[00:00:00.400] - Dr. Gordon

Having the condition of either ADD or ADHD raises your risk of Alzheimer's, and, and this is the part that really surprised me, treating it reduces your risk.

[00:00:16.780] - Dr. Lemanne

Our listeners know that I am very interested in the development of treatment resistance and how that is not addressed in current oncology. It's just accepted, well, we're going to treat you with this medication until it stops working. And the until it stops working is never questioned, never pushed back against until now. So we pushed back against that with this patient, and then we were able to treat it again successfully. 

You have found your way to the Lemanne Gordon podcast where Docs Talk Shop. Happy eavesdropping. I'm Dr. Dawn Lemanne. I treat cancer patients.

[00:01:01.100] - Dr. Gordon

I'm Dr. Deborah Gordon. I work with aging patients.

[00:01:04.940] - Dr. Lemanne

We've been in practice a long time.

[00:01:06.600] - Dr. Gordon

A very long time.

[00:01:08.900] - Dr. Lemanne

We learn so much talking to each other.

[00:01:11.010] - Dr. Gordon

We do. What if we let people listen in?

[00:01:14.640] - Dr. Lemanne

Welcome back to Docs Talk Shop. Today's episode might be our most surprising yet. We answer some of the most common questions we receive from listeners, and the answers may upend your assumptions about brain health, sleep, and even cancer therapy.

[00:01:37.120] - Dr. Gordon

You'll hear how treating ADHD and restless legs can lower the risk of Alzheimer's. And then we dig into new Alzheimer's blood tests you can order today and why social jet lag, just shifting your bedtime by an hour or two on the weekends, can double the risk of breast and prostate cancer.

[00:01:59.600] - Dr. Lemanne

We discuss my team's newly published case of directed evolution therapy for metastatic prostate cancer, where when the tumor began resisting standard testosterone-blocking treatment, instead of giving up and starting chemotherapy- Which doesn't work well in this situation, and usually heralds the end of the story.

[00:02:19.870] - Dr. Gordon

Right.

[00:02:20.820] - Dr. Lemanne

Well, we did something unthinkable to most oncologists. We gave our patient high doses of testosterone. You'll hear how this A backwards approach allowed us to successfully steer this patient's tumor back to a treatable state, a first in oncology.

[00:02:38.120] - Dr. Gordon

That is so awesome. Anyway, if you think you already know how sleep, brain health, and cancer treatment work, this conversation will challenge you. We're excited to share it.

[00:02:52.560] - Dr. Lemanne

Hey, Deborah.

[00:02:53.720] - Dr. Gordon

Hey, Dawn.

[00:02:54.370] - Dr. Lemanne

I hear, I don't know what our listeners will think about this, that You've been part of another podcast. I forgive you. I think it's pretty cool, actually. Why don't you tell us a little bit about what it is and what you're doing there?

[00:03:14.780] - Dr. Gordon

Okay. Well, I've been very excited for the last year plus to be working head to head with Dr. Dale Brettison. He has an online program for patients interested who either do or don't do not yet have a doctor working with them to prevent or reverse their Alzheimer's.

[00:03:34.910] - Dr. Lemanne

I'm going to just tell our listeners right here. I'm going to break in and tell them that Dr. Brettison has done a groundbreaking research on dementia Prevention and Dementia Reversal. And Dr. Gordon, you've actually published some papers with him on this. You've collaborated with him on some of this research. It's really important research, the first in the world for this this particular?

[00:04:00.920] - Dr. Gordon

It is really important research. And what's amazing about Dr. Brettison is he could run into somebody who's barely heard about this over the oranges for sale at the farmer's market and be able to have a reasonable conversation with them. And he can be at very high fluten levels. He's published a lot of papers. I was just one of the researchers in one of his published trials. He's very conversant at a scientific and a human level. One of the features that his website offers is a Q&A. And ahead of time over the month, either patients or pre-patients or what are called participants in the program, submit questions, and separately, people providing his inspired treatment and care of patients can ask questions. So we have a Participant Forum and a Provider Forum. And Every month, he talks about these questions with either myself or Dr. Anne Hathaway, who will be a familiar name to our audience.

[00:05:12.760] - Dr. Lemanne

We did an episode with Dr. Hathaway.

[00:05:15.060] - Dr. Gordon

We did, and it's going to be published now that I have recovered from COVID and vacation and gotten the final edits on it. It's going up today, I promise. Anyway, so she was doing it every month and invited me about almost two years ago, asked me if I would share them with her and do half of them. So every other month, I get about a week to prepare about a dozen questions each from participants or providers. And I learn a tremendous amount from solidifying my own knowledge base to answer the questions. But I get to hear Dr. Dale Brettison's take on them as well. And we have a good sense of humor about it. He goes, I know, I know, Deborah, you're going to tell them to eat more protein. Just several themes that we know we have in common. But hormone questions, he always differs to myself or Dr. Hathaway. And it's been a great exchange and a great experience for me for the last couple of years.

[00:06:15.160] - Dr. Lemanne

And so you asked me if we could do an episode on questions and answers, a Q&A episode. And I think that's a great idea. I'm really excited about that. So we've both prepared some questions, and I have your list of questions in front of me, and you have quite a few. And I think you have my list of questions. And these are questions from people who've listened to our podcast and have written to me and said, Could you talk a little bit about this? So I've picked some of the most common ones. And I have here in front of me, I have a favor to ask you.

[00:06:54.860] - Dr. Gordon

Okay.

[00:06:55.640] - Dr. Lemanne

Yeah. Can I pick my favorite question to ask you first? Out of this list that you've got.

[00:07:02.400] - Dr. Gordon

Okay, you can. All right.

[00:07:04.780] - Dr. Lemanne

And I think that my favorite question out of the ones that you've had here is a little bit not as common as some of the other ones. And that is, you've labeled it number 6, what other brain conditions can lead to Alzheimer's? Talk a little bit about that.

