Curing Alzheimer's Horizon

Our memories make us who we are,

but it's thought 30 million people today are losing them

due to the curse of our time - Alzheimer's.

Despite their best efforts, scientists have, until now,

failed to stop this disease,

but the latest generation of research has unleashed a new front

in the war against this devastating disease.

This is a very exciting time.

There's a new window of opportunity.

New technology allows us to see

the signs of Alzheimer's disease earlier than we ever could before.

Today, a series of drugs trials have been launched across the world,

drugs that are targeting the disease in its early stage.

We believe that this trial marks the dawn of a new era

in Alzheimer's prevention research.

Initial results are exciting.

They reveal that there are drugs which are reducing

signs of the disease.

Scientists are confident that a cure is tantalisingly close.

If we treat early enough, we may stave off Alzheimer's disease

completely and we may never have to worry about it again.

Horizon asks - can we end the curse of Alzheimer's forever?

"I won't need a shopping list this week. I'll just...

"I'll remember that." And then you get halfway round a supermarket

and you think, "What did I have on that list?

"What did I have to get? I know there's something."

"Why have I gone upstairs?

"Have I come up for something, have I left it behind?

"Was it not upstairs in the first place?"

I remember faces and I'm still good at that, but not names.

As we grow old, we all start to forget things,

but in the back of our minds, there hangs a terrible fear.

My mother has Alzheimer's,

so if you've had a day of forgetting a few things, you do get

gripped with a sort of panic that this is it, this is the beginning.

About every four minutes, somebody new is told they have the disease.

The panic grows as the epidemic sweeps across the globe.

Alzheimer's disease is now one of the most feared medical

conditions, particularly in people over the age of 45.

And that's understandable, because we now, tragically,

most of us know somebody

who has got Alzheimer's disease.

This degenerative brain disease leads to a loss of memory

and eventually the loss of most other brain functions.

Horizon meets five ordinary people

whose lives are overshadowed by Alzheimer's.

Each one in their own way is making an extraordinary

contribution in the worldwide war against the disease.

Can you tell me what letter that is?

In London, Tom has a rare form of Alzheimer's

which baffled his doctors.

My brain doesn't compute what they are.

It's a sort of a jumble.

It's not, it doesn't mean anything.

New scanning technology is revealing what's happening in his brain.

In Phoenix, Arizona, Jamie lives in fear.

My great-grandmother had Alzheimer's disease.

Her daughter had Alzheimer's

and then my two great-uncles also died of Alzheimer's.

And then my father just recently died a couple of years ago

with Alzheimer's.

The gene she carries dramatically increases her

risk of developing Alzheimer's.

It's the target of a new generation of research.

Oh, they're ruined. They're absolutely burnt to a cinder.

In North Wales, the disease means Gareth is retraining his brain

so that he can continue to live independently.

IN SPANISH:

In Columbia, Flor's family carries a rare genetic mutation

which causes Alzheimer's at a very early age.

Her sister already has it.

New research could prevent Flor from ever developing the disease.

And in New England, Neil believes a breakthrough drug

has transformed his life.

I mean, I don't know what else to attribute it to,

you know, unless there's a miracle I'm unaware of.

All these people face a threat of Alzheimer's.

The disease has long been hard to study, but scientists have recently

made great advances in understanding how it affects the brain.

Inside a healthy brain, there are billions of cells called neurons.

Our thoughts and emotions are transmitted between them

via connecting synapses.

But in an Alzheimer's brain,

a protein starts to build up in the synapses,

blocking the electrical signals and disrupting the flow of information.

This protein is called amyloid beta.

As the disease progresses, it continues to accumulate

and creates huge sticky clumps called plaque.

Even at this stage, there can be no apparent symptoms.

For some reason, the brain can tolerate a certain

level of amyloid for a number of years, possibly many years.

And it's as though the amyloid, which may be driving the process,

needs something else to then go on to produce that

destruction of brain cells that causes the symptoms

and the devastation at the individual level.

The culprit is thought to be another protein inside the brain cell.

It's called tau.

Tau normally functions in brain cells like the railroad track

to take critical nutrients

up and down brain cells.

As these tracks disintegrate,

the supply of nutrients to the neuron is stopped.

The tau then forms into tangles

which kills the cell.

It may take 15 years from the onset of the disease

for the tau to start creating tangles

and only then do the symptoms of the disease start to appear.

The new era of research is focusing on treating

the disease in its earlier stages.

This work is happening in some surprising places.

