Alcohol and the Brain: One Drink a Day Associated with Brain Shrinkage

Transcript

Intro: I’m Dr. Nathaniel Chin, and you’re listening to Dementia Matters, a podcast about Alzheimer's disease. Dementia Matters is a production of the Wisconsin Alzheimer's Disease Research Center. Our goal is to educate listeners on the latest news in Alzheimer's disease research and caregiver strategies. Thanks for joining us.

Dr. Nathaniel Chin: Welcome back to Dementia Matters. According to the Dietary Guidelines for Americans, adults of legal drinking age should limit their alcohol intake to two drinks or less in a day for men and one drink or less in a day for women. Now, if you’re one of my clinic patients and over the age of 65, you’ll hear me mention the National Institute on Alcohol Abuse and Alcoholism guidelines, which recommend people (male or female) drink no more than seven drinks per week and not more than two in one day. Most people might interpret these guidelines as safe levels of alcohol consumption, but more and more research is telling us even these moderate levels of alcohol use have negative consequences for health and pose an increased risk for some diseases. My guest today is here to talk about his recent research that found even one drink a day can shrink your brain. Remi Daviet is an assistant professor of marketing at the Wisconsin School of Business who uses machine learning and artificial intelligence to understand large data sets. Thank you for joining me today on Dementia Matters.

Dr. Remi Daviet: Hi. It's a real pleasure to be chatting with you today.

Chin: Let me start by saying, your results are not welcomed by many people but since they are so important for us to understand let's really jump into this. Where did the idea for this study come from, and how did you – actually you and your team work on this project?

Daviet: So, it started with a very different objective. I do some neuroeconomics; that was my specialization during my PhD along with computational statistics. I was looking to find patterns in the brain that will be associated with drinking but find the causal link in the other direction. What different patterns are linked to more drinking using instrumental variables based on genetics so if people might be more favorable to drinking, see if we could identify the part of the brain that will lead to drinking. The issue is that it seems that alcohol might have such a strong effect on the brain so early in consumption that it draws all the signal I had from my statistical method to try to identify the reverse pattern. So my research – my original project didn't work out the way I wanted, but when I talked to people who are more specialists of brain and addiction, the other people who joined the team thought that was actually really interesting. That's how we pursued that project.

Chin: That's interesting, so this is like an incidental finding that was really quite remarkable and kind of put you on a new path.

Daviet: Exactly.

Chin: Well the scientific research on alcohol consumption can be really confusing, particularly for the general public. On one hand, there are studies that show that some alcohol can be good for the heart or help lower the risk of diabetes, particularly in women, but then on the other hand there are studies that show even minimal alcohol use will increase their risk of cancer and now your study about the very serious associations between alcohol and brain changes. Before we get to the actual results of your publication, when you're with other people how do you suggest they balance all of these conflicting messages?

Daviet: Well, I can first present it as good news. The good news is that up to one drink a day, we don't find any effect even in a very very large sample. So you can drink one bottle of wine per week and we don't detect any difference in the brain. That's good news, I think. Now for above this consumption, even though we don't really have a causal effect identified, we have strong suspicion – let's put it like that –you will have to drink two small glasses every day of the week to reach the level where we find that there is some negative association. Even at this level, the equivalent in age would put it at two years, but 2 years in brain age is not that much. I don't think my brain is very different from what it was two years ago. I don't know how you feel about yourself, but that scale of time is not – I wouldn't be too worried. However, when you go above this – you start drinking three units or four units, four small glasses every day – because the effect is exponential that's where we start seeing really strong magnitude in terms of the association. That's when I would be more worried. The good news about that, again, is that if you just cut the last glass you might cut the effects in half, if there is an effect. So it's easy to – you don't have to stop drinking. Just removing the last glasses is where you have actually the strongest potential benefits.

Chin: And that's a great teaser, because I am going to ask you about more of these specifics of how much and at what point, but your paper also mentioned something I think is really important for our listeners to hear. You talk about gaps in research, one of them being that many studies look at alcohol use disorder – so actually having a medical problem – and not really directly at mild users, so recreational use. The other gap that you identify is that there's a lot of other potential factors that could be influential when you study the impact of alcohol on health. You list things like age, sex, body mass index, and even your genetics. Were you able to account for any of these kinds of gaps or factors in your particular study?

