#2892

It doesn’t say dementia but cognitive impairment. But yes if you’re worried about PD, I would definitely take precautions. Despite that, lowering apoB is still a must.

2 Likes
#2893

The data you showed points to potentially a trade-off with the statins (though I think that randomized trials have suggested otherwise so the MR effect on cognition impact might be impacted by having HMGCR inhibition during fetal development or early childhood stages of life when the brain needs extra cholesterol - which is not when you’d now drug that pathway via a statin as an adult).

In any case, you have other options than statins. As one example, the paper you quoted form above has a sentence before what you quoted in it’s abstract that says:

Using data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area.

#2894

The effect is too small, it doesn’t matter. It’s not clinically significant.

Relatedly, the finding that HMGCR inhibition was associated with slowed reaction time translated to an increase of 0.067 milliseconds per 1 SD decrease (38.7 mg/dL) in LDL-C. For comparison, previous work evaluating choice reaction time tasks among healthy adults aged 18-65 years found an increase in reaction time latency of 2.8 milliseconds per year, suggesting a small impact of HMGCR inhibition.62 Therefore, we emphasize that any potential adverse effects of HMGCR inhibition on neurocognition found in this study likely do not outweigh the cardiovascular benefits of statin use.

It’s relatively small and can be mitigated in other ways.

#2895

@adssx this is perhaps the 10th time you have taken a holistic concept and picked out a more narrow subset, criticized that subset but not evaluated the larger holistic concept.

In this case, I never mentioned the word “statin”. (And while I support them in many cases, I have personally never taken a statin in my life). My comment was about that (a) cardiovascular is a massive risk for virtually anyone (except genetic mutants in PSCK9) and

(b) Not until you have optimal Apo B should you be satisfied if health and longevity optimization is your goal.

and

(c) Especially in the context that there are powerful meds with side effects profiles that are good.

As @AnUser argued you many not have to worry about the statin effect, but let’s assume for sake of argument that you should worry about that, what do you think about the rest of statement (c)? Just as examples, you could do really low statin (most of the cardiovalular protection comes as very low dose and then is more incremental dose response from their) alone or combined with Eze of Bemp Acid. Or you could do those without any statin at all or you could use one that don’t cross the blood brain barrier as the others do. Or you could do PCSK9i - or any other low dose combo of the many powerful options without statins at all.

and importantly, what do you think about part (a) and (b) of my post that you replied to?

1 Like
#2896

If someone wants to live 200 years they must have optimal apoB.
If someone just wants to live to 50-80 yrs old and avoid PD, that’s different.

Even if the very small increase risk of PD is realized, all else equal, lower apoB might allow one to live longer for curative treatment. It’s an important consideration, but it just means the risk have to be mitigated in other ways for me, as there is no way to leave apoB off the table, or even worse, try to increase it.

2 Likes
#2897

I agree and would even say that threshold probably starts kicking in already if one wants to live to 70 or 80

just think about how many life ending or crushing strokes or heart attacks still occur in 60-70 year olds

4 Likes
#2898

I approach this a bit differently

I want to keep my supplements stack as low as possible to avoid unintended interactions and because there is a small contamination risks with each agent that is added

On the data size I want as much possible, subject only to when the economic costs is do high.

In general more data can decrease risks in decision making while more supplements can increase risks

Since cholesterol markers are generally on the cheaper side, it’s an area where the small cost to also see that is happening beyond Apo B is often worth it for me.

But of course costs do matter and there are a lot of other tests that I have triage and not do all off at each blood draw

1 Like
#2899

I know i have the test, but it is part of a package and i dont know what it means.

The package costs GBP 255 for two tests. It is IMO really good value.

2 Likes
#2900

But it does beg the question, what is optimal apoB? And does that optimal range vary if inflammation, bp, oxidation and other factors are optimal.

1 Like
#2901

I apologize; I didn’t frame my comment correctly. I did not mean to criticize anything. That said, please chill out and assume good faith and best intentions. We’re all here to help each other reach our goal(s). These goals might be different. And not everything is rational; we may have our own fears, justified or not. Or at least, I have. So I should have been clearer in my previous reply that because I have a family history + genetic risk of neuro-psychiatric conditions (MDD, AD, PD, etc.), I put more weight on this risk than on others such as CVD. Maybe unreasonably so. Still, @AnUser summed it nicely, “If someone wants to live 200 years they must have optimal apoB.” and “If someone just wants to live to 50-80 yrs old and avoid PD, that’s different.” I feel like I prefer to die at 80 from a heart attack than live 100yo with AD or PD starting at age 60 and seeing myself decline every single day, incontinent and demented. Again, it might be illogical, but that’s how I feel now. I didn’t care that much before when my ApoB was at 68 mg/dL, but in my latest test, it surprisingly jumped to 97, and now I wonder what to do :sweat_smile: (First, redo the test… :slight_smile: ) There are more and more MR and longitudinal studies published so I’m convinced that this question will be solved in the next 24 months. Researchers might find that non-statin lipid-lowering agents have a better long-term safety profile for people at risk of PD (or other NDDs). Or they might actually dismiss all the previous fears around statins and prove that the effects were not causal. Time will tell. For now, for me, the jury is still out. For the general population, I agree with your statements (a), (b), and (c).

