Statin Use

[staillie]

I have started doing some research on the effects of statin use with ApoE4 and am finding some conflicting and older studies anyone have some things within the forum they can point to on is it recommended to continue use or not.

thanks

[TheresaB]

We have discussed statin use before. If you go to our Wiki to the subect 9.1 "How-To" Get the most out of the ApoE4.info website and then to the subheading "searching the site for information" https://wiki.apoe4.info/wiki/%22How-To% ... nformation it will walk you through what you need to do to research what we've discussed on statins.

[dcox]

Welcome staillie!
Great to have you join us here at APoE4.info! Thank you for your interest in the effects of statins on those who carry the E4 gene. Unfortunately most of the research lumps everyone together regardless of E4 status. I hope you will find some answers here as there has been a lot of talk from both sides of this issue giving a broad perspective on statin use.
Here are a couple of links I thought may be of interest to you, I found them using the search method described by TheresaB above. This one is from the Wiki page where you can find more in depth information on many of the topics discussed on the site: Statins .
Here is a forum thread that might give you some insight too: Statin use

As you can see as you begin to search the site the amount of information here can be overwhelming, I encourage you to use the "How-To" get the most out of the APoE4.info website page, it is very easy to use and will allow you to spend your time on the site more efficiently. I also highly recommend the Primer it's a great place to get started and was written by Stavia, one of our most active members who is also a doctor, and is E4/E4 herself.

We would love to hear your story, feel free to post it on the Our Stories forum when you are ready to share. We are a great community full of energetic, encouraging, and extremely hopeful people who help each other navigate their paths through Alzheimer's, dementia and cognitive decline in general. You will find people from all walks of life here sharing their stories, what works for them and what dosen't. It's a great place to find new perspectives and reinforce the ones you may already have.

Enjoy your journey, stay positive and find hope,
Deb

[Fiver]

I've had to study this and come to a decision for my own health. I found these 3 recent articles helpful. Here are the summaries of each. I don't think there is a clear answer, or one that fits everyone.

Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
Nophar Geifman1,2* , Roberta Diaz Brinton3, Richard E. Kennedy4, Lon S. Schneider5,6 and Atul J. Butte7

Background: Despite substantial research and development investment in Alzheimer’s disease (AD), effective
therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy.
Methods: Here we investigate the possible protective and therapeutic effect of statins in AD through the analysis of datasets of integrated clinical trials, and prospective observational studies.
Results: Re-analysis of AD patient-level data from failed clinical trials suggested by trend that use of simvastatin may slow the progression of cognitive decline, and to a greater extent in ApoE4 homozygotes. Evaluation of continual long-term use of various statins, in participants from multiple studies at baseline, revealed better cognitive performance in statin users. These findings were supported in an additional, observational cohort where the incidence of AD was significantly lower in statin users, and ApoE4/ApoE4-genotyped AD patients treated with statins showed better cognitive function over the course of 10-year follow-up.
Conclusions: These results indicate that the use of statins may benefit all AD patients with potentially greater
therapeutic efficacy in those homozygous for ApoE4.


The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms
Bob G. Schultz, Denise K. Patten and Daniel J. Berlau*

Nearly 30% of adults 40 years and older in the United States are on a statin. Their widespread use heightens the importance of careful consideration of their varied effects on the body. Although randomized controlled trials have not confirmed cognitive impairing effects with statins, continuing evidence suggests statins have the ability to cause reversible cognitive impairment in some patients. Paradoxically, statins have also been shown to decrease the risk of dementia, Alzheimer’s disease, and improve cognitive impairment in some cases. However, randomized controlled trials have similarly failed to find the beneficial effect. Supporting evidence for both claims is compelling whereas known limitations of the clinical trials may explain the lack of findings. This narrative review aims to explain why there is still controversy and how both effects can, and may, be possible. The mechanisms that have been hypothesized for each effect are seemingly independent from one another and may explain the contradicting results. Being mindful of the complex effects of statins, health care providers need to be able to identify patients who are at risk for or already experiencing cognitive impairment from statin use while also identifying those who could potentially decrease their risk of dementia with statins.