Medellin, a city dominated by the Andes mountains of Colombia

in South America.

It's been notorious for clandestine drug smuggling and kidnappings,

but its people hold a darker, older secret.

At its heart are a group of families

and they may hold the key to the future of Alzheimer's research.

IN SPANISH:

Flor lives with her daughter Danielle and her sister, Olga.

Olga is only 47, but in 2013 she was diagnosed with Alzheimer's.

Olga is not the only one in Flor's family who has developed

Alzheimer's in their forties.

This family carries a gene mutation which can be traced back to

an ancestor who arrived from Spain 400 years ago.

Carriers of this gene start to develop the first

symptoms as early as 45.

It used to be thought they'd been cursed by a wicked witch

but - in the 21st century - their plight has captured the attention

of one of the leading researchers in the field, Dr Eric Reiman.

Meeting almost a thousand family members for the very first

time was a life-changing experience.

To see what those families have gone through,

not only the clinically-affected person

but the entire family who has rallied around their loved one

to provide care, and the impact that it has had on their lives.

It underscored the urgency we should all

have in the fight against Alzheimer's disease.

Flor and her family live with the disease every day.

Flor's sister Olga has to be looked after by her 70-year-old mother.

The disease forced Olga to give up work two years ago.

THEY LAUGH

For centuries, these families in Colombia have suffered helplessly

from the ravages of the gene mutation,

but now they are at the forefront of the new era of scientific research.

We have this wonderful relationship with families in Colombia

sharing this common interest.

We all find it a privilege to think about how we can advance

the fight against Alzheimer's disease in a way that

actually helps these families along the way.

In Colombia, Dr Reiman and the Banner Institute are partners

in a massive new drugs trial,

the first-ever major Alzheimer's prevention trial in the country.

He hopes it'll stop any more members of these

families from developing the disease.

Unfortunately, it'll be too late to help Olga.

IN SPANISH:

Most of the time, Olga is unaware of the severity of her condition,

but occasionally she realises what is happening to her.

Her family is determined to protect her from the horrors of the disease.

They want to wrap her in their love and support.

SHE SOBS

The genetic mutation which afflicts the families in Colombia

offers a rare opportunity for research

into the earlier stages of the disease.

But there is another more common gene which is

also attracting the attention of the Alzheimer's researchers.

It's called APOE4.

Carriers have an increased risk of developing the disease

later in life, in their seventies.

One of the largest centres for the genetic

investigation into the disease is in Phoenix, Arizona.

Scientists here are searching for people who carry

this more common gene.

Jamie Tyrone is a 55-year-old retired nurse.

She has known about the disease most of her life.

I have a very, very strong family history of Alzheimer's disease.

My first memory was when I was ten years old and I visited

my great-grandmother, who was my first exposure to Alzheimer's.

She was in a wheelchair and had no cognition

and her eyes were very empty.

The next person to get Alzheimer's was her daughter,

my grandmother, and here's a picture of her.

And then her two brothers, my two great-uncles,

also died of Alzheimer's.

And then my father just recently died a couple of years ago

with Alzheimer's.

So, you kind of have the whole picture right here with my family.

Because of her family history,

six years ago Jamie decided to find out which genes she carried.

She sent off a sample of her DNA to be tested.

Dr Eric Reiman's institute is focusing on the APOE4 gene,

because it's so closely connected to the way the disease progresses.

APOE4 has a number of effects on the brain, several of which could

contribute to the development of Alzheimer's disease.

The leading theory is that it leads to the development of Alzheimer's

disease by reducing our ability to get rid of amyloid in the brain.

His colleague, Dr Jessica Langbaum, has calculated the increased

risk carriers of the APOE4 gene face of developing Alzheimer's.

If you have two copies of the APOE4 gene, meaning you have one copy from

Mum and one copy from Dad, your risk of developing Alzheimer's dementia

in your lifetime is approximately 30 to 55%.

If you have one copy of the APOE4 gene,

your risk is approximately 20 to 25%.

And if you have zero copies,

your risk is approximately 10% to 15%.

Not long after Jamie had sent off her DNA results,

she received a reply.

One night, I get a message in my e-mail,

letting me know that my study results had come in.

And what you can see here is that I have two copies of the APOE4 gene.

Jamie's discovery that she carried a double copy of the gene,

which massively increased her chance of getting the disease,

drove her to despair.

When I did find out my genetic status, I didn't have any genetic

counselling at all and it was quite anxiety-provoking.

