Exercise 0:00 0
“if you don't exercise if you don't make sure that your heart is pumping at a high rate regularly during the week those tiny vessels that are even smaller than your air in terms of diameter they will start to collapse and you don't have and remember the capillaries it's it represents 90 percent of your brain vasculature all these tiny blood vessels so if you start not see if you don't do enough exercise you will start chronically to have some vessels that will basically constrict and collapse and disappear meaning that the surrounding neurons that are here and they need oxygen and nutrients and everything from these vessels if these vessels disappear you're going to lose neurons right”

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Disease prevention 1:03 0
“you're gonna turn uh you know the Easter prone to go to cognitive design because let's say you have a major genetic risk but if on top of that you don't exercise you're gonna accelerate as we know from study and and that's one of the biggest thing we have to to put that um you know we have to put to the world like okay we need to exercise that no matter what I mean if you want to stay healthy in terms of brain function yeah no other choice”

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Disease prevention 7:43 0
“we can predict future cognitivity tract so the people having more leakiness at Baseline when we scan them on when we measure on their plasma of CSF serum spinal fluid the level of vascular problems in the brain we know that there are more uh they're going to decline more faster than the people that have low levels of these biomarkers”

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Disease prevention 10:48 0
“we have screened people by the major genetic risk factor for Alzheimer's disease which is a polyproprotein E4 so we know that the people carrying this particular Gene have more chance to develop Alzheimer's disease than other people”

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Disease prevention 9:22 0
“we know that having vascular dysfunction will promote also um the formation of amyloid plaques in the brick so it's still unclear how this is uh going what we know for sure is based early vascular problems and we need to fix that to make sure that the brain doesn't develops and function normally to avoid dementia”

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Genetics 14:17 0
“screening people by ApoE genotype so if you have the genetic risk you could get the treatment”

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Disease prevention 15:25 0
“if we fix the blood vessels we may not be able to cure the disease but at least we will be able to postpone the symptoms by quite a few years for sure which is a big deal”

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Cognitive stimulation 15:12 0
“screening for a prohibit also screening for other things around that will tell you okay this particular individual will benefit from getting a drug that will fix the blood vessel”

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Inflammation 21:32 0
“the more you have the more inflammation the what we call Neural inflammation the more information you have in your brain so that's a normal aging process”

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Inflammation 23:51 0
“inflammation of the blood vessels might be one trigger and that's uh something we can Target therapeutically relatively easily by injecting drugs IV”

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Nutrition 24:28 0
“omega-3 being one of you know at the Forefront of um one you know omega-3 transport has been shown um mechanistically at least in animal studies to regulate blood-brain barrier function”

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Exercise 27:07 0
“we have to do some exercise some hierarchic exercise to make sure that the vessels we have tiny blood vessels in the brain so if you don't exercise you don't make sure that your heart is pumping and high rate regularly during the week those tiny vessels that are even smaller than your air in terms of diameter they will start to collapse”

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Exercise 28:14 0
“so exercise is the number one thing you have to to to do that not only for the brain obviously for the heart it's true for the eyes obviously or if you don't exercise you're gonna tend to lose eye vision quicker than the normal person as you age but very important for the brain.”

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Exercise 29:30 0
“if you don't exercise you're gonna get small vessel disease I mean you have it's a bit more complex and and I think that's a word I didn't say uh at the beginning but this dementia Alzheimer's disease is one but the second magic you know major form of Dimensions cerebral small vessel disease.”

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Cognitive stimulation 34:55 0
“we look at cognition whether there is some predictive value or whether there is some correlational association between these biomarkers and cognitive problems”

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Genetics 35:35 0
“this is the sporadic form of small vessel disease but there is also the genetic form”

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Disease prevention 35:14 0
“we have to fix these blood vessels very quickly to make sure that these people don't go into the small occurrence microblades and other things that will make them deteriorate very quickly in terms of cognition”

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Metabolic health 39:53 0
“reduced brain glucose metabolism can be measured up to decades even before any Alzheimer's disease symptoms or dementia symptoms occur”

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Nutrition 43:08 0
“I remember reading um a couple of studies years ago where uh animal studies where omega-3 deficiency caused a reduction in in glute one Transporters in the brain.”

