The Latest Science on REVERSING Cognitive Decline | Dr. Dale Bredesen

0:00 All right, well, you just mentioned the trial.

0:02 Let's get into the details there.

0:04 The way I understand it, this...

0:06 was...

0:07 unofficially published at the end of 2025

0:09 and the peer review process is underway now...

0:11 Soon we're going to get the final paper, is that right?

0:12 Yeah.

0:15 Exactly right, yes...

0:17 So what we did was this is now out as a preprint.

0:20 So the preprint makes it public,

0:22 it makes it searchable, and it makes it citable...

0:25 So those are all accomplished.

0:27 But you're right, we also want to have a peer-reviewed paper out there,

0:31 and so we're just finishing that up.

0:33 So that should be out.

0:34 It's going to be a few months.

0:36 By the time...

0:37 you get the reviews, they often will want some edits,

0:40 et cetera, some revisions to the paper.

0:42 And so that'll be a few more months,

0:44 but it'll be out and it will be somewhat similar.

0:46 We've got a few additional things we've added over the preprint.

0:49 But again, you can see in the preprint, you can see the summary of what we saw.

0:53 All right, well, the way I understand it,

0:56 you've done a bunch of research leading up to this paper,

1:00 but this is the first "RCT," which is

1:02 the gold standard when it comes to research.

1:05 Right.

1:06 So let's talk about the layout of this study and then

1:07 what you can share at this point what you found.

1:08 Mmhmm.

1:10 Yeah, you made a great point which is that you...

1:14 ultimately this is the gold standard.

1:17 So we started with anecdotes.

1:18 So we had the first couple of people, then we had 100 more...

1:22 So the anecdotes showed that again and again

1:24 and again we could see reversal of cognitive decline,

1:27 which just hadn't been reported before.

1:29 We reported the first ones back in 2014.

1:32 So then we advanced to a proof of concept trial.

1:35 So we then published that in 2022 and showed, no question,

1:39 that was a peer-reviewed paper to show that yes,

1:41 we can reverse cognitive decline.

1:43 Then there is independent confirmation by Doctor "Heather Sandison" and her team

1:48 that came out in 2024 and that was showing that, yes,

1:52 same sort of thing, they saw very much the same thing we did,

1:55 that you could reverse cognitive decline.

1:57 So then finally, all of those led up to this randomized controlled trial.

2:02 So in this controlled trial then, you have people coming in.

2:06 Now, people have argued that, how is it ethical to do a trial...

2:10 now that we know what we know, how is it ethical to do a trial with...

2:14 You have people who are getting standard of care when

2:18 the standard of care is not showing reversal of cognitive decline.

2:22 So what we do is that this is a nine-month trial...

2:25 and so you either, you randomize two to one.

2:28 So there's a 67% chance you'll get in the treatment group...

2:32 and a 33% chance that you'll get in the standard of care group.

2:36 After nine months, then that standard of care group is offered...

2:41 They can have a free six months of being given

2:45 the precision medicine approach where we're looking at all these things,

2:50 and you could see in fact the people who are

2:53 in the standard of care going downhill and then bouncing up and improving...

2:57 after they got on the treatment.

2:59 So the way it's set up, you then randomize and then you are looking

3:03 at what happens to those people over the nine months.

3:07 You're looking at...

3:08 cognitive changes, you're looking at imaging changes,

3:11 you're looking at biomarker changes,

3:13 you're looking at biochemical changes, all of those things.

3:17 And what we found was striking...

3:19 So you see that the people, for example, if you look at their memory scores,

3:24 verbal memory plus visual memory,

3:27 the group that is getting standard of care is going down,

3:30 down, down during the nine months,

3:32 the group that is on the precision medicine approach is going up,

3:36 up, up and improving in their cognitive scores.

3:39 Really striking differences.

3:41 And then of course the most important thing of all is the statistics.

3:45 What did the statistics actually show?

3:47 Was this statistically significantly different or not?

3:51 And these were hugely different.

3:54 Most of the values were p less than .001.

3:57 So in other words, there was only a one in a thousand...