I was told not to talk about it

for fear that I'd be discriminated against.

I didn't know what to do with this information and I didn't

want my family to go through what we had previously had gone through.

And it came to a part of my life

where I had to decide what road to take.

Do I take the dark road and...

..possibly leave this earth?

Or do I make meaning of it and take the bright road?

The carriers of the gene do bear a terrible burden,

but in the new era of research into the early stage of the disease,

they have a special role to play.

It's hard for researchers to identify

participants for trials who may have the disease in its early stages,

before the symptoms appear.

But by working with APOE4 carriers, who are most likely to develop it,

they dramatically increase their chances.

Now the Banner Alzheimer's Institute has launched a drugs trial

aimed at APOE4 carriers like Jamie.

I'm very hopeful and excited about this trial.

For the first time in history, we are

now doing clinical trials on people who are at

high risk for developing the signs and symptoms of Alzheimer's disease.

Up until this point, people had to wait until they had memory

and thinking problems or had a diagnosis,

until they were given access to a clinical trial.

Now we are giving clinical trials,

offering clinical trials to people who are at high risk

to see if we can stave off the onset of the disease.

MUSIC: Got To Give It Up By Marvin Gaye

Jamie is still too young to join the trial.

However, the new research gives her great hope.

When you look at the APOE status and the increased risk

and be able to merge the two together, and really create

studies specifically for us, is very exciting and very promising.

And I hope in my lifetime that there will be a prevention or cure.

I do not know, but if there is,

I'm very touched to be a part of that process.

-APPLAUSE

-That's hard.

The trials are accelerating new research into how to slow down

and even prevent the disease.

But the new era also aims to understand what is happening

inside the brains of sufferers

as the disease develops from its earlier stages.

Until now, scientists have only been able to work with

the brains of Alzheimer's patients once they have died.

In Colombia, families who carry the Alzheimer's gene mutation

have played their part in advancing knowledge of the disease.

When Flor's father died of Alzheimer's, aged 52,

the family donated his brain to be studied.

IN SPANISH:

Dr Francisco Lopera has built up a bank of 200 brains

donated from patients.

Until recently,

these brains have been his only way of investigating the disease.

IN SPANISH:

For most of the last 100 years,

doctors could only research the disease by doing brain autopsies.

This limited their understanding to the later stages of Alzheimer's.

Now, new scanning technology has changed all that.

It allows scientists to identify what's happening in the brains

of sufferers in the earlier stages of the disease.

Tom Jarvis is helping scientists reveal

the effectiveness of this new technology.

The 72-year-old former railway engineer from Derby

has come to London with his wife, Hazel.

He has a very rare form of Alzheimer's

which was misdiagnosed for two years.

In the very first place,

I was being treated for having a lazy eye which affected my reading.

He was prescribed vari-focals

and they seemed to make things worse.

And yes, you went to see the ophthalmologist

and you had an eye operation, didn't you,

in February 2013?

And that didn't work. And then he was discharged.

His doctors were unable to identify that Tom was having problems

not in his eyes but in his brain.

But fortunately for him, he was referred to Professor Nick Fox.

Normally, Alzheimer's disease starts with problems with memory

and that's the disease affecting the hippocampus early on,

but it doesn't always have to.

The disease can start at the back of the brain,

areas to do with visual processing, and then it is even more

likely that people have trouble getting a diagnosis.

Professor Fox has invented a technique comparing

a sequence of yearly scans which track the progress of the disease.

He was able to give Tom a correct diagnosis.

What we see is how tightly packed this is here,

but you might be able to make out that the back, there's a little

bit more space that you can see there than you might have expected.

That's in exactly the areas that you've been experiencing problems.

And that's the area which is to do with

processing of visual information, also related to calculation

and complex hand movements.

That is last year and this is the change over one year.

And that's the second scan, first, second.

What you see is this fluid-filled space here increasing as we go

from the first to the second and that is because

there is brain loss here at the back,

which reflects the progressive nature of this problem.

The scans are essential in understanding the early

stages of the disease.

The new technology has allowed us to see

a window of maybe a decade before those symptoms.

And that's where the new trials are starting to target.

We hope to have trials of promising treatments when people are well

and when they have the most, in terms of brain cells, to save.

That's the window of opportunity.

-Good, have a seat.

-Thank you.

Professor Fox and his team want to find out how the disease

affects the functioning of Tom's visual processing.

First, I'd like to test your vision if that's all right?

Can you tell me what letter that is?

The letters have been fragmented to find out

if Tom can identify a shape from a complex visual image.

