Do statin drugs cause dementia or prevent it?
Including what ApoE4 carriers need to know about statins
Hello, everyone. I am writing to you from Rancho la Puerta in Tecate, Mexico where I am wrapping up cooking classes for the week. My students cooked their hearts out. It’s always a revelation when one starts to look at food through the lens of brain health, and there were many aha moments this week.
Last month on the newsletter we have been diving into the topic of heart health: how preventing cardiovascular disease can also fend off Alzheimer’s and vascular dementia. After covering how hot flashes and night sweats are not just bothersome menopausal symptoms—they could be the first indication of blood vessel disease in the brain—we looked at the new thinking about managing cholesterol—how the ecosystem works in the body, how it impacts the heart and the brain, and why the standard lipid profile is long overdue for an update. Next, I covered the dietary strategy for lowering cholesterol and my list of 10 foods that make doing so delicious.
A major takeaway from this series is:
When low-density lipoprotein cholesterol (LDL-C) goes down, so does the risk of Alzheimer’s and vascular dementia. In other words, cholesterol is a modifiable risk factor—something we have the power to change.
Today’s topic is the last in our heart-and-brain mini-series: the impact of cholesterol-lowering drugs on the brain. Statins (like Crestor, Lipitor, and Zocor) are the most commonly prescribed drugs for lowering cholesterol for good reason: they are safe and highly effective. Statins block cholesterol synthesis in the liver and increase the receptors that bind it up in circulation. Depending on the type of statin and dose used, these drugs lower LDL-C by 20 to 50%—well enough to get it out of the danger zone.
Statins are powerful Alzheimer’s risk-reducing drugs, but at what cost? They have a reputation for causing debilitating muscle pain. In reality, this occurs in less than 5% of users and completely resolves once the drug is discontinued. Even more worrisome is the possibility that statins may cause brain fog and memory problems. Spurred by a handful of anecdotal cases, the Food and Drug Administration put a black box warning on statins in 2012 to say the drug’s impact on cognitive function was under investigation. Since then, it is not uncommon to read in the press that “statins cause Alzheimer’s.” Could it be true that a drug could both increase and decrease dementia risk?
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The short answer is no. Statins do not increase the risk of cognitive impairment. In fact, the FDA’s warning has since been fully investigated with this randomized controlled trial of over 2000 participants and this 2022 meta-analysis of 46 studies. It turns out that taking a statin will not only lower your cholesterol, it will reduce your risk for Alzheimer’s, too.
Here’s what we’ve learned about statins and dementia risk:
Taking statins reduces Alzheimer’s risk by 20% in those over age 60
Taking statins reduces Alzheimer’s risk in persons living with diabetes by 13%
Taking statins slows the progression of mild cognitive impairment to Alzheimer’s
In persons living with Down’s syndrome, taking statins slows the progression to Alzheimer’s
This is fantastic news for anyone who needs to get their cholesterol numbers down to target levels. More good news: statins are just one class of drug to tackle this problem. Those pesky muscle pain issues are real for the 5% who experience them, and switching to a different class of drug (like a PCSK9 inhibitor) effectively lowers cholesterol without this side effect.
Takeaways for Lowering Your Cholesterol with Drugs
Getting blood cholesterol below target levels is a proven way to reduce the risks of ASCVD, Alzheimer’s, and vascular dementia.
The dietary strategy is highly effective for lowering LDL-C. But sometimes it’s not enough to achieve target levels.
Statin drugs do not increase the risk of Alzheimer’s and have proven to reduce risk by as much as 20%.
People who carry one or two copies of ApoE4, an Alzheimer’s risk gene, are doubly at risk for ASCVD. Aggressive treatment of cholesterol problems is recommended.
Certain drugs for lowering cholesterol cross the blood-brain barrier and may impact brain cholesterol levels. ApoE4 carriers on statin drugs should monitor desmosterol, a biomarker for declining cognitive function.
Beyond statins, there are several other classes of drugs that will get the job done. Each class has its own set of pros and cons.
If your cholesterol numbers are less than perfect, it is optimal to work with a preventive cardiologist or another experienced health care provider to create a multi-pronged plan—diet, exercise, smoking cessation, good-quality sleep, and possibly medication.
4 smart reasons to consider a cholesterol-lowering drug
If you’ve read my book or been following me here, you know that I am all about maximizing food as medicine. And that’s exactly what the dietary approach to lowering cholesterol is: a nutritional intervention that can lower harmful LDL-C levels by as much as 30%. This newsletter describes how to do this in detail.
If it’s possible to lower cholesterol through diet, why would anyone need to take a drug? Here are 4 good reasons:
Partial treatment. The dietary strategy may only partially reduce LDL-C and lipoproteins. In order to get them under target levels, more intervention could be needed.
The dietary strategy is a far cry from the Standard American Diet (SAD). It is not easy for many to shift gears from the SAD to a diet that is low in saturated fat, added sugars, and plentiful in plant proteins and whole soy foods.
Risk factors for atherosclerotic cardiovascular disease (ASCVD). Having one or more risk factors (tobacco use or secondhand smoke exposure, diabetes, family history of cardiac events, unhealthy weight, sedentary lifestyle, and an unhealthy diet) is an indication for more aggressive lowering of LDL-C.
Having an ApoE4 risk gene for Alzheimer’s. ApoE4 is a very common gene variant that increases the risk for Alzheimer’s by 3- to 15-fold. Many people know that ApoE4 increases Alzheimer’s risk, but it’s not generally known that it also doubles the risk for ASCVD. The current recommendation is that carriers be especially aggressive about getting LDL-C and its troublesome carrier proteins below (or way below) target levels.