4:01 chance that there was not a difference between the two groups.

4:05 So, striking differences.

4:07 And then we also compared, we did what's called a forest plot,

4:12 where you're looking at the overall impact.

4:14 So the forest plot is telling you...

4:17 what was the impact...

4:18 of the treatment...

4:20 And the impact of the treatment was greater than any published trial.

4:24 In fact, it was seven...

4:26 times the impact of...

4:30 one of the quote, breakthrough drugs and four

4:32 times the impact of the other breakthrough drug.

4:36 And in fact, of all the trials previously published,

4:39 the one that had the second best, this was 90%...

4:43 better than that.

4:45 So again, just striking improvements in these people.

4:48 And it tells you that you need,

4:50 in people who have cognitive decline and these were

4:54 at the mild cognitive impairment to early dementia,

4:56 very similar to the drug trials.

4:59 When you look at these people, you really do need to evaluate all the different

5:04 things that can potentially be giving them problems.

5:08 Various infections, various toxins,

5:09 various metabolic problems, hormonal insufficiencies.

5:13 All these different things need to be

5:16 considered if you're going to get best outcomes.

5:19 By the sounds of what you're sharing here,

5:21 this is going to make waves in the brain research and science realm.

5:26 What do you expect to come of this when people start to see these findings?

5:30 I think with all these...

5:32 Medicine unfortunately has a history of changing very slowly.

5:37 And if you go back, for example, to scurvy,

5:41 which was a huge problem, 1600s, 1700s, etc.

5:45 It took hundreds of years for people.

5:47 So at each...

5:48 century, 1600s, 1700s, 1800s, people would say,

5:51 I think we know what to do about this.

5:54 And then the doctors would push back and say, no, no, no, no, that's not right.

5:58 And more people would die of scurvy, which is sad.

6:01 I think it's really sad.

6:03 Medicine often doesn't pick up on new therapeutics quickly enough.

6:07 So I expect that there will be some pushback...

6:10 People will say, well, we want something different, we want something more,

6:14 what have you, despite the fact that the statistics are very clear.

6:19 There— are...

6:20 commercial interests, unfortunately.

6:24 And so, there's going to be pushback in various areas.

6:30 I think it'll be harder and harder to deny

6:32 that this approach is getting the best outcomes.

6:35 And I think in the long run, you're going to see a fusion.

6:38 So there will be targeted therapeutics,

6:41 targeted drugs, for example, or other approaches that...

6:45 are going to go with the overall

6:48 precision medicine approach to get even better outcomes.

6:51 So my hope is that people...

6:53 will not look at this as a final answer,

6:55 but we'll look at this as the beginning, as a step in the right direction.

7:01 Now, for the first time, we unquestionably.

7:05 You can't argue anymore with the idea that this can reverse cognitive decline.

7:09 People have said over the years, nothing can reverse cognitive decline.

7:12 No, we're documenting it daily now.

7:15 So my hope is that people will ultimately start looking

7:18 at, how do we now continue to make this better?

7:20 Now, in the trial, 90%...

7:23 of the people who were treated with the precision medicine approach improved,

7:28 but some of them improved a lot and some of them improved a little.

7:32 So how do we get 100% of people to improve a lot?

7:36 That's the next question...

7:37 The other...

7:38 big question coming up is how do we get people who are further along?

7:43 You have to remember that in the drug trials and in our trial,

7:47 we took people who were in that third and fourth stage...

7:51 "MCI," mild cognitive impairment and early dementia,

7:54 but we didn't take people who are in late-stage dementia.

7:58 That's another big question.

7:59 What can we do for people who have "MoCA" scores of zero?

8:03 For example, Montreal Cognitive Assessment scores of zero.

8:06 We have seen people...

8:08 anecdotally improve with those scores,

8:10 but we haven't seen them improve all the way back to normal...

8:14 So what do we need to add?

8:15 And then perhaps the most important thing of all,

8:19 can we get people to come in earlier?

8:22 So the first two stages are pre-symptomatic,

8:25 where you've already got the beginnings of the pathophysiology,

8:29 but you don't have any cognitive loss...

