November 16, 2025 • 13 mins
We examine a phase two randomized controlled trial testing a 20-week, intensive lifestyle program for people with MCI or early Alzheimer’s and find evidence of measurable improvement. We unpack the four-pillar design, the cognitive and biological results, and the adherence threshold that drove success.
• Participant profile and trial structure for MCI and early AD
• Four pillars explained: diet, exercise, stress care, social support
• Clinical outcomes improving daily function and global status
• Biomarkers shifting: Aβ42/40 ratio, microbiome, telomeres
• Dose response and why 71% adherence mattered
• Strengths, limits, and feasibility in real-world care
• Practical steps to build structure and track adherence
This podcast is created by Ai for educational and entertainment purposes only and does not constitute professional medical or health advice. Please talk to your healthcare team for medical advice.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
SPEAKER_00 (00:00):
When we approach the topic of cognitive decline,
whether we're talking about mildcognitive impairment or MCI or
maybe the early stages ofAlzheimer's disease, the
conversation is almost alwayspessimistic.
SPEAKER_01 (00:12):
Aaron Powell It is.
The goal is usually tostabilize, right?
Slow the inevitable trajectory.
SPEAKER_00 (00:16):
Aaron Powell Exactly, just buy some time.
But what if the deep dive intothis new research points to
something far more, I don'tknow, ambitious, something
surprising.
SPEAKER_01 (00:26):
Aaron Powell Well, that's it.
It points to measurable,quantifiable improvement.
SPEAKER_00 (00:29):
Aaron Powell Not just slowing down.
SPEAKER_01 (00:31):
No, the possibility of actual reversal.
That's the jaw-dropping findingwe're analyzing today.
We're drilling down into areally rigorous phase two
multi-center randomizedcontrolled trial, an RCT, from
Dean Ornish and his team.
SPEAKER_00 (00:44):
Aaron Powell And this wasn't just watching people
over many years.
This was a targetedintervention.
SPEAKER_01 (00:49):
Aaron Powell A very targeted, 20-week intervention.
It was focused entirely onintensive, multi-domain
lifestyle changes for people whoare already diagnosed with
either MCI or early stage AD.
SPEAKER_00 (01:00):
Aaron Powell So our mission for you today is pretty
simple.
We're going to dissect thedesign of this program because
it sounds like it required amonumental effort.
Aaron Powell It really did.
And then we'll translate whatthe results, both cognitive and
biological, actually mean.
We need to understand why thesefindings suggest lifestyle
medicine isn't just forprevention, but maybe for early
(01:20):
stage reversal.
Trevor Burrus Aaron Powell, Jr.
SPEAKER_01 (01:22):
A viable adjunct, or maybe even an alternative.
It's a huge claim.
SPEAKER_00 (01:26):
Aaron Powell Okay, let's unpack this.
So the first thing we need toacknowledge is that when the
researchers asked people to jointhe intervention group, they
were signing up for a completeoverhaul, right?
SPEAKER_01 (01:36):
Oh, absolutely.
SPEAKER_00 (01:36):
Trevor Burrus, Jr.: What exactly did that involve?
And who are the people in thisstudy?
SPEAKER_01 (01:39):
Aaron Powell So they enrolled 51 participants in
total.
It was split pretty evenly, 26in the intervention group and 25
in the control group.
The average age was around 73.
SPEAKER_00 (01:49):
Aaron Powell And they all had confirmed
impairment.
SPEAKER_01 (01:51):
Yes.
Clear, established cognitiveimpairment.
This is crucial.
To get in, you needed a MOCAscore.
That's the Montreal cognitiveassessment of 18 or higher.
So these weren't people justworried about forgetting their
keys.
SPEAKER_00 (02:04):
Trevor Burrus, Jr.
No, this was a clinicaldiagnosis.
SPEAKER_01 (02:05):
Aaron Powell Exactly.
Confirmed diagnosable impairmentdue to AD.
SPEAKER_00 (02:09):
Trevor Burrus And the control group, they just
carried on as usual.
SPEAKER_01 (02:11):
Yep.
They continued with what thesesources call usual care.
Meanwhile, the interventiongroup got this very structured,
very intensive, multi-domainprogram.
It was all built around four keypillars.
SPEAKER_00 (02:25):
Aaron Powell And that structure is everything
here, isn't it?
SPEAKER_01 (02:27):
It's vital to the results.
This wasn't about, you know,just adding a supplement or
taking a walk.
It was comprehensive.
SPEAKER_00 (02:34):
So what was the first pillar?
SPEAKER_01 (02:35):
The first pillar was diet.
This was a whole food, minimallyprocessed, plant-based diet.
