Dementia: risks, diagnosis and prevention

Hello and welcome back to mind over chatter.

The Cambridge University podcast.

I'm Annie, I'm nick.

And I'm Naomi.

And once again, we're inviting you to join us in our conversations with clever, curious people here in Cambridge.

In this third series, we're talking about health.

In this episode, we're focusing on dementia.

We're going to cover everything from.

New diagnosis techniques.

Current and potential future treatments.

And Tau tangles, which as you'll see.

And find out aren't in fact a new kind.

Of Greek noodle.

So who are we talking to in this episode?

A clinical neuropsychologist

Hi, I'm Barbara sahakian.

I'm professor of clinical neuropsychology.

I'm based in the Department of Psychiatry at the University of Cambridge.

A neurologist.

Hi, I'm James James Reimer, neurologist and professor of cognitive neurology, which means dementia here at Cambridge University and also nationally associate director for the Dementia Platform UK.

And a sociologist.

So I'm Richard Milne.

I'm a sociologist and I work at welcome connecting Science, which is based at the Sanger Institute and I also lead work on ethics, law and society within Cambridge Public Health.

As usual, we begin by asking our guests to tell us about their research.

So my my research interests are primarily in questions related to the social and ethical implications of new medical technologies of innovation.

Yes, my getting new treatments for people with dementia and related conditions based on understanding what's special about the human brain.

And the way it has diseases and how could we use that knowledge to to get new treatments?

My interest is in cognition and also in in the brain, and I'm very interested in first of all, assessing cognition in an objective way using modern tools such as computerized testing and also looking at new treatments for dementia.

And so I I look at.

Drugs, but also I investigate how we can.

Improve cognition using games such as sort of brain training apps.

The whole episode today is going to be about dementia, so we're going to start by defining what that even is, so James can you start by telling us what is dementia and what causes it?

Yes, a dementia refers to a family of different disorders, but they're all characterized by a loss of those mental brain functions to do with thinking and memory, or language and dementias happen, we lose more than one of those capacities, and to an extent where it gets in the way of a normal, everyday life.

So they're typically progressive conditions are coming on in in mid or later life, but it's really it's.

It's quite a broad umbrella term for many different disorders, and one of the excitements of work in dementia is how you know we're all different in our good health and therefore we're also all different into how dementia affects us individually, and that's something that's a real challenge.

Excitement for researchers.

So you sort of answered some of what I was going to ask next, but first I wanted to check with Barbara. Do you have anything that you would want to add to James's definition?

Well, I I think that was a great, but what I would say is dementia is a neurodegenerative disease with a decline in cognition and functionality as he mentioned and Alzheimer's disease is the most common form of dementia, affecting about 50 to 75% of those with dementia, and it's characterized by severe.

Changes in memory and other forms of cognition early on in the disease process, and these changes will eventually affect activities of daily living.

So two questions just to follow up on that.

You use the word cognitive function or cognition there and also neurodegenerative.

Can you tell us what those mean please?

Well, neurodegenerative refers to the changes in the brain that you get the neuropathological changes and these include neurofibrillary tangles which are aggregates of Tau protein and amyloid plaques and the amyloid plaques are deposits of amyloid beta protein.

So that's really what happens when we have these.

Changes in Alzheimer's disease in the brain.

And it's progressive and that's why we term it a sort of neurodegenerative disease.

Just to add to that, instead of everyday language you might think of as wear and tear or dying back of the brain cells.

Not all the brain.

Often it's you know particular bits of the brain are affected more than others, but it's it's over and above normal aging.

So the changes we get with normal aging they're different and the dimension is different from normal aging, but essentially dying, dying back of nerve cells, they die.

Back because of a whole series of reasons.

Often it's related to a build with junk proteins that change their shape and get sticky and claggy within the brain cells, and that's those amyloid plaques and Tau tangles that the Barber referred to.

But there's other other things that are part of the pathology.

Sometimes very specific to each disease individually, and sometimes there's things.

All these dementias have in common under the microscope.

OK, so I'm wondering if Richard it would be useful to understand a little bit about kind of the scale of the disorders.

So who does dementia impact?

estimate in the UK is that by: 2040

that if you'd predicted that: 1015

Even higher, and so there has been a kind of drop in in the number of people developing dementia.

The percentage of people developing dementia.

Richard, just to clarify that so age for age our brains are in better condition than 30 years ago, but the population is changing so much.

and: 95105

Day is better than 30.

Years ago that the overall numbers are increasing rapidly, we remember that you know one in three of us are going to get dementia as things stand, and that's you know good looking on the screen.

I can look to the left and look to the right and we could draw lots.

You know, one in three.

It's an extraordinary D high statistic and many other families.

Listening will know that from families, grandparents, neighbors, and so on, so.

That that translate into this figure of 1.2 million at any one time in a few years time.

But across our lifetime, one in three, and I think that that really brings it home.

Just how big this problem is and the challenges.

Yeah, just to add to that, I mean one in six people over the age of 80 have dementia in the UK.

And actually, the World Health Organization estimated that around 55 million people worldwide have dementia.

million in: 2030

And just going back to a point that you made there, James, uh, there's some ways in which everybody is impacted by dementia, even if they don't suffer from the single person.

Oh, it's exactly it's.

It's not just a person with dementia, there's a huge impact on their family, both in the distress it can cause often.

