 How does the food you eat contribute to your health? Do supplements help prevent disease? For the past 25 years, the Linus Polling Institute has served as a world-renowned research center at Oregon State University. Our mission is to promote optimal health through cutting-edge nutrition research and trusted public outreach. We use a synergistic strategy connecting several scientific fields to bring a better understanding to dietary components and the role that they play in obtaining optimal health. We provide that information to the world, allowing people everywhere to live longer, better lives. Welcome to the Linus Polling Institute's webinar series. Hi, everyone. Welcome to the next edition of our webinar series. As people start to come online, I'd like to start with a couple brief introductions. First, I'd like to introduce myself. My name is Emily Ho, and I'm the director of the Linus Polling Institute. The Institute is a research center within Oregon State University in Corvallis, originally founded by two-time Nobel Prize winner, Dr. Linus Polling. And our mission is to promote optimal health through our nutrition research and outreach programs. In other words, we are the scientists that look at the foods that you eat and the supplements that you take to determine how they can help you live longer, better lives. Today, our webinar is our first presentation on healthy aging with the focus on brain function. Our speaker today will be Dr. Kathy Magnuson, our resident neurobiologist, who will review what changes in the brain we can expect with aging and maybe just a few things we can all do to make it better. Just a quick note, this is our third webinar in our series for 2021. And this year marks our 25th anniversary of coming to Oregon State University. Our first webinar in the series was on vitamin C in health back in February, and our last webinar in May was on vitamin D and immune function. Links to both these webinars and many other resources can be found on our website. We'll have that addressed for you at the end of our talk today. So that's enough for me for now. Now, hand off the range to Dr. Alexander Michaels, who will be our moderator for today's events. Thanks, Emily. Thanks for getting us started. Hello, everyone. For those who don't know me, my name is Dr. Alexander Michaels. I'm both a researcher and a communication officer for the Lions Falling Institute. I have served as a moderator for our previous webinar series, and I'm happy to be back and see you back all for our latest presentation. The turnout for this presentation is pretty amazing. We have over 700 people registered, almost 800 people registered for this webcast. We're always glad to see the interest everyone chose in the Institute and topics related to research focus at the Lions Falling Institute. It means a lot to have you here today with us. So it's my honor to introduce Dr. Kathy Magnuson today, but before I do, I'd like to run down how this webinar is going to be running. We have about an hour with our speaker today, and we'll start with her presentation outlining the basics in brain aging. After that is over, she and I will spend the rest of the time handling questions. So people have been submitting questions both before during the registration process, and they can also submit questions during the Q&A portion or any time during the talk because there's a Q&A button right below me. If you can enter your question there, we will see it, and we'll try to get to all questions that we can during the Q&A session, but if we can't and we run out of time, we'll provide some extra resources for you to get in touch with us if you don't have your question answered. So at this point, I think it's a good time to get started. Kathy, can you turn on your camera? So Kathy comes to the Lions Polling Institute. Well, I guess I'll go through the long road to the Lions Polling Institute. She received her DVM degree. So Kathy is both a DVM and a PhD, but she started with a DVM from the University of Minnesota, College of Veterinary Medicine, and took care of Darry Cowes. She says in two years in Central Minnesota, sorry, say Montana, I'm in Minnesota, before returning to the University of Minnesota to pursue a PhD in veterinary anatomy and neuroscience. Following her PhD, she went to Colorado State, College of Veterinary Medicine, and then to the WWAMI Medical Program at the University of Idaho. Since, as she puts it, the medical students weren't interested in hearing about treating milk fever in cows at minus 40 degrees, she applied to work at Oregon State University's Veterinary School. She's currently a professor in the Department of Biomedical Sciences at the College of Veterinary Medicine and a principal investigator in the Lions Polling Institute or Oregon State University. The primary research focus of the Magnuson Lab is investigating the effects of aging and DAA receptor, and you'll learn more about that receptor in just a moment during Kathy's talk. She's recently begun to do some delving into Alzheimer's disease research, so that would be really exciting to hear about. And in her spare time, she takes advantage of the McDonald Douglas Forest to exercise her dogs and reinvigorate herself. And she never seems to have a shortage of Monty Python quips at her disposal. So with that, I'll let Kathy take it away. Thank you very much, Alex, for that introduction. Welcome, everybody. And thank you for joining us. I'm hoping that you'll be able to garner some tidbits about how to help your brain age a little bit better. So without any further ado, I will get my slideshow started. Okay, so today, we're going to address that old age question of why you and your dog can't find your keys. So the focus of the LPI's healthy aging program is improving health span. So this is the number of years of your life that you live without disability. So we can see some curves here of decreasing vitality with increased age. We're interested in finding interventions that will push that out such that you have greater vitality for more years. And