9 Likes
#2902

MDD - statins are positive, not negative.
AD - mixed results, LDL increase, increases risk iirc in MR. ApoE4 genes tend to increase lipids.
PD - slight decreased risk for higher LDL.

I like to work with one disease at a time, and find the causal pathways for that disease, especially the necessary conditions. First I solve heart disease, then the next one, and so on.

Remember that heart attacks are no fun, and the atheroschlerosis preciding that probably does cause damage to the brain, heart, increase risk of strokes, mini strokes, which can cause depression, etc and hurt the brain.

I think that meditation helps with worrying about dementia risk. I remember a meditator called Shinzen Young said that he’d prefer to live one day in his state of mind of enlightenment, than decades of being extremely rich, large house, lots of sexual partners etc, like a rockstar, but without that state of mind. He is an advanced practitioner.

He did try an experiment where they withdrew a medication for the thyroid I think for a study, which leads to a large deficit in cognition, and he was able to maintain the state of awareness he prefers. So it’s possibly to be quite happy despite losing one’s cognition, I think.

4 Likes
#2903

Also worth remembering that it’s not just your heart and brain that apoB is damaging, it also causes ED.

1 Like
#2904

Atherosclerosis in the brain looks so nasty and it makes sense how bad it is for blood flow / brain function, can cause vascular dementia, as well as causing ED.

image

image

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#2905

They’re positive when combined with antidepressants (Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials 2021), alone, I don’t know, probably neutral.

And among PD patients, statins accelerate motor decline and potentially also cognitive decline.

The difficulty being that PD starts at least 10y before diagnosis, so you don’t know whether you’re a PD patient or not.

Of course, that’s why I’d love to find something that can both lower apoB AND the risk of PD/DLB. Or at least be neutral towards PD/DLB. As I said there, ezetimibe might be the way. There’s some weak positive signal for fenofibrate in some papers as well. Bempedoic acid might be too recent to have data on it.

(and yes, meditation helps a lot :slight_smile: )

2 Likes
#2906

Study might’ve been too small to detect an effect, I was basing my claim on that meta that did detect an effect combined with anti-depressants but most importantly all the association evidence.

Yes true.

Sure, but it also depends on your age. PD diagnosis happens mostly in 50’s I’d guess? So until 40 statins are ok to use. In 10 years we will have more meds / possibly gene therapy to lower cholesterol. I’m not going to do nothing until that time since it’s 10 years of exposure to above optimal apoB.

Ezetimibe is very weak and it won’t work on its own.

#2907

I’m below 40, and I wouldn’t take the risk still (“About 10%-20% of those diagnosed with Parkinson’s disease are under age 50, and about half of those are diagnosed before age 40.”) People who care about PD because of family history, genes, pre-PD symptoms, or environmental risk (such as lifetime exposure to pesticides like paraquat) might share the same worries (justified or not).

Weaker than statins for sure, but I wouldn’t say “very weak”:

2 Likes
#2908

I don’t know how to combine the result in the simvastatin trial with the 10-20% probability of the PD diagnosis with the PD diagnosis risk. It seems small to me, even with family history. The cases of Parkinson’s in my family history is from people living on a farm. I think it might’ve been pesticides or something. How heritable is the disease? What’s the relative risk increase?

#2909

No one really knows. “About 15 percent of people with Parkinson’s disease have a family history of the condition”. Some think that “Parkinson’s Disease Is Predominantly an Environmental Disease” (from 2 weeks ago). Indeed, living near farmland is not amazing:

Finally, genetic differences also cannot readily explain the near perfect correlation between use of pesticides and PD prevalence [29], the strong association between agricultural activities and its incidence […] For example, in France the increased risk of developing PD is not limited to farmers [39, 40] but extends to those living near farmland or vineyards [30]. Pesticide exposure may also lead to faster disease progression after the diagnosis has been established.

By the way, from Sept 2023: Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association

They conclude:

Although some older retrospective, case-control, and prospective longitudinal studies suggest that statins and LDL-C lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion, at least over the course of the trials that varied from a median of 1.6 to 6.0 years of follow-up. Additional studies are needed to ensure cognitive safety over longer periods of time. In the interim, contemporary guidelines recommending the risk-stratified attainment of lipid-lowering goals are reasonable.

Importantly, they did not include Parkinson’s in their assessment. Parkinson’s dementia and Lewy body dementia were not specifically explored but included as part of “all-cause dementia” I assume.

2 Likes
#2910

Head injury is also a major risk factor (think M Ali)

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#2911

If we even assume some heritability, then the RR increase from using statins for 10 years must be very small, the total absolute risk. If the base rate is 2%, increases to 4% with genetic risk, 0.8% (20% of 4%) chance that PD develops before 50, or is my math off? Then you increase the 0.8% risk by whatever the RR increase is for statins which I don’t think we know. If we assume no heritability then it is half.