Other husbands, wives or children need to step out of the work market in order to help care for people, particularly globally.

That's the case that brought burden of looking after some with dementia falls within families in many parts of the.

World, but also the cost in in the UK alone. Five years ago the cost of the UK was 25 to £30 billion a year.

Year on year and it's been the number one cause of death year on year before, during and after the COVID pandemic.

And that's something we should all bear in mind.

Uh, if you look internationally, it's it's the the cost of dementia is in trillions, so we all feel that that's a burden that we all pay through our taxes and through productivity.

And yes, it's it goes far beyond just those people who have the dementia themselves, so it's a shared problem.

Do you have anything to add to that?

No, I mean I, I think it is that I think.

It's important to to recognize that it's a problem for for individuals, for families and for societies as a whole as to how we, yeah, how we engage with with dementia in the future, and how we work to kind of reduce.

The the prevalence of dementia.

OK, now that we've laid sort of the foundation of what dementia is and how it impacts all of us, and I wonder if James you could tell us a little bit about an overview of a typical patient experience for someone who is in the process of getting diagnosed or about to be diagnosed.

So what would their symptoms be and how does that diagnosis typically happen?

Yeah, and I think, well, I think the the sort of view of this has changed a lot in the last 10 years, so I might push talk, talk through what I might call a lifespan of the dementia.

And that is the the process is.

Well, we haven't perhaps start at beginning.

We're born with a genetic variability that increases or decreases our predisposition.

So not just by single genes that are rather rare, but you know the combination of all our genes.

What's called polygenic risk puts us at a higher or lower lifetime risk of dementia.

Then without our knowing it as we come through our 20s and 30s, those processes that will later see under the microscope, such as these tangles and envelope locks, they're beginning to be present from early adult life and they would be readily seen.

It could be detected with even modern day technologies.

Certain sorts of brain scans by our 40s and 50s.

But with no symptoms, our brains are very resilient to these early processes, but it's under way the 20 thirties 40s well under.

Then more typically by perhaps by in one 60s we might start to get early symptoms initially, not knowing their significance either.

Thinking it's just to do with changing in the stages of life of work pressures or you know retirement issues, mild forgetfulness, perhaps thinking it's common or normal at at that age.

And not knowing when is it the normal experience of going up the stairs and forgetting why you've gone?

There were popping into shopping for getting way there.

That's a normal experience and not dementia.

But when is that different from losing the car in the car park or forgetting things regularly?

There's a very soft start to these early, mild symptoms, and that may go on for some years, and people then may have more persistent, but typically memory problems that would often go by the name of mild cognitive impairment MCI.

Maybe, although it's mild, it can be really annoying and it is part of the illness. It can be intrusive in everyday life, but but normal life is pretty much business as usual, maybe even for five or five 6-7 years.

But then after that time, either the memory deficits are just so severe they they make it difficult to live a normal life, or perhaps by then other problems start arising difficulty in articulating 1 speech, getting jumbled up in where things are not, seeing the world correctly.

And perhaps some some problems and movement or balance can creep.

And so it becomes a more complex illness as well as a more severe illness. And at that point the impact on everyday life marks it out under this dementia by another, we know that the D word, but again, for many people would live with that dementia at home with with degree of support from friends and family for many years, 567 years.

Perhaps on average and for some, although by no means all the latter part of the illness, the last small number of years might for many want professional help, either through residential or nursing homes because of the increasing level of support you need for basic activities of daily living.

So from first symptoms to the end of the illness with the common dementias, like Alzheimer's disease, once typically thinking of a 10 to 15 year umso period, it depends a bit on how old one is when it starts, but it is quite a long illness.

Changing though during that time, but it's important to recognize that comes on the back of perhaps 20 or 30 years of hidden illness in the brain in the body, which we had no awareness of, and I think that's a really exciting opportunity.

To to you know to try and get in and treat and prevent those dementia processes too to prevent symptoms ever showing up and a reminder of how how resilient our brains can be to that growing disease is in this that's hidden.

So that I see as a sort.

Of a lifespan of dementia.

OK, let's hang on a minute and recap where we've got two so far.

So dementia.

Yep, that's it.

We learned that dementia is a group of disorders, all characterized by the loss of normal brain.

Functions such as thinking, memory, language and so on.

The loss of these brain functions get in the way of normal life, as you'd imagine.

Sort of similar to the definition of mental illness.

If you remember that episode.

Dementia is usually a progressive condition, which means that after it arrives, which it tends to do in mid to later life, it usually gets worse over time and it gets worse at a rate which is faster than what you'd expect from just regular aging alone.

Barbara told us that Alzheimer's is the most common type of dementia, somewhere between 50 to 75% of people with dementia have this.

Type and as you may already know, Alzheimer's is characterized by memory loss.

Barbara says that dementia is neurodegenerative, which means that some of the brain tissues stops working or dies.

At this point we should add that the second most common form of dementia is vascular dementia, which is usually considered not to be degenerative, but can be caused by problems with the brain's blood supply.

In the case of Alzheimer's, Barbara told us this is called by aggregates of Tau proteins.

Tau tangles, she said.

And amyloid plaques.

Basically, clumps of extra proteins.

Junk proteins James Corden.

Both of which gunk.

Up the brain and stop neurons from working properly.

Tau tangles sounds like a new type of Greek noodle.

That, or the latest hairstyle, fashion praise.

