0:00:04 > 0:00:06Our memories make us who we are,
0:00:06 > 0:00:11but it's thought 30 million people today are losing them
0:00:11 > 0:00:14due to the curse of our time - Alzheimer's.
0:00:15 > 0:00:19Despite their best efforts, scientists have, until now,
0:00:19 > 0:00:21failed to stop this disease,
0:00:21 > 0:00:26but the latest generation of research has unleashed a new front
0:00:26 > 0:00:30in the war against this devastating disease.
0:00:30 > 0:00:31This is a very exciting time.
0:00:31 > 0:00:34There's a new window of opportunity.
0:00:34 > 0:00:36New technology allows us to see
0:00:36 > 0:00:39the signs of Alzheimer's disease earlier than we ever could before.
0:00:39 > 0:00:44Today, a series of drugs trials have been launched across the world,
0:00:44 > 0:00:48drugs that are targeting the disease in its early stage.
0:00:48 > 0:00:53We believe that this trial marks the dawn of a new era
0:00:53 > 0:00:55in Alzheimer's prevention research.
0:00:56 > 0:00:59Initial results are exciting.
0:00:59 > 0:01:01They reveal that there are drugs which are reducing
0:01:01 > 0:01:04signs of the disease.
0:01:04 > 0:01:09Scientists are confident that a cure is tantalisingly close.
0:01:10 > 0:01:14If we treat early enough, we may stave off Alzheimer's disease
0:01:14 > 0:01:17completely and we may never have to worry about it again.
0:01:17 > 0:01:23Horizon asks - can we end the curse of Alzheimer's forever?
0:01:33 > 0:01:35"I won't need a shopping list this week. I'll just...
0:01:35 > 0:01:38"I'll remember that." And then you get halfway round a supermarket
0:01:38 > 0:01:40and you think, "What did I have on that list?
0:01:40 > 0:01:43"What did I have to get? I know there's something."
0:01:43 > 0:01:44"Why have I gone upstairs?
0:01:44 > 0:01:46"Have I come up for something, have I left it behind?
0:01:46 > 0:01:49"Was it not upstairs in the first place?"
0:01:49 > 0:01:53I remember faces and I'm still good at that, but not names.
0:01:54 > 0:01:58As we grow old, we all start to forget things,
0:01:58 > 0:02:01but in the back of our minds, there hangs a terrible fear.
0:02:03 > 0:02:05My mother has Alzheimer's,
0:02:05 > 0:02:09so if you've had a day of forgetting a few things, you do get
0:02:09 > 0:02:12gripped with a sort of panic that this is it, this is the beginning.
0:02:12 > 0:02:18About every four minutes, somebody new is told they have the disease.
0:02:18 > 0:02:22The panic grows as the epidemic sweeps across the globe.
0:02:22 > 0:02:26Alzheimer's disease is now one of the most feared medical
0:02:26 > 0:02:28conditions, particularly in people over the age of 45.
0:02:28 > 0:02:32And that's understandable, because we now, tragically,
0:02:32 > 0:02:34most of us know somebody
0:02:34 > 0:02:36who has got Alzheimer's disease.
0:02:38 > 0:02:42This degenerative brain disease leads to a loss of memory
0:02:42 > 0:02:46and eventually the loss of most other brain functions.
0:02:51 > 0:02:54Horizon meets five ordinary people
0:02:54 > 0:02:57whose lives are overshadowed by Alzheimer's.
0:02:57 > 0:03:00Each one in their own way is making an extraordinary
0:03:00 > 0:03:05contribution in the worldwide war against the disease.
0:03:05 > 0:03:07Can you tell me what letter that is?
0:03:07 > 0:03:11In London, Tom has a rare form of Alzheimer's
0:03:11 > 0:03:12which baffled his doctors.
0:03:12 > 0:03:15My brain doesn't compute what they are.
0:03:15 > 0:03:17It's a sort of a jumble.
0:03:17 > 0:03:19It's not, it doesn't mean anything.
0:03:19 > 0:03:24New scanning technology is revealing what's happening in his brain.
0:03:26 > 0:03:30In Phoenix, Arizona, Jamie lives in fear.
0:03:30 > 0:03:32My great-grandmother had Alzheimer's disease.
0:03:32 > 0:03:34Her daughter had Alzheimer's
0:03:34 > 0:03:39and then my two great-uncles also died of Alzheimer's.
0:03:39 > 0:03:42And then my father just recently died a couple of years ago
0:03:42 > 0:03:43with Alzheimer's.
0:03:43 > 0:03:46The gene she carries dramatically increases her
0:03:46 > 0:03:48risk of developing Alzheimer's.
0:03:48 > 0:03:52It's the target of a new generation of research.
0:03:52 > 0:03:56Oh, they're ruined. They're absolutely burnt to a cinder.
0:03:58 > 0:04:02In North Wales, the disease means Gareth is retraining his brain
0:04:02 > 0:04:05so that he can continue to live independently.
0:04:05 > 0:04:07IN SPANISH:
0:04:09 > 0:04:13In Columbia, Flor's family carries a rare genetic mutation
0:04:13 > 0:04:16which causes Alzheimer's at a very early age.
0:04:16 > 0:04:18Her sister already has it.
0:04:22 > 0:04:26New research could prevent Flor from ever developing the disease.
0:04:28 > 0:04:31And in New England, Neil believes a breakthrough drug
0:04:31 > 0:04:33has transformed his life.
0:04:35 > 0:04:38I mean, I don't know what else to attribute it to,
0:04:38 > 0:04:41you know, unless there's a miracle I'm unaware of.
0:04:41 > 0:04:44All these people face a threat of Alzheimer's.
0:04:44 > 0:04:49The disease has long been hard to study, but scientists have recently
0:04:49 > 0:04:53made great advances in understanding how it affects the brain.
0:05:02 > 0:05:07Inside a healthy brain, there are billions of cells called neurons.
0:05:07 > 0:05:10Our thoughts and emotions are transmitted between them
0:05:10 > 0:05:12via connecting synapses.
