Can Low LDL Cause Dementia? Your Questions Answered

Does lowering LDL cholesterol cause dementia? And how much dementia is actually “vascular” dementia versus Alzheimer’s disease?

In this video, I’m answering two viewer questions about dementia, vascular risk, statins, LDL cholesterol, and brain health. First, we look at the relative prevalence of vascular dementia compared with Alzheimer’s dementia — and why that distinction gets messy fast. Vascular dementia may be less common as a primary diagnosis, but vascular disease often contributes to cognitive decline even when the label is “Alzheimer’s.”

Then we spend most of the video on the bigger fear: whether lipid-lowering therapy — including statins and achieving low LDL-C — increases dementia risk. The short answer: no. Based on the evidence we have, lowering LDL does not appear to cause dementia, and in many patients, reducing cardiovascular and cerebrovascular risk may actually help protect the brain over time.

This is not about pretending statins are perfect or ignoring legitimate questions about brain health. It’s about looking carefully at the evidence instead of letting fear drive the conversation.

If you’re worried about statins, low LDL, Alzheimer’s disease, vascular dementia, or how heart health and brain health overlap, this one is for you.

If you missed the original: https://youtu.be/Rzz2g9gRL_8?si=z5Fcd-e8o2pYT19j

Chapters:
0:00 Viewer questions on dementia and lipid lowering
0:40 Is vascular dementia less common than Alzheimer’s?
2:00 Why dementia diagnoses overlap
3:17 The vascular contribution to cognitive decline
5:22 Why cardiovascular prevention matters for brain health
6:43 Can very low LDL or ApoB cause dementia?
8:16 Lipid-lowering drugs and the blood-brain barrier
10:14 What the overall evidence says
12:02 Randomized trials, meta-analyses, and dementia risk
13:30 Very low LDL in PCSK9 inhibitor trials
16:09 Could statins reduce dementia risk?
18:34 Midlife cholesterol and later dementia
20:00 The PCSK9 genetics question
22:15 Evidence strength: what we know and what we don’t

Are you more worried about heart disease risk, dementia risk, or the tradeoff between the two?

Disclaimer:
This video is for general educational purposes only and is not individual medical advice. Please talk with your own physician before making changes to medications or treatment plans.Sign up for more information on my own practice here: https://corsighthealth.com/

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___________________________
🧬 About Dr. Lily Johnston
  
Dr. Johnston is a double board-certified vascular and general surgeon in San Diego, specializing in metabolic and cardiovascular prevention. She’s the founder of CorSight Health and a passionate advocate for reimagining how medicine approaches chronic disease.
  
#MetabolicHealth #CardiovascularPrevention #HeartHealth #Longevity #InsulinResistance #DrLilyJohnston #DrLily #WomenInMedicine #Surgeon #VascularSurgeon #PreventiveMedicine #PADPrevention #HeartAttackRisks #HealthPortfolio #California #SanDiego #Arizona #Virginia #Minnesota