according to this cartoon, the ideal is to push out to your maximum life potential, lose your chlorophyll, and fall off the tree. But I think that refers to a different species, but you get the idea. So the bad news is, is there's multiple cognitive kinds that occur during aging. So the blues are long-term memory tests, grays are working memory, greens are speed of processing. All of these show a downward trajectory with increased age. Now it's not all bad news. So world knowledge, vocabulary, vocabulary, all of that increases with age. So I say just use big words and talk about foreign locales and you'll have a step up on the young people. So the goal of my research is to make this curve shallower and to allow basically improve the health span of your brain. This has two benefits. One, increased quality of life. But two, Alzheimer's disease is a disease that is on top of aging. And so the more you can age better than if you do develop Alzheimer's disease, you're going to push out the years in which you become debilitated. So other reasons that we care about brain aging, it can impact our activities of daily living. So these higher ones are like doing chores, going shopping, volunteering and more basic ones like getting yourself out of bed, feeding yourself, getting yourself dressed. And as the brain ages, that impacts your ability to do these. The age of brain contributes to you having a slower gait and to having gait instability because it's not able to integrate the sensory information that's coming in as well. And then as the rest of your body develops disabilities and you have diminished sensory input, you rely more on your cognitive resources to try and make sense of that. And if your brain is not aging well, then you're not going to be able to adapt as well. So the talk today, we're going to focus on cognitive aging, but we'll also talk about other changes that involve the brain. Then we're going to talk about what's going wrong with functions and structures, and then what's going right and current recommendations. And then because our pets have become part of the family and their brains age as well, we'll talk about their cognitive dysfunction syndromes and what can be done. So let's define cognition. So basically this is the process of acquiring knowledge and using it to think, to integrate that new knowledge with your experience and with what your senses are bringing in to be able to synthesize and analyze. So cognitive functions include memory, language, speed of processing, and then executive functions like cognitive flexibility, attention, and working memory, and we'll talk about those. Let's start with the good news on functions. So I've already said world and verbal knowledge increases. Short-term memory, we used to say that you could remember a number as long as it took to dial it, and that's seven numbers, and that is relatively spared as we get older. To sustain the tension is maintained. So when we decide to focus on something, we are able to maintain that focus. Language is mostly preserved. So phonology, being able to correctly pronounce written words, your vocabulary, your ability to apply the rules, governing sentence structure, that's all well-preserved into old age. Where we do have a little bit of a lapse in languages with semantic, but it doesn't happen until our 70s. And so we test that by verbal fluency, asking you to name as many animals as you can, as many vegetables that begin with the letter C, or show you objects and ask you to name them. And you can see that here in the naming task, humans show a decline in their 70s. All right, so now getting into some more of the sort of bad news. So executive function is affected by brain aging, and cognitive flexibility is one of these executive functions. The way that I think about it is you probably have a usual route to get to work or to your doctor's office. But if you live in a place like Minnesota, where there's two seasons, winter and road construction, you're inevitably going to run into an obstacle to your usual route. And that first day that you do that, you're going to be late. But if you're cognitively flexible, you'll be able to use what you know about the area around you to come up with a new route. And more importantly, because road construction never takes one day, you will remember that you need to use that alternative route because the rules have changed. If you persist and can't think of an alternative, or if you forget that you needed to use your alternative, then we say that you're persevering on the old route. And you can see that perseveration increases with increasing age and cognitive flexibility therefore declines. Some form of attentions do show declines with aging. And one of them is divided attention. I like this picture because it's a couple who's hugging while both are looking at their phones. So that ability to do that is going to decline with increasing age. And then your ability to attend to a specific thing when there's a lot of background noise or interference, that also declines with increasing age. So this kind of goes to our theme about forgetting where you put your keys or where you parked your car. So part of that is that you don't pay attention. You're often doing two different things when you're doing those things. When you park your car, you're headed to the mall. When you drop off your keys, you're headed to do something in the house. So my hint here is stop and pay attention to what you're doing where you parked your car, where you put your keys, and you're more likely to make a memory of that. Another executive function, working memory, that declines with increasing task difficulty. So this is a short-term form of memory, but you need to be able to manipulate the information as things change. This involves the prefrontal cortex and other parts of the cortex. So the way that I think about working memory, a good example is plain bridge. So you have to remember what the bid was. And then as the cards are laid out, you have to remember where the danger cards are, have they already been