How Scents Can improve Memory, Autism and Depression | Dr. Michael Leon

We found that dozens and dozens of neurological disorders are also accompanied by olfactory loss. In all, I've counted 137 medical disorders that are accompanied by olfactory loss. So we're thinking that maybe the loss of olfaction can actually increase the risk of having these symptoms expressed for all of these neurological disorders.

Well, hello everyone. I'm Dr. David Perlmutter. Welcome again to The Empowering Neurologist. What a show we have on deck for you guys today. You know, when it comes to treating things like cognitive decline and autism and even anorexia, we don't have a huge array of tools, but now we've just discovered a new therapy that might offer incredible benefit for these individuals. And who knew? It's called Olfactory enrichment. In other words, providing scent therapy to individuals that has been shown to actually improve brain function in the domains, in the areas that I have just talked about. And we are so fortunate to have arguably the number one researcher on the planet looking at this notion of olfactory enrichment, how providing scent therapy, if you will, is extremely powerful in terms of changing brain function. and changing brain architecture. I'm really excited about this program today with Dr. Michael Leone. He is our guest. Let me tell you a little bit more about him. Michael Leone is a professor emeritus, received his PhD from the University of Chicago and joined the professorate at the young age of 24. He's currently, as mentioned, professor emeritus in the Department of Neurobiology and Behavior at the University of California, Irvine. And also a member of the Center for the Neurobiology of Learning and Memory, as well as the Institute for Memory Impairments and Neurological Disorders at UCI. In a recent analysis from Stanford University, he was ranked among the top 2% of scientists on the planet. So we are indeed very fortunate to be able to spend time with Dr. Michael Leone today. We're going to get right to our podcast now. Dr. Leon, it's so great to have you join us on the podcast today.

My pleasure to be here.

It's an interesting topic, that's for sure. And I think for many of our viewers, the notion that an intervention based upon presenting them various types of things that they will smell and that that can be therapeutic for their brains is a bit of a stretch. But I think by the time we're done today, they're going to really have a good understanding of it. I'd like to begin by asking, how did it all begin? I mean, how did a guy like you end up connecting olfactory enrichment with improvements in the brain?

Well, there's this enormous literature that shows that if you take lab animals, rats and mice, they're normally kept in box cages, typically alone and without much to do, and Their brains are competent, you know, they can learn, they can have motor interactions. But if you put them in a so-called enriched environment, that is a much larger cage with a bunch of friends and a lot of things to do, places to run, places to investigate, their brains become much more complex and they become much more capable. And even more interesting is that scientists have made animal models of human neurological disorders. And they show their human-like symptoms when they're in the standard box cage, when they have a low level of stimulation. However, when they're put into an enriched environment, they lose many or all of their human-like symptoms. So somehow the brain can compensate for these interventions that cause neurological disorders in the brain. So we took that information and wondered why people hadn't used it. with people. And our assumption is that everyone thinks we're getting too much stimulation rather than too little. But the kind of stimulation that we probably don't get enough of is olfactory stimulation, odor stimulation. And so if you look at people in our modern world, we just don't have much olfactory stimulation. If you take a deep breath now, you probably won't smell anything at all. And so we thought that maybe what was happening is that they didn't have enough olfactory stimulation. And maybe we could treat a neurological problem with that. And so the first thing we did was notice that there were many animal models of autism, and they all had reduced symptoms in the enriched environment. And so it was also the case that there's a human sort of experiment that went on in the times when Ceaușescu ruled Romania. He decided to eliminate all kinds of contraception, and at the same time, he ruined the economy. And so there were a lot of kids with parents who didn't have any money, couldn't feed them. So they brought them to the state orphanage, which also didn't have much money, but they kept them alive. But basically, they were going into their own box cages. They kept them in single cribs with nothing much to do, no interactions except for feeding. And 33% of these kids developed autism-like symptoms compared to 1 to 2% currently. And even more interesting is that they took them and they took them and gave them to full-time foster parents, so an enriched environment relative to their orphanages, and many of them improved their autism symptoms. Anyhow, we thought we could do this in Irvine with children with autism. We gave them an enriched environment. We gave them— the parents a kit, and they gave their kids stimulation in the morning and the evening. We changed it on a regular basis, and we focused it on giving them olfactory enrichment. That is, they got different kinds of olfactory stimuli at different times of the day, along with other kinds of sensory stimulation as well. And in 6 months, they had a remarkable improvement. 21% were no longer regarded as having classic autism compared to 0% in standard care. 42% had a major improvement in their symptoms compared to 7% in standard care. Communication went up by over 200% compared to almost nothing in standard care. So it looked like this actually was having a big impact on these kids.

