Could you predict your brain health? An interview with Owen Phillips Ph.D. founder of BrainKey

‍

Welcome to the first HealthyLongevity.guide interview where we talk with experts in the field of longevity, medicine, and diagnostics. Here we spoke with Dr. Owen Phillips, a neuroscientist and a founder and CEO of BrainKey – an AI and neuroscience startup developing a platform to help patients manage their brain health. In this interview, we will speak about neuroscience, aging, and the brain's longevity.

Image 1 cover

Link to the record here.

Agnieszka Szmitkowska (A.S.): How it happened that you become a neuroscientist? Where was the beginning?

Owen Phillips (O.P.): Oh, well, normally, people don't step back that far, but I was always interested in the brain. Such an exciting area. There's so much we don't know about the human brain. I got my start at UCLA. I was working at the Laboratory of Neuroimaging at UCLA. I just got so interested in visualizing the brain, understanding what was happening, especially in aging and neurodegenerative diseases. That was over ten years ago, and so much was coming out. And it was such an interesting field that I just really dove into that and started publishing. I continued my career from there and then eventually did my postdoc at Stanford University. Even before Stanford, I was so into artificial intelligence and combining that with everything we were learning about the brain. This has been such an amazing field to be part of the past ten years, and I think the next ten years is even going to be even more exciting.

A.S.: Yeah, I believe so. Is there one fact that made you think, okay, this is the thing that I want to pursue in neuroscience?

O.P.: For me, it really started to hit home that so much of what we understood about the human brain was based on really old studies. It's kind of terrible, but a lot of old neuroscience was based on lesion type studies where they'd actually cut into a patient or an animal's brain and then make some observations. And it's such a brute force approach. MRI imaging specifically, so in vivo imaging of a healthy person or a sick patient just allows you to get so much information about a living person without doing damage to them. And that for me, this visualization, was a huge conversion. If you're not too familiar with imaging, what I'm showing you here is actually a human brain (shows the 3D model of the brain from BrainKey visualization).

‍

Image 2

‍

This is a patient's brain where we took their MRI data and reconstructed it in three days. We're able to do things like this of a healthy person and track metrics about their brain health. This is the kind of thing that really makes it real. We tend to think of our own brain health and our own sense of who we are as something abstract. But when you get to visualize it and get real statistics about what's happening in your brain it becomes so much more real and that's really been exciting.

The other fascinating thing is that we can 3D print people's brains. We can do things like that, which are, of course, a little gimmicky. But it is actually really fun and nice to have your own brain 3D printed. The reason I mentioned that is that taking something that is in your head, protected by thick skull, and being able to really bring that home and put it in your hands is a way that you can understand your brain. It is so exciting to me.

A.S.: If we have an image of a brain or a 3D rendering of a brain, can you see a difference between a young and an older brain? When and where do the changes in the brain start when we are getting older?

O.P.: Yeah, let me pull this up. (shows the 3D model of the brain from BrainKey visualization). 

Image 3

Do you see this curve here, this light blue curve? That's kind of this downward trajectory. On the bottom here, this X-axis, we've got age ten, and at the far end of it, we've got age 80. What we're measuring here is how much gray matter you have in the frontal lobe of your brain. So, in the region, that's involved with all your really high executive functioning. It's involved in pretty much everything that you do as a human being but what happens as you age is that your gray matter – so the concentration and density of all your neurons - start to decrease. Part of that is just senescence. The cells kind of maybe wear out, and they die. But part of that is synaptic pruning. So, you just get rid of connections that you no longer need when you're older. So when you're younger, you have all this potential built up there, and you have this excess capacity, but not necessarily the efficiency to use it. As you get older, you get more and more efficient and get better at these pathways that you use. So, you can actually get, in a lot of ways, more efficient and smarter as you get older. But the tradeoff there is that maybe you have less capacity to just absorb new information or plasticity to learn new things. And the most obvious example is you see kids, little babies, they can make sounds, they can pick up languages, become bilingual very quickly. That's a little harder for an adult. That's an easy example. But physically, what's happening really is that your brain is actually changing as you age. So, we don't usually think of it, but your brain does age similar to your body, there are physical changes happening. So far it has generally been thought of as inevitable. But what's so exciting about the longevity movement is we're finding out that there are more and more things you can do to actually preserve your brain health as you go forward.