My guess is it's an F.

Good guess.

Looks like an F again.

Looks like an F?

If I trace it out with my finger, does that help?

Ah, is it an R? No?

It's like an R. It's a P.

Oh, right.

The tests show that his brain's ability to process images

is deteriorating.

My brain doesn't compute what they are.

It's a sort of a jumble, it's not, it doesn't mean anything, really.

It's just little black squares joined together.

Next, I'm going to say three words

and if you could just repeat them back to me

and then remember them, because I'll ask you again in a moment, OK?

Bus, table, rose.

Bus, table, rose.

The team investigates

how other parts of Tom's brain are being affected,

especially those more commonly associated with Alzheimer's,

like memory.

What were the three words that I asked you to say?

The last one was rose.

That's right.

I can't remember.

The tests show that the disease is spreading.

Scientists have, until now, been using scans to understand how

amyloid plaque affects the various stages of the disease,

but the new techniques allow them to investigate the other culprit - tau.

So Tom undergoes a lumbar puncture,

which draws out spinal fluid

containing tau from the brain.

The lumbar puncture today will tell us how much tau is elevated and that

will tell us how much tau is being released from those brain cells.

I would guess it might be two or three times what the

normal range might be.

How does that feel to you at the moment?

The lumbar puncture shows the levels of tau,

but Professor Fox's team want to identify exactly where it is

in the brain.

They use cutting-edge scanning to do so.

First, a radioactive liquid containing a marker

is injected before scanning.

Three, two, one - go!

What's being injected is a tracer

that has a radioactive probe attached to it.

The tracer will circulate round the body, enter into the brain and

will attach if there is tau there and therefore it gets stuck there.

For the first time, images are revealing which

parts of the brain are affected by the tau tangles.

So what we see here in these bright colours,

those are areas where the tracer has stuck to the tau protein.

And the bright colour is that radioactivity,

which is how we detect it.

And what we're seeing here in this area, which is the

hippocampus which is critical for memory, we see just full of tau.

And we think that tau is in some ways more closely related

to the damage that is critical in Alzheimer's disease

than its partner in crime, amyloid.

This research technology is bringing astonishing new insights into how

the disease builds up in the brain, and then destroys its functions.

But new research is also revealing that there are changes

we can make in our daily lives which could significantly reduce

the chances of developing Alzheimer's.

Professor Matthew Walker from University of California

is investigating how plenty of deep sleep could

preserve our memories and help fight off the disease.

So, what we've known for some time now is that as we get older,

our learning and memory abilities start to decline,

but what we've also known is that a physiological signature

of ageing is that your sleep starts to get worse.

And so, based on how important sleep is

for effectively hitting the save button on new memories,

we wanted to explore whether that sleep deterioration

in ageing and in Alzheimer's disease is not simply a symptom

of the process, but perhaps a cause of the underlying memory problems.

His work is based on research into the brains of mice,

which shows that during deep sleep, amyloid is cleared from the brain,

while too little deep sleep may cause it to build up.

Professor Maiken Nedergaard has made an astonishing new discovery

which explains why this happens.

Her scans of mouse brains found small gaps between neurons.

These expand by up to 60% when the mice are asleep.

The gaps allow spinal fluid to sweep through the brain,

clearing out the waste products.

As soon as the animal fell to sleep, it was turned on,

almost like a dishwasher, where these gaps open up and suddenly

you see the fluid fluxes

that enter the brain and flushing all the toxic waste product

the brain produce when we are awake out when we sleep.

The left scan is a mouse brain when awake, but on the right,

we see the spinal fluid washing through when asleep.

Professor Nedergaard has named this the glymphatic system.

Here we see a sleeping rodent brain

and we can see the glymphatic system working.

So, you see the fluid flowing into the brain

and literally washing beta amyloid away.

The same thing happens in humans.

During the day, amyloid builds up in our brains

and if we don't have regular deep sleep, it starts to accumulate.

And we need eight hours of good sleep to actively clean up

the amyloid that build up when we are awake.

It's clear that the amyloids start to aggregate very early in life

and if we don't have the long, eight-hours continuous sleep

when we are young, when we are middle aged,

we risk that amyloid will build up when we're older.

Sleep seems to play a crucial role

in preventing the accumulation of amyloid.

So Professor Walker is

trying to find ways of artificially inducing deep sleep.

Success could slow the development of disease

and strengthen our memories.

To start with, he's experimenting with younger brains.