Cholesterol, Statins, and Dementia: What the Cardiologist Should Know
Brett L. Wanamaker, MD; Kristopher J. Swiger, MD; Roger S. Blumenthal, MD; Seth S.
Martin, MD

Alzheimer dementia (AD) is an important clinical problem that appears to be closely tied to comorbid
cardiovascular disease, making it a relevant topic for the clinical cardiologist. Determinants of cardiovascular
health, especially midlife dyslipidemia, are associated with an increased risk of dementia based on molecular
and epidemiologic data. Given the potential role of dyslipidemia in the development of dementia, statins have
been investigated as potential therapeutic options to slow or prevent disease. This review discusses the role
of dyslipidemia and other cardiovascular risk factors in the pathogenesis of AD, with a focus on the existing
evidence for the use of statin medications in the treatment and prevention of AD from observational studies
and randomized clinical trials. Clinical questions for the practicing cardiologist are addressed.

[hairyfairy]

I was prescribed statins for high cholesterol 5 years ago, but I developed drowsiness and severe muscle pain & stopped taking them even though they brought my cholesterol down. I just couldn`t handle the side effects.

[Hector888]

Hi all
Anyone understand this
See link
https://www.nature.com/articles/s41586-022-05439-w
Article
Published: 16 November 2022
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

Joel W. Blanchard, Leyla Anne Akay, …Li-Huei Tsai Show authors
Nature volume 611, pages 769–779 (2022)Cite this article

48k Accesses
52 Citations
649 Altmetric
Metrics details
Abstract
APOE4 is the strongest genetic risk factor for Alzheimer’s disease1,2,3. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to develop targeted therapeutics for individuals carrying APOE4 and other risk factors for Alzheimer’s disease4,5,6,7,8. Here, to gain more comprehensive insights into the impact of APOE4 on the human brain, we performed single-cell transcriptomics profiling of post-mortem human brains from APOE4 carriers compared with non-carriers. This revealed that APOE4 is associated with widespread gene expression changes across all cell types of the human brain. Consistent with the biological function of APOE2,3,4,5,6, APOE4 significantly altered signalling pathways associated with cholesterol homeostasis and transport. Confirming these findings with histological and lipidomic analysis of the post-mortem human brain, induced pluripotent stem-cell-derived cells and targeted-replacement mice, we show that cholesterol is aberrantly deposited in oligodendrocytes—myelinating cells that are responsible for insulating and promoting the electrical activity of neurons. We show that altered cholesterol localization in the APOE4 brain coincides with reduced myelination. Pharmacologically facilitating cholesterol transport increases axonal myelination and improves learning and memory in APOE4 mice. We provide a single-cell atlas describing the transcriptional effects of APOE4 on the aging human brain and establish a functional link between APOE4, cholesterol, myelination and memory, offering therapeutic opportunities for Alzheimer’s disease.

This is a preview of subscription content, access via your institution

[Jane S]

Hi all
Anyone understand this
See link
https://www.nature.com/articles/s41586-022-05439-w
Article
Published: 16 November 2022
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

Joel W. Blanchard, Leyla Anne Akay, …Li-Huei Tsai Show authors
Nature volume 611, pages 769–779 (2022)Cite this article

48k Accesses
52 Citations
649 Altmetric
Metrics details
Abstract
APOE4 is the strongest genetic risk factor for Alzheimer’s disease1,2,3. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to develop targeted therapeutics for individuals carrying APOE4 and other risk factors for Alzheimer’s disease4,5,6,7,8. Here, to gain more comprehensive insights into the impact of APOE4 on the human brain, we performed single-cell transcriptomics profiling of post-mortem human brains from APOE4 carriers compared with non-carriers. This revealed that APOE4 is associated with widespread gene expression changes across all cell types of the human brain. Consistent with the biological function of APOE2,3,4,5,6, APOE4 significantly altered signalling pathways associated with cholesterol homeostasis and transport. Confirming these findings with histological and lipidomic analysis of the post-mortem human brain, induced pluripotent stem-cell-derived cells and targeted-replacement mice, we show that cholesterol is aberrantly deposited in oligodendrocytes—myelinating cells that are responsible for insulating and promoting the electrical activity of neurons. We show that altered cholesterol localization in the APOE4 brain coincides with reduced myelination. Pharmacologically facilitating cholesterol transport increases axonal myelination and improves learning and memory in APOE4 mice. We provide a single-cell atlas describing the transcriptional effects of APOE4 on the aging human brain and establish a functional link between APOE4, cholesterol, myelination and memory, offering therapeutic opportunities for Alzheimer’s disease.

