Your Brain on Cholesterol

New thinking about lipids and dementia

Hello, everyone. I am writing from my home in Jackson, Wyoming with both dogs draped across my feet. Is there any better foot warmer than that? The mornings lately are frosty and chilly and the afternoons are warm enough to ride bikes. There’s a collective sense of urgency this time of year here to get outdoors every day. It’s as if everyone senses that soon it will start snowing and basically never stop.

Last week we kicked off a mini-series about how heart health impacts brain health, diving into the connection between hot flashes and dementia. If you missed it, find the article here (scroll to the bottom if you just want the takeaways). 

Today’s topic is one that everyone should be keenly interested in: your cholesterol and what to do about it. The more we learn about Alzheimer’s and vascular dementia, the more we know that cholesterol is a key player. Over decades, too much cholesterol in circulation leads to narrowed arteries, a situation that incites inflammation and reduces blood flow to the brain.

There’s good news here: The field of lipidology is advancing by leaps and bounds. But, there’s some distressing information, too: High blood lipid levels often go untreated, posing a significant risk factor for not just heart disease but for dementia, too. 

In this and the next few posts, I hope to clear up some of the confusion out there about cholesterol. To get a handle on what cholesterol numbers mean for brain health, and what to do about them, read on. Before we get started, consult my guide to lipid terminology (at the end of this post).

Cholesterol: Good, Bad, or Not An Issue?

Almost every day, I read something that says that cholesterol is no longer a substance of concern. Okay, okay, this is mostly on social media, and always from proponents of diets high in saturated fat (keto, carnivore, and the like), but still. The popularity of this sentiment is impressive. 

Then I head over to PubMed, where I read peer-reviewed scientific papers and am constantly blown away by the width and depth of studies that show the opposite. Studies like this one show the impact of having a high LDL-C over time, even if low risk: a 50 to 70% increase in the risk of dying of a cardiovascular event. Or this 2022 study of more than 1.8 million people over 20 years showing that elevated LDL-C is an independent risk factor for the presence of Alzheimer's pathology (like amyloid and tau protein deposition) ten years later. 

The data now exists to reduce if not eliminate the most common type of heart disease that results from unhealthy cholesterol numbers: Atherosclerotic cardiovascular disease (ASCVD). And preventing ASCVD can help protect the brain from Alzheimer’s and vascular dementia. 

Cholesterol is an Ecosystem

Think of “cholesterol” as an ecosystem of different fats (called lipids) attached to proteins (lipoproteins) that circulate to and from the liver in a constant loop. The actual cholesterol particles get picked up and carried by the lipoproteins. Sometimes they get taken back to the liver (thanks to HDL), and get taken out of circulation. Other times they get dumped in the blood vessel wall, the beginning of a plaque. The cholesterol is neither “good” nor “bad” (but it can certainly be too plentiful). It’s actually the carrier proteins—the lipoproteins—that determine if they become problematic. 

In this ecosystem, I envision the lipoproteins as boats—specifically the white water rafts that float down the Snake River near my house. All summer, these boats are filled with visitors and locals, which I picture as cholesterol particles. There are big rafts that carry a lot of people and small ones that carry only a few. There are rafts that pull over to the riverbank for a long time as people get in and out. And there are rafts that hook up with other rafts and float down the river as one big party boat. 

In our river rafting analogy, the boats that keep pulling over to let people out are like the sticky lipoproteins (ApoB being the most common) that dump their cholesterol particles into the blood vessel wall. The longer they stay, the more damage they do. The party boats are highly dangerous, too. They are like the Lp(a)s—able to carry tons of cholesterol. When these complexes crash, they cause a lot of damage. HDL-C are lifeboats; they pick up the cholesterol that may have gotten dumped and take it back to safety, aka the liver.

Here’s what you want for a healthy cardiovascular system and brain: minimal excess cholesterol, very low levels of the dangerous carrier proteins, and squeaky clean and smooth arteries. If the lining of your arteries are damaged by tobacco use, diabetes, high blood pressure, and inflammatory particles (AGEs) from food, it is like an invitation to the lipoproteins to attach and dump cholesterol. 