A.S.: It is known that lifestyle impacts even the size and health of the brain. What is the correct type of lifestyle that we could pursue to make sure that our brain will be as healthy as possible for as long as possible?

O.P.: I think we're still finding out what is the optimal lifestyle. And I think it's different for every patient. And that's what's so important, working with good physicians to make a real plan for yourself that's optimal for you. But we are finding that things are not ideal, like continual alcohol usage over a long period of time in excess. (shows the 3D model of the brain from BrainKey visualization).

Image 4

What I'm showing right here is the hippocampus. So that's a small structure that's involved in learning and memory. So when you recall memories, everything is really going through these small little structures. And this degenerates in patients with memory issues or Alzheimer's dementia. But we've seen that alcohol use or drug use can contribute to actually reducing the volume of structures like the hippocampus. So, lifestyle factors can really impact your brain health and the actual physical structures responsible for your brain functioning. It's also very important to stay socially engaged. Isolation and loneliness have been huge factors in brain changes, especially negative changes in volume. So that's, again, the type of thing where you want to talk with your physician. You just don't want to isolate yourself totally. So, it's a bit of a tradeoff there understanding what works best for you but definitely, in general, alcohol is not the best thing.

A.S.: What about physical exercise? I know that there has been some new research on this that physical exercise can help as well.

O.P.: Yeah, that's a huge one. I'm blanking on the exact quote, but essentially physical exercise is the best possible pill by far we have for treating brain health and brain longevity. If you could package exercise into a pill, you'd be worth billions. So, there are companies working on trying to replicate the effect of exercise on the brain and pharmacology approach, but really exercise can help structures again like the hippocampus. There have been studies on yoga practitioners, meditation, and rock climbers. Essentially engaging in physical activity can really help different parts of your brain. When you think of exercising, you're getting the cardio, you can get the strength, but you're also going to be using your brain a lot in coordination and then interacting with other people and understanding yourself in some states. So, it's really physically and mentally demanding to be doing the exercise. The way I think of it simply is an amazing pill. It takes some effort, of course, but you're going to get more results there than with anything else that we've had that's been developed.

A.S.: In 2018, you published a paper about the impact of insulin resistance and brain volume. So, what is the correlation between type two diabetes and neurodegenerative disorder?

O.P.: Yes, we are still figuring out exactly what that correlation is but, essentially your brain is incredibly energy-intensive. Your neurons are firing; all of those synapses are making all of these connections. It's incredible machinery that your brain is, and you need a ton of energy. The majority of energy resources actually go into your brain compared to any other part of your body—even your heart. If you think about anything that could disrupt your energy flow - diabetes type I or II is essentially messing with the regulation of how your body is getting enough energy there. And you don't want to have any sort of issue where your energy production is impacted. When your energy production is impacted, what's the thing that's going to be the most influenced is going to be the structure that depends on energy - the brain. So, what we are finding is in older patients where the energy flow is impacted, then they have reduced volume in the brain, and they will have memory issues and cognitive issues associated with that. Really depressingly, we also find that in children as well. Developing brains are even more energy-intensive, so early childhood diabetes and obesity seem to be associated with negative traits in terms of brain health. This is still all early research, but the conception is that your brain is really energy-hungry, so you want to make sure it's got the best energy flow possible.

A.S.: Aging is very often connected with chronic diseases. Do you think that neuroscience in the future will understand the brain enough to keep it sharp until 100 years of age and more? Do you think this will be possible to make us as sharp as we are in our 20s when we are in the 100s?

