Dan Nation is a professor of gerontology and medicine at USC. His research focuses on vascular factors in the brain and how they affect memory decline and dementia in older adults. He joined us to talk about studying blood vessels in the brain to identify early signs of dementia and potential therapies to treat it.

Transcript

Speaker 1 (00:01):

The variability in your blood pressure day to day, month to month, year to year, and sometimes even beat to beat–the variability in your blood pressure is predictive of dementia risk. So higher levels of blood pressure variability are bad, even if you have very well controlled blood pressure levels. And this is important because currently we only treat average blood pressure. There is no treatment for variability in blood pressure. So it's a new area that we should try to look into controlling to see if we can prevent dementia in people who have high variation, even if they're already treated for hypertension.

Speaker 2 (00:45):

From the USC Leonard Davis School of Gerontology, this is Lessons in Lifespan Health, a podcast about the science and scientists improving how we live and age. I'm Orli Belman, Chief Communications Officer. On today's episode: how Professor Dan Nation is studying blood vessels in the brain to identify early signs of dementia and potential therapies to treat it. Dan Nation is a professor of gerontology and medicine at USC. His research focuses on vascular factors in the brain and how they affect memory decline and dementia in older adults. Welcome to our podcast Dan, and thank you for being here today.

Speaker 1 (01:26):

Thanks for having me.

Speaker 2 (01:28):

I wanna start by asking you about blood vessels in our brain. Is there anything unique about the brain's vasculature system, and how did it become the focus of your research?

Speaker 1 (01:39):

Yeah, it's a great question. So there's actually several things that are unique about the brain vasculature. For one thing, just the number of blood vessels. So you might think about the larger vessels that you can see with the naked eye, but most of the vessels are microscopic. And we have so many blood vessels in the brain that there's actually one blood vessel for every neuron. So every brain cell basically has its own microscopic blood vessel. So it's billions and billions of blood vessels, and this is likely the case because the brain has an incredible need for blood flow to support its very high metabolic rate. And the brain cannot store energy unlike other tissues in the body, and so any energy that the neurons need, they have to get on the fly from blood. So there's a torrential amount of blood flow that's disproportionate to the size of the brain.

Speaker 1 (02:34):

In addition to that, blood is actually toxic to brain tissue. And so the neurons need a special environment to operate, and so that milieu has to be well controlled. So the blood contains proteins, cells, infectious agents, metals, ions–all of which, if it were to get into the actual brain compartment, would be very toxic and would cause degeneration of the brain cells, cell death. And so their brain has a special structure that divides the blood off from the brain. This doesn't exist in other parts of our body; it's called the blood brain barrier. So that has to have integrity in order for the brain to survive and function properly. In addition, because of that, the way waste products of regular cellular metabolism and so forth, any other toxins that are in the brain, the way that gets moved out of the brain is different than other parts of the body because the lymphatic system in the brain is really different because we have to have this blood-brain barrier. So for a number of different reasons, the vessels are special. A lot of it has to do with the blood-brain barrier because the separation of the blood from the brain means that all of the nutrients have to be pumped actively into the brain. And all of these, again, waste products have to be pumped actively out somehow. And so any dysfunction there could lead to the buildup of toxins in the brain, which would cause degeneration.

Speaker 2 (04:11):

So your PhD is in psychology, correct?

Speaker 1 (04:14):

Yeah, neuropsychology.

Speaker 2 (04:15):

Neuropsychology. So how did you get interested in the vascular system?

Speaker 1 (04:19):

Yeah, I actually have always studied the vascular system because I was in a neuroscience lab that was focused on relationship between behavior and cardiovascular disease and basically neurovascular function and in particular as a clinical neuropsychologist we're involved in treating patients with neurocognitive disorders of aging, like dementia of Alzheimer's disease. And so I became interested in how these neurovascular factors may contribute to those diseases and to cognitive decline from those experiences.

Speaker 2 (04:54):

This sounds like a very complex system. What happens to it as we age?

Speaker 1 (04:58):

So as we get older, most people will develop a number of different vascular changes or will be at risk for different age-related vascular diseases. The most common is hypertension or high blood pressure. As we get older, the odds of developing high blood pressure just go up and up, and ultimately if you live long enough, most people will develop hypertension at some point. The majority of people over the age 65 have high blood pressure. And so that has to do with changes in your overall vascular system that can lead to a hardening or stiffening of the arteries and development of specific changes in the way the blood vessels of the brain work, which can damage the blood-brain barrier, lead to leakage of blood into the brain, decreased blood flow to the brain. And also what we've found is that older adults, their micro blood vessels don't dilate as well, and so they need to be able to dilate in order to provide more blood flow as needed to support brain health.

Speaker 2 (06:11):

It sounds like you know a lot about what's happening and the inner workings of our brain. Have updated imaging technologies improved our understanding of the role of these small blood vessels, and what can you tell us about your research in this area?

Speaker 1 (06:24):

Yes, so brain MRI has been very useful because it's usually relatively non-invasive, and we can use MRI to actually study the functioning of these microscopic blood vessels that would be otherwise very difficult to study. And we can actually visualize some microscopic changes such as small bleeds in the brain because they have this blooming artifact on brain MR. So we can see things that are microscopic, and we can study how the blood vessels can dilate or constrict using brain MRI. And we can study whether anything is leaking from the blood into the brain using brain MRI. So there's a lot more that is happening in MRI science that we're constantly monitoring and trying to incorporate into our studies. So I think there will be further advances, and we'll be able to study brain blood vessels even better in the future.

Speaker 2 (