8:31 And then the second stage,

8:33 which is "SCI," subjective cognitive impairment, where something's not right,

8:38 but you're still able to score within the normal range on cognitive testing...

8:43 People in those two groups, 100% of them do great.

8:46 Unfortunately, most people wait until the last two stages...

8:49 Stage three, which is "MCI," mild cognitive impairment,

8:53 where now you're not scoring normally...

8:55 on the testing...

8:56 And then of course, stage four, which is dementia,

8:59 where you're now having trouble with your activities of daily living.

9:03 So if we can just push people to come

9:05 in earlier that really will make things optional.

9:09 You hinted at this before when you were talking

9:11 about ethics in the control group in your study.

9:14 Yes.

9:15 But...

9:15 it's important we point out...

9:17 conventional treatment to this point has been abysmal

9:19 when it comes to cognitive decline in Alzheimer's,

9:22 and there's actually been fraud in the research.

9:26 I don't want to take a big part of the conversation getting into this, Yeah.

9:31 but really high level,

9:31 just so we have a full lay of the land here, explain that part.

9:34 Hmm.

9:35 Yeah, such a good point...

9:37 So there's a wonderful book by "Charles Piller,"

9:40 who's an esteemed science writer from "Science" magazine.

9:44 And he did a...

9:45 an exhaustive study looking at all these things,

9:48 talking about the evidence of fraud, which is, as multiple sites.

9:52 It's really been a huge problem because

9:54 people see this is such an impactful area...

9:58 with respect to...

9:59 hundreds of billions of dollars in the pharmaceutical market,

10:03 with respect to potential Nobel Prizes for the researchers.

10:07 It's such an impactful area.

10:10 And so what's happened is you've got...

10:12 papers and in fact, as he points out,

10:14 one particular one that was very impactful and really

10:18 changed a lot of research for a lot of people,

10:22 turned out to be fraudulent, unfortunately.

10:25 And unfortunately led to millions of dollars of grants

10:27 and a lot of stuff going in the wrong direction.

10:31 And it was related to this idea that amyloid is the cause of Alzheimer's.

10:36 And what we understand much better now is

10:40 your body is responding to these various insults.

10:43 The amyloid is a mediator...

10:45 it's not the cause.

10:46 So what happens is your brain recognizes when you have changes.

10:51 For example, you've got a change in your oral microbiome...

10:55 and there is a connection there...

10:57 You can have a change in your rhinosinal microbiome.

11:01 You can have leaky gut, you can have exposure to toxins,

11:05 you can have metabolic changes on and on and on.

11:08 And it responds to those...

11:10 by producing this stuff, amyloid, which is a little bit like...

11:15 taking molasses.

11:16 And what it does is it surrounds the pathogens,

11:20 sequesters them, isolates them and inactivates them.

11:25 So when you-— start having this is again why...

11:28 "P.

11:29 gingivalis," one of the oral pathogens, when it gets into the brain,

11:34 you make that amyloid, which coats it and inactivates it.

11:38 So what we're learning is that all of these different...

11:41 proteins...

11:42 that have been associated with neurodegeneration,

11:46 and of course the claim has been a misfold...

11:49 folded proteins quote.

11:51 And that's again, that's an outdated thought process...

11:54 with respect to these diseases.

11:57 These are all...

11:59 antimicrobial proteins.

12:00 In other words, they are part of your immune

12:03 system and specifically your innate immune system.

12:07 So they are upstream.

12:09 And my argument is that they're actually

12:11 from the upstream in that they are a pre...

12:15 inflammatory component...

12:16 In other words, if you have...

12:19 small amounts of these various pathogens, you can get away with just

12:24 coating them and not activating inflammatory pathways.

12:28 And indeed, that's exactly what you see.

12:31 There are people who will walk around

12:33 with amyloid in their brains for 20 years...

12:36 and think just fine.

12:38 So your brain is really trying to help you out.

12:41 When you activate the inflammatory pathways now you are losing synapses...

12:46 Now you've got— complement on these synapses.

