APOE4 and brain stress: why your hs-CRP, ferritin, and iron need a different lens

[0:00]If you carry ApoE4 your inflammation test is probably lying to you. Here is what I mean. Your doctor pulls up your CRP which is the standard inflammation marker. Sees a one and says fine. But for us, a one is not a one because of a single mutation, we produce less of that marker.

[0:25]So the number reads lower than the inflammation actually is. Normal can be hiding a fire in your brain. I'm Dr. Kevin Tran, I'm an ApoE4/4 carrier. And that's exactly why I sat down with Dr. Grant Fraser to go through the blood panel that actually matters for carriers like us.

[0:45]One marker at a time. In this episode, we are covering So the real numbers Dr. Fraser targets not the labs normal. And we are talking about why extra iron spreads up amyloid in our brain specifically and the one rule that saves you from wasting money on tests that change nothing if you are serious about protecting your brain.

[1:11]This is the one to watch. Let's get into it. Welcome back, so in part one of this video series Dr. Grant Fraser and I we set out to cover all the different APOE4 biomarkers panel. but we only made it through two markers homocysteine and omega 3. So that video is on YouTube.

[1:31]The reason why we only covered two when we thought we covered way more is because they deserved a lot more time than anticipated, and all the answers are very new and so we feel like We felt like it was very important to deep dive into each one of those.

[1:43]That's why this video is now a three or four part video. As always, to vote for the next topics that we cover or to ask your own questions, because we cover them during this type of discussions, go directly into the the Phoenix community, into the thread that is called podcast, and then you can ask all your questions there and then we'll cover them.

[2:02]So now in this episode we are moving into the markers that tells us whether your brain is under stress or not. So we're looking at inflammation, iron, oxidative stress hormones as well, and thyroid. same goal as before. We're not just covering is this normal or not, we're also covering what does this mean from an ApoE4 specific lens.

[2:24]All right, Dr. Fraser, Grant, let's continue. So let's start with hs-CRP or CRP itself. Yes, so it's high sensitivity CRP is something which traditionally is used To look at vascular inflammation and kind of has a has a good set of prognostic data as far as vascular events. So something where a lot of people measure it as part of you know things like you know, leavento age is it.

[2:52]There's a lot of things that have to do with this is a good thing to have a low value of. So reduction is mainly due to inflammatory cytokines, interleukin-6 and Interleukin-1 beta, tumor necrosis factor alpha, which run upstream, and then your liver actually produces the high sensitivity CRP.

[3:12]And it is something where in individuals that have an APOE4, it does look as though the tendency is for the CRP to run lower than somebody who doesn't have ApoE4s, which is an interesting thing. And and it's not that you have less inflammation. It's kind of an artifactual thing that, you know, that your CRP of of one might be equivalent to another person who doesn't have an APOE4.

[3:42]Maybe one and a half, where there's kind of a so following the trend is a reasonable thing, but the absolute values may need to be a little bit lower because of this tendency for this to just be produced at the lower level. do APOE4 I mean, it's fascinating, just all the changes that happened due to the single mutation that you just see see roll through so many different pathways that it all all have some risks, but it is something where our our goal as far as putting a number on it is somebody that has ApoE4, especially homozygous We're really looking to try and get the high sensitivity CRP less than 0.5.

[4:19]We're typically other patients who don't have this, I would say getting it under one is where the evidence is. so and I think that as you get over a value of one, that you probably want want to be looking at specific things. and you know, it's kind of the the things to be aware of is that any significant source of inflammation in your body is going to increase that high sensitivity CRP.

[4:41]Oftentimes overlooked is going to be dental disease, which is also critically important for people that have ApoE4s, including, you know, do you test your oral microbiome for whether you have P gingivalis Which, if you have that and have an ApoE4, that worsens outcome and you can't eradicate that.

[4:58]you know, do you have sleep apnea? Do you have excess visceral fat? Do you have chronic infections? Do you have an inflammatory arthritis in your system? it be a gastroenterologist. it can be rheumatoid arthritis, lupus, any of these things are going to increase the value value. And you know, it's fascinating.