0:05:13 > 0:05:15But in an Alzheimer's brain,
0:05:15 > 0:05:19a protein starts to build up in the synapses,
0:05:19 > 0:05:23blocking the electrical signals and disrupting the flow of information.
0:05:25 > 0:05:28This protein is called amyloid beta.
0:05:28 > 0:05:32As the disease progresses, it continues to accumulate
0:05:32 > 0:05:36and creates huge sticky clumps called plaque.
0:05:36 > 0:05:40Even at this stage, there can be no apparent symptoms.
0:05:40 > 0:05:43For some reason, the brain can tolerate a certain
0:05:43 > 0:05:47level of amyloid for a number of years, possibly many years.
0:05:47 > 0:05:53And it's as though the amyloid, which may be driving the process,
0:05:53 > 0:05:57needs something else to then go on to produce that
0:05:57 > 0:06:01destruction of brain cells that causes the symptoms
0:06:01 > 0:06:04and the devastation at the individual level.
0:06:05 > 0:06:09The culprit is thought to be another protein inside the brain cell.
0:06:09 > 0:06:11It's called tau.
0:06:13 > 0:06:17Tau normally functions in brain cells like the railroad track
0:06:17 > 0:06:20to take critical nutrients
0:06:20 > 0:06:22up and down brain cells.
0:06:22 > 0:06:25As these tracks disintegrate,
0:06:25 > 0:06:29the supply of nutrients to the neuron is stopped.
0:06:29 > 0:06:31The tau then forms into tangles
0:06:31 > 0:06:34which kills the cell.
0:06:34 > 0:06:37It may take 15 years from the onset of the disease
0:06:37 > 0:06:40for the tau to start creating tangles
0:06:40 > 0:06:44and only then do the symptoms of the disease start to appear.
0:06:46 > 0:06:49The new era of research is focusing on treating
0:06:49 > 0:06:52the disease in its earlier stages.
0:06:53 > 0:06:57This work is happening in some surprising places.
0:07:03 > 0:07:07Medellin, a city dominated by the Andes mountains of Colombia
0:07:07 > 0:07:09in South America.
0:07:09 > 0:07:15It's been notorious for clandestine drug smuggling and kidnappings,
0:07:15 > 0:07:19but its people hold a darker, older secret.
0:07:20 > 0:07:22At its heart are a group of families
0:07:22 > 0:07:27and they may hold the key to the future of Alzheimer's research.
0:07:29 > 0:07:32IN SPANISH:
0:07:34 > 0:07:39Flor lives with her daughter Danielle and her sister, Olga.
0:07:39 > 0:07:45Olga is only 47, but in 2013 she was diagnosed with Alzheimer's.
0:07:55 > 0:07:59Olga is not the only one in Flor's family who has developed
0:07:59 > 0:08:01Alzheimer's in their forties.
0:08:17 > 0:08:22This family carries a gene mutation which can be traced back to
0:08:22 > 0:08:26an ancestor who arrived from Spain 400 years ago.
0:08:28 > 0:08:32Carriers of this gene start to develop the first
0:08:32 > 0:08:35symptoms as early as 45.
0:08:35 > 0:08:38It used to be thought they'd been cursed by a wicked witch
0:08:38 > 0:08:43but - in the 21st century - their plight has captured the attention
0:08:43 > 0:08:48of one of the leading researchers in the field, Dr Eric Reiman.
0:08:49 > 0:08:53Meeting almost a thousand family members for the very first
0:08:53 > 0:08:57time was a life-changing experience.
0:08:57 > 0:09:02To see what those families have gone through,
0:09:02 > 0:09:05not only the clinically-affected person
0:09:05 > 0:09:10but the entire family who has rallied around their loved one
0:09:10 > 0:09:15to provide care, and the impact that it has had on their lives.
0:09:15 > 0:09:17It underscored the urgency we should all
0:09:17 > 0:09:19have in the fight against Alzheimer's disease.
0:09:26 > 0:09:30Flor and her family live with the disease every day.
0:09:30 > 0:09:34Flor's sister Olga has to be looked after by her 70-year-old mother.
0:09:49 > 0:09:52The disease forced Olga to give up work two years ago.
0:10:38 > 0:10:40THEY LAUGH
0:10:54 > 0:10:59For centuries, these families in Colombia have suffered helplessly
0:10:59 > 0:11:02from the ravages of the gene mutation,
0:11:02 > 0:11:07but now they are at the forefront of the new era of scientific research.
0:11:07 > 0:11:11We have this wonderful relationship with families in Colombia
0:11:11 > 0:11:14sharing this common interest.
0:11:14 > 0:11:18We all find it a privilege to think about how we can advance
0:11:18 > 0:11:21the fight against Alzheimer's disease in a way that
0:11:21 > 0:11:23actually helps these families along the way.
0:11:25 > 0:11:29In Colombia, Dr Reiman and the Banner Institute are partners
0:11:29 > 0:11:31in a massive new drugs trial,
0:11:31 > 0:11:35the first-ever major Alzheimer's prevention trial in the country.
0:11:35 > 0:11:38He hopes it'll stop any more members of these
0:11:38 > 0:11:41families from developing the disease.
0:11:41 > 0:11:45Unfortunately, it'll be too late to help Olga.
0:11:45 > 0:11:48IN SPANISH:
0:11:54 > 0:11:59Most of the time, Olga is unaware of the severity of her condition,
0:11:59 > 0:12:02but occasionally she realises what is happening to her.
0:12:05 > 0:12:09Her family is determined to protect her from the horrors of the disease.
0:12:09 > 0:12:12They want to wrap her in their love and support.
0:12:19 > 0:12:22SHE SOBS
0:12:41 > 0:12:45The genetic mutation which afflicts the families in Colombia
0:12:45 > 0:12:47offers a rare opportunity for research
0:12:47 > 0:12:50into the earlier stages of the disease.
0:12:50 > 0:12:54But there is another more common gene which is
0:12:54 > 0:12:57also attracting the attention of the Alzheimer's researchers.
