefits are allegedly tiny. That tiny effect is computed from relatively short treatment duration (under five years). But as we know, the effects are cumulative, and only show up robustly longer term.

Perhaps the same obtains in the cognitive realm. For a neurocognitive effect to show up in two years, you might need a lot of subjects in the active molecule (atorvastatin) arm, so there may be questions about whether it was adequately powered. The age group is also important - the older, the more dementia is prevalent, but we also know from AD studies that starting treatment late in life may not be effective, because the disease has already done damage, so effective treatment needs to start decades before, when the disease process is starting. There are of course some parallels here with atherosclerosis, but it’s a distinct disease, (which is why this study exists to test whether atorvastatin works here!), and like with AD, the need for early intervention is particularly acute.

Bottom line, I would like to see a study of longer duration, with various age groups, adequately powered (and a pony too🤣).

2 Likes
#79

I’m from the UK, so I don’t have access to the specific scans you mentioned. Would a CAC scan be the next best option? The NHS is excellent for many things but currently falls short on preventive measures, and it’s quite a challenge to see my GP. My main focus is maintaining optimal brain health. I’ve been proactive in this regard—I’m measuring my Omega-3 levels using the OmegaQuant test next week. I don’t drink or smoke, my diet is largely plant-based, including regular homemade yogurt and oily fish. I try to follow the guideline for brain health regarding lifestyle choices but I do still have trouble sleeping.

Here’s a list of the supplements and medications I’m currently taking:

Vitamin D & K2
Omega-3s (EPA 1.5g, DHA 1g)
B Complex (Life Extension)
Creatine 10g
Lithium Orotate 5mg
Magnesium, Taurine, Glycine, Hyaluronic Acid, Alpha-Lipoic Acid.

Rapamycin 4mg, taken with a GFJ every two weeks
Acarbose 50mg, twice per day with main meals
Empagliflozin 12.5mg
Telmisartan 80mg
Atorvastatin 10mg
Brillo EZ (Ezetimibe & B Acid)
Tadalafil 2.5mg

Is there anything else you think I might be missing or can suggest? I want to be aggressive with prevention, especially given the risks associated with being APOE4/4.

I am also exploring GLP-1s; although I don’t have a weight issue, recent studies suggest they might still offer benefits for someone like me. I haven’t thoroughly researched 17 alpha-Estradiol yet.

I would definitely consider a video consultation at some point. Do you have any patients from the UK, and if so, how does that work?

It seems my next move should be to look for the best possible heart scan I can find near Bristol, UK.

Thank you.

2 Likes