played? But then when the hand is over, you have to forget all of that because it has no relevance to the next hand. So with increasing task difficulty, we do see some declines with age. The worst news is with respect to long-term memory. So some forms are affected very early. Now, procedural memory is not. So if you learned how to play an instrument, if you learned skills, that is typically spared with increasing age. But your ability to remember events and things that you can declare that you know, that already starts to decline in your 30s and progressively deteriorates. And new learning is affected more than old. Visio-spatial ability is also impaired. We test this by having people identify incomplete figures. Or this particular study, they showed them a slideshow through a neighborhood. And then later showed them two images and asked them to estimate how far apart those images were. And when it was presented in logical order, you can see that the older adults did as well as the young. But when they scrambled the order, then the older adults were impaired. And their interpretation was that they were not able to make a cognitive map and then draw from it as well as the young. So my research career has been focused on this decline in spatial memory. I primarily use a task called the Morris water maze. And you can see that here. It's basically a water tank with colored water, a platform submerged beneath the surface. And we've got cues around the room or high on the tank wall for the animal to make a spatial map. And if they have good spatial memory, then they will get more and more efficient at finding that hidden platform. Now, one of the problems that we have seen with translational research going from rodent studies to human is that we often don't use the same cognitive tests. And so my lab in collaboration with Scott Moffitt and Jimmy Zong at Georgia Tech University, we designed a virtual water maze version that appears to mimic what we see in mice. We were able to apply this study to looking at young and old men. And we can see that the older men were impaired in the water maze compared to the young participants. Now, some good news about that from our mouse studies. So we can see that the mice, again, the old mice were impaired compared to the young. But if you give them enough training, then they can perform as well as the young. So it appears that in old age, we just need more repetition. So my advice is rather than watching Jeopardy once and forgetting everything, DVR it, watch it several times, and then you're likely to own that knowledge. Another thing that changes early, starts early, is speed of processing. So your ability to perform simple, repetitive, cognitive tasks very quickly and fluently. And we can see that three different ways that this is tested all show declines with increasing age. So some other changes that are related to brain aging, but also involve the rest of the body. So we see declines in muscle strength and tone. Some of that is integral to the muscles themselves. But some of it has to do with the fact that your motor cortex is not, if it's not functioning well, it's not sending out commands to move. Gait also, a lot of these things are influenced by the muscles and the joints. But if the brain is not able to integrate the sensory information coming in and adapt to changes in the body movement, then you end up with diminished arm swing, shorter stride, and a feeling of being imbalanced. Also with respect to sensory function, the majority of problems are in the periphery, your eyes, your ears, other sensory organs. But it still requires the brain to integrate that information in order for you to respond to the environment. And as we age, that becomes less fluid. All right, so we've been talking about cognition for the most part. And what influences the cognitive aging is changes in brain structure that we'll talk about, changes in brain function. And all of these are influenced by other factors. Now, education and genes, I think of that as kind of giving us our set point, but as we'll talk about their lifestyle changes that can impact the trajectory of brain aging. So what's going wrong structurally? So we know that we get a decrease in brain weight size with increased age. And the ventricles, which are the fluid field spaces inside the brain, they tend to enlarge. So you see here a young brain in an MRI scan. The white out here is the skull. And so you can see that the young brain pretty well fills this cavity in the skull. And the ventricles are a nice small size. But in this 87 year old, you can see that we've got a lot of space in between the gray matter areas here and the ventricles are enlarged. So basically you've got less gray matter to work with with increased age. And this is also an example of that. A nice healthy brain here. Here you can see that the folds have shrunk. Now, this decrease in size is not homogeneous throughout the brain. So the prefrontal cortex, which is where our executive functions are being established and produced, is more affected. And the temporal cortex, including the hippocampus, which are important for memory formation, are more affected than regions like the primary visual cortex. So the way that neurons communicate with each other is that the axons of one neuron will release transmitter onto the receptors on another neuron. And so there are a lot of transmitter systems that show decline with age. Now, my lab and my research career, I've been focused on the NMDA receptor because of its importance for making new memories. And it shows declines in density with increased age. So this is density of binding in mice and the yellows and the reds are high densities and the blues and the greens are low. And so you can see in an older mouse, we have reductions in density of NMDA receptor binding throughout the cortex, including the prefrontal, which we're focusing on today, as well as declines in the hippocampus. So my job has been to try and characterize these changes and try and see how we can intervene to prevent these changes or revert