0:12:57 > 0:13:00It's called APOE4.
0:13:00 > 0:13:03Carriers have an increased risk of developing the disease
0:13:03 > 0:13:06later in life, in their seventies.
0:13:11 > 0:13:14One of the largest centres for the genetic
0:13:14 > 0:13:17investigation into the disease is in Phoenix, Arizona.
0:13:19 > 0:13:22Scientists here are searching for people who carry
0:13:22 > 0:13:24this more common gene.
0:13:28 > 0:13:32Jamie Tyrone is a 55-year-old retired nurse.
0:13:32 > 0:13:35She has known about the disease most of her life.
0:13:35 > 0:13:40I have a very, very strong family history of Alzheimer's disease.
0:13:40 > 0:13:44My first memory was when I was ten years old and I visited
0:13:44 > 0:13:49my great-grandmother, who was my first exposure to Alzheimer's.
0:13:49 > 0:13:51She was in a wheelchair and had no cognition
0:13:51 > 0:13:54and her eyes were very empty.
0:13:54 > 0:13:58The next person to get Alzheimer's was her daughter,
0:13:58 > 0:14:02my grandmother, and here's a picture of her.
0:14:02 > 0:14:06And then her two brothers, my two great-uncles,
0:14:06 > 0:14:08also died of Alzheimer's.
0:14:08 > 0:14:12And then my father just recently died a couple of years ago
0:14:12 > 0:14:13with Alzheimer's.
0:14:13 > 0:14:18So, you kind of have the whole picture right here with my family.
0:14:18 > 0:14:20Because of her family history,
0:14:20 > 0:14:25six years ago Jamie decided to find out which genes she carried.
0:14:25 > 0:14:28She sent off a sample of her DNA to be tested.
0:14:29 > 0:14:34Dr Eric Reiman's institute is focusing on the APOE4 gene,
0:14:34 > 0:14:38because it's so closely connected to the way the disease progresses.
0:14:38 > 0:14:43APOE4 has a number of effects on the brain, several of which could
0:14:43 > 0:14:46contribute to the development of Alzheimer's disease.
0:14:46 > 0:14:50The leading theory is that it leads to the development of Alzheimer's
0:14:50 > 0:14:55disease by reducing our ability to get rid of amyloid in the brain.
0:14:55 > 0:15:00His colleague, Dr Jessica Langbaum, has calculated the increased
0:15:00 > 0:15:05risk carriers of the APOE4 gene face of developing Alzheimer's.
0:15:05 > 0:15:09If you have two copies of the APOE4 gene, meaning you have one copy from
0:15:09 > 0:15:13Mum and one copy from Dad, your risk of developing Alzheimer's dementia
0:15:13 > 0:15:16in your lifetime is approximately 30 to 55%.
0:15:16 > 0:15:18If you have one copy of the APOE4 gene,
0:15:18 > 0:15:21your risk is approximately 20 to 25%.
0:15:21 > 0:15:23And if you have zero copies,
0:15:23 > 0:15:25your risk is approximately 10% to 15%.
0:15:25 > 0:15:29Not long after Jamie had sent off her DNA results,
0:15:29 > 0:15:31she received a reply.
0:15:31 > 0:15:38One night, I get a message in my e-mail,
0:15:38 > 0:15:42letting me know that my study results had come in.
0:15:42 > 0:15:49And what you can see here is that I have two copies of the APOE4 gene.
0:15:50 > 0:15:54Jamie's discovery that she carried a double copy of the gene,
0:15:54 > 0:15:58which massively increased her chance of getting the disease,
0:15:58 > 0:16:00drove her to despair.
0:16:00 > 0:16:05When I did find out my genetic status, I didn't have any genetic
0:16:05 > 0:16:11counselling at all and it was quite anxiety-provoking.
0:16:11 > 0:16:16I was told not to talk about it
0:16:16 > 0:16:18for fear that I'd be discriminated against.
0:16:18 > 0:16:22I didn't know what to do with this information and I didn't
0:16:22 > 0:16:28want my family to go through what we had previously had gone through.
0:16:28 > 0:16:31And it came to a part of my life
0:16:31 > 0:16:34where I had to decide what road to take.
0:16:34 > 0:16:36Do I take the dark road and...
0:16:38 > 0:16:41..possibly leave this earth?
0:16:41 > 0:16:44Or do I make meaning of it and take the bright road?
0:16:44 > 0:16:49The carriers of the gene do bear a terrible burden,
0:16:49 > 0:16:53but in the new era of research into the early stage of the disease,
0:16:53 > 0:16:55they have a special role to play.
0:16:55 > 0:16:58It's hard for researchers to identify
0:16:58 > 0:17:03participants for trials who may have the disease in its early stages,
0:17:03 > 0:17:05before the symptoms appear.
0:17:05 > 0:17:10But by working with APOE4 carriers, who are most likely to develop it,
0:17:10 > 0:17:13they dramatically increase their chances.
0:17:14 > 0:17:19Now the Banner Alzheimer's Institute has launched a drugs trial
0:17:19 > 0:17:22aimed at APOE4 carriers like Jamie.
0:17:22 > 0:17:24I'm very hopeful and excited about this trial.
0:17:24 > 0:17:26For the first time in history, we are
0:17:26 > 0:17:29now doing clinical trials on people who are at
0:17:29 > 0:17:33high risk for developing the signs and symptoms of Alzheimer's disease.
0:17:33 > 0:17:36Up until this point, people had to wait until they had memory
0:17:36 > 0:17:39and thinking problems or had a diagnosis,
0:17:39 > 0:17:42until they were given access to a clinical trial.
0:17:42 > 0:17:44Now we are giving clinical trials,
0:17:44 > 0:17:46offering clinical trials to people who are at high risk
0:17:46 > 0:17:49to see if we can stave off the onset of the disease.
0:17:49 > 0:17:51MUSIC: Got To Give It Up By Marvin Gaye
0:17:57 > 0:18:00Jamie is still too young to join the trial.
0:18:00 > 0:18:04However, the new research gives her great hope.