[00:07:25.700] - Dr. Gordon

Somebody asked a question on one of the I do with Dr. Brettison about the use of marijuana leading to Alzheimer's. And he said, no, in fact. And then we got into a whole discussion and he gave me the first two answers that I'm going to provide for you today, having a history of schizophrenia, whether or not it's treated and managed, but that was before Dr. Georgia Eid, who's also been on our podcast, Metabolic Treatment for Mental Illness. But schizophrenia, no matter how it was has ignored or managed, has previously been an increased risk factor for Alzheimer's. Genetics aside, genetics unknown, that stays with people in some way, even if they have recovered from their main schizophrenia symptoms. And the other one that comes up that can come from very early in life is early trauma, so PTSD. I would say I have a number of patients with PTSD who associated themselves with episodes of impaired short term memory. There is good data in the literature for it, and there isn't much data for treating PTSD and whether or not that improves your cognition. So this is still a field in progress.

[00:08:58.940] - Dr. Lemanne

And by trauma here, trauma has two meetings in medical ease. And one, if you go to the trauma department at an emergency room, you are not going to see psychotherapy or exploration of personality traits. You're going to see wounds and surgery broken bones, head injuries. Trauma in the the older medical term has to do with physical injury from an accident or an attack or something like that. Crush injuries, burns, car accidents. But what we're talking about here is emotional, interpersonal trauma, correct?

[00:09:36.670] - Dr. Gordon

That is correct. And sometimes they go together. Absolutely, sure. But not always. Somebody who seems to have come from a very comfortable life and never had anything bad happen to her can certainly have PTSD from relationships she endured as a young girl.

[00:09:53.940] - Dr. Lemanne

So we're talking about relationship trauma, mostly in this case. But you know, head trauma is also associated with Alzheimer's disease and also certain operations. So for instance, cardiac surgery that requires a long term cardiopulmonary bypass. If you have to be put on the heart-lung machine during your surgery, that's known to be associated with brain damage in pretty much everyone to the extent that the doctors have been trying very hard to figure out ways to avoid that particular machine during heart surgery. So So literally both types of trauma. But I think what's really interesting and not intuitive to a person who's casually thinking about this is that emotional events can lead to brain damage.

[00:10:44.340] - Dr. Gordon

Can lead to brain damage. And I would say it has happened more than once that I'm working with somebody and they are following my recommendations and their brain function is getting better, that they suddenly really see, feel, are affected by their early painful memories, which previously they've either 99% or 100% kept in the background of their awareness.

[00:11:16.080] - Dr. Lemanne

So you say early trauma. Is there an age cut off? Is this before puberty? Is this before you can speak? Is it before the age of 40? What does early mean? And does that mean that people who have emotional trauma after a certain age are not going to have brain damage from it?

[00:11:37.040] - Dr. Gordon

So it isn't brain damage. It's an increased risk of Alzheimer's. And how it is actually measured has not been defined or qualified. They just say that, oh, if you look at a general population and you take the people who have a distant emotional trauma and those who don't, there's an increased frequency of Alzheimer's in the ones who've had the history of trauma. I think the observation in this category is when it happened at a pre-managérial age. So I think somewhere between 9 and 13 or 14, most people develop a sense of agency about their life. And I think the more impairing emotional insults happened before that. Okay.

[00:12:24.180] - Dr. Lemanne

And you wouldn't call it a type of... See, I would call that a type of brain damage. If it results in some change that later on presents as a deficit in a disease.

[00:12:35.830] - Dr. Gordon

I would just say, yes, that has not been- But that's a philosophical point. I was thinking of anatomically, and I can't anatomically say what was damaged. Although I imagine if you look at some of the limbic system, thalamus, amygdala.

[00:12:54.960] - Dr. Lemanne

Amygdala, hypothalamus.

[00:12:57.260] - Dr. Gordon

That those areas are either going to be a little swollen or a little atrophied. Probably more swollen.

[00:13:01.650] - Dr. Lemanne

If we could look close enough, we would see the damage in some form. We have to look at the right level. I would postulate that. Of course, I-Yeah, well, now I'm going to look further into that.

[00:13:12.960] - Dr. Gordon

Thank you. And I got a couple of patients I'm going to submit to more advanced... Well, I have a couple of patients whose MRIs I can look at and see if there's anything they have in common. Thank you for that suggestion, Dr. Le Bon. I wanted to bring up, though, two areas that You may not think about these as... Well, doctors would know that one of them, but most of us don't know that the other one leads to an increased risk of Alzheimer's. And in both cases, you have an option to treat it or not. And the first one that I think most doctors would recommend put you at risk for some neurodegenerative disease is Restless Leg Syndrome During Sleep.

[00:13:53.600] - Dr. Lemanne

Interesting. Yeah, I've heard of that in connection with a prodrome to Parkinsonism.

[00:13:58.300] - Dr. Gordon

Exactly.

[00:13:59.070] - Dr. Lemanne

And Parkinson's disease and those related syndromes.

[00:14:02.400] - Dr. Gordon

That is more common, and there is a treatment for it, and you are better off treating it. It slows the development, or it's somehow beneficial in terms of your future risk.

[00:14:19.220] - Dr. Lemanne

It interrupts the progression.

[00:14:20.340] - Dr. Gordon

It interrupts the progression.

[00:14:21.840] - Dr. Lemanne

And what is that treatment?

[00:14:23.700] - Dr. Gordon

It's a prescription medication. I think it's called. I'm going to fix it if this is not right. It's Pramapexal. And one of the things that's very important, if someone has restless leg syndrome, they may not know it. They just may think that everybody's bed is a mess when they wake up in the morning and not realize that they have really kicked the sheets out of where they belong. But a lot of times, bed partners will know it, but solo sleepers may not really recognize that. Two things are important if you have this condition. Number one, And melatonin makes it worse, so you shouldn't take melatonin, which is interesting because you think melatonin as being calming. And the treatment makes it better and makes your overall brain function better. I think you did a quick search while I was rambling on. Am I right about Pramapexal?