It's really a classic kind of, uh, description of the beauty of neuroplasticity, of whatever you can do to enhance neuroplasticity, and, and perhaps in those kids as well some neurogenesis, uh, because their environment was enriched. Um, but what, what motivated you to go, uh, motivated you to go olfactory in these kids? I mean, you were trying to— when you enriched their environment, you— I'm sure there were other modalities, but Where did you pull the olfactory thing from?

So I had been working on olfaction for decades, mostly trying to understand early learning with olfaction. That is, we showed that infants— rat infants, mice infants, human infants— rapidly learned to identify the odor of their mother. And this kind of learning is a very dramatic kind of learning, a very strong kind of learning, and it happens so early that people didn't think that these animals or humans were capable of learning. Humans can learn this on the first day of life. And it's just a critical form of learning because they have to be able to find the mother and stay attached to her. And so we looked at all sorts of things about how the odor is produced, but we were very interested in the neural changes that accompany this kind of learning. And they are very large anatomical, physiological electrical nerves, neurotransmitters, a lot of things are going on. And so we spent a fair bit of time researching that. And we then moved to trying to understand how odors are coded. That is, we can recognize thousands and thousands of odors. How do we do it? How does the brain recognize one odor compared to another? So we Again, looked at that for many years. And we then were interested in seeing whether we can do something to treat people and to treat their neurological problems. And after we did the autism studies, there was a study that came out showing that if you take older mice whose memory is failing, just like older adults and humans, And you give them just olfactory enrichment, different odors on a regular basis, they had the same improvement as mice who were kept in an enriched environment. They had increased learning and improved neurogenesis, the production of new neurons. And so we thought that, well, you know, maybe we can do something with this for older adults who maybe don't want to do half an hour of stimulation and doing things. Maybe they just want to sit and smell things. And so it turned out that we tried this during the day in a preliminary study with older adults just sitting and reading or watching television, and it improved their memory on a specific memory test by 181%. We then realized that there weren't a lot of people who were going to do this on a regular basis. And so we decided to automate the system. And we had it— we gave them diffusers that they turned on at night. And that allowed them to have virtually 100% compliance because they were in bed all night and all they had to do was breathe. There was then another study that was published. where they had 40 odors twice a day. And this improved the memory and the depression symptoms of older adults with dementia. And that's just extraordinary because people have been trying to find something that works for dementia for decades. And the recent drugs that have been approved by the FDA are awful drugs. They don't improve memory. They just make it a little— your decline goes a little bit more slowly, slowly enough that you wouldn't actually recognize it. And it comes with brain inflammation, brain bleeds, brain shrinkage. They're just not the best drugs. So it was amazing to find that we could improve the the memory of people, even in dementia. And it turns out that olfactory loss is present in all forms of dementia, not only Alzheimer's disease, but Lewy body disease, you know, frontotemporal disease, all forms of that disease. And we found that dozens and dozens of neurological disorders are also accompanied by olfactory loss. And somatic diseases also accompanied by olfactory loss. So heart disease, cancer, liver disease, lung disease, kidney disease, all of those are affected by olfactory loss. In all, I've counted 137 medical disorders that are accompanied by olfactory loss. So we're thinking that maybe the loss of olfaction can actually increase the risk of having these symptoms expressed for all of these neurological disorders.