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Nutrition 43:14 0
“Omega-3 deficiency also breaks down blood-brain barrier.”

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Nutrition 44:59 0
“I'll send you my paper I wrote a a sort of interactive review article back in gosh it must have been like 2018 or something I think and um it was it was on the important role of mfsd2a and omega-3 in apoe4 carriers and I have references because I for a lot of the studies like the the deficiency in omega-3 causing one Transporters to go down and uh so I'll send you my review.”

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Nutrition 45:47 0
“Omega-3 the fact that you give omega-3 tune to aged animals and I told you what as you age here for information like like an hyper activation of the brain on the tillium and a couple of studies I I've given some omega-3 to the mice and I remember seeing the reduction of one particular protein that I really like to study and we are currently studying is vcam what vascular cell Edition molecule one and that and uh and omega-3 was able to reduce these levels.”

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Disease prevention 50:27 0
“in if you compare a control brain someone cognitively normal though no issues whatsoever and another service brain or a small vessel disease brain you start seeing what we call this um extravascular deposition of fibrinogen is one protein that is supposedly in the blood it shouldn't be in the brain at all but we start seeing this extravascular deposition of fibrinogen which means that to cross it has you have to have some degree of breakdown of the of the barrier.”

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Disease prevention 51:24 0
“we found that it's neurotoxic so toxic to neurons it's also toxic to oligodendrocytes where we found that the the original sites are basically cells that are making up myelin and make sure that the white matter is intact and we can function properly and those those articles are crucial in the break and we show that when you have a leaky barrier and you have cyber engine going in the oligos are very sensitive to that to that fibrinogen so they take it up so the internalized fabinogen and they die by what we call autophagy so it's almost like a suicide cancer test and which leads to white metal disease.”

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Disease prevention 54:04 0
“fibrinogen can activate uh the brain resident immune cells that are microbial cells through cd11b so that's a specific receptor so when fibrinogen gets in it can bind to microglia so it will induce an over reaction over inflammation of the brain which will be detrimental for uh for many things for the functions of the cell surrounding and that reminds me that there is a fantastic researcher uh Katarina kasudu she is a Gladstone University UCS set value where she I think she developed an antibody that blocks the interaction between fibrinogen and microvia to avoid that over uh like over expression of information or over activation of microbial cells because she's also a strong believer that let's give it this functional very early and the major contributor to Dimension so that's a very interesting research.”

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Disease prevention 55:52 0
“people so air particulate matter so when you have like air pollution particular matter when people are exposed to high amounts of it it causes their fibrinogen to go up right it's again an inflammatory marker as well but people that were taking in high amounts of Omega-3 it blunted the increase in fibrinogen and plasma and so it would be very interesting to see if in some of the animal models you were discussing if omega-3 could blunt you know the white matter dysfunction caused by fibrinogen getting into the into the brain.”

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Substances 56:43 0
“this uh kind of vicious cycle where omega-3 may play a major role into uh vascular functions of course it's not even they play I think they did that's pretty raw um and it might be even a more important role in people as risk for Alzheimer's”

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Environment 57:02 0
“Airborne particles like pollution right and each I think it it's linked to what we've said earlier so there is as I risked you to keep it simple if we think about ourselves it's a multi-factor of disease so you have genetic risk possibly you have um you have a lifetime exercise and everything the J is also and what we call environmental environmental factors and pollution is what and there is multiple studies as you know showing that if you if you live in the city big city you have more chance to develop some sort of dementia”