Not sure I have enough hair to sport any Tau tangles personally.

James and Richard told us that the total number of people with dementia is increasing rapidly because the world population is aging.

And dementia affects a lot of people, Jane said.

One in three are likely to develop dementia as they age.

Barbara added that The Who.

Uh, I think you mean the World Health Organization and not the band.

Yes, the World Health Organization.

million by: 2030

Which is a lot of people thoughts more than the population of the UK.

But dementia doesn't just affect the people who have it.

Their friends and relatives are also impacted, and it costs us all in more ways than one.

The financial cost of looking after people with dementia in the UK is somewhere between 25 to £30 billion per year.

That's a lot.

Just think what we could do with that money.

Mind over chatter.

Private hovercraft equipped with nappy changing robot Butler anybody?

And amazingly, and sadly, dementia was both the number one cause of death in the UK before and during the pandemic.

So more people died of dementia than COVID wow.

James told us that there are some genetic factors were either born with or not, which increased the risk of developing dementia and that physical signs of dementia.

Like tangled protein clumps in the brain can be visible on scans many years before any symptoms appear.

Also, it can be difficult to tell the difference between normal forgetfulness with old age and early symptoms of dementia.

I can confirm from bitter personal experience that forgetfulness definitely increases with age.

Now if only I could remember, I put that child.

It isn't until more severe symptoms appear later on, such as speech or movement difficulties, that it might become apparent that a person has dementia.

And people are able to live with the milder symptoms for many years, relatively independently, often with support from friends and family.

It's only towards the end of their illness that many people require professional help.

The long illness and one which changes throughout its course, and the fact that it remains hidden for a long time before even the mild symptoms appear, points towards just how resilient our brains actually are.

It's pretty remarkable that they continue to function so well for such a long time, despite all of the junk proteins they're accumulating, even if they do eventually begin to stop working properly.

So Barbara, just to pick up on something and James said there it feels like the earlier that dementia is detected, the better the outcomes could be for the patients.

But can you tell us a bit about how that would work?

How is dementia usually diagnosed and detected?

What the tools that we've got there for doing that?

Yes, so it's very important that it be detected early because we do have some symptomatic treatments.

I worked on some of the earliest 1, the cholinesterase in him.

There's our drugs like Donepezil which now approved for mild to moderate Alzheimer's disease.

And you know they're very useful for treating the symptoms.

So it is important.

Normally, as James said, you after you'd realize there were symptoms, you go to a CIA.

Neurologist specialist perhaps who would look at brain scans and do medical assessments to see if there's it's something like Alzheimer's disease or some other form of a neurological disorder.

And also a psychologist or neuropsychologist would probably do cognitive testing.

James mentioned the early memory problems that we see and we call these in Alzheimer's disease.

These early memory problems are usually termed episodic memory problems, and we look also for or as a neuropsychologist.

Or decline in cognition.

At the University of Cambridge, we've done a lot of work on these, and we've set up one of the earliest memory clinics to detect Alzheimer's disease, and I actually Co invented a set of tests called the cantab battery.

The Cambridge Neuropsychological Test automated battery and the paired associate learning.

Test so it's called for short cantab pal.

And Cantab Pal is a computerized test which can be administered via an iPad or over the Internet now, and the test requires you to remember where patterns go in boxes, and so there's different patterns and you have to place them using a touch screen in boxes and.

If you are unable to learn where they go initially, you have an opportunity to learn where they go.

And episodic memory relies on a neural network which includes the hippocampus in the brain and which is one of the first areas to be affected by the changes in the brain that we see in Alzheimer's disease.

The neuropathology.

And the neural network involving the hippocampus has also been shown to be critical for the performance on the cantab PAL test.

So episodic memory is really important because as you heard from James, we use it everyday.

It's kind of memory where we try to remember where you parked your car in a multistory carpark or try to remember where you left your mobile phone in the house.

So it's absolutely essential to our functioning from day to day.

And the Cantab Palace actually helped to increase early detection of Alzheimer's disease because it's a very sensitive test to the memory problems in Alzheimer's disease.

And so we can detect it early and.

As I said, it was Co invented by myself and Trevor Robbins and then the technology was transferred to the company Cambridge Cognition so that it could be accessed worldwide.

I'll I'll jump to Richard with a question about.

Are there any controversies about early diagnosis or is there any reason why people wouldn't want to find out early that they have a disease like Alzheimer's?

Yeah, I mean that that that that's a very good question, and it's been a very big question this this how you establish the value of early detection and early diagnosis has been kind of ongoing issue, I mean.

I think.

The part of the part of the question.

Is if you take the trajectory that James described, so where if you have somebody who has symptomatic dementia, they will have gone through these kind of various stages of disease.

But when you look at it at a kind of group level, I suppose in the other direction forwards that some people at every stage.

Some of the people who have pathology in their brain will not move on to then develop mild cognitive impairment.

Some of those people who have mild cognitive impairment will not go on to develop them.

And so if you're the earlier you move in terms of detecting the presence of disease rather than detecting dementia specifically, the more uncertainty comes with that, the more you're talking about somebody. Somebody's risk of developing dementia in the future, and that then creates a. It creates a set of questions.

They've been around, really, I mean.

seriously asked in the early: 1990

The forms of dementia were were identified, and particularly, the identification of the APPOI gene, which is the gene that predisposes you to developing Alzheimer's disease, but it's not predictive.