Chris is a research graduate.

-Good to meet you.

-Good to be here.

First, he is asked to memorise connections between faces and words.

OK, Chris.

So, what we're going to do is a learning and memory test.

So, what you'll see on the screen in front of you are some faces

and underneath there will be a word.

And your job is to try to connect those two things,

to learn that those two things are associated together.

And then later, we'll come back and test you.

Professor Walker also wants to find out whether a newly-developed

magnetic brain stimulator can enhance sleep and memory.

First, Chris's brain is mapped

to make sure the magnetic pulses are correctly targeted.

Then two magnets are placed over his head.

So, the machine itself is going to insert pulses

of magnetism into the brain and stimulate those brain cells

and the pathways that we know are critical for sleep and memory.

So, what we're trying to essentially do is prime

or sort of grease the pathway, as it were,

with electrical stimulation.

And as a consequence, enhance the sleep and memory benefit.

Electrodes are fitted onto Chris' head

so that Professor Walker can observe how much deep sleep he's getting.

The sleep stimulator seems to be working.

The monitor shows sharp movements in Chris' brain waves

which are the signatures of deep sleep and memory processing.

Now Professor Walker needs to know

whether this extra sleep has strengthened Chris' memory.

Now we're just going to perform the memory test.

Chris has to recognise faces from the earlier test.

If he remembers the face, or it seems to be familiar,

he has to click on it.

Then he has to recall the word which related to it.

The initial results of this experiment are very encouraging.

So what we're finding is that you need sleep after learning

to essentially cement those new memories.

And as a consequence, when people wake up the following morning,

those memories are more robust.

People have forgotten far less information across sleep

than they would if they'd remained awake.

It will be many years before the sleep stimulator is on the market.

By then, Professor Walker hopes enhancing deep sleep will be

a major weapon in the fight against Alzheimer's.

Can we, in those people who are fighting that battle with

Alzheimer's disease, improve sleep quality and try to bring back

online some degree of learning and memory function?

That's the first goal.

The second goal, however, is to regress the time-line back.

In other words, can we find ways to start to improve

sleep in people in their thirties, forties and fifties, to see if

we can actually move from a model of treatment to a model of prevention?

Until then, the research is beginning to show that

regular deep sleep throughout our lifetime

could lower our risk of developing the disease.

Sleeping is just one way we could change our lifestyle to

stave off Alzheimer's, but it's increasingly clear that what

we eat plays a role as well.

There is evidence that a diet should be rich in fish,

vegetables and olive oil,

but it's more important to have one main goal in mind.

In different studies, researchers have looked at different forms

of this diet, but what they all have in common is the ability

to protect the heart.

So, if there is a diet out there that is protective of the heart,

it may have that additional benefit of promoting

healthy ageing and reducing the risk of Alzheimer's disease.

Once the disease has started to develop,

choosing what to eat becomes much more complex.

Professor Richard Wurtman is a world expert on how nutrition

affects the development of the brain.

In a series of studies here in Boston, he started

looking at why people with Alzheimer's had so few synapses.

What the first slide shows is the part of a neuron, the part

of a neurocell that's involved in making new synapses and the

specific part are these little white dots you see running along the side.

Each one of those dots is very likely to become a new synapse.

Now, this is a similar part of the brain and what you can see is,

in Alzheimer's disease, you have many fewer of these white dots

and so you're producing many fewer synapses.

It had been found that the disease reduced existing synapses,

but that it also stopped new ones developing to replace them.

Professor Wurtman wanted to find out why this happened

and examined the role that nutrients, which help create

these new synapses, played in the development of the disease.

Alzheimer's patients quite generally have difficulty in smelling food

and in tasting food,

And they also have difficulty in absorbing most nutrients

and in producing some of the nutrients in their own livers.

So, they start out with nutritional deficiencies.

His studies have discovered three nutrients which are essential

for making new synapses to replace those destroyed by the disease.

They are choline,

uridine,

and docosahexaenoic acid, known as DHA.

Here you see an excellent source of DHA in the diet.

This is a fish. It happens to be a salmon.

Patients with Alzheimer's disease do have some

difficulty in absorbing DHA.

Choline is present in abundant quantities within egg yolks, OK?

And if you have three eggs and three egg yolks,

then you're doing pretty well in terms of getting choline.

And again, Alzheimer's patients have some difficulty in absorbing it.

The third, uridine, can't be obtained from food,

but is normally created in the liver,

something people with Alzheimer's have difficulty doing.