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Environment 57:47 0
“we expose the mice to Airborne particles from Los Angeles we're taking from the the highway the particles and giving it to the mouse to see what's the impact of the pollution on vascular function because there's some evidence also using scans those people have tend to have more weight better disease and things like that so we started looking into that and we felt very interestingly we we found a high peak of a vascular uh it's a longitudinal disease but with very rapidly a few days after giving the particles to the mouse we were seeing blood brain by breakdown and parasite degeneration very quickly one of the first sign that we could see”

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Environment 59:52 0
“it makes me wonder about filtering out the air I mean if there's some HEPA filter or something that helps a little bit as well as omega-3 has been shown I know it's it's it's you know it the research shows it you know so”

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Disease prevention 1:04:14 0
“we know after stroke when you have a blood clot in the in your brain you have within to the next few hours you have a breakdown of the prevalent barrier and the biggest scanning collision and things like that and we know that this breakdown is correlated with high levels on the mmp9”

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Disease prevention 1:04:44 0
“Interestingly, when you have an ischemic stroke you have a second breakdown a few days later.”

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Disease prevention 1:07:53 0
“we were able to partially and significantly restore vascular function so just by blocking cytophene a we were able to restore tight junctions we were able to restore the pericyte coverage of the vasculature and ultimately those mice had less neuronal damage and less cognitive problems”

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Disease prevention 1:12:21 0
“if you're having a dysfunctional blood-brain barrier you're you know if you're basically having blood brain breaker breakdown everything you've been describing um the glymphatic system which is when you sleep it squirts the cerebral spinal fluid into the brain to clear out the amyloid plaques is that is that also impaired somewhat”

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Disease prevention 1:14:18 0
“so in my opinion that that sort of puts of course the the vascular function and blood brain barrier Integrity Upstream of amyloid in a way because you'll lead you know having that dysfunction first will then lead to more you know amyloid accumulation you know if you're not able to clear it out right”

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Disease prevention 1:16:52 0
“Maybe 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 one um you know blood pressure so it's actually very common you know in at least in the United States almost 50 percent of the US adults have hypertension and uh 20 of young adults do age 13 18 to 39.”

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Disease prevention 1:17:53 0
“if you have early hypertension if you're young then you have hypertension it's possibly more harmful than if you have it later in life”

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Disease prevention 1:18:25 0
“hypertension is known to impact the brain and there's like the basal ganglia and those deep structures that suffer quite a lot from hypertension”

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Disease prevention 1:19:51 0
“there is some studies showing that the giving anti-hypertensive drugs as a positive impact on cognition as well”

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Exercise 1:23:03 0
“it's never too late to start exercising and there have been studies showing even in the 70s you can have cardiovascular improvements”

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Substances 1:24:50 0
“if you're a chronic Drinker of alcohol you tend you you will have some vascular issues it has been linked so if you chronically drink alcohol you have a leakier blood-brain barrier it has been shown”

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Substances 1:25:37 0
“moderate drinking is up is impacting your brain function but not only brain function but vascular properties of the brain”

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Substances 1:27:01 0
“chronic drinking is uh is uh of course people will have a more chance to develop dementia very quickly”

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Substances 1:28:16 0
“red wine are full of polyphenols that you know from The Grapes which has been shown to be very important for brain functions and also for vascular functions”

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Cognitive stimulation 1:31:41 0
“you know in people with that had high homocysteine um when they were treated with a B6 B12 folate sort of concoction to help lower their homocysteine it improved their cognition and also a Microsoft blood-brain barrier”

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Disease prevention 1:32:13 0
“there has been a lot of Paradigm shifts in people's thoughts on Alzheimer's disease with them thinking about it being a metabolic disease in a way right um type 3 diabetes you'll hear but like I think this vascular dysfunction is it's so crucial”

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Cognitive stimulation 1:32:39 0
“identifying some of these early biomarkers that you were mentioning even in plasma I don't know how early or if they're even available to people to measure are they it's still at the research um phase”

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