The New Thinking About Cholesterol

Some of the information I am sharing here may be new-to-you or challenge current concepts about dealing with cholesterol. Like I said, the field of lipidology is growing by leaps and bounds! These concepts stand out as a starter pack to refresh current thinking. 

1. Cholesterol is essential, and your body makes the amount it needs. Cholesterol is an essential building block of hormones and vitamin D. It’s crucial for good brain health, too, providing structure to the cell membranes of brain cells. That being said, your body is well supplied with all the cholesterol it needs, thank you very much.

2. Excess cholesterol damages blood vessels that supply the brain. This is not new thinking, but perhaps the most important concept to know. Over time, a cholesterol system that is out of balance (too many dangerous lipoproteins + an excess of cholesterol) leads to blood vessel damage, spurring inflammation and reducing blood flow to the brain. The result: vascular dementia, Alzheimer’s, or a mixed dementia with features of both.

3. The brain is a cholesterol factory. You may read that it’s important to consume a lot of cholesterol-rich foods because the brain needs cholesterol for structure and function. Not true! The brain absolutely needs cholesterol to maintain its structure and function, but the brain is its very own cholesterol factory. It does not rely on dietary cholesterol from foods like shrimp, butter, and red meat—a good thing since that bulky fat molecule won’t cross the blood brain barrier. 

4. “Good” and “bad” cholesterol is an oversimplification. Physicians have been calling cholesterol “good” or “bad” since forever. In reality, it’s the concentration and types of lipoproteins that determine the fate of cholesterol particles. 

5. HDL-C (the “good” cholesterol) is no longer thought to be protective of heart disease. The common conception used to be “The higher your HDL-C, the better.” Now, new data shows that when HDL-C is very high, it no longer functions as the bloodstream’s lifeboat and clean-up crew. Conversely, it was long thought that a low HDL-C puts a person at increased risk for ASCVD. This may be true, but it’s not a direct effect of the HDL-C. Five clinical trials all showed the same result: using drug therapy to bump up HDL-C does not translate to a reduced risk of heart disease. 

   Interestingly, a recent study found that the combination of high blood pressure and high levels of HDL-C increases the risk of developing Alzheimer’s disease in some people. Just having high HDL-C was a risk factor for Alzheimer’s in this study, increasing the risk by 15%. 

6. Lipids that go up and down may be especially dangerous. In this 2023 study, participants with the greatest variability in total cholesterol levels had a 19% increased risk for Alzheimer’s within 12 years compared to those with stable levels. In addition, those with the highest variability in triglycerides had a 23% increased risk. This builds a case for getting cholesterol numbers down and keeping them down over time.

7. LDL-C (the “bad” cholesterol) is still considered harmful, but it’s been eclipsed by a worse “bad” lipoprotein: ApoB. Measuring ApoB levels in the blood is a more accurate marker for cardiovascular risk than just looking at LDL-C. It’s still important to get LDL-C below target levels. New thinking: The lower LDL, the better, irregardless of risk factors. (More on this below.) 

8. It’s actually saturated fat from food that creates harmful levels of cholesterol in the body. We’ve known for a long time eating cholesterol-rich foods doesn’t impact blood lipid levels for most people. (Caveat:15% of the population, dubbed “hyper responders”, do need to limit cholesterol from foods like eggs and shrimp.) 

   Saturated fat in the diet is what drives harmful levels of LDL-C and ApoB by stimulating the body to: a) make more cholesterol particles, and b) make less cholesterol receptors which keeps more of LDL-C and ApoB in circulation. 

9. The best dietary strategy for a healthy cholesterol ecosystem is to limit saturated fats.  Foods high in saturated fat include coconut oil, butter, cheese, bacon, lard, ghee, fatty chicken and red meat. If you’ve been following a brain-healthy dietary pattern, it has you covered to prevent ASCVD, too, by emphasizing unsaturated fats over saturated ones. Many people, it’s important to note, still have problematic cholesterol levels despite good dietary habits. Either they are hyperresponders to dietary cholesterol, or are genetically predisposed to having a lot of ApoBs or Lp(a)s. 