The professor's work reveals that an Alzheimer's brain could benefit

if more of these nutrients could be absorbed to grow new synapses.

A new supplement has been created

which provides doses of these nutrients.

There have been two large-scale clinical trials

and in both trials it significantly improved memory function.

It also improved the connectedness between different

parts of the brain and that's critically important in people

with early Alzheimer's disease.

Although the trials showed the supplement helps early-stage

Alzheimer's patients,

people who have the more advanced stage of the disease do not benefit.

Across the world, researchers are searching for ways

not just of renewing the synapses,

but of improving the functioning of the brain in general.

Millions of people practice cognitive exercises,

known as brain-training.

Cognitive exercises are probably helpful for all of us.

It's good for us to keep our brains working and we know that

if you engage in a lot of cognitive activity,

it can help to reduce your risk

of developing cognitive impairment and dementia.

However, we've systematically reviewed the evidence,

the research evidence, about brain-training people with

Alzheimer's disease and, unfortunately, we haven't been

able to find any strong evidence that this is beneficial.

Alzheimer's patients need to concentrate on much more

frequent and routine ways of training their brains.

This could help people like Gareth Hulston,

who lives in North Wales.

He's 68 years old

and was diagnosed with Alzheimer's a year ago.

He's surrounded by reminders of a rich and full life,

but gradually, he's forgetting their significance.

His daughter, Virginia, is doing her best to stimulate his memory,

asking him what he's been up to.

What did you do on Saturday, Dad?

Hang on....

What did I do on Saturday?

Can't remember.

But fortunately for Gareth, he's been chosen to take part

in an important new trial run by Professor Linda Clare.

She hopes it will teach him

to focus on improving everyday tasks which are causing him problems

and, in the process, engage his brain many times every day.

What we try to do is get them to think with us

about all of the different steps involved in the activity

that they want to manage better.

And then to really engage their brain in

figuring out where the difficulties are coming in that process.

And we work with them to develop strategies that they can apply

at the different stages so that they may manage that activity better.

Therapist Sue Evans is visiting Gareth to find out

which everyday skills he wants to improve.

-Hi, Sue. How are you? Come on in.

-Nice to see you, Gareth.

At the moment, he's having problems with cooking.

Right. Are these the eggs, are they?

Watch, don't, don't. You need a cloth, they're hot.

How are you today, then, Gareth?

Not too bad. I keep going, don't I?

-Take a pew.

-OK, I will do.

I'm just going to sit and watch and listen to you

and Virginia for a bit, OK?

Sue observes him for 30 minutes to see how the disease is

affecting his planning and concentration.

What are you going to have for dinner tonight?

Haven't a clue, not a clue.

You not planned anything?

No, I might go to see Bill.

Can you smell anything, Dad?

No, my smell's gone, hasn't it? I can't smell at all.

What did you put on before?

Oh, I put some eggs on to boil.

Yeah, so what's burning?

Do you want me to go and have a look?

I would, I'd go and have a look.

Just in time.

What's burning, Dad?

Hang on, what's in the oven?

Oh, you're joking, Virginia.

Oh, they're ruined.

They're absolutely burnt to a cinder.

Sue wants to help Gareth work out a series of steps which

will become part of his routine and stop him burning his meals.

-So you told me there was a pizza in the fridge.

-Yes.

So, do you want to get it out?

Yeah, all right.

Let's have a look.

So, if you're going to cook this one, let's have a look and see.

What would you find out?

Eight to ten minutes here.

Yeah? So, come over here and write that information down, yeah?

So you'd write pizza.

OK. And what time is it going to be ready?

And then the next thing I need you to do is set the timer.

So the reason I'm getting you to write all this down

is that I'm making you think about it more, which one -

it means it's gone through more processes in your brain,

because you've had to read it, think about it and then write it.

But also, this also works as a back up.

She hopes that by thinking through these steps several times a day,

Gareth's planning abilities will improve.

Sue also wants to work on his semantic memory -

his ability to remember facts.

His challenge is to remember the names of his grandchildren.

Who's that?

I cannot remember.

-Rachel.

-Rachel?

So, Rachel.

She's the boss.

She's the boss, that doesn't surprise me.

Sue has one simple recommendation.

-Maybe that's a project to do to get an up-to-date photo of her.

-Yeah.

By having that photo in your hand,

you're able to build up more of an image of them

and then hopefully what we'd be aiming for is that you'd be able to

build up that image of them without needing the photo in your hand.