0:18:04 > 0:18:10When you look at the APOE status and the increased risk
0:18:10 > 0:18:13and be able to merge the two together, and really create
0:18:13 > 0:18:18studies specifically for us, is very exciting and very promising.
0:18:18 > 0:18:25And I hope in my lifetime that there will be a prevention or cure.
0:18:25 > 0:18:30I do not know, but if there is,
0:18:30 > 0:18:33I'm very touched to be a part of that process.
0:18:36 > 0:18:38- APPLAUSE - That's hard.
0:18:43 > 0:18:47The trials are accelerating new research into how to slow down
0:18:47 > 0:18:50and even prevent the disease.
0:18:50 > 0:18:54But the new era also aims to understand what is happening
0:18:54 > 0:18:56inside the brains of sufferers
0:18:56 > 0:19:00as the disease develops from its earlier stages.
0:19:00 > 0:19:03Until now, scientists have only been able to work with
0:19:03 > 0:19:07the brains of Alzheimer's patients once they have died.
0:19:13 > 0:19:18In Colombia, families who carry the Alzheimer's gene mutation
0:19:18 > 0:19:22have played their part in advancing knowledge of the disease.
0:19:22 > 0:19:26When Flor's father died of Alzheimer's, aged 52,
0:19:26 > 0:19:31the family donated his brain to be studied.
0:19:31 > 0:19:34IN SPANISH:
0:19:35 > 0:19:40Dr Francisco Lopera has built up a bank of 200 brains
0:19:40 > 0:19:41donated from patients.
0:19:41 > 0:19:43Until recently,
0:19:43 > 0:19:47these brains have been his only way of investigating the disease.
0:19:47 > 0:19:49IN SPANISH:
0:20:27 > 0:20:30For most of the last 100 years,
0:20:30 > 0:20:34doctors could only research the disease by doing brain autopsies.
0:20:34 > 0:20:40This limited their understanding to the later stages of Alzheimer's.
0:20:40 > 0:20:44Now, new scanning technology has changed all that.
0:20:44 > 0:20:47It allows scientists to identify what's happening in the brains
0:20:47 > 0:20:51of sufferers in the earlier stages of the disease.
0:20:52 > 0:20:55Tom Jarvis is helping scientists reveal
0:20:55 > 0:20:58the effectiveness of this new technology.
0:20:59 > 0:21:03The 72-year-old former railway engineer from Derby
0:21:03 > 0:21:06has come to London with his wife, Hazel.
0:21:06 > 0:21:09He has a very rare form of Alzheimer's
0:21:09 > 0:21:12which was misdiagnosed for two years.
0:21:12 > 0:21:14In the very first place,
0:21:14 > 0:21:19I was being treated for having a lazy eye which affected my reading.
0:21:19 > 0:21:22He was prescribed vari-focals
0:21:22 > 0:21:25and they seemed to make things worse.
0:21:25 > 0:21:29And yes, you went to see the ophthalmologist
0:21:29 > 0:21:32and you had an eye operation, didn't you,
0:21:32 > 0:21:34in February 2013?
0:21:34 > 0:21:37And that didn't work. And then he was discharged.
0:21:38 > 0:21:42His doctors were unable to identify that Tom was having problems
0:21:42 > 0:21:45not in his eyes but in his brain.
0:21:48 > 0:21:54But fortunately for him, he was referred to Professor Nick Fox.
0:21:54 > 0:21:57Normally, Alzheimer's disease starts with problems with memory
0:21:57 > 0:22:00and that's the disease affecting the hippocampus early on,
0:22:00 > 0:22:02but it doesn't always have to.
0:22:02 > 0:22:05The disease can start at the back of the brain,
0:22:05 > 0:22:10areas to do with visual processing, and then it is even more
0:22:10 > 0:22:13likely that people have trouble getting a diagnosis.
0:22:13 > 0:22:17Professor Fox has invented a technique comparing
0:22:17 > 0:22:22a sequence of yearly scans which track the progress of the disease.
0:22:22 > 0:22:26He was able to give Tom a correct diagnosis.
0:22:26 > 0:22:30What we see is how tightly packed this is here,
0:22:30 > 0:22:34but you might be able to make out that the back, there's a little
0:22:34 > 0:22:40bit more space that you can see there than you might have expected.
0:22:40 > 0:22:44That's in exactly the areas that you've been experiencing problems.
0:22:44 > 0:22:46And that's the area which is to do with
0:22:46 > 0:22:52processing of visual information, also related to calculation
0:22:52 > 0:22:55and complex hand movements.
0:22:55 > 0:23:01That is last year and this is the change over one year.
0:23:01 > 0:23:05And that's the second scan, first, second.
0:23:05 > 0:23:10What you see is this fluid-filled space here increasing as we go
0:23:10 > 0:23:14from the first to the second and that is because
0:23:14 > 0:23:17there is brain loss here at the back,
0:23:17 > 0:23:21which reflects the progressive nature of this problem.
0:23:21 > 0:23:25The scans are essential in understanding the early
0:23:25 > 0:23:27stages of the disease.
0:23:27 > 0:23:32The new technology has allowed us to see
0:23:32 > 0:23:36a window of maybe a decade before those symptoms.
0:23:36 > 0:23:39And that's where the new trials are starting to target.
0:23:39 > 0:23:45We hope to have trials of promising treatments when people are well
0:23:45 > 0:23:48and when they have the most, in terms of brain cells, to save.
0:23:48 > 0:23:50That's the window of opportunity.
0:23:50 > 0:23:53- Good, have a seat.- Thank you.
0:23:53 > 0:23:57Professor Fox and his team want to find out how the disease
0:23:57 > 0:24:00affects the functioning of Tom's visual processing.
0:24:00 > 0:24:03First, I'd like to test your vision if that's all right?
0:24:03 > 0:24:05Can you tell me what letter that is?
0:24:05 > 0:24:08The letters have been fragmented to find out
0:24:08 > 0:24:12if Tom can identify a shape from a complex visual image.
0:24:13 > 0:24:14My guess is it's an F.