O.P.: That's incredibly ambitious, but I am hopeful we can get there. Those pictures I was showing you, those 3D renders of the brain - your brain is made out of cells, so if we do figure out the ways of modifying our cells to be better lasting a long time, then this opens up the possibility of really having optimal brain health, to live longer and longer. The portion of the population that is living longer just keeps increasing. There are so many people that are now 60 plus. Just from a business perspective, it's become so attractive to try to make therapies that extend life so that these people have an optimal lifestyle going forward—not just surviving but actually really having a great life and high-quality functioning. Of course, your brain health is such a hugely important part of who you are. There is no point in having a healthy heart or healthy liver function if you have dementia and you don't recognize your kids. We are working very hard to make this possible for you as a patient and for physicians to understand what's happening to the patient's brain. We really look forward to what's going to happen next. As I mentioned earlier, the next ten years, I think, are going to be so exciting for brain health.

A.S.: Is there something that's the main obstacle at the moment in neuroscience that is keeping us from stopping neurodegenerative disorders? I know that we still don't really understand them much, and there are still not many medicines or therapies that can help us with that.

O.P.: I think that this idea that we don't understand much is a bit outdated now. We were told that the human brain is this last unexplored frontier, but it is not, actually. The amount of literature going into neuroresearch is just exploding. It's hard to keep up even if you are in the field. There is almost an overabundance of knowledge. Taking all that knowledge and providing actionable recommendations, whether it's around the physical exercise, mental stimulation, or developing pharmacology to target specific drugs, specific symptoms, or specific diseases, was the big challenge. How do you take all this knowledge that's coming out, really exploding with these new advances in AI? The quality of data that you're able to collect on a patient - these visualizations I was showing you - is so data-rich. Then you add the genomic data, full genome sequencing, and so many other methodologies of collecting very high-value data. It's becoming more and more of a data problem. We are inundated with so much knowledge, and how do you break that down into something that could really impact a patient? I think that where we are at now is a bit of an inflection point. Before, it was so hard to get through the thick skull, too, to understand what was happening in the brain. Now we're really getting so good at that, and now it's a bit of how we wrestle with that data and translate all this information we're getting into action.

A.S.: I know that omics at the moment are a very big thing, not only in neuroscience but in general medicine. Is there any ongoing research project out there that, in your opinion, is the most hopeful in neuroscience? Something that really catches your eye that's going to be probably the future?

O.P.: (pointing at the 3D model of the brain from BrainKey visualization) Yes, so what we are doing at BrainKey – I am showing just the sample of the physician account - this has never really been possible as a patient to track your brain health. Here I actually see the hippocampal volume – I've got it at three different time points - so this patient has come and gotten an MRI scan three separate times over the past year. Being able to track this across different parts of your brain and have all this information at your fingertips is both so empowering for the patient and also empowering for the physician. To provide recommendations for the patient as well and find out what's working for them and what is not working for them. And then from the neuroresearch side, all of this is data that is so valuable to be able to do research on, to understand what is normal, what a healthy brain trajectory looks like. With all these different variables going into this profile of the patient, we are starting to be able to understand what's optimal for certain types of patients. Just to give a very specific example, there are movement disorders like Parkinson's disease, but there are some types of separate diseases such as multiple systems atrophy. These patients both have very similar movement problems. But when we actually look at the brain data, we can see that there are separate biological drives between those two different diseases. What that really shows is that using the same treatment for Parkinson's and multiple systems atrophy is not going to be effective. You need separate treatments for both diseases. So, these types of insights that we and other groups are developing are really leading to personalized treatments that are going to be able to help these patients going forward. And that's the big thing here that we are involved with - really bringing that back to you as a patient and directly to the physicians, so they can understand their patients better than they ever had before.  

A.S.: Thank you very much for this interview. It was a pleasure to speak with you.

O.P.: This was great. Feel free to reach out to me. You can contact me through the BrainKey website at https://www.brainkey.ai/. Thanks for the chat.

‍