Sue returns every week to ensure Gareth is incorporating these

techniques into his daily routine.

Three months later, now it's time for Sue to find out

whether Gareth's planning abilities and memory have improved.

-Hiya, Sue!

-Hi, Gareth.

-Come on in.

-How are you? Nice to see you.

First up, can he remember not to burn his food?

OK, Gareth, so you're going to show me how you're doing

the cooking now, now you've been using the strategies for a bit?

He's been putting them in action, helped by a new hi-tech oven.

Right, all you do then is get that from there.

Now cooking instructions, 20 to 25 minutes.

Gareth has become so good at planning this task that he

no longer needs the white board.

He just uses the timer as a prompt.

He sets it for 20 minutes.

Right. And this is what I do, as a rule.

This is where I usually put it, on there, and I usually take this seat.

So, Gareth, have you managed to get an up-to-date picture of Rachel?

That was one of the jobs I gave you last time, wasn't it?

Yes, I got the photograph. There she is.

There she is. Oh, that's a nice one.

-At her right age.

-Yeah.

-Much better.

TIMER RINGS

Oh!

Go on, then.

The plan has worked.

Gareth appears to have retrained his brain to connect

the sound of the timer with the cooking.

Right.

-So, this turns itself off too, then?

-Yeah.

-Yeah?

So, no risk of burning any more.

They look good. So they're done?

They are absolutely ready, yeah.

Yeah? Excellent.

And now for the ultimate test.

Has his training improved his semantic memory?

-Hiya, Rache!

-Hiya, Grandad.

Come on in.

She's my grand-daughter, my Rachey-wachey.

HE LAUGHS HAPPILY

Oh, I'll never give in. I'll never ever give in.

Might put me in my box, but I'll never...I'll never give in.

I do believe I've improved tremendously.

We'll go from this side across, yeah, and you can tell me

who everyone is now.

-That's Nathan.

-That's Nathan.

-Holly...

These simple steps help people like Gareth to manage their lives better,

but they can also improve the functioning of their brains.

Dwayney, the decorator.

People who had had the cognitive rehabilitation programme

showed greater activation when they were doing a memory task

in certain brain areas, particularly the bilateral frontal areas.

Whereas people in the control group who hadn't had the programme

showed reduced activation in those areas.

We tentatively suggested that this might reflect

some improvement in functioning in those areas of the brain.

And, of course, that relates very much

to the way the intervention works,

where we're asking people to think about strategies

and engage in particular strategies to manage everyday activities

that help them to manage those better.

Simple lifestyle changes seem to re-train

and strengthen the functioning of the brain in people

who are suffering from early-stage Alzheimer's.

But in this new era of research,

there is a much more dramatic ambition.

This is a really exciting time for patients with Alzheimer's disease

because we're starting to see trials that are starting

to show evidence of efficacy.

And I think there's a lot of excitement now,

because there's some new data that looks very promising.

This new data has launched worldwide drugs trials.

One is taking place in Colombia.

Here, the Alzheimer's gene mutation, which afflicts families like Flor's,

offers a rare opportunity for research.

In these families, the gene causes the amyloid to start building up

in people as young as 30 and symptoms appear at 45,

as has happened with Flor's sister Olga.

Researchers want to find out if a drug can interrupt its progress.

The prospect that Flor might have the early stages of the disease

makes her a valuable participant.

Every two weeks, Flor goes for physical and cognitive tests

and she's given an injection which could be the brand-new

Alzheimer's drug crenezumab or it could be a placebo.

Crenezumab is an anti-amyloid treatment that had several

characteristics we thought were especially

suitable for prevention trials.

It seemed to attack different forms of amyloid

and there was a suggestion that it could reduce amyloid and

might have a role if it was started in people at an earlier stage.

IN SPANISH:

For Dr Lopera, the trial offers a new future.

IN SPANISH:

Five one way.

Meanwhile, 4,000km away in New England, Neil Corkery

is part of another trial which already has promising early results.

Ten years ago, the 75-year-old former head teacher

and local politician first noticed he had the symptoms of Alzheimer's.

We were going to an event for one of the state officials who was

leaving and the Governor was supposed to speak.

So he was late and they said, "Would you say a few words?"

And I said, "Sure, I'll be glad to." And I got up and I started

and I was fine and then I got to a point,

I blanked out on a word and that's when I went for some tests.

Doctors scanned his brain and diagnosed him with Alzheimer's.

The news was devastating for Neil and his wife, Maureen.