them. So what else is going wrong? Neuropathology. There are some typical pathologies that occur in the aging brain. So if you've heard of Alzheimer's disease, you may have heard of senile plaques, which are accumulations of beta-amyloid protein extracellularly, and then neurofibrillary tangles, which are an abnormal twisting of the tau protein that seems to accumulate inside neurons and kind of choke them off. And so these pathologies are hallmarks of Alzheimer's disease, but we also see them in just the aging brains of normal cognitively functioning people. And so now we're trying to figure out what is it that takes you on a course to Alzheimer's disease versus just normal aging here. So another thing that we're interested in in the Linus Pauling Institute is Alzheimer's disease. And so these hallmarks of amyloid beta and tau, they actually start accumulating two to three decades before you get a diagnosis of Alzheimer's disease. And so we're interested in collaboration with the Hagan lab. My lab is working on studying this early window of changes in an animal that has amyloid overexpression. We think this is going to be the best place to intervene to prevent the development of Alzheimer's disease. You've probably heard of atherosclerosis, the hardening of the arteries. This is a problem for cognitive function, both because it can lead to strokes and mini strokes, but also it just decreases the amount of blood that gets to the brain and can interfere with the diffusion of nutrients across the vessel. And so atherosclerosis is a contributor to cognitive aging. And then cerebral energy metabolism declines up to 10 to 30%. And what's shown here is a type of metabolism called aerobic glycolysis. And that tends to be very high, this yellow area, in areas of the brain in young that are very, very plastic and able to change and learn. And you can see that even in a cognitively normal adult, there's a decrease in this type of metabolism, suggesting that you have less reserve capacity at this stage. All right, enough of the bad. What's going right? So the brain is still plastic. The old brain is still plastic. So neurons respond to the environment. You can increase the volume of different parts of the brain by using those functions associated with those parts. So use it or lose it does seem to be a key for positive brain aging. What else is going right? So when I was young, I was told that I was born with all the neurons that I was ever going to have, and that they decline, they die off as we get older. Well, that turned out to be a factor of the way that they were studying the brain. So it turns out that now that we're able to better estimate actual neuronal numbers, you can see that rats maintain their neurons throughout life, even ones that are impaired, cognitively, and that humans don't have as great a downward trajectory as we had originally thought. Now, the neurons do shrink in size, and that does have functional consequences. But again, going back to the fact that we've got the ability to be plastic, as long as those neurons are there, we have the possibility of preventing that shrinkage. And also, new neurons are born throughout the adult life. So all these green cells here are new neurons that were born after the animal reached adulthood. Now, the bad news is in this study, they're looking at six-month-old rats and 18-month-old rats. The birth rate does decline with increased age and the survival of those new neurons declines. But we've still got new neurons being born. And the neuronal dendrites can still grow. So this is the cell body here, this triangle, and the majority of these processes are called dendrites, and that's where a neuron receives most of the communication from other neurons. And you can see that with certain interventions, we can increase the complexity and the length of these neurons. And this was a study in humans showing that in this study, you could actually see an increase in the length of these dendritic processes from the 50s to the 70s. But unfortunately, it did then decline in variable age. So loss of contacts can cause adaptation. So this represents the different colors of axons here are different sets of neurons. And this is an experimental model where they lesion these pink axons, leaving this part of the dendrite bare. And what they find is over time that these other healthy axons will branch and will move to cover those openings on the dendrite. And if you give them enough time, the old rats can get up to the same number of synapses as the young. It just may take longer. So basically the bottom line is you need to focus a little bit more, you need to do more repetitions, and you need to give yourself a little bit longer to recover from any insults. So what are the current recommendations? So these are the recommendations from the National Institute on Aging. They recommend physical exercise, brain exercise, social interactions, and a healthy diet. So although they do not currently have a recommendation for any specific diet or specific supplements, they do believe that you should at least use the USDA's MyPlate for Older Adults as your guideline for health and diet. So let's see the evidence for these things. So rodents who are given a running wheel show evidence of new neurons, more new neurons being born, and better memory. So this is an example. These black dots represent new neurons that have been born. And you can see we have a lot more being born than in the control, and that the runners keep, have more survival of those new neurons than in the control. And then this shows the same trial for the runners, and they showed more efficiency at finding that hidden platform than the controls did at the same stage. So more new neurons, better memory. Exercise in humans has also been shown to show positive changes. So this was people who exercise. This was aerobic exercise over a year versus those that just did stretching exercises. The exercisers showed an increase in hippocampal volume, that region that's important for making new memories. So the evidence for