If you have the gene, it's not a kind of it's not a guarantee that you're going to develop.

Ourselves to see in the future.

And the question then is what's the?

What's the value in knowing?

In knowing this and that's being debated in back and forth in many ways, and so we end up in a situation now where you can go into a personal genetics, consumer genetics company and you can order a 20.

You can order an appoi test.

Kind of freely well, not freely.

You pay for it, but you can.

You can order it on the Internet without any requirement for consulting anything about whether whether you should do that.

But really, the debate revolves around like is this useful information does it?

Is it something that you're going to make a change on the basis of or is it something that your doctor is going to make a change on the basis of?

Or is it simply something that sits in a box where which for some people might be interesting or useful, and for some people?

Might be worrying or anxiety inducing, and so there's been a lot of.

A lot of research effort really over the.

Last: 2530

Really, I mean, it's it's a very interesting, but it's also very problematic case in the sense that because the arguments about early detection.

Can be more difficult to make around dementia than it is around other diseases because you have a lack of clear prevents.

Can I come in there?

Richard, I have I have to object to this.

I've been objective this online I hear this a lot and I think it's I think it's the wrong argument.

It sent us on the stigma of dementia.

If dementia was not stigmatized, we wouldn't have the same type of discussion.

Heart disease and stroke are not stigmatized.

Therefore people have No Fear or this sort of convolutions around.

Checking for diabetes, blood pressure, cholesterol, you do it, and you deal with those risks and you tackle your long term risks.

Actually, a very high proportion of dementia can be prevented with even before new magic bullet drugs 40% is estimated could be prevented by simple practical measures.

We could all implement and you know that should be empowering to inform people about their risk, whether it's genetic risk or health factors to be engaged with, and I think.

We hailed these convoluted arguments about, well who it wants to know.

We hear this because of the fundamental stigma of dementia and actually we should all want to know because we can all do something about it to reduce our personal risk.

And so I mean, I would.

I would completely agree.

I mean I.

Think that that if you.

Look in the argument around.

ons around cancer in the late: 1970

Changed part of the reason it's changed is because of the clear ability to do to to treat, but also because we've we have had a.

A mature societal discussion about what it means to have cancer, and it's now much more possible to talk about a cancer diagnosis than it was 40 years ago, and one would hope that as one moves to kind of using these early categories of disease that we can do a similar thing around dementia.

And I think I mean one of the issues as it stands is.

So like you said, there's kind of 40% of dementia may be kind of preventable or due to preventable risk factors, and they are things that all of us.

Can do and the question is.

Do you have to have information about risk?

If they're things that everybody can do, or are they simply things that everybody should be recommended to do in the same way that we recommend?

We recommend lifestyle changes across kind of cardiovascular disease, regardless of whether you have high cholesterol, it's still good to have a healthy diet and exercise.

Sorry, I was going to.

I was going to support James very much on this because I do think that well.

You might think that it's good to tell everybody to do these things if you actually.

Realize that you can reduce your risk of dementia by, say, being physically active, not smoking.

Avoiding harmful use of alcohol.

Controlling your weight.

Eating a healthy diet.

Maintaining health, healthy blood pressure and cholesterol and blood sugar levels.

People are more likely to do these things and also if you detect early patients have the time to actually ensure that their financial and personal affairs.

Affairs are in good order, so they can actually arrange things and there are treatments, so there are the cholinesterase inhibitors for symptomatic treatments for cognitive problems such as the drugs we mentioned donette possess.

And they're approved by Nice.

And then there's new drugs now which are not yet fully approved, but are available in the USA like Biogen Zoldan.

And they're using those drugs for treating the underlying disease process.

So as we move on.

They'll it'll be even more important to detect early so that you can actually get these treatments early before there's too much damage in the brain to have the treatments work.

Can I just ask a question just to make sure I understand like we're going to move on to treatment in a moment, but just about early diagnosis to sort of tie that up?

We heard you know you can get direct to consumer genetic tests to find out if you have a gene that predisposes you to condition like Alzheimer's and Barbara mentioned.

Ken Todd Powell, which I believe is a cognitive function test, but is there a way to actually look for the clumps of protein that are in your brain to have like?

Is there a physical test to see if that problem is there at an early stage?

There are at the moment their cost and some other disadvantages and their cost and invasiveness have meant they're largely only in the research context rather than in sort of NHS brain health clinics.

But that's shifting quite rapidly.

Recent advances showing how some blood tests looking at sort of the chemical signatures in the blood with the way these junk proteins.

Spillover into the blood can be extremely sensitive.

But I think I want to ID emphasize the technology because that's moving rapidly, and that's merely in this or that technology.

I think the bigger question is how you use that information, how you contextualize it, how you understand it in terms of 1 personal risk and one personal steps you can take to reduce risk we've we've seen already.

Perhaps wrongly, interchangeability around the use of screening versus diagnosis versus risk, these things are not the same. You know, diagnosis is a very you know, particular thing around A cause of a set of symptoms you have. It's not the same as saying you have a 50% risk.

In of dementia in the next 10 years, that's not a diagnosis that's around.

Risk looking at sort of quasi diagnosis before symptoms to say you have in your body the changes that we think of with Alzheimer's disease.

You don't know it yet.

You have no problems with memory, but those changes are underway.