In looking at the relationship between loss of olfaction in various forms of dementia that you mentioned, and sort of as a harbinger to the development of dementia, cardiovascular disease, diabetes, Parkinson's especially, we've known about that for a long time, we've kind of just written that off over the years saying that There's a process going on in the brain, and it's affecting multiple brain areas, like the areas for interpretation of scent, and therefore interesting association. But you looked at it a different way. You looked at it through kind of a reverse engineering perspective, saying that, no, this is an inroad, that this is— these path— these connectivity pathways. You talk about one major pathway connecting to the prefrontal cortex. Yeah. the uncinate fasciculus, for example, and that if you can regenerate that, then perhaps you might see more benefits than just an associated improvement in the ability to smell things. And indeed, I guess I'm jumping the gun. We're going to get to your more recent research. I'm wondering if, aside from things that go on in the olfactory bulb, olfactory tract, the things near, uh, in the nose and around the nose, If there may be a shared mechanism that relates not just the brain degeneration in Parkinson's and Alzheimer's and all the various forms of dementia that you described, but also things more peripheral, cardiovascular disease, diabetes, obesity, etc., with some fundamental mechanisms that are involved in the degeneration of these pathways, like inflammation. And, you know, at least centrally in the brain, one wonders if Perhaps there is some microglial activation that's leading then to degeneration in these pathways as a consequence of body-wide inflammation that might, you know, represent some kind of relationship. So I would love to know at some point in the future if there is anything correlative that you can see between dysnosmia, anosmia, or loss of sense of smell completely, And, you know, activation of these microglia or just markers of inflammation in general. Do you see a relationship between just mechanistically inflammation and loss of sense of smell?

So our minds are working in the same direction. I love that. So I've just looked at the literature, and of the 137 medical disorders I found that are accompanied by olfactory loss, 135 are also associated with increased inflammation. So that suggests that inflammation may be involved. Even more interesting, again, is if you give humans pleasant odors to smell, it decreases inflammation. Wow. And so it may be the case that the improvements that we see in the brain and behavior are due to the fact that we are decreasing inflammation in these individuals with olfactory enrichment.

Well, all of our viewers, you know how we, uh, how we focus on inflammation through all the lifestyle interventions that we talk about. And here we now see likely another powerful lever to pull, another powerful inroad to, uh, To reducing inflammation. Again, for our viewers, that, you know, we focused on inflammation over the years, and this, you know, may well represent yet another powerful tool in the toolbox for reducing inflammation. So you have then— you have a recent study that came out where you looked at olfactory enrichment and in terms of memory function in elderly individuals, I think. You had 43 people. You would have had more, but there was COVID. Tell us about that study.

Well, we thought that we could get people to get the kind of olfactory stimulation that we think that they need if we did it at night, because it's not a chore for people to sit there for 2 hours and sniffing odors. And so we gave them diffusers with 7 different odors, all pleasant. And that allowed them to just put in a new bottle each night, turn it on before they went to sleep, and for 2 hours they got a different odor. And after 6 months, they had a 226% better memory than individuals who had a very, very low level of odor in their diffuser. And to my knowledge, that's the largest improvement in memory that anyone has ever reported. for healthy older adults. It is—

Can we do that again, please?

Yes. To my knowledge, it is the— it's the largest improvement in memory that anyone has reported.

So this is a 226% improvement, albeit in one of your measurements, a measurement of auditory-verbal learning. But having said that, you mentioned earlier the so-called Alzheimer's drugs, which don't lead to improvement. They simply and minimally lead to a slowing of the decline by about 3 months over an 18-month period. So, uh, with associated risk of brain bleeds and edema that you mentioned. So you actually showed improvement by exposing people to a series of scents. Was it 7 different types of scents? Yeah. And maybe we'll talk about why you chose those, but That's pretty exciting.

It's also the case that we're not the only one who's doing this. There are about 20 or so articles that show that olfactory enrichment of one form or another improves both the brain parts that control memory and memory itself. So I think it's really important to look at whole literatures, in addition to looking at single papers, but this is consistent with everything that everybody else is finding. It's also the case that when you remove olfactory stimulation, one reason or another, the memory parts of the brain and memory also decline. And so if you don't have enough of it, things go south. If you stimulate it, things improve. And I think the combination of all of those findings is really fascinating.

