Welcome to Dr. Warrick's podcast channel. Warrick is a practicing cardiologist and author with a passion for improving care by helping patients understand their heart health through education. Warrick believes educated patients get the best health care. Discover and understand the latest approaches and technology in heart care and how this might apply to you or someone you love. Hi, welcome to my podcast and videocast station and today I'd like to talk about cholesterol and statins and their potential impact on the brain. Now I get asked fairly regularly, how low can you send your cholesterol without it altering brain function? And I also get asked fairly regularly, do statins cause problems with mental function or cognition? Well let me start with cholesterol levels and how low can we go. Well there's not a lot of absolutes around this but there are aspects that we can infer from. There have been some trials that have specifically looked at lowering LDL cholesterol and assessing cognitive function or mental function. With these new PCSK9 inhibitor agents, which get people's cholesterol levels down very low, there was a trial called the Ebbinghaus study where the research was directed at seeing what happened to brain function with very low cholesterol levels. Now we're talking levels. Lower than what we normally see with our current treatment for people who've had a heart attack. Very low LDL cholesterol levels. Well, that Ebbinghaus study went for a number of years. They specifically set it up to look at function of the brain. And they were unable to demonstrate any cognitive impairment by lowering cholesterol levels to these really low levels that we might try and achieve these days. for people who are very, very high risk. So there's a reassurance there. That was using an agent that's not a statin, but a PCSK9 inhibitor, one of the new monoclonal antibodies directed at a component of the receptor that's related to LDL absorption within the liver. We know if we look at newborn babies that their cholesterol levels are very low at time of birth. We're talking LDL cholesterol levels of around 50 to 70 milligrams per deciliter or somewhere around 1.3 to 1.8 millimoles per liter. These are pretty low levels and they're the sort of levels we'd generally be happy with if we wanted to treat someone who was at high risk of heart attack. Well, these levels are being measured in newborn babies at probably the most synthetic, productive, metabolically active period of their lives, the most active out of utero brain development time that any of us would ever have. And so at the time that we are looking... to be most aware of our brain function at the time of birth our LDL cholesterol levels are really very low. That's not proof but it is an inference and it will tell us that the brain at least the brain of an infant baby works very well at those low levels. I think it gives us some reassurance. It's not proof but it is some reassurance. The other thing is that we know through finding the PCSK9 inhibitors that there are families that have overactive PCSK9 and these people have too much cholesterol in their bloodstream and these people run a high risk of coronary event. But there are people who have non-functioning PCSK9, which is a protein attached to the LDL receptor in the liver. These families who have PCSK9 not working have very very low levels of cholesterol as well and they appear to lead completely normal lives without any brain dysfunctional or abnormality and they tend to live those long and protracted lives without incidence of coronary or vascular event. So a nice extra bit of information. Those three bits of data, those three bits of information about the Ebbinghaus trial, the cholesterol levels of a newborn, and the families with very low cholesterol, I think all provide some reassurance. Again, they're not absolute, but they are a really good starting point and allow us to be fairly reassured when we're looking to get people's cholesterol levels right down. The question then comes, do statins have a problem with cognitive function? And certainly there are case studies and patients will report mental fogging or issues when they take a tablet. Well, what's the data tell us? There was a trial called the Protective Study of Pravastatin in Elderly at Risk for Vascular Dementia. And they took some of the letters out of that and called it the PROSPER study. This was using Pravastatin, one of the older cholesterol agents at about 40 milligrams, nearly 6,000 patients. And they did nine monthly cognitive testing over about a three and a half year period. As expected, because it was an elderly group, the cognitive function across the board went down. There was a decline. However, there was no difference between the treatment and non-treatment groups. Another study called the Heart Protection Study using Simvastatin at 40 milligrams followed a large number of patients for about three to five years for follow-up and found no difference in cognitive outcome between the treatment and non-treatment groups. This provides some reassurance. There was another trial not specifically set up for testing brain function, but they did look in on it. That trial was the justification for use of statins in primary prevention, an intervention trial evaluating resuvastatin. Now, they took the letters out of that and called it the Jupiter trial. You may have heard of it. They looked at nearly 20,000 odd people. men more than women, they found no change in cognitive decline. There was a report of increased confusion on statins, and this actually led the FDA in America to add potential impact on thought processes as part of the side effects that could be seen with resuvastatin. Not designed to look at brain function, not compelling in terms of... cognitive decline, some reports of some slight clouding of thought. There have been some other small trials specifically looking at this question, about 12. Of those 12 trials, nine of them showed no difference at all. One of them suggested a decline in function, in cognitive function for the group on cholesterol iron therapy, and two of those trials suggested a benefit. Well, we can't be absolute. There is suggestion from that data that there is no clear cut evidence that taking statins and lowering cholesterol is a problem. I think it's really important we need to look at the individual because some people will respond differently to the crowd. And some people, for example, might report that their thinking is a bit clouded if they drink coffee. Some people might report their thinking is a bit clouded if they have Too much sugary food. And some people may report mental clouding on a medication, including a cholesterol agent. So we need to be aware of that. There is a little bit of a recommendation that if there is a concern, that we use tablets, cholesterol tablets, that are less likely to be absorbed into the fatty tissue of the brain. So some cholesterol tablets are lipophilic. That means lipofat. filic love to be absorbed into fat and some medications are lipophobic that means they don't get absorbed into fat so for example atorvastatin more likely to be absorbed into fat potentially more likely to have an impact on the brain rosuvastatin tends to stay within water solution it's lipophilic sorry, hypophobic, doesn't get absorbed so much into fatty tissue, less likely to be implicated into brain tissue and perhaps a preferred agent. So we can also think about choosing the cholesterol-lowering agent if someone does report an issue around cognitive ability or mental fog, etc. I hope that makes a bit of sense for you. I hope you've enjoyed that. If you have any queries or questions, drop us a note at the usual place. Thank you for joining me. Till next time, I wish you the very best in health. Look after yourself, have a laugh, and please don't die from a heart attack. Goodbye. You have been listening to another podcast from Dr. Warrick. Visit his website at drWarrickbishop.com for the latest news on heart disease. If you love this podcast, feel free to leave us a review.