0:24:14 > 0:24:16Good guess.
0:24:24 > 0:24:25Looks like an F again.
0:24:25 > 0:24:27Looks like an F?
0:24:27 > 0:24:30If I trace it out with my finger, does that help?
0:24:34 > 0:24:37Ah, is it an R? No?
0:24:37 > 0:24:40It's like an R. It's a P.
0:24:40 > 0:24:41Oh, right.
0:24:41 > 0:24:45The tests show that his brain's ability to process images
0:24:45 > 0:24:47is deteriorating.
0:24:47 > 0:24:50My brain doesn't compute what they are.
0:24:50 > 0:24:54It's a sort of a jumble, it's not, it doesn't mean anything, really.
0:24:54 > 0:24:57It's just little black squares joined together.
0:24:59 > 0:25:02Next, I'm going to say three words
0:25:02 > 0:25:04and if you could just repeat them back to me
0:25:04 > 0:25:07and then remember them, because I'll ask you again in a moment, OK?
0:25:07 > 0:25:10Bus, table, rose.
0:25:10 > 0:25:13Bus, table, rose.
0:25:13 > 0:25:15The team investigates
0:25:15 > 0:25:17how other parts of Tom's brain are being affected,
0:25:17 > 0:25:22especially those more commonly associated with Alzheimer's,
0:25:22 > 0:25:23like memory.
0:25:23 > 0:25:26What were the three words that I asked you to say?
0:25:33 > 0:25:35The last one was rose.
0:25:35 > 0:25:36That's right.
0:25:40 > 0:25:42I can't remember.
0:25:43 > 0:25:47The tests show that the disease is spreading.
0:25:50 > 0:25:54Scientists have, until now, been using scans to understand how
0:25:54 > 0:25:58amyloid plaque affects the various stages of the disease,
0:25:58 > 0:26:03but the new techniques allow them to investigate the other culprit - tau.
0:26:04 > 0:26:07So Tom undergoes a lumbar puncture,
0:26:07 > 0:26:09which draws out spinal fluid
0:26:09 > 0:26:11containing tau from the brain.
0:26:11 > 0:26:17The lumbar puncture today will tell us how much tau is elevated and that
0:26:17 > 0:26:23will tell us how much tau is being released from those brain cells.
0:26:24 > 0:26:28I would guess it might be two or three times what the
0:26:28 > 0:26:30normal range might be.
0:26:30 > 0:26:32How does that feel to you at the moment?
0:26:32 > 0:26:35The lumbar puncture shows the levels of tau,
0:26:35 > 0:26:39but Professor Fox's team want to identify exactly where it is
0:26:39 > 0:26:40in the brain.
0:26:40 > 0:26:43They use cutting-edge scanning to do so.
0:26:43 > 0:26:47First, a radioactive liquid containing a marker
0:26:47 > 0:26:49is injected before scanning.
0:26:49 > 0:26:52Three, two, one - go!
0:26:52 > 0:26:55What's being injected is a tracer
0:26:55 > 0:26:59that has a radioactive probe attached to it.
0:26:59 > 0:27:04The tracer will circulate round the body, enter into the brain and
0:27:04 > 0:27:09will attach if there is tau there and therefore it gets stuck there.
0:27:09 > 0:27:12For the first time, images are revealing which
0:27:12 > 0:27:15parts of the brain are affected by the tau tangles.
0:27:15 > 0:27:19So what we see here in these bright colours,
0:27:19 > 0:27:25those are areas where the tracer has stuck to the tau protein.
0:27:25 > 0:27:27And the bright colour is that radioactivity,
0:27:27 > 0:27:29which is how we detect it.
0:27:29 > 0:27:32And what we're seeing here in this area, which is the
0:27:32 > 0:27:38hippocampus which is critical for memory, we see just full of tau.
0:27:38 > 0:27:44And we think that tau is in some ways more closely related
0:27:44 > 0:27:47to the damage that is critical in Alzheimer's disease
0:27:47 > 0:27:49than its partner in crime, amyloid.
0:27:50 > 0:27:55This research technology is bringing astonishing new insights into how
0:27:55 > 0:28:00the disease builds up in the brain, and then destroys its functions.
0:28:03 > 0:28:07But new research is also revealing that there are changes
0:28:07 > 0:28:11we can make in our daily lives which could significantly reduce
0:28:11 > 0:28:14the chances of developing Alzheimer's.
0:28:19 > 0:28:23Professor Matthew Walker from University of California
0:28:23 > 0:28:26is investigating how plenty of deep sleep could
0:28:26 > 0:28:30preserve our memories and help fight off the disease.
0:28:30 > 0:28:33So, what we've known for some time now is that as we get older,
0:28:33 > 0:28:36our learning and memory abilities start to decline,
0:28:36 > 0:28:41but what we've also known is that a physiological signature
0:28:41 > 0:28:44of ageing is that your sleep starts to get worse.
0:28:44 > 0:28:47And so, based on how important sleep is
0:28:47 > 0:28:50for effectively hitting the save button on new memories,
0:28:50 > 0:28:54we wanted to explore whether that sleep deterioration
0:28:54 > 0:28:58in ageing and in Alzheimer's disease is not simply a symptom
0:28:58 > 0:29:03of the process, but perhaps a cause of the underlying memory problems.
0:29:05 > 0:29:08His work is based on research into the brains of mice,
0:29:08 > 0:29:14which shows that during deep sleep, amyloid is cleared from the brain,
0:29:14 > 0:29:17while too little deep sleep may cause it to build up.
0:29:20 > 0:29:24Professor Maiken Nedergaard has made an astonishing new discovery
0:29:24 > 0:29:26which explains why this happens.
0:29:26 > 0:29:30Her scans of mouse brains found small gaps between neurons.
0:29:30 > 0:29:35These expand by up to 60% when the mice are asleep.
0:29:35 > 0:29:39The gaps allow spinal fluid to sweep through the brain,
0:29:39 > 0:29:41clearing out the waste products.
