Are We Diagnosing Dementia All Wrong? Part 2

Hello, everybody. Welcome to another brand new

episode of The Truth, Lies, and Alzheimer Show. I'm Lisa

Skinner, your host. Now, today's episode is a continuation of the

last episode, and the name of it is, Are we diagnosing dementia

all wrong? This is part two. To recap, in part one, I shared

with everybody a very famous and very important study called the

Nunn Study, and what those results and findings showed our

scientists that to me have been baffling for a couple of

decades. What really causes Alzheimer's disease? There was a

contradiction about that in the findings. So I discussed that

none study, so you'd have a really comprehensive

understanding of the results of that study, which are actually

really important. So, as we fast forward to today's episode, I

did a lot of research to find out if the information that was

revealed in the next study is still consistent with the

research today. So that's where we are starting off. So, what

questions are researchers today still trying to answer? Well,

when and why does amyloid start to build up in different people,

which forms of amyloid are most harmful, and how do they

actually interact with tau? Why tau spreads in some people but

not others, and how to stop it? What is the best combination of

therapies, and the best time to start them. How can we predict

who will progress and who might stay stable longer? What's the

bottom line for the public? Alzheimer's is driven by

multiple brain changes, with plaques and tangles playing

central roles, but we now know they're not acting alone. So

early detection and multi-pronged treatment

approaches do hold promise, especially if they're started

before significant brain damage occurs. So result of the men

study sparked all these other questions, and they've been

questions that have been in my mind for since I learned about

the nun study. I don't think that we know everything, but we

know more than we did. What are the main things scientists find

in Alzheimer's brains, well, they find amyloid plaques, which

are sticky clumps of a protein fragment called amyloid that

build up outside brain cells. They also find tau tangles,

which are twisted threads of another protein called tau that

build up inside the brain cells, so together with nerve damage

and brain cell death, these changes lead to what we see,

memory loss and cognitive decline, so the 64 bazillion

dollar question here is still, do plaques and tangles cause

Alzheimer's? And the answer is, it is still very complicated,

because in some people, especially those with genetic

forms of the disease, amyloid plaques do seem to kick off the

whole process in most people who get Alzheimer's disease later in

life, plaques are a risk indicator and may help start the

process, but they still don't explain everything. Now, the tau

tangles tend to be more closely linked to how bad the symptoms

are or get, and many researchers now think that Alzheimer's is

not caused by one thing alone, primarily test plaques and

tangles. It actually, the new theory is that it is a mix of

several factors working together, amyloid buildup, tau

problems, inflammation in the brain, blood vessel health,

aging, and other accompanying health conditions. What did the

latest research say about the role of plaques? This is what I

that plaques often appear before symptoms and raise the

risk of developing dementia. Some studies showed that the

tiny soluble forms of amyloid, not the big plaque clumps may be

especially harmful to brain connections and thinking skills

in older people. A lot of people have plaques but don't have

dementia yet. This is what they found in the autopsies of the

nuns who participated in the nun study, which means that plaques

aren't the whole story, and what about those tau tangles? Well,

they light up with how severe memory and thinking problems

are, more than the plaques do, especially as the disease

progresses. The tau seems to spread through the brain in a

way that follows connected brain networks, which does help

explain why certain areas get hit in a predictable pattern.

Researchers are testing these therapies that target tau to see

if they can slow down or stop the spread of the damage, so

what does this mean for diagnosis and treatment now?