brain exercise and social interactions, there's an intervention called enriched environment that we use in rodents, where we put them in a larger arena and give them running wheels, give them toys to play with, give them other mice to interact with. And that shows increases in volume in the visual cortex, in the somatosensory cortex because they're touching different things in the motor cortex because they're exercising and then also in cognitive tasks. So the enriched environment, this is the intervention that I showed here. It was due to enriched environment that you got this increase in size and complexity in older animals. And then enrichment produces new neurons again. So we can see enrichment at six months of age and in the older rodents as well. OK, so practically what does that enriched environment means? Well, when I first started studying it, I thought, OK, it means we have to go to Disney World every day, but they have to change the rides every two weeks so that we have more novelty. But we can do things closer to home. So one thing is change your habits. So if you always take the same route to the store, same route to the doctor, it's like take a different route. You don't realize it, but you're on remote control because you're so used to that route. You're not attending to anything in your environment. And so by having to take a new route, you have to sort of watch out for where the school zone is, where children are playing, where the stop lights are, all that kind of stuff engages your brain and will help. Also just changing how you get started in the morning when the order in which you brush your teeth and take your pills and get dressed. Change that up and you're going to get your brain active. Develop new interests or hobbies, especially ones that will challenge your mind and learn something new, learn a new language, learn a new skill. All this will help your brain. Have a diverse array of daily activities. So this was a 10-year follow-up study where they asked people about where they were they working, were they volunteering, were they interacting with children, were they having leisure activities, were they exercising. And those individuals that showed high activity, high diversity of activity at both visits, as well as those that increased their activity over the 10 years, they showed really good performance on cognitive tests, including executive functioning and episodic memory. But those that decreased their diversity or had low overall did more poorly. With respect to cognitive training, basically the good news is that it helps with what you're specifically training for. So if you do memory training, that will improve memory. The bad news is it doesn't generalize to other functions. It doesn't have a general effect on the whole brain. But that just means that you need to do interval training. Do vary the type of training that you do for your brain and you'll get a more overall effect. Now, the good news is, is that it can have more practical effects on different functional outcomes. And so practically speaking, it has some cross-activity. This was an interesting study where they looked at the effects of simultaneous brain training and exercise and basically found that it appeared to have a greater effect than cognitive training alone and a greater on cognitive outcomes and a greater effect on physical outcomes than physical exercise alone. So this is something like learning some complicated steps to a dance while you're performing them or it can be doing brain games while you're on a stationary bike or treadmill. Social interactions, there's evidence that those people with higher levels of social interaction have better cognition. Unfortunately, this did not hold up as well for dementia or Alzheimer's disease. But again, if you can maintain a good brain function throughout aging, then you're less likely to have the debilitating effects of dementia. Okay, so what about diet? So again, National Institute on Aging does not have any recommendations right now for specific diets. They do recommend the My Plate for Older Adults that was established by the USDA and that's shown here, fruits and vegetables, whole grains, fish and white meat, a little bit of dairy, et cetera. These are considered a healthy diet for older adults. Now the Mediterranean diet is promising. They are currently doing the double-blinded controlled studies with that. And it is similar in composition to what is recommended for the My Plate. Polyphenols show improved cognitive performance and decreased risk of Alzheimer's disease and polyunsaturated fatty acids, particularly those high in omega-3s, also show some cognitive benefits and decrease Alzheimer's disease risk. And so examples of polyphenol-rich fluids are shown here. Blueberries and strawberries have shown really strong cognitive improvement in old rodents and polyunsaturated fats, things like fish, walnuts, soybeans have shown some promise. With respect to vitamins and minerals, the one thing we do know is that preventing deficiencies is important. So particularly vitamin C, vitamin D, vitamin E, and vitamins B6, 9, and 12, all are important for good cognitive function. And so making sure that you're not deficient is important. The jury is still out on whether supplementing beyond the requirements can help with cognitive aging. So sort of stay tuned for that. And as always, if you are considering a dietary supplement, consult your doctor first because they can interact with drugs that you're taking. So for more information on the nutrients that are good for cognitive function, I will direct you to the Linus Pollen Institute's Micronutrient Information Center and then for general advice on taking dietary supplements, the National Institute on Aging. With respect to multivitam and multimineral pills. So I sort of go by the advice of our former director, Dr. Baltz-Fly, where you don't want the supplement to replace a healthy diet, but most of us don't get all of our requirements through our diet every day. And so that pill is a very cheap insurance