It was also extremely low insaturated fat and refined carbs.
SPEAKER_00 (02:45):
Aaron Powell And why that specific diet?
SPEAKER_01 (02:47):
Well, because that's where a lot of the
anti-inflammatory power comesfrom.
You're targeting the chronicinflammation that often goes
hand in hand with AD pathology.
SPEAKER_00 (02:54):
Right.
SPEAKER_01 (02:55):
And it's also foundational for the microbiome,
which they also tracked.
SPEAKER_00 (02:58):
Right, the gut brain axis.
Okay, so pillar number two.
SPEAKER_01 (03:01):
Exercise.
They required moderate dailyactivity, a combination of
structured aerobic exercise andstrength training.
SPEAKER_00 (03:07):
Which is about more than just heart health.
SPEAKER_01 (03:08):
Oh, much more.
It's about increasing blood flowto the brain and maybe even
stimulating neurogenesis, thegrowth of new brain cells.
SPEAKER_00 (03:16):
The third pillar was stress management.
SPEAKER_01 (03:19):
Correct.
Things like meditation, yoga,guided imagery, all done
regularly.
I mean, chronic stress elevatescortisol, which is neurotoxic,
especially to the hippocampus.
SPEAKER_00 (03:29):
The brain's memory center.
SPEAKER_01 (03:30):
The memory center.
So reducing that stress is adirect physiological way to
protect brain function.
SPEAKER_00 (03:36):
And finally, something that feels so
necessary given the disease: social support. (03:38):
undefined
SPEAKER_01 (03:42):
Yes.
And it was structured supportfor both the patient and their
study partner or caregiver.
Cognitive decline can be soisolating.
SPEAKER_00 (03:51):
And that isolation creates a horrible feedback
loop, right?
Of stress and depression.
SPEAKER_01 (03:55):
Aaron Ross Powell Exactly, which just makes
cognition worse.
So by creating this supportedsocial network, they were
addressing the psychologicalburden of the disease.
It's this multi-pronged approachthat's so key.
AD is a multifactorial disease.
You can't just treat it with onehammer.
SPEAKER_00 (04:10):
Okay, so given that level of intensity, and that's a
huge commitment for 20 weeks.
Let's get to the core results.
What did all that effortactually achieve, especially
compared to the usual caregroup?
SPEAKER_01 (04:19):
Aaron Ross Powell, the contrast is what's
staggering.
After just five months, if youlook at the control group, they
followed the expected path.
Which is they got worse.
Across all four of the primarycognitive outcome measures, that
is sadly the standardprogression for this disease.
Aaron Powell Okay.
SPEAKER_00 (04:39):
And the intervention group.
SPEAKER_01 (04:41):
The intervention group showed significant between
group differences and but thisis the critical part, actual
improvement.
SPEAKER_00 (04:48):
Aaron Powell Not just stability.
SPEAKER_01 (04:50):
Trevor Burrus No, improvement.
In three of the four primaryclinical outcomes.
SPEAKER_00 (04:54):
Trevor Burrus Okay.
Let's quickly define thosescores for everyone listening,
because these are the thingsclinicians really rely on.
What improved?
SPEAKER_01 (04:59):
Aaron Ross Powell So we're talking about the CGIC,
which is the clinical globalimpression of change.
That's basically the clinician'soverall gut check.
Is the patient better or worse?
SPEAKER_00 (05:07):
Trevor Burrus And that got better.
SPEAKER_01 (05:08):
Significantly better.
They also saw improvements inthe CDRSB and the CDRG, the
clinical dementia rating sum ofboxes that tracks a person's
functional ability.
Trevor Burrus, Jr.
SPEAKER_00 (05:18):
So things like personal care, judgment.
Trevor Burrus, Jr.
SPEAKER_01 (05:21):
Community affairs, exactly.
Showing improvement here meansthey were actually functioning
better in their daily lives.
SPEAKER_00 (05:25):
Trevor Burrus That is a powerful statement.
It's not just an abstract memorytest score improving, it's how
they manage their day-to-daylife.
SPEAKER_01 (05:33):
Aaron Powell Precisely.
The fourth measure was the ADSCOG.
It's often seen as the goldstandard for performance testing
in AD trials.
On that measure, theintervention group showed less
progression.
SPEAKER_00 (05:45):
So they didn't decline as much.
SPEAKER_01 (05:47):
Right.
And the difference wasborderline statistically
significant.
SPEAKER_00 (05:51):
Aaron Powell This is where the source material is
just so explicit, and I think wereally need to hammer this home
for a second.
The researchers themselves notedthis is one of the first
randomized controlled trials toshow improvement.
