#102

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.

2 Likes
#103

Yeah Iā€™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.

1 Like
#104

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;
Ezetimibeā€™s cognitive effects may be independent of lipid-lowering action;
Findings highlight caution when prescribing ezetimibe to cognitively impaired patients.

Predicting Alzheimers & Dementia (and minimizing risk)
#105

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):

2 Likes
#106

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.

2 Likes
#107

Itā€™s possible. Might explain why itā€™s published by the ā€œDepartment of Anesthesiologyā€ (lol) of a university in the random ā€œJournal of Affective Disordersā€. If it was of higher quality it would be published in Brain by a Stanford team. Iā€™m sure other teams looked at ezetimibe MR and dementia and found nothing and didnā€™t publish anything.

2 Likes
#108

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

3 Likes
#109

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 = 1.23ā€“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.

2 Likes
#110

Thatā€™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 donā€™t always align.

Concerning about PCSK9i and AD though.

1 Like
#111

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