That's a half way to a diagnosis, but you're still well at that stage.

And it still is really around, but it was using the language of screening and into preventative interventions.

So what we're not looking to do is to take people who are perfectly well getting on with their lives in their 50s and 60s, and say you have Alzheimer's dementia that would.

That would be wrong as well as harmful, but we can be saying you have a risk that you can do something about to reduce and perhaps even within a very small number of years.

There are other treatments.

We can give to try and eliminate that risk, so there's things that your doctors can do with some of these disease.

Modifying treatments that are coming, but we didn't wait.

There's things you can already do yourselves.

It takes effort.

It takes effort to take to take, exercise to sleep, better drink, less, smoke less.

But that effort is worth it if we can, you know, give people advice that this is not just the advice doctors give to everybody.

This is really particular for you because you now have an increased risk that that you want to do something about.

Yeah, if I could, just if I could just follow up on that.

I think.

I think there are a couple of things I think one is that.

That within a conversation about dementia, I think it's really important to reflect the fact that there has been.

Within the research field, I think a significant shift over the last couple of decades whereby what you talk about in terms of Alzheimer's disease or other specific diseases is no longer perfectly aligned with dementia, and I think this is a really important thing that often when we talk about when people talk about some disease.

They regard it as being one and the same with dementia, and often in a research space.

Now this is.

This is not.

This is not.

Yeah, that's not the case that you can talk about a disease process that started 20 years beforehand.

Still, as part of an Alzheimer's disease process, but it's not dementia.

I think this is part of that discussion about about stigma that James is mentioning, and I think the other.

The other thing is about being dumb.

I suppose having kind of ours.

Our eyes open about the possibilities of behavior change because one thing that we know kind of fairly well from.

Public health research is that giving people information on its own doesn't help.

Doesn't lead to behavior change, and so it's about putting into place systems that allow people and that support people to change behavior where that's appropriate and also recognizing that if you look at those preventative factors, many of them are things like air pollution or early life education, which are actually structural.

Factors or their to do with kind of questions of HealthEquity and that it is not all about individuals making change, but it's about policy change.

And about health system change as well.

Just to follow that up, Richard.

I mean, in addition to the ones that you just mentioned, the other additional risk factors are things like depression and social isolation and cognitive inactivity.

So we have to make sure that people keep their minds active and that they don't end up socially isolated.

To ensure that they you know have better health into the future.

You're in less risk of dementia.

So we're still talking about diagnosis, yes?

Yeah, that's right.

Barbara says early detection can help with the success of treatments.

And she mentioned drugs like.

8 cholinesterase inhibitors.

Dog and alerts.

These prevent the breakdown of acetylcholine, a neurotransmitter in the brain.

This is called a symptomatic treatment because it helps improve symptoms like memory loss in patients with dementia.

This is just one type of drug that can be used to treat Alzheimer's.

What about some of the ways in which a patient might be diagnosed?

Well, a psychologist or neuropsychologist would probably use cognitive testing to diagnose a patient.

One early sign of Alzheimer's is problems with episodic memory.

This is the type of memory that records specific events in your life, including what happened when it happened and where it happened.

Contrast this with procedural memory, which is knowing how to do a certain task, like riding a bike, tying your shoes, and so on.

Things that you do over and over without having to consciously think.

Procedural memory is also impaired in dementia, particularly in later stages of the disease, but early signs and symptoms tend to be associated with episodic memory issue.

Barbara Co invented a test for Alzheimer's, which is called the Cantab PAL, which stands for Cambridge neuropsychological test.

Automated battery paired associates, learning.

Wow, what a name.

Cantab Powell can be administered over an iPod or the Internet and is very good at detecting Alzheimer's even at an early stage.

How it works is you have to remember and learn where things go into boxes that you see on a screen.

This mimics everyday situations like working out where you left your keys at home, or as Barbara said, where you parked your car in a multistory carpark.

My trick for that is just wandering around the carpark, pressing the button on the keys until the car flashes that, or leaving a trail of bread crumbs behind and just hoping there aren't any geese about to mess my cunning plan up.

Can topowl basically tests how well your hippocampus is functioning, as this is one of the first things to go awry in dementia.

The hippocampus is sort of a shrimp shaped structure near the center of your brain.

The name comes from the Greek word for seahorse, so maybe it looks a bit like a seahorse too.

I bet there are some pretty grumpy seahorses out there right now, having been compared to a lowly shrimp.

If I were a sea horse, I'd be fuming.

But Richard pointed out that detecting the potential presence of the disease early May not be a uniformly good thing.

For example, he mentioned a variant of the APPOI gene called Appoi 4, which predisposes some people developing Alzheimer's.

But not all people with this variant of the gene develop Alzheimer's and not all people with Alzheimer's have this version of the gene.

So although people can get direct to consumer genetic tests to find out if they have the variant Richard points out, it's an open question whether this is useful information.

Maybe it's just one more thing to worry about because there isn't anything you can do to definitely avoid developing the disease.

Now James objected strongly to this way of thinking. He says that current estimates indicate around 40% of dementias can be prevented with what he called simple practical measures.

Which can be implemented relatively easily.

But Richard's point was whether you need to know if you're at increased risk. Maybe all of us should take these preventative measures in the same way, it's recommended that everyone eat a balanced diet and exercise to prevent conditions like heart disease.

Barbara helpfully sheds some of the ways to reduce the risk of developing Alzheimer's.