Initially - I've never told Maureen this - I did things like put

music on that they could use when I, when they have the funeral.

Like Glen...

who's, Glen, Glen Campbell, who's a noted singer.

He has, he's got a song that they had him sing

and it's just a beautiful song.

# I'm still here but yet I'm gone... #

So I was kind of romancing the kind of negative side of it,

I guess, but I've been through that, I hope, you know.

I think we both felt depressed after the diagnosis,

because you know there's no cure.

The future for the Corkerys looked bleak.

Luckily for them,

tests had just started on a new drug to fight Alzheimer's.

In 2014, the man behind the drug was on the way to his office

when his chief executive called with the results of its Phase 1 trial.

I was driving down the street.

When he started to tell me the results, I had to pull over,

because they were so exciting.

And he was telling me

that the drug had unexpectedly shown an effect on cognitive decline.

Our drug was slowing cognitive decline in patients

with Alzheimer's disease.

I'm glad I pulled over, because I was so excited

and I...I was smiling from ear to ear.

The drug, called aducanumab, was what everyone had been hoping for.

The results sent share prices

in the pharmaceutical company Biogen rocketing.

The trial showed that the drug was having a remarkable

impact on the brains of people with Alzheimer's.

So what we're looking at here is a slice of a human brain

in the living patient with Alzheimer's disease.

And what we see here is a red colour and yellow.

And the red colour shows where the amyloid plaques are in the brain.

And the more red it is, the more plaque there is.

This shows what happens after treatment with our drug.

We see that the redness has been reduced and that

means that the amyloid plaques have been removed from this brain.

The scan on the right shows just how effective

the drug has been in removing amyloid plaque from the brain,

but a major complication has now been discovered.

The main side effect that we saw with this drug in the clinical trial

was a thing called ARIA.

And what we see here is a picture of ARIA.

And what we see is a whiteness here in this...in the brain,

which signifies oedema or swelling in the brain.

And that's not a good thing,

because the brain is in an enclosed space

and swelling can be harmful to patients.

Researchers hope to stop the swelling by initially giving

a low dose of the drug and then gradually increasing it.

Extensive phase III trials

are being rolled out across Europe and America.

There is even a possibility that the drug will combat the tau tangles,

that other great hallmark of Alzheimer's disease.

But the results won't be known for four years.

-How are you today?

-Very good.

Neil Corkery is now participating in the trial.

He doesn't know whether he's on a placebo or the drug,

but taking part has made all the difference.

Recently, he was even able to speak off the cuff at his son's wedding.

I was like my old self. I really...

Yeah, it was extemporaneous

and there wasn't any rehearsal or written words or anything.

He just got up and he spoke and it flowed.

It was nice, it was really nice.

She's been by me all the time.

She's, she...

She knows what's right.

It has made me feel better, yeah, absolutely.

I mean, I don't know what else to attribute it to,

you know, unless it's a miracle I'm unaware of.

Neil is convinced he is benefiting from the drug trial,

although it could be the famous placebo effect.

TANGO MUSIC PLAYS

For Flor, who's taking part in the Colombia trial,

the curse of Alzheimer's which has hung over her family for

so long could at last be lifted.

IN SPANISH:

The first results from this trial

will also become available in around four years.

These trials, and others around the world,

are bringing hope to millions.

We believe it marks the dawn of a new era

in Alzheimer's-prevention research.

And that gives us now the opportunity to rapidly evaluate

the range of promising but unproven prevention therapies.

And maybe, just maybe, find and support the approval

of effective prevention therapies within the next ten years.

There's a lot of hope for Alzheimer's patients.

We're in the final stages of clinical trials with a drug

that looks very promising.

We can remove the amyloid from the brains of patients

with Alzheimer's disease.

My hope is that if we treat early enough, we may stave off Alzheimer's

disease completely and we may never have to worry about it again.

Up until now, a treatment for Alzheimer's has eluded scientists.

We can all make changes to our lifestyles and help

stave off the disease, like eating well and getting enough sleep.

But innovative scanning techniques and a new generation of drugs

are giving people with Alzheimer's, and those at risk of developing it,

new hope that they will hold on to their memories and their lives.

# I'm still here but yet I'm gone

# I don't play guitar or sing my song

# It never defined who I am

# The man that loves you till the end

# You're the last person I will love

# You're the last face I will recall

# And best of all

# I'm not gonna miss you

# I'm not gonna miss you

# I'm never gonna hold you like I did

# Or say "I love you" to the kids

# You're never gonna see it in my eyes. #