[00:15:18.200] - Dr. Lemanne

Yes, you are. It's a dopamine agonist. And it's also mentioned as gabapentin as a treatment. So primupexal, mirupex or Requip, apparently, are the brand names. Interesting. It doesn't iron deficiency cause-Yes.

[00:15:35.640] - Dr. Gordon

So the first thing you have to do is rule out that they're not iron deficient.

[00:15:39.480] - Dr. Lemanne

So is that one of the things that happens when someone comes to you and says, I've got restless leg syndrome, they get an iron workup?

[00:15:45.960] - Dr. Gordon

They get an iron workup along with 150 other things. But the one that is more surprising to me and so surprising that I had to ask Dr. Brettison about this, I was watching, there's a program that doctors can sign up for where every day you're alerted to a video presentation that some doctor has done on some topic. And I typically bypass 95% of the ones that are offered to me. It's called VueMedi. Do you subscribe?

[00:16:14.420] - Dr. Lemanne

I Are you good there, Ed? Yes.

[00:16:16.640] - Dr. Gordon

So I was invited to listen to one time about the causes of Alzheimer's. So I thought, oh, I'll see what somebody else has to say. And this is a doctor, I hope I get this right, to Charles Robin. Who's an MD neurologist on a teaching staff, I believe in a Chicago University. I should have really thought all this through before we... But he's an academic person. He has about half a dozen lectures on Alzheimer's, but this one particularly piqued my interest because he said, Having the condition of either ADD or ADHD raises your risk of Alzheimer's, and, and this is the part that really surprised me, treating it reduces your risk. Before we go on, may I ask you a quick favor? Hit the subscribe button. You're hitting that subscribe button really, really matters. You're making sure cutting edge ideas that matter to you move to the center of medical discourse, where they belong. Thank you. Having the condition of either ADD GD or ADHD raises your risk of Alzheimer's. And, and this is the part that really surprised me, treating it reduces your risk.

[00:17:39.980] - Dr. Lemanne

Those are treated typically with stimulants, which increase neuroplasticity. So increasing the number of nerves and connections makes things better, huh? That makes sense.

[00:17:53.160] - Dr. Gordon

You know what? I guess I have this association, which I've learned to discard, that stimulants just make you anorexic, lose your appetite, lose weight, and run like a Jack Rabbit on track.

[00:18:09.720] - Dr. Lemanne

Stimulant abuse or overdose. Yeah. But I think they're drugs. I mean, caffeine is my favorite stimulant, personally. And sure, if I take too much, it's bad news. But at the right doses, yeah, it adds to my life. Definitely. Improves my concentration, ability to learn, mood, those kinds of exercise capacity. Yeah, I mean, you don't like coffee as much as I do, do you?

[00:18:37.100] - Dr. Gordon

No, I don't.

[00:18:38.000] - Dr. Lemanne

You're not a big coffee drinker. Well, we coffee drinkers understand the use of stimulants.

[00:18:45.240] - Dr. Gordon

Yes. So I've come to appreciate a little bit the use of prescription stimulants. And young people who have ADD or ADHD, and you know that's an increasing percentage of the youth population now compared to 30 30 years ago. And the casual remark is, Oh, 30 years ago, we just told them to go out and run around the playground and come back in. Well, that was probably 50 years ago. But there are more young people who are diagnosed with ADD, ADHD than have been in the past. There are an increasing number, and there are online screening tests for it, diagnosing and treating older people, even quite older people. Like, for instance, a A 27-year-old I know quite well from my mirror. There's an online test you can take, and the dosing of stimulants in adult ADD is almost homeopathic compared to what young people take. It takes very... And maybe it's just people who are as sensitive to caffeine as I am, but in general, I think it's true for everybody. It's the metabolism, it's the loss somewhat of the complexity of youth. But a young person might take 30 milligrams of Adderall twice a day, an older person might take two and a half milligrams once a day.

[00:20:11.700] - Dr. Lemanne

Yeah, so that's a big difference. Big difference. Order of magnitude. Yeah. Yeah. Well, that's really interesting. I'm not surprised. If you look at the caffeine and coffee literature, there's some association between coffee drinking in a beneficial way and decreased risk of dementia, depression, concentration disorders like ADHD and ADD. So the idea that a stimulant might be actually permanently helpful is That's what it's encouraging, I think.

[00:20:47.290] - Dr. Gordon

Yeah, it's opened my mind thinking about that, because I guess what I have always thought before is that if you have any tendency to use stimulants, I have to stop drinking my caffeine by 10: 00 in the morning, that you're not going to sleep very well. And I think we've talked a fair amount about sleep, but I'm also interested in something that somebody asked me recently, but we talked a little bit, and this is really a question for you. Can you talk to me about sleep regularity? And why is that important in your world?

[00:21:23.000] - Dr. Lemanne

Yeah. Sleep is important in everyone's world, brain health and cancer. Those are the two worlds, right?

[00:21:31.720] - Dr. Gordon

Wait, there are others?

[00:21:34.360] - Dr. Lemanne

I think sleep is one of the most misunderstood and mismeasured and handled parts of many people's, I'm going to actually say most people's health program. So even the people who are very, very active in managing their own health will often make their sleep for granted. And they'll say to me, oh, I sleep just fine, and there's nothing wrong with sleep. And then I say to myself, usually, Okay, then why are we dealing with this cancer situation? Because cancer and sleep abnormalities are very, very closely intertwined. And one of the things that I think I want people to understand is that changing your bedtime from day to day, even just on the weekends, and changing your wake up-time just by an hour. For instance, Social jet lag, if you heard of that? Where you get up Monday through Friday at a certain time, and then on the weekend, you change that time. You usually go to bed later and get up later. If you do that, and the change is just one to two 2 hours between your weekday and weekend wake up times, you almost double your risk for prostate cancer if you're a man.