Well, hi everyone, Dr. David Perlmutter here. We hope you're enjoying this content, and if you would do so, go ahead and hit the like button. And if you're not already a subscriber to our channel, please consider doing so. We're really grateful to have you as part of our community. So let's get right back to the presentation. We mentioned, or I mentioned earlier, the notion of COVID One of the things that happens in COVID, and happened to me briefly, was loss of sense of smell. And there was a study that I wrote about about 18 months ago, but it came out well before that, from Oxford UK Biobank, looking at 785 individuals, and they were able to scan their brains prior to and post-COVID and found a pretty remarkable change in brain volume and even the thickness of various areas of the brain that are actually involved in interpretation of, of olfaction, of things that we're exposed to. So, you know, this, this can be a permanent issue in some people. And, um, there— what was recommended, in fact I wrote about this as well, was olfactory retraining, where, where people challenge themselves with various types of scents. And they've had some limited success in allowing people to regain their ability to smell things, but You know, based upon what you're telling us today, losing your sense of smell is important as it relates to the brain.

Yeah. So that study from Oxford was just a spectacular piece of work. And what they found, you're right, is that the olfactory superhighway, that is the only path that goes directly from the sensory system to the memory parts of the brain, all the other senses affect the memory centers, but they have to go through the thalamus, which basically is the side streets of the brain. The olfactory system is the only direct superhighway, and so consequently, it has much larger impact on the brain than anything else. And so the loss of olfaction is really a much more serious thing than most people think. Most people regard olfaction as their least important sense. But it turns out that the loss is really important. And when people lose it, for example, as they get older, they don't realize that they've lost their olfactory ability. But when they lose it abruptly, as so many people did with COVID then everybody realizes that there's a problem. And these researchers at Oxford found that months after people had recovered from mild COVID, not even serious hospitalized or anything, they still had the damage in their olfactory superhighway and its connections. And they still had cognitive loss. And another group found that you could predict the extent of the cognitive loss from the extent of the olfactory loss. And so it is— you can also predict which older adults are most likely to get mild cognitive impairment, the first problem on the way to dementia. Of those individuals, you can predict which ones will develop develop Alzheimer's disease based on their ability to smell things. And of those individuals, you can predict which will develop their symptoms more rapidly than others based on their ability to smell things. And there are actually now 7 major epidemiological studies showing that by middle age, your all-cause mortality— that is, whether you live or die for any reason— can be accurately predicted by your ability to smell things. It's more accurate than if you had cardiovascular disease. And so it may be the case that many of these diseases interact with the olfactory problems, perhaps via inflammation, and the loss of olfaction may actually make you more vulnerable to these symptoms.

Well, I've discussed before on, I think in a blog, the notion that we have receptors for bitter taste in the mouth, of course, but also throughout the digestive system, and that when we eat bitter foods, we activate some pretty powerful anti-inflammatory pathways, as well as a pathway that we're really fond of called the NRF2 pathway, which beyond being anti-inflammatory has some antioxidant and even perhaps some mitochondrial upregulation activity. So, which leads me to think about for a moment, could there be any inroads with taste? And what's this— what is the relationship of taste to olfaction?

So taste is also very often confused with olfaction, particularly when people are eating things. So many people during COVID thought that they lost their taste, because their food didn't taste the way it should. And it turns out that there are 2 kinds of olfaction. One is the information coming in the regular way through the nose— both, I guess, are regular ways— but the other one is called retronasal olfaction. And that's when you're chewing on something in your mouth, it pushes up the olfactory information into your nasal passages from behind. And these 2 pathways really don't communicate with each other. If you've experienced something from— with retronasal olfaction, you won't necessarily recognize it through orthonasal odors coming in through your nose. So taste is just sweet, sour, salty, and bitter, and umami, which is a proteinaceous kind of taste. All the other flavors that you get in what you eat are olfaction from this retronasal mechanism. And you can see this very easily if you're drinking coffee in the morning. Just pinch your nose when you're drinking it, and you'll find that that wonderful coffee flavor is reduced to the bitterness of the taste.

That's a trick that kids learn early on when they don't want to eat a certain food, they hold their noses.

