Statins and Dementia studies

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giftsplash
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Statins and Dementia studies

Post by giftsplash »

I am not sure if this has been brought up before but I have seen a few studies that point to statins being protective against dementia. I think those studies should be viewed very skeptically due to the fact that most do not include drop outs from the study in their results.

Quick math:

10,000 people start in the study by taking statins.
1,500 drop out due to not being able to handle statins (memory loss, brain fog, ect) [This could be caused by compromised BBB which would lead to high chance of dementia]
8,500 people are left in the study all show lower rates of dementia compared to general population.

But this is all due to the fact that the high risk pool dropped out so you are left with low risk statin users who can handle the statin.

I might be wrong, but I think this needs to be considered when looking at these studies.
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Julie G
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Re: Statins and Dementia studies

Post by Julie G »

But this is all due to the fact that the high risk pool dropped out so you are left with low risk statin users who can handle the statin.
You bring up a good point. Those who can't tolerate a statin for whatever reason (cognitive decline, myopathy, etc.) usually aren't included in these studies. BUT, it's worth considering the mechanism of action when looking at this correlation. Statins seem to exert both positive and negative effects. Below is a thoughtful review that tries to tease out specific mechanisms. In short, among those who could tolerate a statin, after 8 years there did not appear to be a positive effect on cognition. However, the authors surmise that statins may be more helpful for E4 carriers because of our increased LDL-C and risk for vascular dementia but their analysis reveals that LDL lowering is associated with a cognitive reduction. Tough to tease this one out.

The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations
https://academic.oup.com/biomedgerontol ... 64/7222585
We find statin use is associated with lower performance in global cognition, reasoning, and processing speed at baseline although this association is weakened in men, white ethnicity, and participants with history of diabetes, CHD, or hypertension. In addition, the effects of statins on global cognition were mediated by a decrease in LDL, CRP, and an increase in blood glucose concentrations. About 51.38% of the effects of statins were mediated by LDL and 2.64% by blood glucose concentrations. The proportion mediated by CRP was −11.02%. In contrast, we did not find a significant association between statin use and cognition measured 8 years later. Overall, our findings suggest that statins are associated with negative effects on short-term cognition through lowering LDL and elevating blood glucose, and positive effects through lowering CRP…

This study displays that statin use is associated with both positive and negative effects on cognitive performance which may explain why most longitudinal studies, including ours, have not found a significant association between statins and long-term cognition. This study provides an explanation for the conflicting results of statin effects on cognition and a foundation for further studies to understand the underlying mechanisms. Statin use remains effective in preventing cardiovascular disease which is an important component of cognitive decline and AD onset.
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Re: Statins and Dementia studies

Post by KathleenC »

Julie G wrote: Mon Dec 11, 2023 12:47 pm
But this is all due to the fact that the high risk pool dropped out so you are left with low risk statin users who can handle the statin.
You bring up a good point. Those who can't tolerate a statin for whatever reason (cognitive decline, myopathy, etc.) usually aren't included in these studies. BUT, it's worth considering the mechanism of action when looking at this correlation. Statins seem to exert both positive and negative effects. Below is a thoughtful review that tries to tease out specific mechanisms. In short, among those who could tolerate a statin, after 8 years there did not appear to be a positive effect on cognition. However, the authors surmise that statins may be more helpful for E4 carriers because of our increased LDL-C and risk for vascular dementia but their analysis reveals that LDL lowering is associated with a cognitive reduction. Tough to tease this one out.

The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations
https://academic.oup.com/biomedgerontol ... 64/7222585
We find statin use is associated with lower performance in global cognition, reasoning, and processing speed at baseline although this association is weakened in men, white ethnicity, and participants with history of diabetes, CHD, or hypertension. In addition, the effects of statins on global cognition were mediated by a decrease in LDL, CRP, and an increase in blood glucose concentrations. About 51.38% of the effects of statins were mediated by LDL and 2.64% by blood glucose concentrations. The proportion mediated by CRP was −11.02%. In contrast, we did not find a significant association between statin use and cognition measured 8 years later. Overall, our findings suggest that statins are associated with negative effects on short-term cognition through lowering LDL and elevating blood glucose, and positive effects through lowering CRP…

This study displays that statin use is associated with both positive and negative effects on cognitive performance which may explain why most longitudinal studies, including ours, have not found a significant association between statins and long-term cognition. This study provides an explanation for the conflicting results of statin effects on cognition and a foundation for further studies to understand the underlying mechanisms. Statin use remains effective in preventing cardiovascular disease which is an important component of cognitive decline and AD onset.
Dr. Dayspring weighed in on statin use for APOE4 carriers on twitter/X last week. He first posted the following comment and article.

@Drlipid
"CLICK ON GRAPHICS - Provocative reading about statins lessening dementia in E4 carriers https://alz-journals.onlinelibrary.wile ... /alz.13543


He was then asked if this research changed his opinion on the use of statins in an APOE4 carrier with low desmosterol levels (0.8 absolute value). Dr. Dayspring responded with, "I would not use a statin in anyone with a low desmosterol who had apoE4 allele(s)".