12:49 You're losing them, you're pruning them and now you're

12:52 really pulling back and you've got-— a bigger war.

12:55 It's a little bit like can you fight a little skirmish and just

13:00 keep things localized or are you going to go into a much larger war?..

13:05 It's that inflammatory war going on in your brain

13:08 that is giving you the symptoms of Alzheimer's...

13:12 So the amyloid, again, it's a...

13:14 marker.

13:14 But what it's really telling you is that your brain has recognized...

13:19 insults and has now used this to sequester,

13:22 isolate and inactivate these various pathogens, toxins, et cetera.

13:27 When it comes to the "RCT." How many different things did you guys test for?

13:32 And then what did treatment look like?

13:34 Yeah, great point.

13:36 So we tested for all the things that we've talked about.

13:39 We looked at all the, at various potential causes of inflammation,

13:43 we looked at the various organisms,

13:45 we looked at actually about 20 different organisms,

13:48 the ones that are commonly associated with cognitive decline.

13:51 And we looked at the various...

13:53 viruses, fungi, bacteria, spirochetes,

13:56 all of those, the tick-borne illnesses that I mentioned earlier.

14:01 We looked at the oral microbiome,

14:03 we looked at the epigenetics, we looked at the...

14:06 brain volumetrics, we looked at all these different things.

14:11 We looked at the genetics with "IntellxxDNA" in that particular case.

14:16 Do people, for example, have an increased propensity for clotting?..

14:22 Some of the people will, we had one, for example, in the earlier trial.

14:25 Every time he would get on a plane and go to Europe...

14:28 he would start to get confused and it would

14:31 take some time to kind of get back to normal.

14:33 Then over time, he's getting some decline.

14:36 Well, what's going on there?

14:38 This person turned out to have a tremendous propensity...

14:41 for clotting...

14:42 So it just turned out that you get in that where—

14:46 the oxygenation is not as good and he's now...

14:50 on the edge of what's making the brain work.

14:53 Improving his clotting status, improving his oxygenation status.

14:58 He did great.

14:59 So...

15:00 again, you got to...

15:01 find these things...

15:02 and address them.

15:03 So we looked at all of those and then...

15:06 what we are doing in the treatment is we're

15:11 doing the seven basics and then the two specifics.

15:14 So we're doing, you mentioned earlier "KetoFLEX 12/3" diet, which is a...

15:19 specific high-fiber.

15:21 It is a mildly ketogenic, plant-rich...

15:23 diet with good...

15:24 prebiotics and probiotics.

15:26 You're now bringing back insulin sensitivity.

15:30 It is enhancing your detox.

15:32 It is improving your gut microbiome.

15:35 All of those things are helping to support the brain.

15:39 Exercise and regular exercise, getting your heart rate up,

15:42 both strength training, which improves your insulin sensitivity by the way...

15:47 and aerobics, which improves the blood flow and the oxygenation.

15:51 Sleep, the four parameters I mentioned earlier.

15:55 Stress levels.

15:55 So getting your "HRV" up, really helpful to do.

15:59 Brain training and brain stimulation...

16:01 So we included photobiomodulation as well as "BrainHQ." And by the way,

16:06 you may have seen the paper showing that Double Decision,

16:10 which is one of the things that came

16:12 from "BrainHQ," reduced the risk for cognitive decline even years...

16:17 after the brain training itself was done.

16:19 And then brain...

16:20 detox and then some targeted supplements.

16:23 And so again there are all sorts of supplements.

16:26 And I wanted to say a word about supplements...

16:29 It's been common for people to say,

16:32 well supplements aren't a cure for Alzheimer's.

16:35 Nobody's saying they are.

16:37 What they do is...

16:38 used...

16:38 appropriately, they can optimize and help you

16:42 to optimize these various parameters that we're talking about.

16:45 So, yes, by definition, they are supplementary, but they can be very supportive.

16:51 We talked about creatine.

16:52 There are others, obviously, things like Urolithin A and some

16:56 of the resolvins that can be very, very helpful.