SPEAKER_01 (06:02):
Not just a slower rate of decline.
SPEAKER_00 (06:03):
Using a non-drug, non-pharmaceutical intervention
in patients with confirmed MCIand early AD.
They weren't just stabilizing,they were showing a measurable
reversal of impairment.
SPEAKER_01 (06:13):
And it looks like it might be durable, at least in
the short term.
They followed up withparticipants out to 40 weeks, so
almost a year.
SPEAKER_00 (06:19):
And what did they find?
SPEAKER_01 (06:21):
The results were still very encouraging.
Forty-six percent of theintervention group showed
improved cognitive function.
And another 37.5% showed nodecline at all.
SPEAKER_00 (06:31):
Aaron Powell So you're looking at over 80% of
that group avoiding anycognitive slide over that whole
period.
Exactly.
The functional results areincredibly powerful.
But to be sure we're looking atmore than just symptom relief,
we need to know (06:42):
was this actually impacting the
underlying biology ofAlzheimer's?
SPEAKER_01 (06:47):
Ah, the million-dollar question.
SPEAKER_00 (06:49):
Aaron Powell Were there biomarkers to back this
up?
SPEAKER_01 (06:51):
Yes.
And this is where we see thephysical evidence that those
four pillars were working at acellular level.
They looked at severalindicators, starting with one of
the most critical in ADresearch, the plasma F4T40
ratio.
SPEAKER_00 (07:05):
Okay, we can't just let that acronym slide.
Briefly, why is that ratio soimportant?
SPEAKER_01 (07:09):
Right.
So the F4240 ratio reflects thebalance between two types of
this protein, amyloid beta.
F42 is this sticky, longerversion that clumps together
into the plaques that define AD.
F4040 is the shorter, moresoluble version.
A decrease in that ratio is abad sign.
It suggests poor clearance and abuildup of the toxic form of the
protein.
SPEAKER_00 (07:30):
So what did the lifestyle group show?
SPEAKER_01 (07:32):
They showed the change you want to see.
The ratio actually increased by6.4% in the intervention group.
SPEAKER_00 (07:37):
Aaron Powell, which suggests their body was getting
better at clearing out the badstuff.
SPEAKER_01 (07:41):
Aaron Powell Measurably better at regulating
that toxic amyloid protein.
And compare that to the controlgroup, where the ratio decreased
by 8.3%.
That difference was highlystatistically significant.
It's strong evidence of abiological impact.
SPEAKER_00 (07:55):
That's fascinating.
It's hard evidence that you'removing the dial on a core
mechanism of the disease, notjust, you know, a
lifestyle-related mood lift.
SPEAKER_01 (08:03):
Exactly.
And the systemic effects didn'tstop there.
Because of the plant-based diet,they also measured the gut
microbiome.
They found a statisticallysignificant improvement in
microbiome composition, ahealthier, more diverse
bacterial population, but onlyin the intervention group.
It reinforces that fast actinglink between high fiber, whole
foods, and the gut brain axis.
SPEAKER_00 (08:25):
Probably helping reduce systemic inflammation.
SPEAKER_01 (08:27):
Very likely.
SPEAKER_00 (08:28):
They also looked at markers of cellular aging,
didn't they?
Telomere length?
SPEAKER_01 (08:31):
They did.
Telomere length, which is linkedto aging and how resilient our
cells are, also increased in theintervention group.
Now, that specific findingdidn't reach statistical
significance.
SPEAKER_00 (08:43):
Okay.
SPEAKER_01 (08:43):
But the overall picture is clear.
The intervention was creatingpositive biological shifts
across multiple systems at thesame time: amyloid regulation,
gut health, and maybe evencellular aging.
SPEAKER_00 (08:56):
It sounds like a powerful drug cocktail, except
the ingredients were diet,movement, meditation, and
friends.
Which brings us to this criticalidea of dose response.
Was this just an on-off switch,or did how much you committed
matter?
SPEAKER_01 (09:09):
Adherence was everything.
And this is probably the mostuseful insight for you if you're
planning your own approach.
The study created a lifestyleindex to quantify how well
people stuck to the plan acrossall four pillars.
SPEAKER_00 (09:20):
And they found a link.
SPEAKER_01 (09:21):
A profound correlation.
Higher adherence led directly tobetter cognitive outcomes and
better biomarker outcomes.
SPEAKER_00 (09:27):
So no skipping the yoga sessions and expecting the
same results as someone who'sall in.
SPEAKER_01 (09:32):
Precisely.
The size of the positive resultwas directly tied to the
fidelity of the plan.
They were even able to put anumber on it.
SPEAKER_00 (09:40):
What was the number?