[5:14]There's so many things that bump up high sensitivity CRP. one of the things that we do is prolonged fast, and at the end of the virtual mimicking diet once a quarter. And interestingly at the end of that, we did our blood, and and and our high sensitivity CRPs were greater than 10 and our white blood cell counts were like 16, both my wife and myself So and it was Like we didn't have an infection, we didn't have an inflammation, but just that active fasting you know, people when when it was the beginning of COVID, a lot of times when I was in the ER we you know do more extensive lab tests than I do today, and high sensitivity

[5:50]CRP in people sick with COVID would, you know, and same thing with flu would be greater than 10. so just you know, viral infection will bump bump it up. So these things can be very transient. But I think that the important takeaway point is that when you get this lab test, make sure you don't have an infection.

[6:04]Or an inflammation or something else. So you kind of get a good baseline of where you're at. And then it's a matter of, you know, how do you how do you fix this? And you know, it's like if you've got weight to lose, do that. Optimizing your omega-3 fatty acids, particularly the EPA component, which is more the vascular component of the omega-3.

[6:25]So DHA is more what we're looking for to get into the brain, which ends up being the sticky point. with ApoE4, but as far as your vascular system goes, you know the fish oil that you take, any basic capsule, takes care of your vascular system, the problems your your brain.

[6:40]But as far as getting the high sensitivity CRP down, making sure you have enough EPA is beneficial. Astaxanthin is another one that is a powerful antioxidant and usually 12 milligrams a day is reasonable. There's lots of brands I oftentimes Use double wood for that. Kercumin is another another one that seems to be beneficial.

[7:04]And getting I tend to favor nanoparticle Kercumin just because there are issues with absorption. other things, zone two, zone three, exercise, resistance training, sleep optimization, good periodontal health are kind of the the the low-hanging fruit of how to address this so that kind of be the the rundown.

[7:24]You know, I think the goal is to see if you can be less than 0.5 and if you're running higher than that to take a look and see if there's some of those things on that list that you can optimize a little bit. And you know a diet that is rich in antioxidants and flavonoids is also a good component because it is an anti inflammatory diet when you're doing a Mediterranean or MIND diet or similar where you're ha having lots of different you know colored vegetables, nuts, seeds, other things, all these things you know, feed feed into improving your values.

[7:56]What are the usually the order of magnitude of the effect of these like more lifestyle interventions plus supplements? So you mentioned like a few things, like Kercumin, Astaxanthin, sports your diet and so on. So I'm guessing the diet depends how bad it was initially. but for the others, for the supplements, what what can we expect?

[8:14]Is it like very individual variant variable or Yeah, I I don't think that in it cross populations that that I have good data say saying, you know, that hey, if you add, you know, Kercumin that you're going to get, you know, a 0.5 drop or acetone And I think that this is going to be individualized.

[8:33]and I think the big things are is to take a look and say, is there something in your diet that's pro inflammatory? Are you taking, you know, lots of processed foods are you having you know dairy oftentimes can be you know an inflammatory is issue fermented dairy tends to be tends to be pretty safe but you know there there's a lot of lot of things that um are going to be individualized and you have to try and see what happens you know but you know if you if you have periodontal disease that in and of itself you know can bump up your CRP several fold so getting that under control or if you have a little inflammatory arthritis getting that under control, all those things can make huge differences.

[9:16]but I I'd say that it's individual it is a little bit of trial and error and go, you know, a lot of times you end up kind of addressing all the possibilities and then re-retesting and and seeing seeing where you're at. But I I don't think there's good data on saying you do this and you're going to get this amount of drop.

[9:33]Yeah. You also mentioned the very important information, right, on on the transient aspect of CRP, hs-CRP, once you have a infection and and so on. when it's like linked, because the worst thing that can happen is you do a test every three months and one of those are completely off for something that is not permanent, and then you you freak out and then you you get like a result based on the next one, so you feel like maybe something changed, but actually no, it was just something transient on the previous one.

[9:59]Regarding the diet and everything, so like milk and all these other type of food that pro inflammatory, do you feel like someone should reduce them before doing the test? Do they have like an impact straight away or does it take a long time and accumulated amount? Yeah. I think in general dietary changes may make differences fairly quickly.

[10:20]you know, there there's certainly some you know, fat soluble things that but but most of this stuff is going to be water soluble and is going to quickly change things. And diet changes can make differences pretty quickly, has been my experience. if you eliminate you know, all the processed foods, if you eliminate junk foods and you're replacing them with things that are healthy, that that is something Where you'll end up improving it quickly.

[10:45]And that's with a nuance. One thing that's really important with changing diet is that you need to be careful not to do it too fast, especially with dietary fiber. So the average American has about eight grams of dietary fiber per day in their diet. Optimal, we like to see north of 30 grams per day.