These include regular physical activity.

Not smoking, avoiding harmful use of alcohol.

Eating a balanced diet and maintaining a healthy weight, blood pressure, cholesterol and blood sugar levels.

Another risk factor that people might not think about is hearing loss.

Studies have found that even mild hearing loss doubled dementia risk.

Moderate loss, tripled risk, and people with a severe hearing impairment were five times more likely to develop dementia, which highlights just how important it is to be proactive in addressing any hearing declines over time.

That all sounds like pretty good advice.

Well, yeah, that's the point.

These are all things that are generally advisable one way or the other, although they're probably all easier said than done.

Don't I know it?

But people might be more likely to actually follow this advice if they know early on that they are specifically at higher risk of developing dementia.

And people need support in order to take action to do these things.

So where does that leave us in terms of diagnosing dementia?

Well, there are genetic tests, but to be clear these won't tell you if you have Alzheimer's.

At best they can tell you if you have a genetic variation which may increase your risk.

Then there's Cantab Powell, which can check to see if your cognitive function is already declining.

And James told us you can also get blood tests which can detect abnormalities and help diagnose dementia.

The important point is that determining a person risk is different from detecting the presence of.

The disease, aside from the APPOI 4 gene variant, Barbara told us about a few other risk factors for dementia, which include depression, social isolation, cognitive inactivity.

Sounds a lot like lockdown.

Yeah, I'm afraid so, and we'll hear about another, perhaps surprising risk factor in a moment.

I think one thing we haven't mentioned, which we probably should just say is.

Dementia isn't just a problem of people over 65 years of age, for example. Importantly, there are over 42,000 people in the UK under the age of 65 with dementia. So we we also should bear that in mind.

I thank you bars, but that's really important to point out, and often they can have a slightly different form of dementia can present in different ways and those young onset dementia's often have a stronger genetic component which has repercussions throughout families.

And as well as the different impact on on what sort of services and support individuals need.

Just go back to the modifiable risk factors.

Well, it hasn't come up, but I think it's a really important one is hearing loss.

It's actually as a as a single fact.

It's the biggest single factor that it's been identified as a modifiable.

In other words, a treatable contributor to dementia, and I think people probably aren't aware of this.

And actually, the ability to have some impact on the number of people with dementia some years down the line.

Perhaps even greater from tackling hearing loss than from tackling those familiar things like smoking and drinking.

And you know, we have a lot of ways to help identify and to improve hearing loss, and it's just maybe something that people haven't associated with with dementia.

And it's about modifiable risk.

It's not saying if you have hearing loss, that means you're going to get dementia.

Clearly that's not the case on a, you know one to one.

Basis, but trying to reduce the overall burden of dementia in our society, we should be really thinking about things like hearing loss and and those other societal issues that were dimension of pollution and education.

But hearing loss is is one of the biggest.

If this is something we've touched a little bit on in our conversation so far, but it's something I'd like to hear more about.

And how do we find ways to stop slow down or kind of reverse dementia?

What can we do to ourselves to prevent ourselves from developing dementia?

Well, we heard a bit about that because obviously there's things like exercise keeping physically active, which is very good for you, and that's good for your mood as well as your cognition and and reducing your risks of cognitive decline and not smoking, avoiding harmful use of alcohol, controlling your weights, very important and eating a healthy diet.

Maintaining healthy blood pressure, cholesterol and blood sugar levels.

And as we just heard, you know what you're hearing and social isolation, and obviously some things are beyond our control.

Perhaps like air pollution, but on my own work within the University of Cambridge, more recently has been promoting good brain health through stimulating.

Activities you know.

Cognitive activities, learning new things and evidence based brain training is important and in my laboratory we've developed multiple brain training games, some of which are available through companies called Peek and Pop Reach.

And specifically we developed game show which was for the mild cognitive impairment group that you heard about from James, and that has been shown to improve episodic memory and also functionality in daily life in these individuals with mild cognitive impairment.

So I think those sorts of things are very good for us.

And we they run on your mobile phone or an iPad.

So it's a great way to have fun.

One and also to stimulate the neural circuits in the brain that are important for episodic memory and other forms of cognition.

Thank u bar because I think that the more that these activity steps we can take can be part of a.

You know Norman and interesting life.

The more likely it is that we will do them.

Yeah, we can follow advice and follow steps.

If it's if it's easy and fun to do so.

But exactly what one might do will depend on where you are in life.

Things you would do if you're in your teens or 20s might include, you know, moderate alcohol.

Not exposing yourself to to hearing damage when you're playing sports, play a lot of sport but follow the rules around concussion and minimizing concussion risks and thinking about reducing risk of head injuries.

Where that's inviting or rugby or math, whatever your sport is, you know, so there's things that you might do at that young age that's different to what you might do when you're 40, when it's all too easy to drink a bit more, exercise less.

That might be different to what you do at 60, which is to perhaps feel a bit embarrassed about to hearing loss and not come forward so.

Where you are.

In life will determine what are the steps that you can take.

To help your own risk and also perhaps on behalf of your, you know other Members, your family, your neighbors, your community, be fighting for those more societal issues around equity and education, equity and health, access, pollution.

These are things that we can we can fight for for our, you know, friends, families, neighbors and community more broadly, not just for ourselves.

So at any stage of life there be something you can be doing.