0:29:41 > 0:29:45As soon as the animal fell to sleep, it was turned on,
0:29:45 > 0:29:49almost like a dishwasher, where these gaps open up and suddenly
0:29:49 > 0:29:51you see the fluid fluxes
0:29:51 > 0:29:56that enter the brain and flushing all the toxic waste product
0:29:56 > 0:30:00the brain produce when we are awake out when we sleep.
0:30:00 > 0:30:05The left scan is a mouse brain when awake, but on the right,
0:30:05 > 0:30:08we see the spinal fluid washing through when asleep.
0:30:08 > 0:30:13Professor Nedergaard has named this the glymphatic system.
0:30:13 > 0:30:15Here we see a sleeping rodent brain
0:30:15 > 0:30:18and we can see the glymphatic system working.
0:30:18 > 0:30:21So, you see the fluid flowing into the brain
0:30:21 > 0:30:23and literally washing beta amyloid away.
0:30:29 > 0:30:31The same thing happens in humans.
0:30:31 > 0:30:34During the day, amyloid builds up in our brains
0:30:34 > 0:30:40and if we don't have regular deep sleep, it starts to accumulate.
0:30:40 > 0:30:43And we need eight hours of good sleep to actively clean up
0:30:43 > 0:30:46the amyloid that build up when we are awake.
0:30:46 > 0:30:53It's clear that the amyloids start to aggregate very early in life
0:30:53 > 0:30:57and if we don't have the long, eight-hours continuous sleep
0:30:57 > 0:31:00when we are young, when we are middle aged,
0:31:00 > 0:31:03we risk that amyloid will build up when we're older.
0:31:03 > 0:31:05Sleep seems to play a crucial role
0:31:05 > 0:31:08in preventing the accumulation of amyloid.
0:31:08 > 0:31:10So Professor Walker is
0:31:10 > 0:31:14trying to find ways of artificially inducing deep sleep.
0:31:14 > 0:31:17Success could slow the development of disease
0:31:17 > 0:31:20and strengthen our memories.
0:31:20 > 0:31:24To start with, he's experimenting with younger brains.
0:31:24 > 0:31:26Chris is a research graduate.
0:31:26 > 0:31:29- Good to meet you.- Good to be here.
0:31:29 > 0:31:33First, he is asked to memorise connections between faces and words.
0:31:33 > 0:31:35OK, Chris.
0:31:35 > 0:31:37So, what we're going to do is a learning and memory test.
0:31:37 > 0:31:41So, what you'll see on the screen in front of you are some faces
0:31:41 > 0:31:44and underneath there will be a word.
0:31:44 > 0:31:47And your job is to try to connect those two things,
0:31:47 > 0:31:50to learn that those two things are associated together.
0:31:50 > 0:31:53And then later, we'll come back and test you.
0:32:07 > 0:32:12Professor Walker also wants to find out whether a newly-developed
0:32:12 > 0:32:16magnetic brain stimulator can enhance sleep and memory.
0:32:16 > 0:32:19First, Chris's brain is mapped
0:32:19 > 0:32:23to make sure the magnetic pulses are correctly targeted.
0:32:23 > 0:32:26Then two magnets are placed over his head.
0:32:26 > 0:32:30So, the machine itself is going to insert pulses
0:32:30 > 0:32:33of magnetism into the brain and stimulate those brain cells
0:32:33 > 0:32:37and the pathways that we know are critical for sleep and memory.
0:32:37 > 0:32:41So, what we're trying to essentially do is prime
0:32:41 > 0:32:43or sort of grease the pathway, as it were,
0:32:43 > 0:32:45with electrical stimulation.
0:32:45 > 0:32:48And as a consequence, enhance the sleep and memory benefit.
0:32:50 > 0:32:53Electrodes are fitted onto Chris' head
0:32:53 > 0:32:57so that Professor Walker can observe how much deep sleep he's getting.
0:33:00 > 0:33:03The sleep stimulator seems to be working.
0:33:03 > 0:33:07The monitor shows sharp movements in Chris' brain waves
0:33:07 > 0:33:12which are the signatures of deep sleep and memory processing.
0:33:12 > 0:33:15Now Professor Walker needs to know
0:33:15 > 0:33:18whether this extra sleep has strengthened Chris' memory.
0:33:18 > 0:33:22Now we're just going to perform the memory test.
0:33:22 > 0:33:26Chris has to recognise faces from the earlier test.
0:33:26 > 0:33:29If he remembers the face, or it seems to be familiar,
0:33:29 > 0:33:31he has to click on it.
0:33:31 > 0:33:35Then he has to recall the word which related to it.
0:33:40 > 0:33:45The initial results of this experiment are very encouraging.
0:33:45 > 0:33:48So what we're finding is that you need sleep after learning
0:33:48 > 0:33:51to essentially cement those new memories.
0:33:51 > 0:33:54And as a consequence, when people wake up the following morning,
0:33:54 > 0:33:56those memories are more robust.
0:33:56 > 0:33:59People have forgotten far less information across sleep
0:33:59 > 0:34:02than they would if they'd remained awake.
0:34:02 > 0:34:06It will be many years before the sleep stimulator is on the market.
0:34:06 > 0:34:10By then, Professor Walker hopes enhancing deep sleep will be
0:34:10 > 0:34:14a major weapon in the fight against Alzheimer's.
0:34:14 > 0:34:17Can we, in those people who are fighting that battle with
0:34:17 > 0:34:22Alzheimer's disease, improve sleep quality and try to bring back
0:34:22 > 0:34:25online some degree of learning and memory function?
0:34:25 > 0:34:27That's the first goal.
0:34:27 > 0:34:32The second goal, however, is to regress the time-line back.
0:34:32 > 0:34:35In other words, can we find ways to start to improve
0:34:35 > 0:34:40sleep in people in their thirties, forties and fifties, to see if
0:34:40 > 0:34:45we can actually move from a model of treatment to a model of prevention?
0:34:47 > 0:34:50Until then, the research is beginning to show that
0:34:50 > 0:34:53regular deep sleep throughout our lifetime
0:34:53 > 0:34:56could lower our risk of developing the disease.