Biomarkers, which are tests that measure substances in the spinal

fluid or blood, and the brain scans that look for plaques and

tangles are now helping doctors identify the disease earlier and

more give them more understanding of how it is

progressing, treatments that remove or neutralize amyloid

have shown mixed results. They may actually help. Some people

have started very early, but they have not shown that they do

much for people, for everyone. Treatments targeting tau

inflammation and blood brain blood vessels are being studied

often in combination with anti-amyloid approaches, so the

big idea now is to start treatment early and use a

multi-pronged approach tailored to a person's biology and risk

factors like genetics and other health issues that they also may

have, along with dementia, what is the bottom line for the

public that Alzheimer's is driven by multiple changes in

the brain with amyloid plaques and tau tangles playing a

central role, but they're not the exclusive role as once

believed, early detection using biomarkers and imaging is

improving, and that may lead to better earlier treatments. The

future of therapy likely lies in addressing several disease

processes at once and starting treatment sooner rather than

later, so could plaques and tangles actually be part of the

brain's defense mechanism? This is a new theory now that's being

studied and explored. This idea has a name, it's actually called

a protective response or compensatory hypothesis. It's a

real thing. It suggests that some brain changes seen in

Alzheimer's might arise at least in part as the brain's attempt

to cope with injury, stress, or other problems. So, in this

view, what we measure as plaques and tangles could actually

reflect the brain trying to isolate, contain, and or

stabilize damaged components rather than actually being the

initial cause of the disease, well, this is still a topic of

active research and debate, and most scientists see a nuanced

picture, which is that certain pathological features may be

harmful, while others could be secondary responses to other

underlying problems. Now this makes total sense, and I really

think this needs to be determined before we move on to

what is really the best treatment for Alzheimer's

disease. So how. Does this idea fit with current evidence? It

fits because plaques or amyloid and tangles or tau are

consistently found in Alzheimer's disease brains, but

their roles may differ by disease stage and by each

individual person, the early idea was that amyloid buildup

starts a cascade that leads to tau tangles and

neurodegeneration. That's not the case anymore. The protective

angle, well, in some contexts amyloid or tau might form as a

response to another insult, like a mitochondrial dysfunction or

vascular problems, in an attempt to protect neurons from further

damage. For example, the plaques might actually sequester toxic

fragments, and tangles might wall off damage tau to prevent

it from spreading, but the most, the strongest evidence still

supports a multi factorial model that amyloid may act as an

upstream trigger in many people, especially with genetic

predispositions, and that tau pathology tends to correlate

more closely with cognitive decline and neuronal loss as the

disease progresses, as far as inflammation, blood vessel

health and metabolic factors, well, they believe now that

these things also play a major role. The protective hypothesis

does not yet explain all of these observations. For

instance, in most cases, removing the amyloid later in

the disease provides limited or no cognitive benefits,

suggesting that once neurons are lost, simply clearing the

plaques may not reverse the damage. Some robust data do show

that certain brain responses to stress can become maladaptive

over timing, contributing to a cycle of injury. If plaques or

tangles are partly protective in some contexts, completely

eliminating them without understanding the timing and

context could prove to be less effective or even harmful in

certain patients, and this has implications for timing of a

treatment. Therapies might need to target upstream causes like

the inflammation, vascular health, and or metabolic factors

before the plaques and tangles become dominant, or a

combination of approaches like addressing multiple pathways,

which include amyloid, tau, inflammation, and blood flow,

which may be more effective than targeting one single feature,

taking into consideration biomarker interpretations.