It doesn't have to be stopping all the fun.

I agree with that James, but I think that one thing we should focus more on is promoting good brain health in schools because good habits could be established very early on in life and then continue right through your whole life course to make sure that you.

Have you know?

Good cognition and and well being throughout your whole life.

I think that's a really important point about schools.

It's not just that if you change behaviors in, you know an understanding in children, they have a less risk of dementia 50 years later when they when they're getting older.

Actually, those children will be, you know, they will care about their families, their grandparents and parents.

They will be able to be in families, reminding and educating people.

To be aware of dementia and to take steps to avoid it so we would see perhaps benefits really very quickly.

You know, children are extremely responsible and knowledgeable.

We should.

We should harness that.

Richard, do you have anything to add to this part of the conversation?

No, I mean, I think that I think that does cover it.

Well, I think it is about seeing this as a whole life course question and that it's not simply about individuals, it's it's a question for society, locally and nationally.

Yeah, it sounds.

A little bit like.

It's, you know, very similar to physical maintenance.

You know we should be encouraged to exercise our bodies from an early age and kids can help their parents stay fit if they want to go out and run around and and stuff like that.

But I guess it's similar for brain brain maintenance as well and we just have.

Yeah, and hopefully it should be fun.

Barbara was sort of talking about a game show type intervention that she's developed in her in her lab.

I hope you can't hear the train too loudly there in the background.

So we just have a couple of minutes left in the recording.

We did kind of skip through the treatment section and we went straight for prevention, but if anyone has any last comments they'd like to give anything they didn't get to mention that they wanted to.

I I think it's a really exciting time.

We're at a tipping point in the dementia world, we focused in a discussion on the much more common dementia of Alzheimer's disease.

I actually think we're on the cusp of getting some really transformative treatments for some rather rare dementias, including frontotemporal dementia and Huntington's disease is a rare, often coming on in.

In mid life and highly genetic, but for some particular biological reasons, there's been a way in to really neutralize those gene effects.

These are with a variety of strategies that are in clinical trials, and I think we may see actually in the next very small number.

Of years, perhaps even: 2022

So, and where there's 11 dementia, that's that's solved. There'll be others, you know, right in rapid succession, and it's just.

It's a very exciting time.

With that I should perhaps highlight that this what we can all do and everybody listening is to remind ourselves that this needs research.

Investment research delivers results.

We've seen that.

In COVID, we've seen in count, so C and HIV.

The despite a dementia being so common, affecting one in three of us during a lifetime per patient, it gets a tiny amount of research investment compared to the scale of the problem and we should all be supporting national international government and research efforts to to invest because it will deliver results.

So I think it should be a really positive message.

I'd like people to hear on on the tractability.

This is a solvable problem.

Yeah, and I think it's it's important to point out that all the.

Role that the public can play in and participating in clinical trials and mobilizing the government to put more funding into research and novel treatments for mental health disorders and neurodegenerative diseases.

So it's really important that the public be engaged and they're the ones that have also helped.

To reduce the stigma associated with Alzheimer's disease and other dementias.

So they're incredibly important, the public and in playing a role for translation into clinical practice.

I no, I mean I would. I would echo both James and Barbara's points about the kind of the value of research in this area and the the progress that is being made, I think.

Yeah, I think it's a question of keeping in mind the goals of what we want to do, which is to.

Deliver a.

A health system that can reduce the illness burden for people as they as they age across society.

And that's that's not about it's about recognizing that many of these diseases and these conditions are interlinked, and that people often, as they age, won't simply have.

Diabetes or they might not simply have heart disease, but they'll have lots they'll have or dementia, but they will have.

Combinations of these things and recognizing that we might need to engage across the system rather than working in siloed areas.

Can I just say one more thing you mentioned earlier in the notes and maybe you don't need this, but you talked about repurposing of other drugs, which is very topical area, and we've done a lot of work with Modafinil at the University of came.

Bridge, which is a cognitive enhancing drugs that affects dopamine, noradrenaline, and glutamate function, and our studies have shown it enhances performance on cognitive tests in healthy individuals.

And also in individuals with neuro psychiatric disorders such as depression, schizophrenia and attention deficit hyperactivity disorder and healthy people.

Modafinil has also been shown to increase task related motivation.

Modafinil is a wake promoting agent, and it does seem to have these beneficial effects on cognition and also motivation.

So it would be interesting to have a long term studies, perhaps a a proof of concept study just to look at how well Modafinil might help to improve.

Cognition in Alzheimer's disease.

Modafinil thus far does not appear to be addictive, so this could be quite beneficial.

Sorry if I missed this, but so you start you start off by saying that this drug is being repurposed from some other use.

What was the other use?

Well, the idea would be to repurpose it for the use in Alzheimer's disease because it's a wake promoting agent that has been used for narcolepsy, so that's what it's.

Used for, but it's also used in America for sleep disturbance due to shift work because it found that it reduced accidents and shift work.

And it does seem in our studies to both have alert awake alerting potential, but more importantly, cognitive enhancing studies which we've done with at Cambridge, both in healthy volunteers, but also as I said in these psychiatric disorders.

So it would be useful to just see whether it can enhance cognition and maybe motivation, task related motivation and in Alzheimer's disease or mild cognitive impairment.

That's really interesting.

I could see us doing a whole other episode on how the treatments for different psychiatric and cognitive disorders, like how they're different, but also have overlaps in terms of the treatments and stuff.

