Seeking Guidance on Statins for APOE4 Carrier Mother

[Hazel]

Hello everyone,

I’m posting on behalf of my 69-year-old mother, an APOE4 carrier with a family history of Alzheimer’s but no significant heart issues. She’s been on HRT since her 50s and is generally in good health. Her recent bloodwork shows a serum cholesterol of 6.8, HDL of 2.0, a cholesterol/HDL ratio of 3.4, and her non HDL cholesterol is 4.8. Her doctor has recommended statins, and she has an appointment on September 5th.

I recognize that we’re all working with somewhat unclear information, and I’ve seen people here referencing studies and expert opinions. I’m hoping to gather any general wisdom, research insights, or experiences others might have regarding statins for APOE4 carriers, especially in relation to Alzheimer’s prevention.

• Should she consider statins given her APOE4 status?
• Is there a preferred statin for APOE4 carriers?
• What questions should she ask her doctor to ensure she’s making the best decision for her cognitive and overall health?

Any insights would be greatly appreciated! Being new to the topic of statins, I’ve learned that statins can raise blood sugar slightly, APOE4 carriers may respond differently to statins, and that some studies suggest statins may be protective for brain health in carriers, while others show the reverse.

Thank you!
Hazel

[NF52]

Hello everyone,

I’m posting on behalf of my 69-year-old mother, an APOE4 carrier with a family history of Alzheimer’s but no significant heart issues. She’s been on HRT since her 50s and is generally in good health. Her recent bloodwork shows a serum cholesterol of 6.8, HDL of 2.0, a cholesterol/HDL ratio of 3.4, and her non HDL cholesterol is 4.8. Her doctor has recommended statins, and she has an appointment on September 5th.

I recognize that we’re all working with somewhat unclear information, and I’ve seen people here referencing studies and expert opinions. I’m hoping to gather any general wisdom, research insights, or experiences others might have regarding statins for APOE4 carriers, especially in relation to Alzheimer’s prevention.

• Should she consider statins given her APOE4 status?
• Is there a preferred statin for APOE4 carriers?
• What questions should she ask her doctor to ensure she’s making the best decision for her cognitive and overall health?

Any insights would be greatly appreciated! Being new to the topic of statins, I’ve learned that statins can raise blood sugar slightly, APOE4 carriers may respond differently to statins, and that some studies suggest statins may be protective for brain health in carriers, while others show the reverse.

Thank you!
Hazel

Hi Hazel!

Your mom is lucky to have a daughter who's seeking to find good information for her to weigh her doctor's recommendation. I posted a general conversion chart from the UK/Canadian system of mmol/L to the US system of mg/dL below

UK-Canadian to US cholesterol levels.png

and here's a link that I used to convert your mother's levels: https://www.omnicalculator.com/health/cholesterol-units

In US terms, which is where I live, her results would be reported like this:
Serum cholesterol: 6.8 mmol/L = 263 mg/dL. HDL: 2.0 mmol/L= 77 mg/d:
Non-HDL: 4.6 mmol/L = 186 mg/dL. The cholesterol/HDL stays the same at 3.4.

The results include some good news, which is always worth celebrating! Her HDL would be considered very good by both cardiologists and Dr. Bredesen, I believe.

In both the US and Canada/UK, her total serum cholesterol level of 6.8 would be considered "high". Mayo Clinic: Cholesterol Tests

Non-HDL cholesterol includes LDL (low-density lipoproteins), VLDL (very low density lipoproteins) ILDL (intermediate LDL) and triglycerides. Verywell Health: Non-HDL cholesterol Her non-HDL of 4.6 is quite a bit above the recommended level of <3.4 mmol/L (130 mg/dL).

You mentioned that she has no "significant heart issues", which might mean that she has some heart-related issues? Some may indeed be insignificant, like a quirky heart murmur or a low resting heart rate, which can be a good thing!

If she's willing to let you go along on an appointment to her cardiologist, or her GP can provide her a referral to a cardiologist, it might help both of you to get a good "reading" on her heart health and add to your information about taking a statin. Non-invasive tests beyond an ECG include an NMR stress test on a treadmill, and a coronary artery scan. In the US, most insurance companies won't pay for that, but my doctor wrote a referral for it based on my dad's cardiac arrest and the quick, painless CT scan showed that I had not developed plaques in my arteries.