policy. So I take it for that reason. Here at the Linus Pollen Institute, we are studying multivitam and multimineral supplements in older people starting with older men. And the Hagen lab and my lab are looking at absorption, cellular metabolism, and cognitive function. One diet recommendation I can definitely make is avoid high energy diets. So this was a study done in young mice and high sucrose diets, decreased cognitive flexibility and memory performance in young mice. And in probe trials, both the high fat and the high sucrose showed increased perseveration for the old position in cognitive flexibility tests. Okay, so in summary for humans then, we're recommending physical exercise, brain exercise, social interactions, and maintaining a healthy diet. So what about our pets? So although they have a shorter lifespan, they do have sort of a faster trajectory with respect to years of brain aging. They saw a similar trajectory to us. And so they've identified a cognitive dysfunction disorder in these pets. This abbreviation dishel is a mnemonic for veterinary students to try and remember the symptoms. And there are things like disorientation, confusion, an animal that used to go to the handle side of the door to go out now goes to the hinge side. Or they get stuck in a corner of a room that they should be very familiar with. Social interactions may change, so they may not greet you at the door. They may become aggressive. Their sleep wake cycles may change, and they might be sleeping all day and bothering you at night. Animals that were housebroken may now be having accidents in the house, and that's why she's brought in the entire rug when they ask for a urine sample. Their activity decreases, their anxiety goes up, and this syndrome has been studied in the lab for learning and memory tests. Feline cognitive dysfunction syndrome, again not using the litter box when they've been really good at that their whole lives, showing aggression to other animals or to humans, vocalizing more restless excessive grooming. So to diagnosis is basically a rule out because there's a lot of different medical problems that these older pets get that can show those symptoms, but these other systems we've got diagnostic tests for. So often you run a battery of diagnostic tests to rule these out. If those are normal, then you've got a diagnosis of the cognitive dysfunction disorder. Although dogs do develop plaques, the quantity does not correlate well with the behavioral declines, so imaging has not been helpful. What basically has been helpful is a behavioral questionnaire that your veterinarian can use every visit. They recommend starting in middle age so that you can kind of know what normal is. But if your veterinarian is not doing this, you can every six months fill out one of these questionnaires that are available on the web and be able to track changes. So this is an example of one that I like because it's a little bit quantitative. It asks you how often things are happening. Once a month, once a day, how often do they stare blankly at the wall? How often do they fail to recognize familiar people? And then they ask compared to six months ago, is this more or is it less? So what can we do for them? Well, it's basically along the same lines as what we said for people. So enrich their environment, making sure that they're getting exercise, that they're getting new toys, that they've got other animals to interact with and try and stimulate them, make them hunt for things. I used to do a thing where I would hide these chewable sticks in different places and make them hunt for them. And I would put them in the same places so that I could see if they had remembered. And this, again, is best started at kind of middle age. They recommend maintaining a routine. So animals are experiential learners. They don't understand when I say, I'm going to be home at four o'clock today, not six. They just sort of get into a groove of when things happen in the household. And so that decreases their anxiety and stuff if you maintain a routine. Now, with my life, there's nothing that's routine about it. And so my dogs don't have any kind of a routine. But I reason that I am training them in cognitive flexibility. So either go with the recommendation of maintaining a routine or you can use my rationalization of stimulating their flexibility. There are some drugs that have been used successfully in dogs. So ciligeline is a monamine oxidase inhibitor. So it basically increases the levels of dopamine and norepinephrine, which is like adrenaline for the brain. So basically I think these just allow them to be more alert and more active during the day. But people have used things to decrease anxiety, anti-inflammatory drugs, drugs that enhance alertness or cerebral perfusion or hormone replacement therapy. And then HILS has a diet. So it started out as prescription diet that they did a study on called the brain aging diet. And it's high in vitamin E, C, selenium, L-carnitine alphalopoic acid and omega-3 fatty acids. And they did a study and showed that they could see improvement in cognitive function with this diet. Now I don't see this diet on the web anymore. I believe they have incorporated this into their seven plus regular diet. And then Purina One has a vibrant maturity, seven plus has the same vitamins as above, but they focused on triglycerides to provide different energy source. And then phosphatidylserine. This is a phospholipid that has been shown in rodents, dogs and humans to have some benefits in improving memory and cognitive function. So to summarize, we talked about this downward trajectory for cognitive function, but we do believe that there are some interventions that can help make this a shallower decline. And at the Linus Pauling Institute, we think it's going to take a combination of dietary and lifestyle factors to help increase the health span of both the rest of your body as well as your brain. So if you want to have human research reflecting you and your sort of place in the population, I recommend that you get involved