Yeah, so it's, um, it's, it's a complex interaction, and, uh, there really hasn't been much, uh, study of retronasal olfaction, um, but it's what most people regard as taste. The better word for it is flavor.

Yeah, we all know that when we get a cold, we can't really taste food. There— you've done some work, uh, with respect to depression. And, you know, I think mainstream pharmaceutical approach to depression is— could be better. I'll leave it at that for the 300 million people globally who suffer from depression. So what are the advances in this olfactory enrichment as it relates to depression?

Well, there are a couple of studies now showing that if you give people olfactory enrichment, you reduce their depression. And That, you know, that's remarkable. There's no side effects. It seems to work for a broad range of people, including older adults with dementia. So it's really something that I think we'll be seeing more and more. We just tried a preliminary study with depressed undergraduates at UC Irvine, and we found that it really improved their depression symptoms. So we're going to do a larger study to see if we can make things even better.

It's so exciting. Um, in, in looking at your work and the variety of different scents that you use, it doesn't seem that you're really focusing or leveraging the idea that a particular scent is a great thing, like, uh, you know, lemon balm being calming via aromatherapy, that it's really just the challenge of the notion of olfaction with a variety of inputs That there's no unique type of special gift of one type of aroma versus another. Have I got that right?

Yeah. I mean, the whole field of aromatherapy has done wonderful things, and their focus is on finding specific individual odors that will solve some sort of problem. And they've done a lot of work on this. It's been used for thousands of years. This is a very different idea. And the idea is that you want to give people a great deal of novelty in their experiences. And novelty is the critical feature of an enriched environment. And so if you give people one odor over and over again, it's not going to be novel. And so we have developed a device that puts out 40— 4-0— odors. a night while you're sleeping, twice a night actually, and it's called MemoryAir, and it duplicates the effects that have been shown to improve dramatically the memory and depression symptoms of older adults with dementia. And so we think this is going to be really important for most older adults because we all lose our olfactory ability and we all lose our memory. And so I think it's— we are living in a deprived world because we're not getting the olfactory stimulation that we should be getting. In fact, in many cases when people come to America from the developing world, they talk about an olfactory vacuum, that there just isn't much olfactory stimulation in this world. And so we think that it's just going to be something that people do as a matter of course to prevent the deterioration of their olfactory system and their memory system.

There's an experience I had with— we have a close friend who owns a restaurant, and he knows his wines left, right, and center. One time, a couple years ago, he received a whole shipment, various cases from France, and he Sent them all back because they had they had no flavor whatsoever, and come to find out this was early in COVID. He didn't know he had COVID and lost his sense of smell and taste, and the wines were fine. But anyway, when they bring us a glass of wine, they're always smelling it, and they're saying it has notes of tobacco and plum and melon and all of these things. So I thought that I would buy. There's a kit you can get, sommelier's kit. And, so that if you're training to be a wine tester, taster, you can use this kit. So, I was thinking that might be a kind of a cool thing to do to maybe practice with this thing. Does that make any sense?

So, again, our minds work in parallel. Yes, I have the same kit. You have the kit?

Oh, my gosh.

And, I've been using it for years until our Memory Air device is ready. We I wanted to get the kind of stimulation that I think our brain needs. And so, I have their kit, their 88-odor kit, and I use it every night for years.

I went online. It isn't cheap, but I want to be that guy who can smell the wine and be able to identify all these notes because everybody else seems to be getting it. That's too complex for me.

Well, so, It's also the case that people who are training to become sommeliers, who are sniffing dozens of odors every day in order to be able to learn to identify them in fine wine, their olfactory system stimulates their memory system, and their memory parts of the brain actually increase in size over the course of their training. So it's— you also see this in master perfumers. their olfactory and memory systems get larger with their experience.

Wow. And taxi drivers in England, of course, right?

Well, right. So they— right, they have to learn this very complex spatial organization of the roads in London. And as they do, their brain gets bigger and bigger. And the longer they've been doing this, the bigger their hippocampus becomes, which is critical for learning.

You've done some work and talked a bit about anorexia, and how might this prove effective for that?