[00:23:08.930] - Dr. Lemanne

Double it? Double. And you do double it for breast cancer. That's not trivial.

[00:23:20.580] - Dr. Gordon

That is not trivial. So this-It's just an hour. I thought you were going to talk about, oh, yeah, night shift work. Yeah, they get... But you're not talking about night shift work. You're just talking about going out to dinner with friends on Friday and Saturday night. And sleeping in. Yeah.

[00:23:34.060] - Dr. Lemanne

Wow. So the sleeping in doesn't fix it. So that's, I think, the take home there. Of course, you don't want to be ridiculous about this, but I think people are very, very casual about a risk factor that's pretty high on the par of smoking and drinking and getting exposed to radiation. These are And arguably, even perhaps a little bit higher with the sleep issues than some of those risk factors. And then there's also other diseases like heart disease and stroke. Those kinds of things are also increased by a 60 minute fluctuation in your sleep timing. And this is not made up for by sleep duration. So this is more powerful than sleep duration.

[00:24:27.140] - Dr. Gordon

So I have a question pertinent to the cognitive behavioral therapist who is on Dr. Peter Atia's podcast. I cite her all the time when I'm talking, where she would say, if you go out to dinner late and you're going to bed late on Friday, that you should still get up at your weekday time on Saturday and take a nap if you need to, but not too late in the day, because then that messes with Saturday bedtime. But that it's more important the time you wake up be held consistent than the time you go to bed.

[00:24:59.160] - Dr. Lemanne

Yeah, I don't I don't know if that's true or not. I have no idea. But I do know that it would be important on an individual basis to wear a tracker that tracks your sleep quality and length and actually look at it and see how it changes from weekend to weekday and back again and see what your body needs and how it responds to these changes in various aspects of your sleep hygiene. I don't know. I haven't listened to this person. She sounds amazing. She is. And I tend to, maybe unfairly, distrust blanket statements like, Everybody should do X. Well, Maybe, but I'd like to see how that actually works with 2, 3, 10 of my patients and me and you and see how well that holds up.

[00:25:57.420] - Dr. Gordon

I completely agree with you that one of the things I recommend to people is that in general, it's better for your brain to go to bed when it gets really dark and get up when the sun comes up in the morning. Except one of the most intelligent people I know in the world, Dr. Dale Brettison, stays up till 3: 00 or 4: 00 or 5: 00 in the morning because then he doesn't get any incoming email and does his work and sleeps.

[00:26:20.420] - Dr. Lemanne

But see, I want to put a tracker on him and let's actually see. Let's actually see if he's getting good quality sleep.

[00:26:27.110] - Dr. Gordon

Oh, my goodness. What if he got even smarter if he slept better? Anyway, but you're right. That your point is, he's my verification. But individual variation is really important and testing is really important. When I look at people's sleep, I want a total and I want a duration of rem sleep and deep sleep.

[00:26:49.600] - Dr. Lemanne

That's what I look at. Okay. Yes. And I also look at wake times. I also look at the sleep architecture, and that means-What is sleep architecture? When When in the night are you getting your slow wave or deep sleep? And when in the night are you getting your rem sleep? So for instance, last night, my rem sleep. So two nights ago, I had a very rough night of sleep. There was a solar flare, by the way, which can interrupt sleep in some sensitive people. So I had a rough night of sleep. And not much rem sleep. The following night, my rem sleep was spread out throughout the entire night. And what my rem sleep architecture usually is, is I usually have several hours of deep sleep in the first four hours of my sleep episode. And then the rem sleep gradually kicks in as the slow way of sleep peters out. And for the rest of the night, from about 1: 00 PM till 5: 30, when I get up, the rem kicks in and I have shorter episodes, then longer longer as I get toward waking up. And that's the usual sleep architecture, and that's considered a healthier sleep architecture.

[00:28:06.840] - Dr. Lemanne

But you can tell if you're missing rem sleep, because the next night, you will have your rem sleep starting earlier in the night, and it will take up the space that would have been devoted to slow wave sleep. So you miss out on slow wave sleep. So your sleep is disrupted for a couple of nights. If you've had one night of disruption, it takes a couple of nights to recover completely.

[00:28:30.000] - Dr. Gordon

And of course, deep sleep, particularly of interest to the brain, because two things happen then. Number one, whatever happens in general during sleep, which now I want you to tell me what that is, which is interesting thought. But of course, the brain does house cleaning during that first part of your sleepy night, particularly if you haven't eaten for three hours before you go to bed. The fairly recently identified glymphatic system in the brain does house cleaning, scrubs everything down, rinses it out those first few hours. But there must be more than that that happens during deep sleep.

[00:29:08.900] - Dr. Lemanne

So the immune system becomes activated, especially the antiviral and anti-cancer compartment, which is connected. They go together during deep sleep. And so if you miss your deep sleep, you miss that night's anti-cancer sweep, and you can't get it back. You don't get that during daytime naps. You've just missed out. And I imagine it's the same for the glymphatic system. If you miss that night, you have to live with the damage that's done, and you may not be able to recover from that. But one thing that's interesting is that cancers, often many cancers, like breast cancer, they tend to grow at night. So you really want your immune system to be up and meeting that challenge, excuse me, at night.

[00:29:58.340] - Dr. Gordon

So when you're When you say at night, what if somebody does work shift work and they go to bed at seven o'clock in the morning and sleep till 2: 00 PM? Does their cancer grow more when we experience night or when they experience sleep?

[00:30:12.700] - Dr. Lemanne

That's an interesting question, and nobody's done that study, but nobody's going to do that study. But if I had to answer that question with what we know now, I would say that they're missing out on good anti-cancer surveillance by trying to sleep during the daytime. You do not get used to it no matter how long you've been doing it. And the longer you do it, shift work, longer you sleep in the daytime and work at night, the greater your risk of cancer. There's a dose-response relationship there which suggests a causality. So missing that night time sleep, sleep at night, puts you at high risk for cancer.