Yeah, James has done quite a lot.

Of work.

On Parkinson's disease.

Yeah, so that's right.

So it's one of the features that's coming out of research is although the biology of these diseases, those junk proteins that distinguish different forms of dementia, for example, that we can send the microscope.

They're very distinctive and the jeans are very distinctive, from 1 dimension to another.

And yet, many symptoms have so much in common, so whether it's to do with memory or motivation.

Or mood.

And in apathy and so, whether you're thinking about trying to switch off the biology of the illness to prevent the disease will take you down one a certain direction, but that can be done in conjunction with treatment to think about reducing symptoms.

So the the difference between symptomatic versus disease modifying treatments is often highlighted, and there's tremendous scope.

Learn from things that might be effective in one disease to bring them across and test them in another disease, and to accelerate that process of effective treatments.

The UK is very well placed for this.

I, I think the first reason it's it's got a very strong culture and the you know the the work of the NHS means it's very well set up to try and understand around long term risks but also around the the consequences of symptoms for people with dementia and.

To switch off symptoms like dopamine and Parkinson's disease, it's although we still don't have after 50 years a drug that can stop the illness in its.

Max, actually we've had 50 years of a really effective symptomatic treatment that's transformed the lives of those with the illness.

So I think there should be no shame in focusing on symptoms as well as trying to or hand in hand with switching off the the all this fundamentally, but I don't know whether Richard that has different concerns from a societal perspective.

These are.

Quite different implications, but I think it's that key thing in terms of as we think about developing new therapies that they are things that make a difference to patients lives and to the fact of their families lives and that it's that that's kind of.

The ultimate goal, rather than necessarily making a change to the biology, it's about the outcome and the impact in London.

Well, I think I think the important thing to follow up on what Richard said is that if we can, you know, improve the symptoms and improve people's ability to function in daily life and have better cognition and well being.

That's a really important aim that we should strive for.

If I could just my last.

30 seconds would be.

If you're worried about your memory or someone you live with, your husband, wife, parent, grandparent, please come forward, please talk about it.

Come to GP.

Come to brain Health Center or memory clinic.

Just come forward, talk about assessed and there may be all sorts of reasons and treatments available and understanding for you so.

So don't hold back.

Yes, I would agree, early detection is so important.

So another risk factor for dementia is hearing loss.

Haven't heard of that one before.

Me neither, but hearing loss is thankfully very treatable.

And again, just because you have hearing loss doesn't mean you'll develop dementia, but it does increase your risk.

So is there anything we can do to avoid developing dementia?

Well, as we heard before, lots of the same things that are good for your body turn out to be good for your mind too, so they may help decrease your risk of developing dementia.

Things like physical activity.

And Barbara said that cognitive stimulation.

Basically brain training can also help.

Her lab has developed several computer games that are widely available online.

One of them is called Game show, which is helpful for improving episodic memory. It helps improve People's Daily lives, and it's fun too.

Who could ask for more?

James said that preventative measures can change throughout your lifetime, depending on your age and interests.

Barbara suggested that good habits can be promoted in schools, standing students in good stead later on.

OK, so that's prevention.

But what about cure?

Well, sadly it's more treatment than cure research is essential to producing better treatments, but James said that dementia gets only a very small amount of research funding compared to other health.

And that's despite the large proportion of society affected by it.

Barbara said that everyone can play a role in helping to develop more treatments for dementia from participating in clinical trials to helping destigmatize the disease.

James said that more treatments for other types of dementia are on their way soon, so stay tuned for more on that.

Richard emphasized the need to treat patients holistically, something we'll hear more about in the cancer and AI episode this season, as well as the mental health episode.

Barbara mentioned that another tactic for treating dementia is repurposing existing drugs, which are normally used to treat other condition.

She told us that Cambridge researchers have been working with a drug called Modafinil, which was originally developed to treat narcolepsy, and the tiredness which people who do shift work can experience.

This struggle fights a few different neurotransmitters in the brain.

Neurotransmitters are the chemical signals which neurons use to communicate with each other.

And researchers have found that Modafinil helps both healthy people and people with psychiatric disorders, including depression, schizophrenia, and ADHD.

To perform better on cognitive tests.

Based on these early findings, Barbara suggested that more research should be done to see if Modafinil could help treat cognitive decline in patients with dementia.

We should stress at this point that Modafinil should only be used as part of research.

James, emphasize that the symptoms of different dementias can be similar, but the biological causes can be different.

Depending on whether you target the cause of the disease or the symptoms, your approach to treatment may be different.

But this fact would also point researchers towards drugs that may work for multiple different diseases.

We heard throughout the conversation about the importance of early detection.

So the last point we want to leave you with is that if you have any concern about yourself, a loved one, a friend or someone you live with, talk to your GP and get assessed.

One final final thing.

If you want to take part and support dementia, research whether you're healthy or have dementia.

The single port of call to be put in touch with researchers is the Joint Dementia Research website run by the nurse.

Well, that's it for this episode.

Stay tuned for our next episode on Infectious Diseases.

Before then, please spread the mind of her chatter word.

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A huge thanks once again to our guests Richard Milne, James Rowe and Barbara Sahakian.

And finally, a big thank you to the sickeningly talented Carlow lad for our music and the equally talented Alex Sadler for artwork.

See you next time.