SPEAKER_01 (09:41):
Achieving 71.4% adherence to the overall
lifestyle index.
That was the thresholdcorrelated with either stopping
or improving progression on thatADS COG measure.
SPEAKER_00 (09:51):
Wow.
SPEAKER_01 (09:52):
It tells you that the intensity isn't arbitrary.
It's the therapeutic dose youneed to achieve this kind of
reversal.
The more you put in, thestronger the effect.
SPEAKER_00 (10:00):
Aaron Powell These findings are genuinely exciting.
I mean, they provide an enormousamount of hope.
But we have to ground this inreality.
This was a phase two trial.
Right.
So what are the key strengthsand more importantly, the
essential limitations here?
SPEAKER_01 (10:11):
Aaron Powell The strengths are obvious.
It was a randomized controlledtrial.
That's the gold standard forevidence.
The diagnosis was clear MCI orearly AD, and they used multiple
rigorous outcome measures,functional, cognitive, and
biological.
SPEAKER_00 (10:26):
And the dose response relationship you just
mentioned.
SPEAKER_01 (10:28):
A massive strength.
It offers clear proof ofcausality.
SPEAKER_00 (10:31):
Aaron Powell But wait a minute.
You said this regimen wasintensive, and the source
implies they were activelyproviding meals and structure.
Isn't that a huge limitation?
I mean, that feels sodisconnected from what a normal
person could sustain long term.
SPEAKER_01 (10:45):
That is absolutely the primary limitation.
And we have to be critical aboutit.
The small sample size, just 51people, means we need larger
phase three trials before we cangeneralize.
SPEAKER_00 (10:55):
And the duration was short.
SPEAKER_01 (10:56):
Very short, just 20 weeks for the main outcome.
We need to see if this reversalholds over five or 10 years and
how it really impacts the numberof people who go on to develop
dementia.
SPEAKER_00 (11:06):
And the feasibility issue you just brought up, that
feels like the biggestreal-world hurdle.
SPEAKER_01 (11:11):
It is.
The study structure providingmeals, frequent grief sessions,
high levels of support, that'sprobably not feasible for most
health systems or individuals.
And it wasn't blinded either.
Participants obviously knew ifthey were eating a whole food
plant-based diet or not.
SPEAKER_00 (11:24):
Which introduces potential bias, you know, from
expectation.
SPEAKER_01 (11:28):
Of course.
SPEAKER_00 (11:28):
So we have to see this as a powerful proof of
concept.
It shows the human body cangenerate this healing response,
even if the delivery methodneeds to be adapted for the real
world.
SPEAKER_01 (11:39):
That's the key takeaway.
It sets the bar for what'spossible.
We know what level of intensitycan achieve reversal.
The challenge now is findingways to make that intensity more
accessible and sustainable.
SPEAKER_00 (11:51):
Okay, let's bring this all back to the listener.
For someone out there with earlycognitive concerns, or for those
supporting them, what are theessential practical takeaways
from this?
SPEAKER_01 (12:00):
The first one is to replace fatalism with action.
Measurable improvement, not justslower decline, is genuinely
possible.
SPEAKER_00 (12:08):
And you have to focus on all four domains.
SPEAKER_01 (12:10):
All four.
It's not a buffet where you canjust pick one.
The power is in the synergy ofthat whole food, plant-based
diet, the mix of aerobic andstrength exercise, the dedicated
daily stress management, andbuilding reliable social
support.
SPEAKER_00 (12:23):
And based on that dose response finding, it seems
like the structure, the planitself, is the engine that
drives success.
SPEAKER_01 (12:29):
It is.
And while the study suggeststhat 71% adherence is the sweet
spot for the best results, thecore message is that any
incremental improvement islikely beneficial.
But if you want the robustresults they saw in this study,
you have to build structure, youhave to measure your adherence,
and you have to seek support tohit that high therapeutic dose.
SPEAKER_00 (12:48):
And for clinicians for health systems, this really
shifts lifestyle medicine fromjust being a prevention tip into
being an integral,evidence-based part of the
treatment toolkit for earlycognitive decline, right
alongside standard medical care.
Trevor Burrus, Jr.
SPEAKER_01 (13:02):
Precisely.
The most important nugget fromthis entire deep dive is that
intensive multidomain lifestylemedicine showed robust evidence
of reversing, not just slowing,early cognitive decline.
And crucially, that reversal wassupported by tangible biological
shifts in key biomarkers,showing a real impact on the
underlying pathology of thedisease.
SPEAKER_00 (13:22):
We know how crucial that high adherence, that
therapeutic dose you mentionedwas for these 20-week
improvements.
