Dr. Patrick: So, on the opposite end of treatment would be prevention. And I think looking at dementia and Alzheimer's disease more as a vascular disease sort of opens up the doors for a lot of preventative measures. You know, blood pressure, so it's actually very common, you know, at least in the United States, almost 50% of the U.S. adults have hypertension, and 20% of young adults do, age 18 to 39. So, how does high blood pressure affect the brain and dementia risk?

Dr. Montagne: No, that's very important. So, I would say at least there are three major...at least in my research, I'm not saying major...the three major cardiovascular risk factors, hypertension is one but there is diabetes and hyperlipidemia. But in terms of hypertension, and I think you've sent me a few papers, but I think it's very interesting to know that if you have early hypertension...so if you're young and you have hypertension, it's possibly more harmful than if you have it later in life and I guess it's just a question of duration. If you have a sustained...like, if you have hypertension sustained over many years, obviously, it can impact the stiffness of your blood vessels, it will impact, as we talked, the pericyte function at some point.

So, yeah, I mean, the bottom line is yes, hypertension is known to impact the brain and, like, the basal ganglia and those deep structures that suffer quite a lot from hypertension. Where we see also, there's always an association when people have hypertension, they tend to have more microbleedings also in this area of basal ganglia. So, yes, it does impact the brain and we know there's a few studies that show that hypertension also triggers blood-brain barrier leakage and pericyte loss. It's not the whole story, because in terms of small vessel disease, if we come back earlier, we have thought that one of the causes or maybe the major cause of small vessel disease was hypertension.

But nowadays, we know that's not the case because, to give you an example here, maybe a third or even more of the cohort of small vessel disease patients that we followed didn't have any hypertension, first of all. So, it tells you that there's a big chunk of people that can move to small vessel disease, meaning having white matter disease that was thought to be due to hypertension and how it damages the vessels, but it's not the case. So, that's a bit more complicated, but obviously, it's not good to have hypertension, as we know, for the brain and there are some studies showing that giving anti-hypertensive drugs has a positive impact on cognition as well.

So, it tells you that no matter what, if you have hypertension, you have to try to reduce it, obviously, pharmacologically because it will have an impact. But interestingly, to just go back at the beginning of my answer, it's a bit controversial but if you have early...like in the 30s to 40s, if you have early hypertension, you will have a likelihood and more chance to develop cognitive decline quickly as compared to like a normotensive person of the same age. And interestingly, they were showing also in the paper that if you have hypertension during your 70s, if I remember correctly, it doesn't impact your likelihood to develop dementia.

So, it goes back to I think...just the final point is I think it's very important, the duration, the chronic part of hypertension that is very critical. If you have that for many years...the same thing for inflammaging, as you age, you have a chronic low-grade inflammation that will disrupt your vessels very slowly. Probably the same thing with hypertension. If you have too much hypertension, your arterial stiffness will be, you know, disturbed and damaged over time and this will degrade your blood-brain barrier much faster than the normotensive person.

And this has regional specificity and different sensitivity in the brain, yes, but that's an active area. Again, we have tools now to measure these brain regions, how they leak, and try to compare with people with hypertension. But the difficult part in clinical research is no one is hypertensive and nothing else. There are always comorbidities, obesity, or other things, so it's hard to disentangle what pure hypertension is doing to the blood vessels because there's always other things. You can try to correct statistically with covariance and some things but it's quite hard to study.

Dr. Patrick: So, it does seem like...as you mentioned, cumulative exposure seems to be the more important thing here. And again, people that are probably in their 20s, 30s, 40s aren't even...if they have high blood pressure, aren't probably thinking it's a big deal, when in fact, that's probably the biggest deal because they're starting early with the high blood pressure.

Dr. Montagne: That's my thought and that's what we read, yeah. The same thing with exercise. I think what we hear from these recent studies is the critical window is...I don't know if I'm correct, you may know better than me, but it's like 40 to 55 or something like that, where you really have to exercise. And to come back to the small vessels, you have to open them up and make sure they are functional. That's the critical window. I think it's partly true for sure but I don't know, you may know a bit more than me on that question. But yes, I think that's the time...

Dr. Patrick: Yeah, certainly, it's never too late to start exercising and there have been studies showing even in the 70s, you can have cardiovascular improvements. Of course, earlier is better, you know? And exercise, as you mentioned, it is one of the best ways to improve vascular function and improves blood pressure, arterial function, all those things. And interestingly, the sauna also does that, the heat stress, a lot of the physiological aspects of elevating the core body temperature.

Dr. Montagne: I didn't know that but that is interesting.

Dr. Patrick: And there's a lot of research. In fact, there is...of course, with, you know, observational data, you never can establish causation. As you mentioned, there's all sorts of, you know, covariates and things. But there are studies showing that, you know, dose-dependently, sauna use is associated with like a 60% lower dementia risk and Alzheimer's disease risk if you're using the sauna four to seven times a week. If you use it, you know, two to three times a week, there's like a 20% lower risk after adjusting for other factors as well. But we do know sauna...like, there's intervention studies, I mean, it's comparable to moderate aerobic exercise in terms of the effects on blood pressure, heart rate variability, and stuff. Also, it's sort of just interesting. But exercise being a really important one for, you know, prevention...you know, dementia and Alzheimer's disease prevention as much as you can do.