[00:30:52.840] - Dr. Gordon

And we've talked about that that's considered a reimbursable I know in my daughter's world, when she worked at hospital nursing, they get a definite additional stipend if they take the night shifts.

[00:31:10.220] - Dr. Lemanne

Well, I understand, and this is old now, but I remember reading 15 or 20 years ago that in Denmark, if you were a flight attendant or a nurse who worked nights or unusual hours, which those two occupations are known for, and you got breast cancer, you got a stipend for that as an occupationally related condition.

[00:31:34.380] - Dr. Gordon

Well, I certainly wouldn't... You and I, everybody's had something that has compelled them to stay up at night, and it just reeks It's just a little bit of havoc. If you typically have a fairly regular sleep pattern that you depend on, it wrecks you for a week. And evidently, what you're saying is for longer than that. But it takes quite a while to recover from If I had to stay up all night, it'd be terrible.

[00:32:02.860] - Dr. Lemanne

Well, we know that when you cross time zones, it takes a day for each time zone you cross. There are 24 time zones. So it takes a day to recover for each time zone that you cross and to get used to your new time zone, at least. I think it takes about three weeks to fully recover from a 12 time zone trip, for instance, halfway around the world.

[00:32:25.960] - Dr. Gordon

This is why conferences should really all be remote now that we can really do that.

[00:32:32.620] - Dr. Lemanne

Yeah, well, if it's at night, though, and you can't really participate. Oh, that's a good point. You just listen to the recording later, which maybe, better than... There's some trade offs there. Yeah.

[00:32:42.540] - Dr. Gordon

You can fast forward through the part you don't like.

[00:32:49.300] - Dr. Lemanne

Oh, you do that, too? I have it playing and go do the dishes.

[00:33:00.000] - Dr. Gordon

You talked about working up the Restless Leg syndrome with an iron test. That's a little bit of a pet peeve of mine, iron, because it's current on the internet that iron deficiency in menstruating young women is ignored. And the recommendation is always to test people's... There's two ways to test. Well, there's probably more than that. But the two common ways to test iron, you can test somebody's ferritin. Frankly, if anybody's annual labs are what I would call cursory labs, they probably won't even get ferritin. But maybe every five years, they'll get ferritin. But ferritin is not really a very good evaluation of whether you have sufficient iron in your body because ferritin is also an inflammatory marker.

[00:33:52.000] - Dr. Lemanne

Right. Yes. It goes up if you have inflammation, even if you have no iron.

[00:33:56.520] - Dr. Gordon

Even if you have no, Oh, your iron is great. Your ferritin is 120. 20. That's a little bit high in a menstruating female. I bet that's not iron. And if it is iron, then they've got another problem, which is having too much iron.

[00:34:10.060] - Dr. Lemanne

Well, we could go on about blood tests And one of the questions your patients have sent to you, and that I'm curious about, too, is what is the new blood test to see if I have Alzheimer's? And is it accurate? And is it reversible if the test is positive. That's an interesting... You have smart patients.

[00:34:34.720] - Dr. Gordon

Well, that's because I'm sending them all to our local lab Corp to get this test done, because it is now covered by Medicare for as long as we still have Medicare. And it is very comparable to high-level research-grade testing that costs quite a bit of money.

[00:34:55.430] - Dr. Lemanne

Well, what's the name of this test? And what are they testing?

[00:34:57.630] - Dr. Gordon

So it's called the ATN Panel, and it's amyloid beta. That's the A. T is P Tau, and that's the only one that needs a little bit of discussion. And N is for neurofilament light.

[00:35:13.380] - Dr. Lemanne

So there are three proteins they're looking for, misfolded proteins, amyloid, tau, and what was the third one?

[00:35:20.260] - Dr. Gordon

So the third one is not a misfolded protein. Neurofilament light is something that only is released when your neurological... Your neurons are dying. So you have a certain amount of that that's normal, that's turnover. But if your neurofilament light is higher, I would expect you to have really marked brain atrophy on an MRI. And you've had whatever process is going on has been going on for a long time. But the two tests before that are very interesting because beta amyloid, amyloid plaques in the brain are what are blamed for causing Alzheimer's by the drug companies that know how to remove amyloid plaques in the brain. Even if they do risk a fatal brain hemorrhage, you might cure your Alzheimer's. But of course, it doesn't cure it. It slows the progression a little bit and the people it doesn't injure. But beta amyloid is Alzheimer's type disease progression. And it is It's reversible because it's a ratio between the amyloid that looks like it's coming from the brain and the amyloid that looks like it's coming from the body because we make amyloid throughout our whole bodies. And as somebody writes their other metabolic dysfunctions, their beta amyloid levels switch so that, Oh, no, the amyloid in your blood test is mostly coming from your body.

[00:36:57.520] - Dr. Gordon

And that's just a marker. But The p-tau one is very interesting. There are at least three numbers of p-taus, 157, 217, and you'll get experts quibbling Probably like you do over what's really the best way to drink coffee, over which of these P Tau is the most accurate. And again, we all have P Tau, but this number goes up when the Alzheimer's process or neurodegenerative process accelerates and you get P Tau tangles, and then your P Tau numbers go really up. But what's really interesting about this is we know more and more specifically about what P Tau means different from Alzheimer's. So one of the things it indicates is that they more likely have something toxic going on. But there's also genes that increase other processes so that P Tau goes up, and there are specific things we can do to reverse P Tau different from just treating the Alzheimer's.

[00:38:11.660] - Dr. Lemanne

So let me back up a little bit. So this is a three 3D part test, you get three numbers. You get a number for A, a number for T, and a number for N, and separately. Okay. And you can, if you treat the patient, see an improvement in all of these numbers at the same time, or one or two, depending on what treatment is needed. And you can also tell from the ratio of these treatments, or for instance, if the Tau is high, that you ought to look for and concentrate on removing some type of toxin exposure, for instance, and then the Tau number will go down. Will the A number go down, too, and the N?