Participants needed to hitalmost 75% adherence just to
halt the progression on somemeasures.
So what does this all mean forthe future?
Given the intensity of theregimen which led to such
powerful results, if you, thelistener, could only sustain a
moderate fraction of thisprogram long term, say 50% or
(13:43):
75% adherence, how profoundlymight even that partial sustain
effort still affect the multiyear trajectory of future
dementia incidents?
Something to mull over as youintegrate this new hopeful
knowledge.
When we approach the topic of cognitive decline,
whether we're talking about mildcognitive impairment or MCI or
maybe the early stages ofAlzheimer's disease, the
conversation is almost alwayspessimistic.
SPEAKER_01 (00:12):
Aaron Powell It is.
The goal is usually tostabilize, right?
Slow the inevitable trajectory.
SPEAKER_00 (00:16):
Aaron Powell Exactly, just buy some time.
But what if the deep dive intothis new research points to
something far more, I don'tknow, ambitious, something
surprising.
SPEAKER_01 (00:26):
Aaron Powell Well, that's it.
It points to measurable,quantifiable improvement.
SPEAKER_00 (00:29):
Aaron Powell Not just slowing down.
SPEAKER_01 (00:31):
No, the possibility of actual reversal.
That's the jaw-dropping findingwe're analyzing today.
We're drilling down into areally rigorous phase two
multi-center randomizedcontrolled trial, an RCT, from
Dean Ornish and his team.
SPEAKER_00 (00:44):
Aaron Powell And this wasn't just watching people
over many years.
This was a targetedintervention.
SPEAKER_01 (00:49):
Aaron Powell A very targeted, 20-week intervention.
It was focused entirely onintensive, multi-domain
lifestyle changes for people whoare already diagnosed with
either MCI or early stage AD.
SPEAKER_00 (01:00):
Aaron Powell So our mission for you today is pretty
simple.
We're going to dissect thedesign of this program because
it sounds like it required amonumental effort.
Aaron Powell It really did.
And then we'll translate whatthe results, both cognitive and
biological, actually mean.
We need to understand why thesefindings suggest lifestyle
medicine isn't just forprevention, but maybe for early
(01:20):
stage reversal.
Trevor Burrus Aaron Powell, Jr.
SPEAKER_01 (01:22):
A viable adjunct, or maybe even an alternative.
It's a huge claim.
SPEAKER_00 (01:26):
Aaron Powell Okay, let's unpack this.
So the first thing we need toacknowledge is that when the
researchers asked people to jointhe intervention group, they
were signing up for a completeoverhaul, right?
SPEAKER_01 (01:36):
Oh, absolutely.
SPEAKER_00 (01:36):
Trevor Burrus, Jr.: What exactly did that involve?
And who are the people in thisstudy?
SPEAKER_01 (01:39):
Aaron Powell So they enrolled 51 participants in
total.
It was split pretty evenly, 26in the intervention group and 25
in the control group.
The average age was around 73.
SPEAKER_00 (01:49):
Aaron Powell And they all had confirmed
impairment.
SPEAKER_01 (01:51):
Yes.
Clear, established cognitiveimpairment.
This is crucial.
To get in, you needed a MOCAscore.
That's the Montreal cognitiveassessment of 18 or higher.
So these weren't people justworried about forgetting their
keys.
SPEAKER_00 (02:04):
Trevor Burrus, Jr.
No, this was a clinicaldiagnosis.
SPEAKER_01 (02:05):
Aaron Powell Exactly.
Confirmed diagnosable impairmentdue to AD.
SPEAKER_00 (02:09):
Trevor Burrus And the control group, they just
carried on as usual.
SPEAKER_01 (02:11):
Yep.
They continued with what thesesources call usual care.
Meanwhile, the interventiongroup got this very structured,
very intensive, multi-domainprogram.
It was all built around four keypillars.
SPEAKER_00 (02:25):
Aaron Powell And that structure is everything
here, isn't it?
SPEAKER_01 (02:27):
It's vital to the results.
This wasn't about, you know,just adding a supplement or
taking a walk.
It was comprehensive.
SPEAKER_00 (02:34):
So what was the first pillar?
SPEAKER_01 (02:35):
The first pillar was diet.
This was a whole food, minimallyprocessed, plant-based diet.
It was also extremely low insaturated fat and refined carbs.
SPEAKER_00 (02:45):
Aaron Powell And why that specific diet?
SPEAKER_01 (02:47):
Well, because that's where a lot of the
anti-inflammatory power comesfrom.
You're targeting the chronicinflammation that often goes
hand in hand with AD pathology.
SPEAKER_00 (02:54):
Right.
SPEAKER_01 (02:55):
And it's also foundational for the microbiome,
which they also tracked.