in research and be represented in human research. And here at OSU's Center for Healthy Aging Research, we have a life registry. And if you live in Oregon and are age 50 or older, you can register. When there's a new study, you will get contacted to see if you're interested or to see if you're eligible. And so again, if you want the research to reflect you, then you should get involved in the research. And with that, I will take questions. Thank you for your attention. Okay, Kathy, thank you so much. That was an excellent primer on brain aging. I think we all learned a little bit about what the problems are in the brain as we get older. Hopefully we all found something to keep what we've got around for a little bit longer than we thought. I know a lot of people have been waiting for the Q&A section. I would like to remind everyone that we are going to take questions in the Q&A section only. I've seen some activity in the chat, but if you have questions that you've put in chat, please put them in the Q&A section because we are not monitoring the chat for questions throughout the presentation. And I'm going to settle a couple of ground rules for the questions that I'm going to be answering. We can't ask any, or we can't answer any medical questions We're not a medical facility. We're not medical professionals. We can only advise, we're nutrition scientists. In the case of Kathy, a neuroscientist. So we're not going to ask any specific questions about health conditions, for example. And also we're going to just stick to questions specifically on brain aging as well, or brain function, brain aging. I'm not going to be answering, asking any questions that are about general supplement use or other related questions. Okay, so with that, let's get started. I think one of the first questions that we got was, what exercise can we do to promote memory and brain sharpness? I think the people were asking about different types of exercise. What exercises do you think are appropriate, Kathy? Yeah, so this can be a range. It can be mild to moderate that shows just the same kind of improvement in cognitive health as doing vigorous. So even just walking for maybe 30 minutes a day, something like that has shown benefits. Okay. Let's, so I think the next question is, why do you think there's a difference in the changes in the long-term versus the short-term memory with age and not uniform with both? Right. So that short-term memory, the remembering seven numbers, just long enough to dial it in the old days, that is really just a reverberating activity of a group of neurons. And they're only active as long as you need to remember that and then they stop. But with long-term memory, you actually have to make new protein and make new processes on your dendrites in order to have that long-term memory. And so that takes, there's a lot more chemical reactions that occur in that. And there are a number of ways that the age brain has problems with that process of making the long-term memory. Okay. So to some degree it's a protein synthesis receptor problem. Correct. Just not as agile as we used to be, I guess you could say. Okay. So we were definitely getting a lot of questions about supplement use, supplements and drugs. And I think I know you can't really go into all the individual supplements and drugs. So I'm just going to lump this into a very generic question. Are there any drugs or supplements that you would recommend to people who are interested in trying to fortify their diet or boost? We've heard about supplements on TV. I know there was one that was promoted just recently. There was also drugs from the FDA. Do you have any comment on any of those? So I basically do kind of stick with the recommendation of the National Institute on Aging and say that where we're at as far as the research is just going with the healthy diet. Now, if you are interested, there are a number of different supplements and drugs that have shown promise in rodent research or have shown promise in observational studies. Those people who take it are doing better than those who don't. And so I would refer people to a couple of amazing resources. So one of them is the Linus Pauling Institute's Micronutrient Information Center. You can find out about how different nutrients and such will improve cognitive function. But then there's another resource, the Alts Discovery Organization. And basically I discovered this. They have a huge database where neuroscientists have reviewed the rodent and non-human research, as well as clinical trials, and have come up with summary analyses. And again, it's like there's so many things out there I cannot possibly be an expert on all of them. I find that that is an excellent reference. And I think we're going to put that address in the chat. Yeah, I think we already have. We have links for both the Micronutrient Information Center and the other link that you mentioned. So people can go there if they have any questions on specific drugs, specific supplements. And of course, you know. It also has things on sort of the non-traditional things. They've got a review on meditation. They've got a review on transcardial stimulation, or not transcardial, trans, I can't think of the term. Anyway, stimulation of the brain. So they have, they have some, it's an excellent resource. Okay, I guess this is kind of related, but I'm going to ask you a question about brain games. I mean, I'm a big fan of brain games. And so I've been doing those since I was a kid. Do they, I mean, do these games or these apps that they sell, do you think they really help? Yeah, I do think they do. Now, there aren't any one, you know, app that is again being, you know, generally recommended, but I can tell you that Lumosity and Elevate, as well as the Nintendo's brain age games, I recognize cognitive tests. And so basically their training using the same kinds of tests as we, you know, test cognition. And so for visual spatial, Gasly's group has been working on, they had a neural racer program that, that they used in their experiments. But I found