[00:38:47.620] - Dr. Gordon

Yeah, so the A number-Sorry, a lot of questions there, but this is great. I have never seen the N number shift, but I would say I have a lot of patients who have some degree mild to moderate of cognitive impairment, and I think I've only had patient who had a significantly elevated neurofilament light, my most maybe disabled patient. But the A and the T, I've definitely seen them shift, and we can't always tell what it's about. I have a patient recently who we tested him, and it looked like he had in his urine test, terrible mold toxicity. But everything else we tested showed that he was really just detoxing the mold, that he didn't have mold toxicity. That could have all happened in the background that we wouldn't have even known about had we not done the mold test. And I bet his PTAO was higher when he was really processing the mold and normal again when he finished it because he is somebody whose PTAO has been up when we didn't exactly ever figure out why, and it's gone back to normal. So there are those links to other causes. And now there is this newly discovered protein you can test for, which they say is just...

[00:40:06.380] - Dr. Gordon

I've just learned this actually yesterday. Yes, yesterday. There's this protein called galectin-3. Have you heard of that? I have. And it works in this lockstep walking with two inflammatory markers that you've told me about before, TNF alpha and IL-6.

[00:40:30.000] - Dr. Lemanne

Very interesting.

[00:40:31.280] - Dr. Gordon

So all three of those, but particularly galectin 3, if you have certain genetic variants, your galectin 3 looks like not just a nail with two ends, but a spike with five ends to it, associates P Tau, holds five P Tau or more molecules together, and then they tend to make tangles and fibrils and oligomers. How do you say oligomers, oligomers?

[00:41:02.600] - Dr. Lemanne

I'll say oligomers, but I may not be correct. But I get what you're talking. This is really interesting. So the spiky galectin-3 is associated with these Tau tangles.

[00:41:17.000] - Dr. Gordon

These Tau tangles.

[00:41:18.140] - Dr. Lemanne

Yeah, interesting. Where did we get this spiky galectin-3 from? From mold?

[00:41:25.640] - Dr. Gordon

Well, genetically. So I was doing a I do a fairly big genetics panel that's really a medically... It's not 23andMe based. It's from a medical company. And it's an executive panel, has both cognitive and medical findings. And they've recently just released, added more genes to their panel. And she was very excited about it because she says, We've been able to measure these genes for half a dozen years, but we haven't put them in the report because there's no way for you to measure the effects of the genes, and there have been no studies about what to do about it. So this galectin-3, you can measure it at Labcorp now. Okay.

[00:42:15.000] - Dr. Lemanne

You mean you can see which type you have inherited?

[00:42:17.840] - Dr. Gordon

No, not the gene, but there is a normal and an abnormal level of galectin-3. Like there is a normal and you wouldn't want your TNF alpha to be zero.

[00:42:29.120] - Dr. Lemanne

Right. So we demonize inflammation, but inflammation, if you didn't have it, you would die. That's like AIDS, HIV, AIDS. You have no immune function. So help me understand here. So galectin The type of galectin-3 you have, whether you have this normal kind or the spiky kind, is inherited, but the amount that you have is related to what your body is processing at the moment? Yes. Okay.

[00:42:58.300] - Dr. Gordon

And it I will say it's at least those things are true. There may be more to it than that. For instance, maybe certain viruses change and turn your galectin-3 into multi-armed spikes. But for right now, we know that you can have a genetic tendency, and your galectin-3 can actually be measured in your blood. And if it's too high, you're at increased risk. And this is where... Have you heard of the new Alzheimer's drug TB006? I have It's moved from experimental to accessible. It's an infusion. It's very expensive. It's $5,000 a month. And you need an IV nurse. But all this, they've known about that drug for a while. They've known about galectin for a while, but now there is a blood test and a treatment, and they can link them together. So they've just added that to the genetics panel that I offer to my patients, none of whom are going to really We'll probably sign up for TB006. But there are other things that can affect that, as there are other things that can affect those other inflammatory markers.

[00:44:12.460] - Dr. Lemanne

Well, wow. This is really fascinating. I did not know this about the test, and I'm sure our listeners are really fascinated as well. We're getting close to the end here, and there's one question here that I I think we both can talk about, and that's your reader wrote, I can't take hormones or don't want to because I've had a hormone sensitive breast cancer. I'm off treatment now. What can I do? And I get a similar question, and I'll just put that in here. And that's, I have hormone sensitive breast cancer. I'm on treatment, and the treatment is very, very difficult. And I think I'm going to have to stop. Should I? And if I do stop, what should I do? So I think those two questions are flip sides of the same coin.

[00:45:08.320] - Dr. Gordon

And the first question really is to you, because there are different categories of treatment for hormone sensitive breast cancer. And in your experience, are some particularly better tolerated than others?

[00:45:21.320] - Dr. Lemanne

Particular treatments? Yes and no. So I've had patients have no No problems with the... The two main classes are the drugs in the tamoxifen family, and the others are the aromatase inhibitors. They have names like aromasin and letrazole. And both of And then, of course, those categories have people who do very, very well, and both of those categories have people who do just awful. And then, of course, there are people in between. And then hormone sensitive breast cancer There isn't one thing either. Everybody's hormone sensitive breast cancer is more or less sensitive to hormones than somebody else's cancer. So you might have a hormone, breast cancer that has, for instance, 5% estrogen receptors, meaning 5% of your breast cancer cells under the microscope show we can see estrogen receptors on them, and somebody else might have 99%. And depending on the laboratory, some labs will cut it off and say your breast cancer is hormone insensitive at 5%, and some other labs will cut it off at 10%. And whether you have both hormone sensitive, estrogen receptor expression and progesterone receptor expression matters. If you have just one or the other, that changes how well these drugs will work for you, especially if you have estrogen receptor positive breast cancer, but your progesterone receptor expression is low or negative.

[00:47:04.180] - Dr. Lemanne

That means you may not have great results with estrogen receptor blocking agents. So there's so much complication there.