[11:03]But if you suddenly go from 8 to 30 grams, you are going to have all types of GI distress. It's going to be a complete disaster. And I would say your CRP will go through the roof because the gut Bacteria are going to be very, very upset with you.

[11:16]So it needs to be a change of no more than five grams per day, changed every week, is the maximum. So you know, if you're at eight grams, it may take you five or six weeks to get up because and your gut bacteria are going to be a bit mad because the unhealthy ones are going to be dying off and then and the healthy ones are going to be living on the on the fiber.

[11:36]And it's it's something where don't make that change too fast. Because I would say that if you made that change fast, your CRP is probably going to go through the roof and then you're going to make the conclusion that what you're doing is unhealthy and worsening and you go back to your processed foods and go, it's better now.

[11:50]so yeah. that's a good good image to remember. All right, cool. moving on to ferritin now, so which I believe is a very under appreciated marker, especially for us ApoE4 carriers. why so let's start with the basics, right? Why does iron matter for us? Yes, I I think that iron is a big deal because the higher your iron, the higher your oxidative stress.

[12:17]And iron serves very important functions in the body. so if you're iron deficient Basically, your bone marrow pulls everything and your brain doesn't get the iron that that needs for a number of enzymatic reactions. Your muscles through myoglobin aren't going to get what it needs. You're going to so if you're iron deficient, that's it, that's a quite bad thing, not from an oxidative stress standpoint.

[12:39]But if you're iron overloaded, your reactive oxidative species go up significantly. And it is is something where we know, you know, the the work of the Florey Institute Ayton Group on this is that the more iron you have in your brain it seems as though the accumulation of beta amyloid actually is enhanced, especially in people with ApoE4s, so that you're likely to progress more quickly into Alzheimer's disease.

[13:09]So there's a reason why you want to be in the sweet spot. You don't want to be under, you don't want to be over with this. And one of the nuances is really important is that fair. Ferritin is also an inflammatory marker. And it's and it's not just a measure of what your total iron stores are.

[13:28]So it's very important that you pair a high sensitivity CRP with a ferritin. And if that high sensitivity CRP is elevated, part of that ferritin is going to be due to inflammation, not due to body stores. So if you have a if you have a high sensitivity CRP of six and your ferritin comes back 150, a significant portion of that ferritin is going to be due to the fact that you've got inflammation going on.

[13:54]So you need to get a good CRP that's nice and low in order to truly trust that the ferritin is a real value. So the ferritin will never be lower than what it what it really is, but it can certainly be a lot higher than what it really is as far as a measure of total iron stores.

[14:11]But it is the most reliable test, but just make sure that your CRP isn't significantly elevated. So that you know that it's real and it is something where the sweet spot probably is more in the 40 to 80 area, and it and it is a challenge if you're a lot of people, especially men tend to be overloaded, and your option is to donate blood, which is good good public service.

[14:37]and some people aren't a big fan of it. A lot of times, you know, they use big needles, people don't like that. What I tell people with that is a practical thing is that if you're going to donate blood and you really don't like that, which I can't imagine most people do over the counter you can go to the pharmacy and buy something called emla and you put it on for an hour before and on a couple areas where they might draw the blood, and you won't feel the blood draw.

[15:01]you won't feel feel the stick. So it's a lidocaine mixture that you just put under occlusion, you is over the counter, and um you know you can you know have have pretty good anesthesia, so that ends that part of it ends up not being so unpleasant. But a lot of people, you know the other thing is ferritin is a very important thing for us to be monitoring for other reasons because it's oftentimes the canary in the coal mine of letting you know that you've got that you're having a cold blood loss.

[15:30]You know, if your ferritin's dropping down, which it shouldn't be, that's oftentimes an indication that you're losing through your intestines. And it's kind of a red flag of you know, do you have a colon cancer? Do you have pulps that are bleeding? that's occult, so just as a general health issue, ferritin is a very useful marker.

[15:46]for the brain it is something where we where we really want to make sure that it's in a in a sweet spot, enough iron but not too much because the oxidative stress that that occurs with a high level. I know you mentioned like blood donation. I want to go a little bit off tangent since you're also like a longevity doctor, right?

[16:04]Wha what do you think about this I don't know if it's recent or not, but this trend of people donating a lot of blood, like even like sometimes like every like two or three months for longevity reasons, because it removes the toxins, it removes a lot of things that could not be removed from the body normally.