one called Neural Runner that is from their, from their business. And I'm interested in trying that out. That the neural racer has actually been approved by the FDA for ADHD. So it's the first video game to be approved by the FDA. And so, but Gasly's group has always been interested in aging. And so I expect that he also is probably on a trajectory for, for that too. And when you, when you say ADHD, is it all age groups? Yeah. Yeah. Yeah. For that one. Yeah. Right. Because basically it went, but what it is, is it both helps with spatial memory, as well as multitasking. Okay. Okay. Yeah. All right. That's, that's a good, the good thing I would say, you know, doing crosswords will help keep bringing up old, old memories, plus you're learning new things. So do go, I'm, I'm always kind of questionable about, I sort of got to three main strategies. And felt like I wasn't pushing myself after that. So I don't know, I suspected it's helpful, but, but I'm not a sure. But anyway, all of these are just my experience with, with specific brain games. But I think that Gasly and others who do work on cognitive training, they recommend using things like maybe Minecraft or something like that where you're building new environments or one of them used Super Mario World 3D. And the deal there is you are increasing the novelty and your brain loves that. And your brain is going to respond to that. I guess I'll, I'll transition. We only have a few minutes left. And I apologize for pushing up on five o'clock, but I'd like to transition briefly just to your, the, the study that we're both involved in right now, the multivitamin trial. So you're using that virtual water maze for that trial. Right. And that's almost like a video game. Exactly. Yep. Yep. They use a joystick to basically move through the water and find the hidden platform and use the cues on the side of the room. Yep. Okay. Yeah. And so, yeah, this is a trial just for everyone's knowledge that's looking at the effects of multivitamin supplementation that we hope to have some more information about that one soon. We got a very specific question. I think I'm going to have to leave with this one, but so this will be the last question. But in your animal models, did you measure any, well, specifically the question is about nicotinamide adenine dinucleotide, which the short version is NAD. In the younger and older animals, do you know if NAD levels are changing in specific brain regions? So I don't know. That's not something that I've specifically been interested in. So I'm, I'm more focused in my animal studies on that NMDA receptor and characterizing what's going wrong with that. And it changes dramatically. So your, your old, your old NMDA receptor is not like your young one. And in fact, may even be bad for memory because it has a different makeup of protein subunits. And so I'm trying to figure out how to, how to prevent that going bad. So yeah. And of course, there's always the, you know, what, what vitamin mineral changes in the, a neuron or a specific region of the brain with age. And that's an incredibly difficult question to answer. I know the pieces of brain that you're typically working with are, are quite small. And some of the tests that we can do, you know, just can't get down to that sensitivity, although we're always pushing the envelope. So, so with that, I think I'm going to have to end it here. I apologize to everyone that I wasn't able to get to all your questions, but I'll thank you, Kathy, for, for giving us that presentation and sticking around for a Q&A. All right, very good. Thank you. Yep. And if, if anybody has any lingering questions, you're free to send us that at lpiatorganstate.edu. That's our email address. And we try to address all the questions we can, but, and Emily just preempted me. I was going to invite her back in and give us, close us out for the session today. Emily, take it away. Yes. Thank you all for your time today. Healthy aging is a big research priority for the Lyme's Polling Institute in the spirit of Lyme's Polling. We hope you learned a little bit more about how to live better using the best of what science has to offer. So a couple of resources for those of you want more information. Don't forget to check out our website, especially if you want to revisit the webinar, this webinar, or any of our previous ones. We've already mentioned the Micronutrient Information Center for more information about the brain and cognitive function. And lastly, you want to make sure, we want to make sure you keep in touch with us. You can always email us, subscribe to our newsletter and make sure you're hearing all the latest and greatest about Dr. Magnuson's research and all the other investigations at the institute as well. In terms of the institute's work on healthy aging, we are having another webinar on healthy aging next month with our expert in aging and mitochondrial function, Dr. Tori Hagen, that was also mentioned. This will be coming on August 17th, so look out for more information. Lastly, I want to give thanks to all our generous supporters. The research presented today and all the resources at the institute are funded by many generous donors and these are people like you who have a passion for nutrition and health. If you're interested in the content, please consider donating to the institute. No gift is too small and every little bit makes a difference in helping us produce this content that's helpful to you. For more information, just send us an email or check out our website for ways to give. Again, just before we leave, again a huge thank you to Dr. Magnuson for really thought-provoking presentation and sharing her research with us today. We will be sending out the webinar links as well as the resources that were mentioned today to all of you via email. So we look forward to hearing from you and seeing what we have up next. Thank you also to Dr. Michaels for moderating once more. So that's it. Big thanks to all of you and take the time to learn more about your health. We'll see you next time in August. Thank you.