[00:47:14.200] - Dr. Gordon

There is. And I realized I've never thought, yes, there are these two categories of drugs that treat estrogen receptor-positive breast cancer. What happens to the progesterone receptor-positive component to it? Is there a separate treatment Are there drugs that are effective for that?

[00:47:30.640] - Dr. Lemanne

There can be, but those drugs have a lot of side effects. If you block the progesterone receptor, the patient usually gains a lot of weight, feels mentally sluggish. It's not something that women will put up with at all. So we don't usually use those. We used to use progesterone-blocking drugs for treatment of metastatic endometrial cancer, but that's a whole different story. Which I thought was. The main point is that it is really complicated. You don't want to do this at home. Have this conversation with your oncologist and have a careful review of the details of your pathology report before you try to make a decision like that. But having said that, are there some patients who just can't tolerate one or both of these drugs and they have to stop? And the answer is yes. And depending on who you ask, it's anywhere between 10 and 40 %. And so that's a big enough minority that you want to pay attention to that if you're the oncologist. And yeah, I mean, you know that I've actually worked with you and with some mathematical oncologist to actually toggle actual hormone replacement therapy in patients with breast cancer and with antihormone therapy based on mathematical modeling.

[00:48:52.000] - Dr. Lemanne

This is not just the calendar. We actually do some science here. So that That can work, too. So it's a complicated situation, but the answer is a cautious... Yes, you might be able to work that out if you work carefully with a knowledgeable oncologist and one who will do the work with you. And if you're willing to do the work, if you're just going to say, well, I'm just going to stop these drugs and hope for the best. Well, that is an option, but that probably isn't your only option.

[00:49:24.080] - Dr. Gordon

And from the oncology point of view, if you have a patient who can't tolerate either category those drugs, is there another category of drugs? Is there more surgery or more radiation or anything like that involved as an alternative?

[00:49:39.460] - Dr. Lemanne

All of those things, again, it depends on whether the patient has active disease, meaning the doctors can see the disease on scans or blood work or something else. But most of the time patients are asking this and they have levels of disease that are so low, the doctors think there is some disease there, that's why they're giving them the drug. But the levels are so low that tests can't easily pick them up. We do have better tests now. So circulating tumor DNA, not circulating tumor cells, which is an older test, which isn't very sensitive or useful, but compared to circulating tumor DNA, which is newer and much more sensitive and turning out to be extremely useful because we can see disease activity. We can see little particles of DNA from the patient's breast cancer floating around in the bloodstream, months, sometimes even years before scans will show anything or before the patient will become symptomatic.

[00:50:34.770] - Dr. Gordon

Well, that's handy.

[00:50:35.980] - Dr. Lemanne

It's very handy. Those kinds of tools should be vigorously, aggressively used in patients who are considering stopping their breast cancer treatment because of side effects.

[00:50:51.060] - Dr. Gordon

Leaving them in the unfortunate situation of having way less estrogen than their husband, who doesn't have breast cancer, doesn't take hormones, but he has some aromatase in his body. So he turns his testosterone, a little bit of it, he turns into estrogen. So this is always a shock to women who say, well, my husband doesn't take hormones. He doesn't have osteoporosis. Well, he does take hormones because he's still making his testosterone. So I tell people that the option that, of course, that I offer people, and we've talked about this before in a previous podcast, is is genestine, which is a soy-based isoflavone molecule that is a phytoestrogen. It comes from soy, it can come from pomegranate, and there Now, there are getting to be more and more supplements for that on the market. I would just caution people, probably all of them that say genestine are genestine, but you have to look at the fine print and see how much actual genestine is in each one. And the reason it, as a phytoestrogen, is presumed to be either completely or predominantly safe in a setting of breast cancer, is it the estrogen receptors it activates are primarily the ones in the brain and in the bones, and the ones that it does not activate, does not bind with, or if it binds, blocks it.

[00:52:26.270] - Dr. Gordon

And that's what I'm not sure about that detail. But I I think it actually blocks estrogen receptors in the breast and in the uterus. So something I'll give people who are bleeding that don't want to bleed on their hormones. It'll help with gentle bleeding, but it stimulates estrogen where we want it in the brain and the bones. So for instance, if I have a male patient who's got a little osteopenia, a little cognitive impairment, and he's really skinny and he doesn't make any estrogen, because men usually have a measurable estradiol level of about 15 to 30, 35, something like that. So if he has less than five picograms per milliliter of estrogen, I'll give him Genestein for the sake of his brain and bones. And I think it's something that is more readily available. Swansons, a very popular supplement company, makes a non-soy-based pomegranate form. It's low Genestein, but it does provide some of it. So I'm a fan of Genestein.

[00:53:35.300] - Dr. Lemanne

Well, you taught me something about breast cancer patients on aromatase inhibitors and the use of Genestein, I think for cognitive issues.

[00:53:45.920] - Dr. Gordon

Yes.

[00:53:46.500] - Dr. Lemanne

And tell our readers about that. I found it fascinating. I think it's really important, and I want our readers, our listeners to hear about this from you.

[00:53:57.980] - Dr. Gordon

So what the research, and there may be more recent research, because last time I looked at it was when we recorded the Genestein episode, the aromatase inhibitor eczemastine?

[00:54:10.040] - Dr. Lemanne

Yes, eczemastine. There are three. Just for our readers, I'm going to run down the three aromatase inhibitors. There's one called Letrazole, that's the most famous one, and its brand name is Femara. And then there's a second one called Anastrazole, and its brand name is Arimidex. And then the third one, which is less often used, but is considered a little bit more powerful, usually, is called Xamestane, and its brand name is Aromasin. And what you taught me was quite eye-opening about Aromasin compared to the other two.

[00:54:40.340] - Dr. Gordon

Yeah, so in the research that's been done, and none of these things have been studied over and over again, but for the best research we have is XMS stain and genestine work synergistically in opposing, in preventing estrogen from activating the receptors in the breast. But genestine can run an end run around XMS stain and activate the estrogen receptors that otherwise wouldn't be well-fed in the bones and the brain. And it's an additive effect.