SPEAKER_00 (02:58):
Right, the gut brain axis.
Okay, so pillar number two.
SPEAKER_01 (03:01):
Exercise.
They required moderate dailyactivity, a combination of
structured aerobic exercise andstrength training.
SPEAKER_00 (03:07):
Which is about more than just heart health.
SPEAKER_01 (03:08):
Oh, much more.
It's about increasing blood flowto the brain and maybe even
stimulating neurogenesis, thegrowth of new brain cells.
SPEAKER_00 (03:16):
The third pillar was stress management.
SPEAKER_01 (03:19):
Correct.
Things like meditation, yoga,guided imagery, all done
regularly.
I mean, chronic stress elevatescortisol, which is neurotoxic,
especially to the hippocampus.
SPEAKER_00 (03:29):
The brain's memory center.
SPEAKER_01 (03:30):
The memory center.
So reducing that stress is adirect physiological way to
protect brain function.
SPEAKER_00 (03:36):
And finally, something that feels so
necessary given the disease: social support. (03:38):
undefined
SPEAKER_01 (03:42):
Yes.
And it was structured supportfor both the patient and their
study partner or caregiver.
Cognitive decline can be soisolating.
SPEAKER_00 (03:51):
And that isolation creates a horrible feedback
loop, right?
Of stress and depression.
SPEAKER_01 (03:55):
Aaron Ross Powell Exactly, which just makes
cognition worse.
So by creating this supportedsocial network, they were
addressing the psychologicalburden of the disease.
It's this multi-pronged approachthat's so key.
AD is a multifactorial disease.
You can't just treat it with onehammer.
SPEAKER_00 (04:10):
Okay, so given that level of intensity, and that's a
huge commitment for 20 weeks.
Let's get to the core results.
What did all that effortactually achieve, especially
compared to the usual caregroup?
SPEAKER_01 (04:19):
Aaron Ross Powell, the contrast is what's
staggering.
After just five months, if youlook at the control group, they
followed the expected path.
Which is they got worse.
Across all four of the primarycognitive outcome measures, that
is sadly the standardprogression for this disease.
Aaron Powell Okay.
SPEAKER_00 (04:39):
And the intervention group.
SPEAKER_01 (04:41):
The intervention group showed significant between
group differences and but thisis the critical part, actual
improvement.
SPEAKER_00 (04:48):
Aaron Powell Not just stability.
SPEAKER_01 (04:50):
Trevor Burrus No, improvement.
In three of the four primaryclinical outcomes.
SPEAKER_00 (04:54):
Trevor Burrus Okay.
Let's quickly define thosescores for everyone listening,
because these are the thingsclinicians really rely on.
What improved?
SPEAKER_01 (04:59):
Aaron Ross Powell So we're talking about the CGIC,
which is the clinical globalimpression of change.
That's basically the clinician'soverall gut check.
Is the patient better or worse?
SPEAKER_00 (05:07):
Trevor Burrus And that got better.
SPEAKER_01 (05:08):
Significantly better.
They also saw improvements inthe CDRSB and the CDRG, the
clinical dementia rating sum ofboxes that tracks a person's
functional ability.
Trevor Burrus, Jr.
SPEAKER_00 (05:18):
So things like personal care, judgment.
Trevor Burrus, Jr.
SPEAKER_01 (05:21):
Community affairs, exactly.
Showing improvement here meansthey were actually functioning
better in their daily lives.
SPEAKER_00 (05:25):
Trevor Burrus That is a powerful statement.
It's not just an abstract memorytest score improving, it's how
they manage their day-to-daylife.
SPEAKER_01 (05:33):
Aaron Powell Precisely.
The fourth measure was the ADSCOG.
It's often seen as the goldstandard for performance testing
in AD trials.
On that measure, theintervention group showed less
progression.
SPEAKER_00 (05:45):
So they didn't decline as much.
SPEAKER_01 (05:47):
Right.
And the difference wasborderline statistically
significant.
SPEAKER_00 (05:51):
Aaron Powell This is where the source material is
just so explicit, and I think wereally need to hammer this home
for a second.
The researchers themselves notedthis is one of the first
randomized controlled trials toshow improvement.
SPEAKER_01 (06:02):
Not just a slower rate of decline.
SPEAKER_00 (06:03):
Using a non-drug, non-pharmaceutical intervention
in patients with confirmed MCIand early AD.
They weren't just stabilizing,they were showing a measurable
reversal of impairment.
SPEAKER_01 (06:13):
And it looks like it might be durable, at least in
the short term.
They followed up withparticipants out to 40 weeks, so
almost a year.