Three months is long enough
If you have high cholesterol, I highly recommend taking the dietary guidelines to heart and giving it your best try. But if three months have gone by and your numbers are not on target, it’s time to layer on other interventions: reevaluate your exercise program, improve sleep, manage stress, and consider a cholesterol-lowering drug.
ApoE4 carriers should know about desmosterol, too
While the data solidly says statins do not cause Alzheimer’s but instead are preventive, there is some nuance here with regard to carriers of the ApoE4 risk gene. When statin drugs are used aggressively to get an Apoe4 carrier’s LDL down, they may also suppress the brain’s synthesis of cholesterol. This is where the story of desmosterol comes in—it’s the penultimate cholesterol made in a long pathway that synthesizes cholesterol in the brain. Low levels of desmosterol are a red flag for cognitive decline.
Cholesterol that circulates in the bloodstream cannot cross the blood brain barrier, but some of the statin drugs can and do cross, including simvastatin (Zocor) and atorvastatin (Lipitor). This poses a potential problem because they can suppress cholesterol synthesis where it is crucially needed for brain function.
In a nutshell, here’s what we know about desmosterol:
Measuring desmosterol in the blood is an accurate predictor of desmosterol in the brain.
Desmosterol is decreased in people with Alzheimer’s.
Desmosterol starts to go down before clinical symptoms are apparent; it is a biomarker that alerts of coming decline.
A low desmosterol level in a person taking statins may indicate that brain cholesterol synthesis is over-suppressed.
What we don’t know yet: Do desmosterol levels in the brain from statin use increase the risk of dementia? Until the research becomes clear, it makes sense to take desmosterol into consideration when prescribing cholesterol lowering drugs in ApoE4 carriers. One approach physicians take is to lower the dose of the statin and add another cholesterol-reducing drug (like Ezetimib) to achieve target levels.
Beyond statin drugs
Statin drugs may be the oldest and most affordable options for lowering cholesterol with medication, but there are others. If you have an ApoB problem (too much of one of the cholesterol carrier problems), it can be tough to get it under control with dietary interventions and statins alone. Adding a second drug is a common strategy. All of these drugs may be useful for those with a strong genetic predisposition to high cholesterol, such as familial hypercholesterolemia.
PCSK9 Inhibitors. Acts to increase LDL-C receptors which helps take it out of circulation and back to the safety of the liver to be excreted. These drugs are highly effective; they lower LDL-C by as much as 59%. They are also expensive, which may limit their use.
Bembepedoic Acid. Blocks cholesterol synthesis in the liver.
Ezetimibe (Zetia). Reduces the absorption of cholesterol from the intestines. Useful for those with a strong genetic predisposition to high cholesterol, such as familial hypercholesterolemia.
EPA. Eicosapentaenoic acid (an omega-3 fatty acid) prescribed in high doses (4 grams, or about quadruple the over the counter dose) is FDA-approved to treat cholesterol.
Cholesterol Questions?
I hope our deep dive into the world of lipids and their impact on the brain has been helpful. I am constantly impressed by how you soak up the science I share here and apply it to your own health. Many of you have told me you are acting on this information by asking your health care providers for detailed tests, and voicing your wish to get numbers down. I am proud!
Keep advocating for your brain with your health care team! Paying subscribers: I invite you to leave any questions you may have.
Before I go, I’ll leave you with this article in Nice News about Brain Health Kitchen and HFC, the Alzheimer’s non-profit founded by actors Lauren and Seth Rogen. If you have noticed how healthy and fit Seth is looking in his recent movies, it may be because he has taken brain-healthy living to heart.
That’s all for today. I am off to La Cocina Que Canta (the kitchen that sings) to prep my dish for tonight’s event. I’m collaborating with local chefs on a special Dia de los Muetros dinner and I can’t wait to share what I’m making. I’ll be back this weekend with that recipe—an easy appetizer you can make throughout the holidays.
Love,
Annie
PS: Founding Members—our next live Kitchen Chat and Cooking Class will be December 11, 2023. I look forward to having you over to my kitchen and will be contacting you to see what you want to cook! The Founding Member subscription tier includes 4 live Chats a year + bonus recipes. We discuss a brain health topic, cook a few dishes, and have the best time hanging out together. Join us!
Thank you, thank you, thank you for this incredibly helpful content. I am finding your writings to be invaluable as I work with my current team of doctors, who despite being very lovely have no insight into or training on APOE4. I actually just managed to get my desmosterol levels tested independently, wanted to share with your APOE4 readers that after considerable research the only options I found for testing are the Boston Heart cholesterol balance test or the EmpowerDX at-home testing. I am just an individual patient and have no affiliations with either of these companies! I've been unable to find a practitioner familiar with desmosterol testing or able to order any kind of test for me, so I had to figure this out on my own. If other readers have identified other ways to monitor desmosterol (or any practitioners to guide them) I'd love to hear it! Thanks again Dr. Fenn.
Fabulous article! Thanks so much! The info in your substack is always so accessible, well-organized, & evidence-based. Here's my question: You mention that Zocor & Lipitor may cross the blood-brain barrier & suppress crucial cholesterol synthesis in the brain. Any "intel" on CRESTOR (Rosuvastatin), especially at it's lowest dose of 5 mg. I'm one of those people that did not see a substantial drop in LDL levels following even a strict whole-foods-plant-based diet---with primarily only seeing a drop in my HDL. I don't have familial hypercholesterolemia, & eating a mostly plant-based diet definitely lowers my LDL, but, not to the 73-78 level that Crestor has accomplished. I only started a statin at age 71, & my only regret is that my physician did not suggest it years ago! I'm now a believer! And very low triglycerides also came along with it!