In other words, finding plaques or tangles doesn't necessarily

or automatically tell us whether they're causing harm or

reflecting a protective attempt a additional biomarkers in

clinical context are extremely important in this scenario. So,

what are researchers doing now? They are currently studying how

brain cells respond to stress and injury, including how immune

cells or microlia and blood vessels interact with amyloid

and tau using animal and cellular models to test whether

plaque or tau formation can actually be a protective

response to specific insults and under what conditions it might

become maladaptive. They're designing clinical trials that

consider multiple targets and early intervention rather than

focusing on a single pathology in isolation. They are now

exploring why some people with high amyloid or tau burden do

remain cognitively intact for a long time or for the rest of

their life, which might hint at compensatory mechanisms are at

work, so the quick take for our viewers here is. Is that plaques

and tangles are still believed to be central features of

Alzheimer's, but that their roles are likely much more

complex than we originally thought, and may include both

harmful and potentially protective aspects, depending on

the context. The leading view today is that Alzheimer's arises

from a mix of factors, the amyloid, the tau, inflammation,

vascular health, aging, and other health conditions that are

interacting with one another over time, understanding when

and why plaques or tangles form and how the brain tries to cope

could help us immensely design better earlier and more

personalized treatments. So it's a step in the right direction

from what we knew just 20 years ago. Now, quick summary: some

researchers wonder if amyloid plaques and tau tangles might

partially reflect the brain's attempt to cope with injury or

stress, and in this view, these changes could be protective

responses in certain contexts, or the downstream results of

other problems, like inflammation or vascular issues,

are at hand as well. Now, most evidence now supports a

multifactorial model, where plaques and tangles can be

harmful, but they might also arise as part of the brain's

attempt to shield its neurons, and the timing matters. Early

intervention targeting multiple pathways, not just plaques and

tangles, may turn out to be most effective. So, here's what we

know. Amyloid plaques and tau tangles are still considered key

brain changes in Alzheimer's disease, and that the tau tends

to track with symptoms more closely than the plaques do. And

then, of course, the protective hypothesis, the idea that

plaques and tangles could be the brain's attempt to contain

damage, not cause damage. Examples of that sequestration

of toxic fragments walling off damaged material to slow spread.

And why does this even matter for treatment, because if the

plaques and tangles can turn out to be protective in some

contexts, we will need careful timing and multi-target

approaches for treatment. Treatments may work best when

started early and address inflammation, address blood flow

and address metabolism, in addition to amyloid plaques and

tau tangles. How are researchers moving forward with this?

They're studying brain stress responses, the microlia, the

blood vessels. They're testing multi target therapies in early

disease stages, so at the end of the day, the bottom line is what

we know today, and the evidence supports it, is that Alzheimer's

is likely a mix of harmful and potentially protective brain

processes, and they vary by person and by stage. So early

personalized multipronged strategies will hold the most

promise. Now, now I'm going to kind of dive into Lewy body

dementia and how it differs from the research done on Alzheimer's

disease, and this is information that I found by Dr. Greenland,

who is the founder of the AI growth clinic systems for

private clinics. He is a physician in London, and he's

top 1% health and wellness on LinkedIn. And this is very, very

current information. It was published may 24 of 26 So, for

those of you who are not familiar with the term Lewy body

dementia, or why that it even matters to know about it, I'm

going to give you a quick explanation. Lewy body dementia

is actually one of the most common causes of dementia

worldwide, affecting an estimated one. To 1.4 million

Americans alone, we've recently heard about it, as recently as a

week ago, when Ted Turner passed away, and it was found that he

had Lewy body dementia.

Most people have never heard of it. It's caused by abnormal

deposits of a protein, which is very different than the plaques

and tangles that we find with Alzheimer's disease, and these

deposits in Lewy body dementia are a protein called alpha

synuclein, which forms clumps that they're called Lewy bodies

inside brain cells, and this is again very different from the

amyloid beta that is found with Alzheimer's disease. These alpha

synuclein deposits disrupt how our brain processes movement,

mood, sleep, behavior, and thinking. The clinical picture

is distinctive once you know. Once clinicians know what to

look for, which are fluctuating cognition. Patients can be sharp

one hour and completely confuse the next. They experience visual

hallucinations often early in the illness. Their REM sleep

behavior is disrupted where patients act out their dreams,

sometimes years before the cognitive symptoms appear, and

they also will tend to display Parkinsonian features like

stiffness, slowness, or tremors that are, you know, very

indicative of Parkinson's disease. They may experience

autonomic dysfunction, including blood pressure drops,

constipation, and bladder problems, and despite all this,

it's still routinely mistaken for Alzheimer's disease,

Parkinson's disease, or a psychiatric illness, and that

mistake matters because some of the standard antipsychotic drug

used to manage hallucinations can actually be catastrophic in

persons living with Lewy body dementia. The trouble is that

postmortem studies keep showing us something very inconvenient.