In response to another question, Dr. Dayspring went on to say, "If apoB is elevated no one with apoE 4 alleles should avoid a statin. However, monitor desmosterol (a biomarker related to AD & MCI) to make sure brain cholesterol synthesis is not over-suppressed. If so, can always add other apoB-lowering meds."
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Re: Statins and Dementia studies

Post by shenmen100 »

I have tested my sterols twice and avoided statin use until this year. I decided after listening to Peter Attia and seeing a preventative cardiologist during which a Carotid artery scan showed plaque so we went from prevention to treatment. I started ezetimibe after my first sterol test which showed I was a hyper absorber and hypermaker of cholesterol in 2019. This had minimal impact on my total cholesterols which usual ran around LDL-C 150-60's, HDL-C 90-100's, triglycerides 40-60, CAC zero
I started 5 mg rosuvastatin in 2023, which profoundly changed my LDL-C levels to 100 everything else stayed the same, then my doc wanted me get my LDL's below 70 to try to reverse the plaque. I upped the statin to 10 which did not budge my LDL-C so just moved to 15 mg and will retest soon. I did a second Sterol test ( different lab)with the 10 mg rosuvastatin increase and my sterols definitely changed with the Campersterol falling to normal and my Desmosterol and Sitosterol staying elevated so I feel ok about staying on the statin regarding brain health. I will keep checking the sterols and if I cannot get the LDL's below 70 with the statins it will be on to the PSK9 inhibitors. I am a 3/4 66YO
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Maria4/4
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Re: Statins and Dementia studies

Post by Maria4/4 »

For those who don't tolerate statins, in this interview Peter Attia recommends alternatives to statins (no side effects):

Pcsk9 inhibitors - very safe but expensive
Ezetimibe - cheaper but less potent
Bempedoic acid - very safe and expensive

https://www.youtube.com/watch?v=Dyid7vWO0zI

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Re: Statins and Dementia studies

Post by floramaria »

Maria4/4 wrote: Mon Jan 29, 2024 4:08 am For those who don't tolerate statins, in this interview Peter Attia recommends alternatives to statins (no side effects):

Pcsk9 inhibitors - very safe but expensive
Ezetimibe - cheaper but less potent
Bempedoic acid - very safe and expensive

https://www.youtube.com/watch?v=Dyid7vWO0zI

Maria 4/4
Hi Maria4/4, Thanks for adding this information to the discussion and for providing the link. Have you tried any of these alternatives yourself?
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Maria4/4
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Re: Statins and Dementia studies

Post by Maria4/4 »

floramaria wrote: Sat Feb 17, 2024 1:12 pm Hi Maria4/4, Thanks for adding this information to the discussion and for providing the link. Have you tried any of these alternatives yourself?
Hi Floramaria,

I didn’t try them because my cholesterol levels are low. Perhaps even too low 😒
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Re: Statins and Dementia studies

Post by Plumster »

Maria4/4 wrote: Sun Feb 18, 2024 9:42 am
floramaria wrote: Sat Feb 17, 2024 1:12 pm Hi Maria4/4, Thanks for adding this information to the discussion and for providing the link. Have you tried any of these alternatives yourself?
Hi Floramaria,

I didn’t try them because my cholesterol levels are low. Perhaps even too low 😒

Too low? Care to elaborate? I assume you are not saying that your LDL is 10. You must be referring to HDL or Total?
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Re: Statins and Dementia studies

Post by Maria4/4 »

My total cholesterol was always under 150:
trig under 50
HDL ~70
LDL ~70
HDL/trig between 0,5 and 0,7
A couple of monthes ago I tested it again and LDL was 100. I think it's because I started cooking with saturated fat (ghee). In the past I used olive oil, but I hear more and more doctors (like dr Paul Mason) saying we shouldn't use olive oil to cook because it oxidises easily. Even with this LDL level, my total cholesterol didn't reach 190.

I used to think that the lower the cholesterol the better, but I changed my mind because of the studies that state that people with higher cholesterol live longer. For example, this study shows that the best level for someone over 45 years old is around 220 mg/dL. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367420/

The question is: how to increase total cholesterol in a healthy way? I already do everything that is recomended to increase HDL, except consuming coconut oil, because I don't love the taste, but I am started using it now to see the results.

Sometimes I think I am a weird APOE4... my cholestrol is low and I am extremly sensitive to insulin. My HOMA-IR is always between 0,3 and 0,75. My fasting insulin droped below 2 one year after I implemented the keto diet. I started eating a little bit of rice and legumes pasta to increase my insulin. For us idealy it should be between 3 and 5.

This is a delicate balance and achieving ideal values is so difficult 🤔
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Re: Statins and Dementia studies

Post by Plumster »

An LDL of approximately 70 is great, but not particularly low -- except maybe for an e4.

LDL and apoB are the measurements to pay attention to. Optimal apoB is 40-80, ideally below 62.

I would like to discourage you from attempting to raise either LDL or apoB.
e3/4 MTHFR C677T/A1298C COMT V158M++ COMT H62H++ MTRR A66G ++ HLA DR
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