[16:20]and that's the only way of mechanically remove it. Yeah. I think that it it's something where your your blood makes up, you know, five or six liters of you know, so it's something where it's a small percent of your total body and it you're going to end up removing you know, a unit of blood at a time which is going to be a minuscule amount compared to your total body tissues.

[16:50]So I'd say that it would be a fairly ineffective way to to do this given that given that your it's not if it were just your blood volume where you say, look, I'm removing, you know, a fifth of my blood volume or six of my blood volume. Sure, but you're only removing, you know, one 1% or 1.5% of you know, your body mass with this.

[17:13]So it's going to be a very small thing. the so you're not really going all the toxins, the metals, other things are going to be distributed through your tissues. so I don't think that it's going to make a big difference in that regard. I think it's probably better ways to go.

[17:28]but as far as you know, getting an optimal ferritin, sure, it's going to do a great job of that. And you do have to be careful because I've seen some of my patients over donate and then be iron deficient too. and you know, it is something where your ferritin goes low long before you get an anaemia your anaemia is a late finding, but we'll see people also donate and get anaemic even though they still have adequate iron stores but their body's just not able to keep up, you know, people that are doing kind of double unit donations is something where we sometimes see that.

[18:08]So so I think that there's a sweet spot with this. But yeah, I mean if your ferritin's greater than 80 giving a unit and then it does take really about six to eight weeks for all that to equilibrate to really get a new baseline of where where your iron stores are.

[18:23]And typically, you know, Red Cross won't let you donate more than every quarter. so and I think think that's something where that's sensible, but you do need to have an assessment of your ferritin and your hemoglobin before you decide as to whether you give another unit. Cool, To summarize, right?

[18:39]Because I think that's one of those biomarkers where you you need to have a sweet spot in the middle you don't want it to have like too low because then it's especially for a woman, I'm guessing it can usually get like very, very low. It has like energy, the mood, cognition probably, and then too much it's oxidative stress.

[18:56]right so definitely something to really keep in check. I know you mentioned combining that with HSCRP and so on, looking at those biomarkers for inflammation, we had a few questions coming in. So HSCRP is like more like downstream, right? You you actually mentioned at the beginning of of this, like you look at IL6, TNF Alpha, IL1 Can you talk a little bit about those?

[19:18]Do you combine these or it's is HSCRP like enough because it's usually much cheaper to run that one than the others? Yeah. So so I think there's kind of the the practical issue of what what we end up doing. You know, IL6 is readily available. It's probably the one that's emerging the most as far as, you know, some of my patients are choosing to measure both.

[19:41]it is a little bit upstream of the high sensitivity CRP. That goes up and then you end up making more CRP. And it is something where a lot of times that ends up being a lot a lot of noise that go up and down and up and down, and I'm not sure that we we can really make good decisions on on that alone.

[20:02]I think the high sensitivity CRP remains the best validated option You know, Tumor Necrosis Alpha, we can measure that. something where there's some research value to that, but I think that you know there's other cytokine panels, you know, none of these things have much data around them. So I think at the end of the day, as much as there's lots of fancy things to talk about.

[20:23]You know, there's other brain barriers. Inflammatory things like MMP9. I think that bottom line is that we don't see right now replacing CRP. We see that there's some things that are kind of triangulating around it, but I'm not sure that they're actionable right now. The CRP, as much as it can go up and down very quickly, tends to, in most people, if you don't have an acute inflammatory issue going on or you haven't done something crazy in your diet, tends to be a pretty stable long-term marker for most people.

[20:58]I can say that for for most of my patients, the values, you know, it's 0.33 the next time it's you know less than 0.2, the next time it's 0.4. I mean they're they're all you know the values tend to be pretty consistent and clustering. you know, and if they have a time where you know it comes back at 2.5, 2.5 is not real.

[21:19]Something's happened, they've got an inflammatory infectious thing, okay, let's sort out what this is, and then we recheck And then the next time, you know, it's 0.2 again. so they tends to be a pretty stable test over time, unless there's an acute phase inflammatory issue, but then we sort that out and that's not all that's not a long-term risk as long as you settle that out.

[21:39]Okay, makes sense. All right, moving on to the next one, we're looking at GGT which is a signal for liver stress. tell us more about this one. Do you use it? Because typically people don't really know that one. Yeah. so with GGT, probably the most common use of that has been for looking as to whether somebody's having some alcohol related damage, you know, a lot of times you just end up screening that when you're doing community medicine and go, you know, if this is up, this person's probably drinking fair bit of alcohol.