Statins are not without controversy, so there is no one answer for everyone. Here's two recent developments that I find compelling, since I have two copies of ApoE 4:

• The Lancet 2024 Commission, an international group of experts on Alzheimer's, just released the Lancet Commission 2024 Report. It added two new factors that could reduce the risk of dementia, one of which was high LDL cholesterol. Here's a picture representation of how each factor may add to risk, with high LDL adding 7% risk. 14 risk factors diagram

• In late 2022, researchers at MIT found that ApoE 4 doesn't just lead to increases in LDL cholesterol, it can affect the myelin that acts as a sheath or cover for our nerve fibers, which are essential for our neurons to communicate with each others.

This is an excerpt from a summary of that research by the U.S. National Institutes of Health (NIH) in December 2022:

The researchers found that APOE4 affected gene expression across all measured cell types. The team then took a closer look at genes related to cholesterol and other lipids. Cholesterol-manufacturing genes were overly expressed, and cholesterol-transporting genes dysregulated, in brain cells called oligodendrocytes with the APOE4 gene. Oligodendrocytes are found in the brain and spinal cord. They make and maintain a fatty substance called myelin that surrounds and insulates long nerve fibers. The abnormalities were more extreme in oligodendrocytes with two copies of APOE4 rather than one.
...Oligodendrocytes with APOE4 tended to accumulate abnormal amounts of cholesterol within their cells, rather than using it to make healthy myelin sheaths around nerve fibers.

NIH: Alzheimer’s tied to cholesterol, abnormal nerve insulation

As someone three years older than your mom, with two copies of Apoe 4 and a strong family history of coronary artery disease (my dad died less than a year after a quadruple bypass of cardiac arrest at age 67), I started on 10mg of atorvastatin at 67, and then increased it to 20 mg to get my LDL down to about 70. I have not had any side effects. Combining one statin pill a day with increased exercise and a heart-healthy diet works for me.

Your mom, of course, is the one who gets to make this decision, knowing that you are in her corner always!

Nancy

[Hazel]

Hi Nancy,

Thank you so much for your detailed and heartfelt response! It's reassured us about statins, and your info about the connection between cholesterol and Alzheimer’s was helpful—it's a topic that has always puzzled me, and I’m eager to understand more. Being in Canada while my mom is in the UK means I can't be as hands-on as we'd like, but I try to find her information so she can make well-informed decisions. As an APOE4 carrier myself with many family members with the gene, reading your thoughtful personal experience resonates deeply with me. Thank you for taking the time to share it.

So, our main goal is to keep my mother as mentally sharp as she is now for as long as possible. She eats a healthy diet, rich in vegetables and free from processed foods, though she doesn’t specifically avoid cholesterol-rich foods. Her volunteer work keeps her more sedentary than ideal, but she stays somewhat active with daily walks and the occasional hike.

I'd be curious to hear about your exercise routine and your approach to a heart-healthy diet. You seem motivated and well informed, and so I wonder what you've chosen to do in these areas.

Also, just to clarify a point from my initial message—when I mentioned "no significant heart issues," I meant that there aren’t any known heart problems in our family history, though my understanding here is quite limited. My maternal grandmother and her siblings all lived to old ages, but nearly all faced Alzheimer’s in their later years. I know even less about my grandfather’s side.

My mom had her doctor's appointment yesterday, and she texted that she was referred to Recognition Health Memory Clinichttps://recognitionhealth.com/private-s ... SkQAvD_BwE, which seems promising.

Thanks again for your guidance—it is very much appreciated.

Hazel

[JD2020]

Her doctor has recommended statins, and she has an appointment on September 5th.

Hi Hazel,

My LDLs increased 50 points over the last 15 years (???), which motivated me to do some research. Among other things, I read "The Great Cholesterol Myth", which lead me to a research paper, Houston, et.al, Nonpharmacologic Treatment of Dyslipidemia, Progress in Cardiovascular Diseases 52 (2009) 61-94. It discusses many other options. I am trying Pantethine. I've only been on it for 1 month, so it is too short of a time for me to evaluate effectiveness.

I would link it for you, if I could. I found it and printed it to my hard drive, and now I cannot find it except for what looks to be behind a paywall.

So...perhaps there are other options to try, if you are so inclined. Perhaps a starting point is acquiring the research paper or reading the book. The editing in the book is pretty bad (duplicate paragraphs, etc) but I found the information and the references very helpful.