16:59 There's just a whole you could spend hours just talking about supplements.

17:04 Again, used the right way for the right people

17:08 for the right reasons can be very, very powerful...

17:11 So those are the seven basics.

17:13 And then the two specifics are looking

17:16 at the infections and treating those appropriately...

17:19 So, for example, many people...

17:21 ended up having...

17:23 nine months of valacyclovir.

17:25 That is part of...

17:26 reducing that burden.

17:27 Now, I want to mention there was a trial

17:30 where they just used that, nothing else, just valacyclovir.

17:33 And the people actually got a little worse, not better.

17:37 Well, of course, you're not addressing all these other things...

17:42 You've got to get at all the different things that are driving,

17:46 driving it and address those.

17:48 And then, people would be treated for whatever infections they had.

17:53 A number of people that were treated for Lyme disease or treated

17:57 for "Babesia" or treated for "Bartonella," for example, and then detox.

18:02 And that was relatively common that people ended up having...

18:06 toxicity.

18:07 It's turning out surprisingly to me because we were never taught.

18:12 When I was a neurology resident or a neurology fellow,

18:16 we were never taught that, a common contributor

18:19 to cognitive decline is going to turn out to be...

18:23 mycotoxins.

18:24 It has turned out to be one of the most common contributors...

18:28 Probably number one is what you mentioned earlier, metabolic dysfunction...

18:32 That is...

18:33 probably the most common.

18:34 And of course, if you've got metabolic syndrome, you...

18:38 multiply your risk by about threefold.

18:41 So you have a much increased risk for cognitive decline...

18:45 But I would put as number two, mycotoxin exposure.

18:49 And again, you've got to address those things,

18:51 reduce those to get the best outcomes.

18:54 Well, let's zoom in on mycotoxins.

18:57 Where are these coming in...

18:58 and what are the most common ones?

19:00 Yeah, this is such a good point.

19:03 So most of us don't realize we're being exposed to these things, unfortunately.

19:07 And again, it's something where...

19:09 people say, well, I didn't hear about this, so it must not be important.

19:13 So the typical story is...

19:15 you are either living in or working in a water-damaged building.

19:20 And we have people, for example, that are so sensitive to these mycotoxins...

19:25 that they will tell by their— brain fog

19:28 and their cognitive change when there's been a new roof leak.

19:33 And as an example, one of the people is "Sally," who started years ago.

19:38 She had six great years of doing very, very well.

19:42 She had amyloid-proven, "PET" scan-proven.

19:45 She was one of these people who went on the antibodies and got worse with those.

19:50 She then went on the protocol.

19:52 Her "MoCA" score went from 24, which is "MCI," to a perfect 30...

19:57 Stayed there.

19:57 She's done great...

19:59 After six years, she started having backslide.

20:02 She started noticing some problems like, what's going on here?

20:07 So it turned out, number one, she had a new roof leak...

20:11 She now had more exposure to these mycotoxins.

20:14 Number two, it turned out that she had some undiagnosed sleep apnea.

20:18 And number three, she actually had a fungal infection

20:21 in her sinuses called "Cryptococcus laurentii."

20:24 So those three things were addressed.

20:27 Boom, she gets back again.

20:28 And now she's now in her ninth year with stable improvements.

20:33 She's done great.

20:33 And she's one that she can actually tell if they have a new roof leak...

20:38 So for most of us, we are exposed to these because of mold.

20:42 It's really unfortunate...

20:43 that the people do not build buildings with this idea that, wait a minute,

20:48 we cannot allow wood.

20:51 If we're using wood in the buildings, we cannot allow this to get wet.

20:55 It's just like, yeah, it's left outside.

20:57 How can that be a problem?

20:59 But it is a problem.

21:00 And so unfortunately, as you know, you can.

21:03 Sometimes you look at these buildings and there

21:05 are all sorts of wonderful building inspectors.

21:07 "We Inspect" is one of them...

21:09 There are many others that do this, and you're looking at these and they'll find

21:14 all sorts of "Stachybotrys." So they're the big

21:17 five with respect to the molds themselves.