SPEAKER_00 (06:19):
And what did they find?
SPEAKER_01 (06:21):
The results were still very encouraging.
Forty-six percent of theintervention group showed
improved cognitive function.
And another 37.5% showed nodecline at all.
SPEAKER_00 (06:31):
Aaron Powell So you're looking at over 80% of
that group avoiding anycognitive slide over that whole
period.
Exactly.
The functional results areincredibly powerful.
But to be sure we're looking atmore than just symptom relief,
we need to know (06:42):
was this actually impacting the
underlying biology ofAlzheimer's?
SPEAKER_01 (06:47):
Ah, the million-dollar question.
SPEAKER_00 (06:49):
Aaron Powell Were there biomarkers to back this
up?
SPEAKER_01 (06:51):
Yes.
And this is where we see thephysical evidence that those
four pillars were working at acellular level.
They looked at severalindicators, starting with one of
the most critical in ADresearch, the plasma F4T40
ratio.
SPEAKER_00 (07:05):
Okay, we can't just let that acronym slide.
Briefly, why is that ratio soimportant?
SPEAKER_01 (07:09):
Right.
So the F4240 ratio reflects thebalance between two types of
this protein, amyloid beta.
F42 is this sticky, longerversion that clumps together
into the plaques that define AD.
F4040 is the shorter, moresoluble version.
A decrease in that ratio is abad sign.
It suggests poor clearance and abuildup of the toxic form of the
protein.
SPEAKER_00 (07:30):
So what did the lifestyle group show?
SPEAKER_01 (07:32):
They showed the change you want to see.
The ratio actually increased by6.4% in the intervention group.
SPEAKER_00 (07:37):
Aaron Powell, which suggests their body was getting
better at clearing out the badstuff.
SPEAKER_01 (07:41):
Aaron Powell Measurably better at regulating
that toxic amyloid protein.
And compare that to the controlgroup, where the ratio decreased
by 8.3%.
That difference was highlystatistically significant.
It's strong evidence of abiological impact.
SPEAKER_00 (07:55):
That's fascinating.
It's hard evidence that you'removing the dial on a core
mechanism of the disease, notjust, you know, a
lifestyle-related mood lift.
SPEAKER_01 (08:03):
Exactly.
And the systemic effects didn'tstop there.
Because of the plant-based diet,they also measured the gut
microbiome.
They found a statisticallysignificant improvement in
microbiome composition, ahealthier, more diverse
bacterial population, but onlyin the intervention group.
It reinforces that fast actinglink between high fiber, whole
foods, and the gut brain axis.
SPEAKER_00 (08:25):
Probably helping reduce systemic inflammation.
SPEAKER_01 (08:27):
Very likely.
SPEAKER_00 (08:28):
They also looked at markers of cellular aging,
didn't they?
Telomere length?
SPEAKER_01 (08:31):
They did.
Telomere length, which is linkedto aging and how resilient our
cells are, also increased in theintervention group.
Now, that specific findingdidn't reach statistical
significance.
SPEAKER_00 (08:43):
Okay.
SPEAKER_01 (08:43):
But the overall picture is clear.
The intervention was creatingpositive biological shifts
across multiple systems at thesame time: amyloid regulation,
gut health, and maybe evencellular aging.
SPEAKER_00 (08:56):
It sounds like a powerful drug cocktail, except
the ingredients were diet,movement, meditation, and
friends.
Which brings us to this criticalidea of dose response.
Was this just an on-off switch,or did how much you committed
matter?
SPEAKER_01 (09:09):
Adherence was everything.
And this is probably the mostuseful insight for you if you're
planning your own approach.
The study created a lifestyleindex to quantify how well
people stuck to the plan acrossall four pillars.
SPEAKER_00 (09:20):
And they found a link.
SPEAKER_01 (09:21):
A profound correlation.
Higher adherence led directly tobetter cognitive outcomes and
better biomarker outcomes.
SPEAKER_00 (09:27):
So no skipping the yoga sessions and expecting the
same results as someone who'sall in.
SPEAKER_01 (09:32):
Precisely.
The size of the positive resultwas directly tied to the
fidelity of the plan.
They were even able to put anumber on it.
SPEAKER_00 (09:40):
What was the number?
SPEAKER_01 (09:41):
Achieving 71.4% adherence to the overall
lifestyle index.
That was the thresholdcorrelated with either stopping
or improving progression on thatADS COG measure.
SPEAKER_00 (09:51):
Wow.
SPEAKER_01 (09:52):
It tells you that the intensity isn't arbitrary.
It's the therapeutic dose youneed to achieve this kind of
reversal.
The more you put in, thestronger the effect.