[22:13]But it is primarily an inflammatory marker. it's something where it does indicate there's some oxidative stress. And overall it's something where I don't use it very often, but I tend to think of it as a systemic oxidative stress mark. not just a liver target, you know, liver stuff as far as inflammation, usually STLT is going to be a better idea without the GGT, kind of like a ferritin will go up with inflammation.

[22:42]it can be an early warning for insulin resistance. It will go up. It also for oxidative stress. And then alcohol or toxins are going to be your things that end up um bumping that up. Okay. So if we summarize for inflammation, which one do you typically routinely measure?

[22:59]How often? I think after all the talk of all the other fancy things, you know, including we didn't necessarily dive into, you know, the MMP9 and other things, which I think there is a role for but for kind of general you know, inflammation, I think that monitoring a ferritin and a high sensitivity CRP is really where the focus is and typically quarterly.

[23:25]I don't have any science behind, you know, why do it Quarterly versus every four months versus every six months has just been my pattern that I usually like to get basic labs. And by basic labs I mean a lot more than what most people consider to be basic every quarter and then every year get very detailed panel is typically how I'm running my practice.

[23:45]But you know, the the quarterly does include, you know, high sensitivity CRP, lipids, APOB, vitamin B12 folate, homocysteine. comprehensive panel, ferritin and high sensitivity CRP is you know part of that. so I think that those are probably the main ones that I'm doing a lot of times yearly.

[24:05]you know, we'll doing GGT, especially my patients that are getting their labs through function health, which tends to be their yearly panel tends to be pretty good, but they're one that they do, you know, they're they're more limited one. is isn't that helpful, but they're there one big one is really a pretty good panel and that includes the GGT.

[24:26]yeah, I know in the community we have a few questions from Alex, Christy and and Dara. I'm actually reading them. What about so you mentioned it slightly MMP9 MPO, MPO antibodies, all of those. would you recommend running them from time to time or I think that with the with the MMP9 is one of the things that I have started doing a little more monitoring on that.

[24:52]The thing is I have not really found anybody that's really got a high level. So it's something where what do you do with, you know, a level that you know, I forget what the upper range normal is, but you I think it's like seven hundred or something, you know and most of the levels that I'm getting are kind of, you know three hundred, you know, and that then you also look and go, Well, you know, are there things that you can do to decrease that?

[25:16]And that's less clear. there's kind of been the discussion around, you know, MMP9 inhibitors primarily with doxycycline, low dose doxycycline seems to be something that has you know, mechanistically looks to be a good MMP9 inhibitor and in subantibiotic doses is one of the things that can't can be used.

[25:38]And I do have some patients who are choosing to do that. but it's not something that necessarily modifies the MMP9 level. It's actually inhibiting the MMP9 at the level of the brain. And it's kind of an interesting discussion as to whether that disease that happens due to MMP9 and people with ApoE4s is a is probably a big component of why we have trouble of getting the omega-3s in the same way as other people.

[26:03]So is you know, is there a role of doing an MMP9 inhibitor to protect the blood-brain barrier and normalize that absorption of omega-3. So that's kind of a separate discussion. But the thing is is that with the MMP9 inhibitors, usually you don't change your blood level. It's more just at the at the surface level of the brain that you're inhibiting the effects of MMP9.

[26:26]so you know, same thing with you know Myeloperoxidase you know, it's an oxidative inflammatory marker. I'm not sure that we have more action points with that than doing a high sensitivity CRP. There's fibrinogen which is associated with leaky blood brain barrier and with you know with a pro-thrombotic vascular state that oftentimes is going to be more of an acute phase with some inflammatory state it's usually not gonna be a chronic issue and I'm not sure what we're going to do if that's elevated apart from say you know clean up your diet and more exercise which are things we're already going to be doing So I think think a lot of these things you go, well what does that change from what we're already doing?

[27:06]One of the popular ones that I do have some of my patients do mostly for vascular disease risk is the ADMA, SDMA, which is looking at nitric oxide dysfunction, endothelial impairment. but again, those come back and they're abnormal. The advice is going to be all the same things that we've already advised somebody to do.