21:19 And those are "Stachybotrys," "Penicillium," "Aspergillus," "Chaetomium,"

21:24 and "Wallemia." Those are the big five.

21:27 There are lots of others where they don't really make damaging mycotoxins.

21:31 But those are the big five that you want to know about.

21:36 You mentioned which ones.

21:38 The— two that I worry about the most is...

21:41 "Ochratoxin A," because that one has been shown...

21:45 to be a specific toxin for that damages your hippocampal

21:50 neurons and hippocampal neurons are compromised in Alzheimer's disease.

21:56 So I worry when people have high levels of...

21:59 so-called "OTA" and we see it all the time.

22:03 The other one is various trichothecenes.

22:05 That group which typically come from...

22:08 "Fusarium" or...

22:09 "Stachybotrys." Those are those I also worry about.

22:13 They're quite toxic and they are associated with cognitive decline as well.

22:19 There are others.

22:20 Those are the two ones I worry about the most.

22:23 And so they're the good news again.

22:24 There are ways to detox them.

22:26 You have to be careful.

22:27 It's been shown, if you're overly aggressive,

22:30 these things are now pouring out of the— organs and you

22:34 can spike your blood levels and you can have some transient backsliding.

22:38 So that can be an issue.

22:40 So you really have to be careful.

22:42 It takes months and months and months...

22:45 to continue to just get these things out.

22:47 Getting your glutathione level optimal,

22:50 often with things like "PK" protocol can be helpful

22:53 in terms of getting these things out of your brain.

22:56 But of course, as we've got this dynamic process,

22:59 you're always detoxing them, you're always excreting them.

23:03 You're excreting with multiple pathways,

23:05 which is why binders things like cholestyramine and "Welchol"

23:10 and bentonite clay and things like that have been very helpful...

23:14 in treatment.

23:15 Whether it be mycotoxins, microplastics, metals.

23:19 It sounds like it, but do you recommend

23:22 working with a practitioner to get those out?

23:25 Yes, I think it's a good idea.

23:28 I think in general, you don't necessarily need a practitioner for prevention.

23:33 You can do a lot just read the books, go online.

23:37 There's some wonderful guides.

23:39 "Julie Gregory," who's the one who

23:42 started "apoe4.info" check out "apoe4.info" it's wonderful.

23:45 There are over 8,000 people on there who are all "ApoE" positive.

23:51 They're doing a great job with prevention of decline.

23:54 They share their...

23:56 secrets.

23:57 The...

23:57 majority of them are on some version of the protocol we developed.

24:03 And so— I think all of these things are...

24:07 key.

24:08 You can look at the guides.

24:09 She's produced over 100 guides that are on "Apollo Health." And you can

24:15 look to see various things for what about if I have to go...

24:19 if I can have an operation?

24:20 What about anesthetic agents?

24:22 What do I do to minimize the problem there?

24:25 Because a common problem, as is someone who then had an operation,

24:29 who had anesthesia and then started having cognitive decline.

24:33 So great idea to prepare for that.

24:34 And that's also mentioned in the books as well.

24:38 So these are things that you can do then,

24:40 as you indicated, if you really have cognitive decline,

24:45 especially if you have late stage 'SCI" or "MCI" or dementia,

24:49 any of that region, you really want to work with a...

24:53 practitioner and...

24:54 ask, could I talk to some people...

24:56 that you've worked with who've gotten better?

24:59 Because there are some practitioners, as I mentioned earlier,

25:03 who are not getting people to get better,

25:05 and then there are others who are doing

25:07 a great job getting people to get better.

25:11 For example, one of the six sites,

25:13 every single person who went on treatment got better.

25:17 So that's a really great clinician who knows what she's doing.

25:21 Since you made it to the end of this clip,

25:23 I know you're going to love the full episode.

25:25 Click here to watch.

25:26 I'll see you over there.

25:27 About...

25:28 15% of our population dies of Alzheimer's.

25:31 So about 45 million...

25:33 of the currently...

25:35 living Americans will die of Alzheimer's.

25:39 We can reduce that number-