This is a preview of subscription content, access via your institution

Hello Hector888,

As a Support Team Intern, I'd like to welcome you to the forum! Thank you for joining our site and for posting. I'm sure other members will provide you with some feedback. Hopefully you'll get an engaging and productive conversation going.

I'll share some tools/resources that you can use to explore the site, helping you get the most out of your experience.

The Primer is a detailed and informative resource written by a practicing M.D. with ApoE4/4. It includes information about the biochemistry of the ApoE4 gene and offers a variety of research-based prevention strategies.

Explore our WIKI for various topics that may be on interest to you WIKI Main Page.

Some helpful tips to navigate the site are included in the How-To Guide. It includes topics such as navigating the forum, private messaging, and searching. One great tip is using the quote (") button when replying to a post. Using the button will automatically alert the member of your response.

If you are interested in learning more about other members, you can check out Our Stories. Maybe you'll share a bit about what brings you here, too.

I hope you get a lot out of participating in the forum. Feel free to reach out anytime.

All the best,

Jane

[NF52]

Hi all
Anyone understand this:

APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes Published: 16 November 2022
Joel W. Blanchard, Leyla Anne Akay, …Li-Huei Tsai
Nature volume 611, pages 769–779 (2022)Cite this article

Abstract
APOE4 is the strongest genetic risk factor for Alzheimer’s disease1,2,3. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to develop targeted therapeutics for individuals carrying APOE4 and other risk factors for Alzheimer’s disease. Here, to gain more comprehensive insights into the impact of APOE4 on the human brain, we performed single-cell transcriptomics profiling of post-mortem human brains from APOE4 carriers compared with non-carriers. This revealed that APOE4 is associated with widespread gene expression changes across all cell types of the human brain. Consistent with the biological function of APOE, APOE4 significantly altered signalling pathways associated with cholesterol homeostasis and transport. We confirmed these findings with:

• histological and lipidomic analysis of the post-mortem human brain

• induced pluripotent stem-cell-derived cells

• targeted-replacement mice

. We found that cholesterol is aberrantly deposited in oligodendrocytes—myelinating cells that are responsible for insulating and promoting the electrical activity of neurons. We show that altered cholesterol localization in the APOE4 brain coincides with reduced myelination. Pharmacologically facilitating cholesterol transport increases axonal myelination and improves learning and memory in APOE4 mice. We provide a single-cell atlas describing the transcriptional effects of APOE4 on the aging human brain and establish a functional link between APOE4, cholesterol, myelination and memory, offering therapeutic opportunities for Alzheimer’s disease.

Hi Hector888,

Welcome to the world of dense science articles written for other PhDs! Especially in Nature, which is a respected journal. As a non-scientist who still likes to try to decipher these sometimes, and who always take progress or findings in mice with a recognition that this is usually early-stage research, or in-depth research on a thorny question we can't answer by opening up people's brains. I think this abstract is the second version: trying to figure out how exactly how ApoE 4 causes harmful changes in the brain, and why it seems to be associated with high LDL cholesterol in some people. I bolded the sections I think were key.

First some background that I often forget when we use shorthand like "ApoE"

The APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke.

https://medlineplus.gov/genetics/gene/apoe/

So if ApoE4 doesn't do its job well in moving and removing cholesterol, that might be a problem. I think the article is saying:
We looked as single cells in donated brains of ApoE 4 carriers and non--carriers (ex. ApoE 3/3). We found that ApoE4 changes lots of different types of brain cells in the brain (ex. neurons, astrocytes, oligodendrocytes , macroglia micgroglia), especially those that keep the myelin (insulation around neurons) healthy. We confirmed this using lab-generated stem cells, and mice who have been genetically "targeted" to express ApoE4. We found that giving these mice a drug (pharmacological approach) to improve cholesterol transport also improved the axons between neurons and their "insulation" and that improved the mice's ability to learn and remember (often in a maze or water task). We think that improving myelination (the insulation) in neurons and improving cholesterol transfer could be a promising new therapy in Alzheimer's research.

I'd love to keep my neurons happy and well-insulated! (And FWIW, since I have a strong family history of coronary artery disease, vascular disease and high LDL-C and LDL-P, I take a statin until they share what this new idea is. )