Transcript

SPEAKER_00 0:00

It's time for another comment response video. Hey guys, Dr. Lily Johnston, board certified vascular surgeon, cardiometabolic specialist, though. So hopefully you will never need me as a surgeon. This weekend we dropped the video on the EasyPave trial looking at intensive versus conventional lipid lowering. And as expected, y'all had a lot to say in the comments and some great questions. Let's get into it. So at Lux Deluxe Design says the quote, improvement in creatinine could just be a sign of diminished muscle mass with intensive therapy. Did they assess strength? Did they assess change in body composition in any way? Also, did they report intracranial hemorrhage? So let's take these one at a time. I appreciate the thought that you know statins are myotoxic for some people, and perhaps the improvement in creatinine is something that might reflect that. We're actually not looking at improvement in creatinine. By the way, creatinine is one of the toxins that is filtered by the kidneys. So when we are measuring creatinine, we are measuring the kidney's ability to filter out bad things. What they really measured in the trial was uh worsening of kidney function. So a decline in the ability of the kidney to filter. So they didn't look to see whether creatine improved. They didn't measure it distinctly that way. So we don't know that there was improvement. What we know is that fewer people had worse kidney function in the intensive, which was less than 55 milligrams per deciliter of LDL cholesterol versus the conventional, which was less than 70 milligrams per deciliter. So it's not like kidney function got better, it's simply that fewer people got worse. So we don't have the body composition measurements, we don't have strength or any other sort of metrics that would assess for muscle problems or toxicity. It's a good point and a great question. I will say uh when you look at the diagram for how many people stopped their therapy, not that many patients out of the 1500 per arm were discontinued for myalgia or muscle symptoms. If you want me to put that up, we can look at that later. Uh, but we will show you that figure. Finally, did they measure intracranial hemorrhage? And I went back and looked through all of the adverse endpoints for the trial, and no, they did not. Sorry about that. And at Michael says, where are the plaque measurements? What is the difference in actual plaque burden at carotid, coronary, and femoral arteries? That is necessary, not reducing cholesterol with no proof of stopping placking. So I love looking at plaque measurements. This is an outcomes trial, though, and I actually think that it's important to remember that outcomes are in many ways more helpful than just the plaque measurements. Because what if plaque measurements stayed the same, but we still reduced mortality and heart attacks because we stopped plaque rupture without necessarily changing the plaque volume? These are both very interesting questions, but I actually think here the outcome data are more helpful than the plaque measurement data. From a trial design standpoint, this was done at 17 different centers, and doing all of the measurements, either by ultrasound or by CT angiography, would have been considerably more cost and burden on the study, which doesn't mean it's a bad thing. But from you know the overall design perspective, I think using outcomes is a reasonable thing and it's it's much more of a hard end point than just the plaque volume, which is intellectually interesting, but does not tell us how that impacts what happens to patients, right? If plaque volume goes down, but they still have heart attacks, well, that's actually important to know. So maybe in combination, it would have been even better. But if I had just had to pick one, I actually think picking the outcomes alone is perhaps more useful, at least for the everyday clinician or patient trying to decide what to do for themselves in practice. This also uh touches on another point that was brought up in several of the comments, which is that they did not assess all cause mortality. This is cardiovascular-specific mortality, which is you know internally consistent as an endpoint, but I agree all-cause mortality is an important thing to measure. And it would have been great if the study authors had included that. Uh, it is fairly common not to see a you know all-cause mortality reported, but I agree that would have been really nice to see. At Mike Benson, Michael 2.0 asks, so how does this affect the number needed to treat still in the hundreds? So the nice part about trials like this is you can actually calculate this yourself if you're ever interested, but we'll go through it. The number needed to treat, first of all, depends on exactly which outcome we're talking about. So I told you that they used a combination endpoint in this trial of cardiac mortality, non-fatal heart attack, stroke, and revascularization or reopening an artery either by a bypass or with a stent. So if you look at that combination endpoint, the absolute risk reduction was 3.1%, and the number needed to treat is one divided by the absolute risk reduction. So it's one divided by 0.031, and that gives you a number needed to treat of 32, and you need to take that over the time span of the trial. So the trial is three years. So across three years, you need to treat 32 patients with intensive lipid lowering therapy to get one person to achieve one of those combination benefits. If you step back and you want to say, well, let's talk about heart attack by itself, the absolute risk reduction for heart attack was just under 1%. So if you look at that number needed to treat, it's about 111. And if you take the composite endpoint, meaning the combination of uh cardiac mortality, heart attack, stroke, and you take away the revascularization, and we talked about there's some some potential for bias using revascularization or re-establishing blood flow in this open trial design where everybody knows who's in which arm of the trial. So you could argue that there's bias and people are getting revascularized more in the conventional arm because everybody knows that they're less treated. So if you just take revascularization out and you remove it because maybe that was the highest possibility for bias, and you combine the other endpoints, then we have a number needed to treat of 77. So if it's just heart attack, it is uh over 100. But for the composite endpoint with or without revascularization, we are under 100 for the number needed to treat over just three years. If we extend longer than that, we would expect that the number needed to treat would drop further over time. And last but not least, you guys wanted to know where the money came from. So at JMK says, Dr. Johnston, could you please provide us with the financial disclosures of the authors of the trial? And Dahlia says, as with any study involving the use of pharmaceuticals, I'm interested in who funded the study. Finally, DWP, the study was funded by. In the paper itself, it says that the study was supported by the Cardiovascular Research Center and by Juhan. So if you look it up, Juhan is a pharmaceutical company. It is not a surprise to me or anybody in the clinical trials space that a trial that used pharmaceutical drugs was supported in some way by a pharmaceutical company, probably providing those drugs. It does not specify exactly what the support was. I am inferring that they provided the pharmaceutical drugs for the trial, but I don't know that. And I don't know exactly what level of support they provided. I did, in fact, also pull the author disclosure list. And of the 18 authors, three have any disclosures at all. The other 15 have no conflicts at all whatsoever. Of the three, many of them have multiple grants that are provided to their university, including a couple by Juhan and several other pharmaceutical and device companies, as well as a number of other sources that I did not run down. But again, it is very common to have grants that are provided by industry to support the university. And you can decide for yourself whether that introduces bias within the study or not. All of the authors are from universities. I didn't see anybody that is listed as a only a member of a company. And if you look through the committee, you know, there are multiple different organizers who are designing the trial, adjudicating the outcomes. So if any one individual might have a bias, hopefully that is diluted out by the presence of multiple different people on these study committees. What I do think is a very strong signal for transparency and openness in this trial is a data sharing agreement. So if you go to the supplementary materials of this paper, what you find is a statement that says the authors of this paper are willing to provide the complete de-identified, meaning no patient information, complete de-identified data set to any other investigator who wants to look at the data. This is a great way to reproduce findings and for people to have their work fact-checked. This was a real concern with many of the other lipid lowering trials that have been done. So the Cholesterol Treatment Trials Collaborative, the CC CTT, has kind of sequestered all of the data from many of the big randomized controlled statin trials in the United States and in the EU. And that's been a source of severe frustration and concern amongst people who would love to reanalyze those data and take a closer look and see what's really there. We can't do it. You have to try to apply and get the data, and most of the time they'll say no. So I think this data sharing agreement, the willingness of the study authors and study supporters, probably including the pharmaceutical companies, to provide this data openly and freely suggests to me that they have nothing to hide here, and they are more than happy to share this and stand by their work. So it's always a great idea to double check on those possible conflicts of interest. They are widely available to us to look at, and I appreciate you guys keeping us honest and following up on that. Until next time, take really good care.