[27:25]Getting those lab tests, if they're abnormal, sometimes in patients who are a little bit resistant to doing things, sometimes that ends up being a motivator, as I think is probably the more power powerful thing is that you know you have somebody who goes, Yeah I'm pretty happy with my diet and my exercise, and you know, I don't think I want to take a statin, and you know, and you get these these lab values back that are a little bit concerning, then suddenly, you know same thing, you get a CT Coronary Angiogram back and you see a bunch of disease and you know the person's going like now I'm not worry about lipids hey, I'm worried about my lipids now.

[27:57]I see all this disease. so now I'm motivated. So I think that if you have somebody who's already doing everything right and is and you know doesn't need the reinforcement, the value of these tests is is is probably nil. but for somebody who may need a little bit of a push to go, hey, I really do have something where now I'll track this I'll change what I'm doing and I'll track it and see that it gets better.

[28:19]Sure. but high sensitivity CRP, ferritin are probably really where I would spend the money rather than the other tests as long as you're doing the right things otherwise. Yeah. I love that little nugget of wisdom here, right? Like there there's no point in testing and tracking things if it doesn't change behavior.

[28:38]If you were already doing everything that was needed to improve it, you're not changing anything. And if in any case you won't change anything, there's no point in testing. do you also look at the blood brain barrier integrity? We had a question there, so the soluble platelet derived growth factor receptor beta.

[28:57]Yeah I've not done that because I'm not sure how I'm going to respond to an abnormal result. one of the rules that I that that I learned early on is don't test something that you don't know what to do with. so because inevitably we you'll get an abnormal result and then somebody's going to ask, Well what do I do with this?

[29:15]And you go, I don't know. and I'm not sure what what we do with that result. So it is something where yes you can test these things and I'm not sure the action point yet on that, but I have not done done that is part of part of my practice at this point.

[29:33]If I see some evidence that we've got you know clear prognostic issues with these tests, and there's something which I can do that's going to modify the trajectory, then I think that there's a reason to test but yeah, there's a lot of fancy tests out there. There's a lot of ways to spend money on tests.

[29:52]And there's also a challenge with kind of standardization of a lot of these newer tests as far as, you know, are you even getting a valid result that's actionable and how you know, how quickly do these things go up and down as a stable result. But I've not spent time on that.

[30:07]I guess I'm happier doing some of the more functional things, you know, like, you know, taking a look on yearly MRI and doing a neuroquant, you know, and now using the pre-mas tests which you interviewed the team from Cambridge on and have been using that as far as you know getting functional results to track over time.

[30:29]but yeah it's a challenge with all all the various tests that are available. But I I think that we do need to focus on things that are clearly actionable until we have more evidence. And once I have more evidence, yes I'll probably expand what we do. with this because there's there's so many lab tests out there and a lot of them are not widely available as the other component with this is it if you have something which just a specialty lab does you have real problems with access and the costs oftentimes are quite substantial.

[31:00]Makes sense. you mentioned Frama since we're like doing diverging a little bit. Do you what what's your how do you feel about it and how did you just start using it? Have you seen like a good sensitivity on Yeah, couple of months now. I've been having a lot of my people do that as far as getting a baseline to go, you know, this is something where we've got a baseline with this and then we'll just follow it yearly.

[31:23]and I'm still to do it myself, you know, when we took a foreign trip and I'd told some of my patients that I was gonna take it while I was over in Europe and and somehow I forgot. So that's probably a bad prognostic indication for myself that I can't remember to take the pre-mas test, but I will get around to doing it.

[31:45]but I mean it's fascinating as far as you know the the data looks very good that if you're getting, you know thirty to seventy, that know, there's you know that's that's certainly an indication that there's concern that you're going to have dementia in the next five to ten years.

[32:02]And if you got a value less than thirty, you probably already have dementia. I think the big thing that that test has done for me is not have people have to go in and get a marker test cause it's hard to do that via telemedicine and have something which is better than a marker test that they can do at home.

[32:19]So it's not nice to be able to you know offer that test and have something which gives us a good marker and something which can be followed and repeated. Yeah. you know and for a little sneak peek on what's happening in Phoenix, we're going to provide that test for all the members and we're running a study with the Cambridge University as well on sleep and that test as well.

[32:45]So we're combining the data and we'll see like what comes out of it. so this hopefully is coming in June, July, but yeah, we've been like cooking that one for for a long time. so it's like yeah, very excited about that. yeah, I think it's fascinating looking at how that test is done and that, you know, those are Alzheimer's specific changes that happen.

[33:04]And I think that it's quite a fascinating test and a good set of data. So yeah, that's exciting that you're going to be doing that and that'll be great data collection for them also. Yeah, definitely.