Lewy body pathology often sits alongside Alzheimer's pathology

in the same brain, so we call that mixed dementia, where they

have more than one brain disease developing at the same time, and

that is not as uncommon as a lot of us might think. Diagnostic

accuracy during life remains imperfect, just like Alzheimer's

disease. Many patients labeled with one disease actually have

features of two or three simultaneously, and we've been

arguing about which protein matters most. When the real

story is that several proteins, several systems, and several

insults are usually at play in the same person. The plot twist

that nobody saw coming, and here's where it generally gets

interesting. For years, the proteins that define

Alzheimer's, the amyloid beta, and Lewy body disease, alpha

nucleine, were treated as junk, toxic waste, things to clear

out, but now that view is shifting. Amyloid beta behaves

like an antimicrobial peptide in experimental work, trapping

bacteria, fung fungi, and herpes viruses in neural models. Alpha

synuclein can restrict viral infection in the brain and shows

antibacterial and antifungal activity in lab studies. In

other words, these proteins may have started life as part of the

brain's immune defense. We talked about that in part one,

and this is not proof by any stretch of the imagination that

dementia is an infection. This evidence is experimental. The

human data is messier, and herpes virus links, in

particular, do remain contested, but the bigger picture is hard

to ignore. Post defense, inflammation and protein

misfolding are entangled in ways that the old textbooks never

captured. A protein recruited to protect the brain can become the

thing that also destroys it. Imagine that, especially when

the signal becomes chronic when clearance fails and when the

host is metabolically and immunologically vulnerable, so

why the downstream picture matters more. Because once these

proteins misfold, what happens next looks oddly familiar across

diagnoses, both proteins activate the same inflammatory

machinery in microlia, known as the NLRP three inflammasome.

Both are linked to mitochondrial dysfunction. Both disease

families show significant cholinergic deficits, which is

why drugs like Donanemab and Lecanemab can ease symptoms

without changing the underlying disease. If the upstream

triggers differ, but the downstream damage rhymes, then a

single target single disease mindset starts to look outdated.

What does this mean for clinicians and families? These

practical shifts, in their view, one is to spot Lewy body disease

much earlier than we do watch for fluctuating cognition,

visual hallucinations, dream enactment behavior, autonomic

symptoms, and Parkinsonian features alongside cognitive

change. Now these cues are often still missed, often for years.

Therefore, early recognition does matter, because

antipsychotics can be dangerous in this population, and because

families can then better plan when they know what they're

dealing with. Number two is stop treating the diagnostic label as

the whole story. Roughly half of dementia risk is potentially

modifiable.

The Lancet Commission has just increased their statistic from

40% to 45% and they keep reminding us of the list,

vascular risk and hypertension play a role, hearing and vision

loss play a role, physical inactivity plays a role as a

risk factor, depression and social isolation, diabetes and

obesity, smoking and excess alcohol, poor sleep, these are

all risk factors that are manageable. So, the next decade

of dementia care belongs to the clinicians who can hold two

things at once. The biology is moving from symptom-based

guesswork toward protein-based diagnosis, with new tests for

Alka Alpha synuclein finally sharpening what was previously a

clinical coin toss. The patient is never just a textbook

diagnosis; they're a mixed pathology, they're a multi

system that's complex, they're individual human beings who

deserve an approach that reflects that, and one of the

comments to this article was given by Dr. G, who is like

psychiatrist and functional medicine doctor, and he said,

and I'm going to leave you with this. We have spent years

studying amyloid and tau as the enemy, but if they started as a

host defense mechanism, the real question now shifts not why they

are there, but why did the system stop coping? That's a

very, very different clinical problem. I love that comment.

So, that wraps this episode up for the Truth Lies and

Alzheimer's Show. I'm Lisa Skinner, your host. I hope you

have found episodes one and two of Are We Diagnosing Dementia

all wrong as fascinating as I find it, and that there

definitely is hope on the horizon. That we are making

positive strides to understanding these brain

diseases more than we ever have, and that there's hope to finding

at least a treatment, if not a cure. So, I'll be back next week

with another episode of The Truth, Lies, and Alzheimer's

show, and in the meantime, I hope you all have a wonderful

rest of your week, and as always, try to be happy and stay

healthy, and I'll be back next week with another episode for

you. Bye for now.