[00:55:14.480] - Dr. Lemanne

So it protects the breast. It protects you from breast cancer, a bad interaction with breast cancer, but protects your bones from decay with the aromatase inhibitor. Yeah. That's just And it doesn't do the same with femara or letrazole and rivodex and astrazole?

[00:55:35.840] - Dr. Gordon

It either hasn't been studied as well or there is some evidence that it may conflict with the use. So the only study has been done that shows that they have a... What I would say, if somebody has to take an aromatase inhibitor, I'd really like their oncologist to pick XMS stain for them so that I feel very comfortable giving them Genesteine on top of it.

[00:55:58.280] - Dr. Lemanne

Yeah, I think that's really important, and I'm glad that's in the conversation.

[00:56:01.840] - Dr. Gordon

Are you going to just give a little glimpse into your future publications when we're talking about mathematically modeling for treating cancers that have circulating blood markers? And might there be a research article that you've contributed to coming out in the very near future?

[00:56:21.920] - Dr. Lemanne

Yes, it's actually been published.

[00:56:23.890] - Dr. Gordon

Oh, it hasn't? It hasn't been published.

[00:56:25.400] - Dr. Lemanne

Okay, good. It has a title, something like Directed Evolution to Reverse Treatment Resistant in prostate cancer. And so this was a case report of a patient with metastatic prostate cancer. And my colleagues and I used directed evolution, meaning we're trying to breed treatment sensitive cancer cells in this patient. Our listeners know that I am very interested in the development of treatment resistance and how that is not addressed in current oncology. It's just accepted, well, we're going to treat you with this medication until it stops working. And the until it stops working is never questioned, never pushed back against until now. So we pushed back against that with this patient. We gave him actually when his tumor was starting to become resistant to our treatment, which was withdrawal or blockade of testosterone use by the cancer cells, we actually gave him testosterone to rescue the cancer cells that were sensitive to testosterone and would grow in the presence of testosterone. And it was successful. We did cause the growth of his cancer cells. I know that sounds counterintuitive and unusual, but you have to think outside the box with cancer because our current box doesn't work very well.

[00:57:49.500] - Dr. Lemanne

So we did that. We increased the number of treatment sensitive cancer cells in his body, and we made his cancer grow. And then we were able to treat it again successfully with hormone blocking agents. So that's the gist of the article. And yeah, we have several other patients for whom we're doing similar things, a couple with breast cancer, I think, and endometrial cancer, another one or two with prostate cancer, even a colon cancer case that is not related so much to hormones, but it does have its own treatment and treatment resistance problems in the general oncology realm. Again, treatment is given until the resistance appears, and we're going to try to break that cycle. So we'll let you know if we have any more publications.

[00:58:38.780] - Dr. Gordon

This is cutting edge, and this is so exciting. And it reminds me of a patient we share who came to me, and she really had a very eloquent way of explaining something I'm going to trash. I'm not going to be able to reproduce very well now. But she says, I'm not here to wage nuclear war against my cancer. I know I'm going to be dancing with this cancer for the rest of my life, and I'd like it to be a fairly innocuous dance partner.

[00:59:05.380] - Dr. Lemanne

Well, that's very, very wise. We're all dancing with cancer, and our bodies are able to keep it under control. Sleep, hint, hint, hint, is probably the major tool that our bodies have to do that. And exercise, hard exercise, is another tool that people can use for that. But yeah, she's right. And sometimes the patient needs some help to dance. We can add some lifts to that one short leg or something like that. Put a lift in your shoe. If you're limping, this is metaphorical. Metaphorical limp in your dance and get you dancing with that cancer so that you have a long and healthy life despite the cancer.

[00:59:46.140] - Dr. Gordon

Yes. And she's in a treatment-absent era of her life and getting on with the rest of it. It's great. And the cycles will come and go.

[00:59:58.440] - Dr. Lemanne

Deborah, you had so many questions here that your patients have given you. 15, I think. And then I had maybe four, so maybe 20 questions. Your questions are three parts, five parts. So we have a lot more that we can get into. Do you think we should do this type of episode again?

[01:00:15.270] - Dr. Gordon

I think we do. And I think we should open the floodgates and ask if people have other questions that you're afraid we're not going to ever get to. We really welcome live and current questions because that fuels our thinking and research research efforts, and we have a good time talking about it, don't we?

[01:00:33.090] - Dr. Lemanne

Yeah, we do. We do. Yes, so send us your questions, dear listeners, and we read all of them.

[01:00:39.420] - Dr. Gordon

We do. Well, this has been great. And I do want to ask you some of these other questions that I have for you, but we're just going to wait till our next episode. I know. It's hard. It's really hard.

[01:00:50.880] - Dr. Lemanne

I'm having a hard time closing this episode, but should we say goodbye?

[01:00:54.410] - Dr. Gordon

We should say goodbye. See you next time. Bye-bye.

[01:00:57.120] - Dr. Lemanne

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[01:01:28.420] - Dr. Gordon

You have been listening to the Le Monde Gordon podcast, where Docs Talk Shop.

[01:01:34.340] - Dr. Lemanne

For podcast transcripts, episode notes and links, and more, please visit the podcast website at docstalkshop.

[01:01:43.400] - Dr. Gordon

Com.

[01:01:43.930] - Dr. Lemanne

Happy Eves dropping. Everything presented in this podcast is for educational and informational purposes only and should not be construed as medical advice. No doctor-patient relationship is established or implied. If you have a health or a medical concern, see a qualified professional promptly.

[01:02:10.580] - Dr. Gordon

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[01:02:22.720] - Dr. Lemanne

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[01:02:37.140] - Dr. Gordon

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[01:02:44.000] - Dr. Lemanne

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[01:03:01.420] - Dr. Gordon

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