Well, anorexia is one of those 137 medical disorders that has— accompanied by olfaction loss. Well, we think that maybe these individuals can also experience their brain improving And again, it's just done in a pleasant way. They don't have to eat anything. They don't have to do anything. They just have to sleep. And so we think that this may be a way of approaching difficult medical problems, neurological problems certainly, but other problems as well. And maybe we can decrease the inflammation and other problems that they have by giving them this kind of olfactory enrichment.

The device that, that you've created, MemoryAir, and your interventions, I think, all work at night when the client or subjects are sleeping. And yet we don't really have a conscious awareness of, of odors at night when we're asleep, correct? So it's—

Yeah.

It's not as if this is an experience then that we are having and that these are triggering, uh, we're experiencing them in a conscious way.

No, not at all. It turns out that because the olfactory information doesn't go through the thalamus, the thalamus is connected to the sleep areas of the brain, and so you can wake somebody up with any of your other senses, you know, bright lights or loud sound or touching someone, but you can't wake them up with olfactory stimulation because it doesn't go through the thalamus. And in fact, People have tried to develop olfactory alarm clocks for the deaf, right, because regular alarm clocks don't wake them up. And they've even used the smell of frying bacon, and none of those were able to work because you're just not aware of things. At the same time, you do have reflexes that are very sensitive. So if you're smelling a nice odor, a pleasant odor, The information goes to the part of the brain that controls breathing, the cerebellum, and it increases the rate of sniffing. On the other hand, unpleasant odors actually stop respiration so you don't smell them. And we know that pleasant odors will decrease inflammation. It also is the case that unpleasant odors increase inflammation. And that's thought to prepare you for bad things that might happen when you have these unpleasant odors, but nobody knows that for sure.

What I'd like to do in the time we have left, tell us more about the MemoryAir device. You know, it's giving 40 different scents throughout the course of the night over a couple of hour, 2-hour periods or whatever it is.

Right. So it's 40 odors twice a night. It goes on for about 4 hours as you're sleeping. So no liquid oils. We had some really smart engineers figure out how to do this. The essential oils are embedded in a special kind of wax, and the wax is melted briefly. The odor is pushed out by a silent fan, and You just put in an odor built-in once a month, press a button, close it, and you don't have to do anything else for the rest of the month, right? It's automatic. So, um, otherwise you are not going to get people to sniff 80 odors a day.

How would you ever do that? You could buy yourself a year's kit. You could buy it. You have to wake up for that, I guess.

But you still have to give yourself all of these sniffs, and very few people are going to do that. So this solves that problem and allows people to get the stimulation that their brain needs without any effort. As soon as you ask people to do something, they're not likely to do it. People who've had heart attacks, as you know, many of them won't take, you know, a low-dose aspirin every day because it's too much trouble.

Compliance is a big issue. So people will want to learn more about you. Where can they get more information?

Well, if they want more information about Memory Air, they can go to memoryair.com. And if they want more information about me and on the other things that I've done, they can go to PubMed, for example, and search under my name, and they'll find all the things that I've done.

Which I did and found out all this exciting research. Thank you so much for spending time with us today. This is just an incredible body of work and, and so innovative. And, you know, in terms of risk-benefit for what it can do for the brain and depression, anorexia, and who knows what else— certainly I would think Parkinson's and, uh, and autism— this seems like, uh, that it's a terrible use of the term no-brainer, but a brainer. It seems like this is, uh,

We think it is, and we're very excited about it. We think this is going to be a part of a lot of people's lives.

Great. Well, thanks for being with us today.

My pleasure. Thank you.

Talk to you soon. We sure learned a lot today, and it was an eye-opening experience that exposing ourselves to various types of scents can have such a powerfully positive effect on the brain, really across a wide spectrum of challenges, including anorexia, autism, and even cognitive decline. What a great body of work from Dr. Michael Leone. Again, his website is memoryair.com. I've already been on the website, a lot of great information, and very grateful that he spent time with us today and that you've joined us as well. I'm Dr. David Perlmutter for The Empowered Neurologist. We will be back soon. Bye for now.