SPEAKER_00 (10:00):
Aaron Powell These findings are genuinely exciting.
I mean, they provide an enormousamount of hope.
But we have to ground this inreality.
This was a phase two trial.
Right.
So what are the key strengthsand more importantly, the
essential limitations here?
SPEAKER_01 (10:11):
Aaron Powell The strengths are obvious.
It was a randomized controlledtrial.
That's the gold standard forevidence.
The diagnosis was clear MCI orearly AD, and they used multiple
rigorous outcome measures,functional, cognitive, and
biological.
SPEAKER_00 (10:26):
And the dose response relationship you just
mentioned.
SPEAKER_01 (10:28):
A massive strength.
It offers clear proof ofcausality.
SPEAKER_00 (10:31):
Aaron Powell But wait a minute.
You said this regimen wasintensive, and the source
implies they were activelyproviding meals and structure.
Isn't that a huge limitation?
I mean, that feels sodisconnected from what a normal
person could sustain long term.
SPEAKER_01 (10:45):
That is absolutely the primary limitation.
And we have to be critical aboutit.
The small sample size, just 51people, means we need larger
phase three trials before we cangeneralize.
SPEAKER_00 (10:55):
And the duration was short.
SPEAKER_01 (10:56):
Very short, just 20 weeks for the main outcome.
We need to see if this reversalholds over five or 10 years and
how it really impacts the numberof people who go on to develop
dementia.
SPEAKER_00 (11:06):
And the feasibility issue you just brought up, that
feels like the biggestreal-world hurdle.
SPEAKER_01 (11:11):
It is.
The study structure providingmeals, frequent grief sessions,
high levels of support, that'sprobably not feasible for most
health systems or individuals.
And it wasn't blinded either.
Participants obviously knew ifthey were eating a whole food
plant-based diet or not.
SPEAKER_00 (11:24):
Which introduces potential bias, you know, from
expectation.
SPEAKER_01 (11:28):
Of course.
SPEAKER_00 (11:28):
So we have to see this as a powerful proof of
concept.
It shows the human body cangenerate this healing response,
even if the delivery methodneeds to be adapted for the real
world.
SPEAKER_01 (11:39):
That's the key takeaway.
It sets the bar for what'spossible.
We know what level of intensitycan achieve reversal.
The challenge now is findingways to make that intensity more
accessible and sustainable.
SPEAKER_00 (11:51):
Okay, let's bring this all back to the listener.
For someone out there with earlycognitive concerns, or for those
supporting them, what are theessential practical takeaways
from this?
SPEAKER_01 (12:00):
The first one is to replace fatalism with action.
Measurable improvement, not justslower decline, is genuinely
possible.
SPEAKER_00 (12:08):
And you have to focus on all four domains.
SPEAKER_01 (12:10):
All four.
It's not a buffet where you canjust pick one.
The power is in the synergy ofthat whole food, plant-based
diet, the mix of aerobic andstrength exercise, the dedicated
daily stress management, andbuilding reliable social
support.
SPEAKER_00 (12:23):
And based on that dose response finding, it seems
like the structure, the planitself, is the engine that
drives success.
SPEAKER_01 (12:29):
It is.
And while the study suggeststhat 71% adherence is the sweet
spot for the best results, thecore message is that any
incremental improvement islikely beneficial.
But if you want the robustresults they saw in this study,
you have to build structure, youhave to measure your adherence,
and you have to seek support tohit that high therapeutic dose.
SPEAKER_00 (12:48):
And for clinicians for health systems, this really
shifts lifestyle medicine fromjust being a prevention tip into
being an integral,evidence-based part of the
treatment toolkit for earlycognitive decline, right
alongside standard medical care.
Trevor Burrus, Jr.
SPEAKER_01 (13:02):
Precisely.
The most important nugget fromthis entire deep dive is that
intensive multidomain lifestylemedicine showed robust evidence
of reversing, not just slowing,early cognitive decline.
And crucially, that reversal wassupported by tangible biological
shifts in key biomarkers,showing a real impact on the
underlying pathology of thedisease.
SPEAKER_00 (13:22):
We know how crucial that high adherence, that
therapeutic dose you mentionedwas for these 20-week
improvements.
Participants needed to hitalmost 75% adherence just to
halt the progression on somemeasures.
So what does this all mean forthe future?
Given the intensity of theregimen which led to such
powerful results, if you, thelistener, could only sustain a
moderate fraction of thisprogram long term, say 50% or
(13:43):
75% adherence, how profoundlymight even that partial sustain
effort still affect the multiyear trajectory of future
dementia incidents?
Something to mull over as youintegrate this new hopeful
knowledge.
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