Daviet: Yeah, we tried to control for a lot of things. First, about why we went into moderate consumption and not just heavy drinking or use disorder, I think it's very difficult to study because brain scans are very expensive. Until we had this database provided by the UK Biobank, it would be almost impossible to have the funds to do a study with enough sample size that is large enough to detect small changes like this, right? Brain imaging is blurry; you have to align them. You have to put it through a whole process to try to find exactly what's the size of each part of the brain. That's kind of new that we are allowed to do this kind of research and that's why we are starting to fill the gap. Now, in terms of controls, yes we control for genetic ancestry and for other things like the presence of ADH1B, a very genetic variation that will change the way alcohol is metabolized in the body, age, sex. We did several studies where we looked for linear effect, nonlinear effect interactions, all these kinds of things to try to be as possible. The other issue with this type of research is that you cannot experiment. You cannot take a group and split them randomly and say, ‘Hey, you're going to drink four glasses a day just to see how it affects your brain.’ That's why it's very difficult to identify a causal effect and we can only have some kind of association where these other variables might give the wrong interpretation if there are other causal patterns involved.

Chin: One other question I have for you before we get to the results is, is there an effect of alcohol consumption and interaction with just getting older?

Daviet: It is hard to say because the magnitude of the interaction is very small. Given that we have a very large sample and not able to confirm for sure that there is an interaction, I wouldn't be concerned about this.

Chin: I think that's good for people to know that as they're we're all aging, especially if you're a retired person, that doesn't seem to have a particularly strong interaction when it comes to one's health. Now with all of that context provided, I'd really like to start with the end conclusion from your paper and then backtrack to see how you got there. What did your results show in this publication?

Daviet: The results showed that if you take two persons, same age, same sex, same head size, same genetic ancestry, the one drinking a large glass of beer or wine every day or two small glasses – and I do mean everyday, not once in a while – this person has, on average, a brain with a bit less of gray matter and white matter. If we compare this reduction with the normal reduction of a brain that happens with aging, that's equivalent to two years of aging at 50 years, so that's not that large. Your brain is not that different from what it was two years ago. However, if you go beyond this limit for each small glass you add we can see that the difference is larger and larger. So for four units, now it's not just two years, it's ten years, the difference inside of the brain in terms of equivalent aging.

Chin: Wow. Okay, so I have a couple responses to that. So, Remi, as a geriatrician, two years of cognitive brain health can be significant to people. You're a young person and so I can appreciate you don't feel any different than you did two years ago, but someone in their 70s and 80s might tell you that they might feel it. But two years, so that's what one drink a day – one large drink a day leads to two years of sort of accelerated aging compared to people who don't drink. I appreciate your second point which is that more than that exponentially your brain is shrinking at ten years, perhaps, depending on how much more. It's a pretty significant change.

Daviet: Yes, it is significant. And concerning your point about two years being not that large or being large depending on where you are, that's true. The effect of aging by itself appears to be linear so every year past 45, you lose approximately the same volume of gray and white matter. Maybe there is a threshold at which, when you reach that threshold, you become able to notice it a lot more. That's where maybe you might find that the observable effect of drinking more alcohol interacting with age. They might be more noticeable even though, in terms of brain shrinkage, they might be just the same as they were before when you were younger. Once you have this threshold of lower amount of gray matter, you might see that you start, you know, forgetting things that happened recently – where you put your keys, what you've told, what you ate yesterday, these kinds of things.

Chin: Yeah, so the tipping point kind of theory that, as you've said, at 45 and on it's a linear change but there could be a tipping point where you start to actually notice that change more. How did you come to these findings? I mean, you used some brain imaging, so can you tell us what you looked at and how you came to these conclusions?

Daviet: Yes. The UK Biobank is a large project that was started by public institutions in the UK where they decided to take a lot of people – so we have 500,000 people – and do an extensive medical checkup and get their genome sequenced. Among those, they started doing brain scans and so we had this large sample of 30,000 people with brain imaging. Once we had this large sample and we also have alcoholic consumption and dietary consumption, all these kinds of things, we thought it would be interesting to start looking at these brain scans. We kind of align them or we make the brain comparable, and then we try to see differences among people because the brain differs. You have, first, to make them in – standardize them so that they can be compared. Then the part of the brain is kind of cut into different parts so that we know which part is the hippocampal and what part is the prefrontal cortex. We have the volume of gray matter in that part of the brain, the volume of white matter between parts of the brain because they are acting as connections for transmitting signals, what part is just liquid. Once we have all this data, it's a matter of trying to find statistical associations by using statistical techniques.