0:34:59 > 0:35:03Sleeping is just one way we could change our lifestyle to
0:35:03 > 0:35:07stave off Alzheimer's, but it's increasingly clear that what
0:35:07 > 0:35:10we eat plays a role as well.
0:35:10 > 0:35:12There is evidence that a diet should be rich in fish,
0:35:12 > 0:35:15vegetables and olive oil,
0:35:15 > 0:35:20but it's more important to have one main goal in mind.
0:35:20 > 0:35:23In different studies, researchers have looked at different forms
0:35:23 > 0:35:26of this diet, but what they all have in common is the ability
0:35:26 > 0:35:28to protect the heart.
0:35:28 > 0:35:32So, if there is a diet out there that is protective of the heart,
0:35:32 > 0:35:35it may have that additional benefit of promoting
0:35:35 > 0:35:38healthy ageing and reducing the risk of Alzheimer's disease.
0:35:38 > 0:35:41Once the disease has started to develop,
0:35:41 > 0:35:45choosing what to eat becomes much more complex.
0:35:45 > 0:35:49Professor Richard Wurtman is a world expert on how nutrition
0:35:49 > 0:35:52affects the development of the brain.
0:35:52 > 0:35:55In a series of studies here in Boston, he started
0:35:55 > 0:36:00looking at why people with Alzheimer's had so few synapses.
0:36:00 > 0:36:03What the first slide shows is the part of a neuron, the part
0:36:03 > 0:36:06of a neurocell that's involved in making new synapses and the
0:36:06 > 0:36:10specific part are these little white dots you see running along the side.
0:36:10 > 0:36:14Each one of those dots is very likely to become a new synapse.
0:36:14 > 0:36:18Now, this is a similar part of the brain and what you can see is,
0:36:18 > 0:36:21in Alzheimer's disease, you have many fewer of these white dots
0:36:21 > 0:36:23and so you're producing many fewer synapses.
0:36:23 > 0:36:28It had been found that the disease reduced existing synapses,
0:36:28 > 0:36:33but that it also stopped new ones developing to replace them.
0:36:33 > 0:36:36Professor Wurtman wanted to find out why this happened
0:36:36 > 0:36:40and examined the role that nutrients, which help create
0:36:40 > 0:36:43these new synapses, played in the development of the disease.
0:36:43 > 0:36:47Alzheimer's patients quite generally have difficulty in smelling food
0:36:47 > 0:36:48and in tasting food,
0:36:48 > 0:36:51And they also have difficulty in absorbing most nutrients
0:36:51 > 0:36:54and in producing some of the nutrients in their own livers.
0:36:54 > 0:36:57So, they start out with nutritional deficiencies.
0:37:02 > 0:37:06His studies have discovered three nutrients which are essential
0:37:06 > 0:37:10for making new synapses to replace those destroyed by the disease.
0:37:10 > 0:37:12They are choline,
0:37:12 > 0:37:14uridine,
0:37:14 > 0:37:17and docosahexaenoic acid, known as DHA.
0:37:19 > 0:37:22Here you see an excellent source of DHA in the diet.
0:37:22 > 0:37:25This is a fish. It happens to be a salmon.
0:37:25 > 0:37:27Patients with Alzheimer's disease do have some
0:37:27 > 0:37:29difficulty in absorbing DHA.
0:37:30 > 0:37:34Choline is present in abundant quantities within egg yolks, OK?
0:37:34 > 0:37:37And if you have three eggs and three egg yolks,
0:37:37 > 0:37:40then you're doing pretty well in terms of getting choline.
0:37:40 > 0:37:44And again, Alzheimer's patients have some difficulty in absorbing it.
0:37:44 > 0:37:47The third, uridine, can't be obtained from food,
0:37:47 > 0:37:49but is normally created in the liver,
0:37:49 > 0:37:53something people with Alzheimer's have difficulty doing.
0:37:53 > 0:37:57The professor's work reveals that an Alzheimer's brain could benefit
0:37:57 > 0:38:02if more of these nutrients could be absorbed to grow new synapses.
0:38:02 > 0:38:04A new supplement has been created
0:38:04 > 0:38:07which provides doses of these nutrients.
0:38:07 > 0:38:10There have been two large-scale clinical trials
0:38:10 > 0:38:13and in both trials it significantly improved memory function.
0:38:13 > 0:38:16It also improved the connectedness between different
0:38:16 > 0:38:19parts of the brain and that's critically important in people
0:38:19 > 0:38:22with early Alzheimer's disease.
0:38:22 > 0:38:25Although the trials showed the supplement helps early-stage
0:38:25 > 0:38:26Alzheimer's patients,
0:38:26 > 0:38:31people who have the more advanced stage of the disease do not benefit.
0:38:40 > 0:38:44Across the world, researchers are searching for ways
0:38:44 > 0:38:46not just of renewing the synapses,
0:38:46 > 0:38:50but of improving the functioning of the brain in general.
0:38:53 > 0:38:57Millions of people practice cognitive exercises,
0:38:57 > 0:38:59known as brain-training.
0:38:59 > 0:39:02Cognitive exercises are probably helpful for all of us.
0:39:02 > 0:39:05It's good for us to keep our brains working and we know that
0:39:05 > 0:39:07if you engage in a lot of cognitive activity,
0:39:07 > 0:39:10it can help to reduce your risk
0:39:10 > 0:39:13of developing cognitive impairment and dementia.
0:39:13 > 0:39:16However, we've systematically reviewed the evidence,
0:39:16 > 0:39:18the research evidence, about brain-training people with
0:39:18 > 0:39:21Alzheimer's disease and, unfortunately, we haven't been
0:39:21 > 0:39:24able to find any strong evidence that this is beneficial.
0:39:30 > 0:39:34Alzheimer's patients need to concentrate on much more
0:39:34 > 0:39:38frequent and routine ways of training their brains.
0:39:38 > 0:39:41This could help people like Gareth Hulston,
0:39:41 > 0:39:43who lives in North Wales.