The Standard Lipid Panel Is Outdated

For years, perhaps decades, you’ve been getting your cholesterol checked via a standard lipid panel. This tells you the levels of total cholesterol, LDL-C, HDL-C, VLDL-C, and triglycerides. These biomarkers are still important, but should be looked upon in a new light. The standard lipid panel misses 1 in 4 people who need aggressive treatment to lower lipids. 

• It fails to emphasize that LDL-C should be as low as possible. Target levels for LDL-C are lower than previously recommended. And, in 2023, it’s no longer ok to just watch this lipid drift up with age. Action is required to get it as low as possible. 

• It doesn’t include ApoB, a more accurate predictor of atherosclerotic cardiovascular disease (ASCVD) than LDL-C.

• It doesn’t include Lp(a), a red flag for having an early heart attack or stroke. Everyone should have this checked once early in life.

• A high HDL-C gives a false sense of security. The ratio of total cholesterol to HDL has long been used as a cardiac risk index. “Your LDL is high, but your ratio is good,” was a common explainer of lipid panels. But now we know that high HDL-C doesn’t cancel out or protect from a too high LDL-C.

I introduced these tests in this post about talking to your doctor about brain health along with the rationale of adding ApoB and Lp(a) blood tests to the standard lipid profile. 

Getting To Target Levels

Despite the confusing nuances of blood lipids, there are clear guidelines for target levels for each lipoprotein. Recently revised, these guidelines are more strict than in previous years, meaning there is a lower threshold for starting drug therapy if nutrition and exercise can’t get the numbers down. 

1. Apo-B or Apolipoprotein B-100. Target <80 mg/dL.

2. Lp(a) or “LP little A.” Checked just once in your life, this helps determine if you have a genetic red flag for getting ASCVD, also a risk factor for Alzheimer’s and vascular dementia. Low risk lp(a): 0 to 30 mg/dL; very high risk >50 mg/dL.

3. LDL-C. Target <100 mg/dL. If risk factors for heart disease, target <70 mg/dL. As I mentioned above, some lipid experts recommend everyone get well under 70 irregardless of risk factors.

4. HDL-C. Target > 40 mg/dL, but levels >120 mg/dL may not be beneficial. New thinking: Don’t waste time trying to raise HDL with drugs.

5. Triglycerides. Target <140 mg/dL. Especially important to get this down if ApoB is also elevated.

Next time, we’ll be digging into how to deal with lipid levels through diet. As I mentioned above, if you are already following a brain-healthy way of eating, you are probably eating for optimal lipids, too. But still, those with persistent cholesterol problems should know to pay special attention to some food groups.

Founding Members, be sure to check your email. I just sent out the soup recipes from our Kitchen Chat and Cooking Class on Sunday, along with a link to watch the replay and 2 BONUS RECIPES!

As always, thank you for reading, sharing, and taking the best care of your brains (and your hearts!).

Love,

Annie

Guide to Lipid Terminology

• Lipids: fats, also called fatty acids, of which there are 3 types—sterols, phospholipids, and triglycerides

• Cholesterol: a type of fat (a sterol) essential for structure and function in all cells in the body

• Dietary cholesterol: the type of cholesterol present in foods like eggs, shrimp, and red meat

• Blood cholesterol: the cholesterol that circulates in the bloodstream coming from what we eat or what the liver synthesizes

• Lipoprotein: a protein that binds to cholesterol and transports it throughout the body

• Low density lipoprotein cholesterol (LDL-C): a lipoprotein that carries most of the cholesterol in circulation

• High density lipoprotein cholesterol (HDL-C): a lipoprotein that carries cholesterol back to the liver to be excreted

• ApoB: a lipoprotein that carries cholesterol and tends to stick to blood vessel walls, creating a fatty deposit (atherosclerotic plaque)

• Lp(a): a type of lipoprotein that is especially likely to cause atherosclerotic plaques

• Atherosclerotic cardiovascular disease (ASCVD): the type of heart disease caused by atherosclerotic plaques that narrow arteries resulting in heart attack, stroke, and poor blood flow to the brain

• Vascular dementia: the most common type of dementia after Alzheimer’s; caused by damage to blood vessels that supply the brain.

• Mixed dementia: when someone has both features of Alzheimer’s and vascular dementia. It is estimated that half of all Alzheimer’s victims also have vascular dementia.