Chin: And it was through that that you were able to come to this conclusion of a drink a day leading to two years of accelerated kind of aging, and then even more with more drinking.

Daviet: Yes, exactly. So because we have so many people, we can really compare people by groups of drinkers – people who don't drink, people who drink up to one drink a day, people who drink up to two drinks a day. We had a lot of people in each of these groups, a bit less in the very heavy users, but still enough to detect effects because we were  – or detect associations – because they become so strong basically at some point, so it's hard to miss.

Chin: Were there certain parts of the brain that were more impacted than others based on what you were looking at within the brain scans?

Daviet: Overall, the effects might vary slightly across parts of the brain but I would say that the big picture is that it's everywhere in the same direction by about the same amount.

Chin: I think that's an important finding too. It's really affecting our entire brain and not just our language, or our memory, or our attention. So I think a question that our listeners have probably already been asking as we've been talking is, how are you defining alcohol consumption and can you explain what a unit of alcohol is in terms of beer, wine, and hard alcohol spirits?

Daviet: So it's a bit variable across beers because you can have a very light beer or you can have a very strong beer. For the average beer, a pint or can that's half a liter – the large can – will be two units. Um. For wine – in America the standard glass of wine is almost twice as large as what you would have in Europe – so 175 milliliters, about five ounces, is two units. Then hard spirits, the standard shot is 25 milliliters. That's one unit of alcohol – one unit of alcohol for this study as we count them in Europe. So be careful if you look at guides in the US or in North America in general. Sometimes what they call one unit for them is what we call two units based in Europe.

Chin: And then so your study found that one or two units per day led to the two years of accelerated aging?

Daviet: Two units, so that will be for the US one pint of standard beer that's around, you know, 6-7%.

Chin: Or even a standard glass of wine.

Daviet: Yes, also a standard glass of wine would would match this two units description

Chin: Yeah, and I mean let's not forget that people do what's called the ‘home pour’ and they drink more than what is considered a standard glass. I think that's just really important for people to recognize that these are small quantities of alcohol and even these small quantities have led to changes on the brain scans that you were reviewing. I guess for me, as someone in a clinic, it'd be interesting to know how these individuals that you studied perform on actual cognitive testing and if the changes you saw in the imaging actually had relationships to these performances. I guess I'm wondering, from your perspective, what are the next steps with this type of work?

Daviet: So what is difficult is that if we're really looking at just brain effects or association with brain anatomy, we need larger samples to look at this. We don't always have these large samples and also psychometric tests of cognitive performance, or other kinds of tests. We might start to look at that because I know there is some data available. Otherwise the alternative will be to – yes – to be on the purely psychometric or behavioral dimension and then try to associate alcohol intake with these outcomes. I would be curious actually to hear if  you or your audience have ideas about how to run this and control for all the potential confounds and reverse causality and all the issues you might run into when you run these kinds of studies.

Chin: It's certainly not an easy study to do, but I think you're really onto something even if we may not necessarily like the results that you're coming up with. At least we know they're valid. My last two questions for you are, one, did the findings of this study cause you to stop drinking? And two, regardless of that answer, what do you do to promote brain health after studying so many brains on imaging scans?

Daviet: It didn't really change my drinking habits because I was already below two units per day. I might have two units in one day but that happens every two weeks maybe, so I'm not too concerned about that. Now, what I will advise people – I'm not the best specialist, I do as everybody else. I read the literature about this to make my decisions. If you keep a healthy healthy lifestyle, I feel that's the answer to everything, not just brain health but health in general. Keep using your brain, don't let it go basically. The more you use it, the healthier it will stay. When I look at the association between age and brain shrinking for a group of individuals in the same age within a sex, there is large variations. You have people who are 80 years old with brains that are – they look as young as a fifty year old, and you have people who are 50 years old who have a kind of aged brain who are already like an 80 years old brain. I am hopeful that it's possible to keep a young brain even as we are aging.

Chin: I think that's a nice way of ending. There is a lot of variability, and age is merely a number at times. So with that thank you, Remy, for being on this podcast and sharing with us the findings of this very interesting study.

Daviet: That was a pleasure. Thank you.

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