0:39:43 > 0:39:45He's 68 years old
0:39:45 > 0:39:48and was diagnosed with Alzheimer's a year ago.
0:39:49 > 0:39:53He's surrounded by reminders of a rich and full life,
0:39:53 > 0:39:56but gradually, he's forgetting their significance.
0:39:56 > 0:40:00His daughter, Virginia, is doing her best to stimulate his memory,
0:40:00 > 0:40:02asking him what he's been up to.
0:40:02 > 0:40:04What did you do on Saturday, Dad?
0:40:07 > 0:40:09Hang on....
0:40:11 > 0:40:13What did I do on Saturday?
0:40:17 > 0:40:19Can't remember.
0:40:19 > 0:40:23But fortunately for Gareth, he's been chosen to take part
0:40:23 > 0:40:27in an important new trial run by Professor Linda Clare.
0:40:27 > 0:40:29She hopes it will teach him
0:40:29 > 0:40:33to focus on improving everyday tasks which are causing him problems
0:40:33 > 0:40:37and, in the process, engage his brain many times every day.
0:40:37 > 0:40:40What we try to do is get them to think with us
0:40:40 > 0:40:42about all of the different steps involved in the activity
0:40:42 > 0:40:44that they want to manage better.
0:40:44 > 0:40:47And then to really engage their brain in
0:40:47 > 0:40:50figuring out where the difficulties are coming in that process.
0:40:50 > 0:40:53And we work with them to develop strategies that they can apply
0:40:53 > 0:40:57at the different stages so that they may manage that activity better.
0:40:57 > 0:41:01Therapist Sue Evans is visiting Gareth to find out
0:41:01 > 0:41:04which everyday skills he wants to improve.
0:41:04 > 0:41:09- Hi, Sue. How are you? Come on in. - Nice to see you, Gareth.
0:41:09 > 0:41:13At the moment, he's having problems with cooking.
0:41:13 > 0:41:16Right. Are these the eggs, are they?
0:41:22 > 0:41:25Watch, don't, don't. You need a cloth, they're hot.
0:41:25 > 0:41:28How are you today, then, Gareth?
0:41:28 > 0:41:30Not too bad. I keep going, don't I?
0:41:30 > 0:41:33- Take a pew.- OK, I will do.
0:41:33 > 0:41:35I'm just going to sit and watch and listen to you
0:41:35 > 0:41:37and Virginia for a bit, OK?
0:41:37 > 0:41:40Sue observes him for 30 minutes to see how the disease is
0:41:40 > 0:41:43affecting his planning and concentration.
0:41:43 > 0:41:45What are you going to have for dinner tonight?
0:41:45 > 0:41:47Haven't a clue, not a clue.
0:41:47 > 0:41:49You not planned anything?
0:41:49 > 0:41:51No, I might go to see Bill.
0:41:52 > 0:41:54Can you smell anything, Dad?
0:41:54 > 0:41:58No, my smell's gone, hasn't it? I can't smell at all.
0:41:58 > 0:42:00What did you put on before?
0:42:00 > 0:42:03Oh, I put some eggs on to boil.
0:42:03 > 0:42:04Yeah, so what's burning?
0:42:04 > 0:42:07Do you want me to go and have a look?
0:42:07 > 0:42:09I would, I'd go and have a look.
0:42:14 > 0:42:15Just in time.
0:42:15 > 0:42:17What's burning, Dad?
0:42:17 > 0:42:18Hang on, what's in the oven?
0:42:21 > 0:42:23Oh, you're joking, Virginia.
0:42:23 > 0:42:25Oh, they're ruined.
0:42:27 > 0:42:30They're absolutely burnt to a cinder.
0:42:30 > 0:42:34Sue wants to help Gareth work out a series of steps which
0:42:34 > 0:42:38will become part of his routine and stop him burning his meals.
0:42:38 > 0:42:40- So you told me there was a pizza in the fridge.- Yes.
0:42:40 > 0:42:43So, do you want to get it out?
0:42:43 > 0:42:45Yeah, all right.
0:42:45 > 0:42:46Let's have a look.
0:42:46 > 0:42:49So, if you're going to cook this one, let's have a look and see.
0:42:49 > 0:42:50What would you find out?
0:42:50 > 0:42:52Eight to ten minutes here.
0:42:52 > 0:42:58Yeah? So, come over here and write that information down, yeah?
0:42:58 > 0:43:00So you'd write pizza.
0:43:03 > 0:43:05OK. And what time is it going to be ready?
0:43:08 > 0:43:11And then the next thing I need you to do is set the timer.
0:43:11 > 0:43:14So the reason I'm getting you to write all this down
0:43:14 > 0:43:17is that I'm making you think about it more, which one -
0:43:17 > 0:43:20it means it's gone through more processes in your brain,
0:43:20 > 0:43:24because you've had to read it, think about it and then write it.
0:43:24 > 0:43:27But also, this also works as a back up.
0:43:28 > 0:43:32She hopes that by thinking through these steps several times a day,
0:43:32 > 0:43:35Gareth's planning abilities will improve.
0:43:35 > 0:43:38Sue also wants to work on his semantic memory -
0:43:38 > 0:43:40his ability to remember facts.
0:43:40 > 0:43:44His challenge is to remember the names of his grandchildren.
0:43:44 > 0:43:46Who's that?
0:43:46 > 0:43:47I cannot remember.
0:43:47 > 0:43:49- Rachel.- Rachel?
0:43:49 > 0:43:50So, Rachel.
0:43:50 > 0:43:51She's the boss.
0:43:51 > 0:43:54She's the boss, that doesn't surprise me.
0:43:54 > 0:43:57Sue has one simple recommendation.
0:43:57 > 0:44:01- Maybe that's a project to do to get an up-to-date photo of her.- Yeah.
0:44:01 > 0:44:04By having that photo in your hand,
0:44:04 > 0:44:07you're able to build up more of an image of them
0:44:07 > 0:44:11and then hopefully what we'd be aiming for is that you'd be able to
0:44:11 > 0:44:15build up that image of them without needing the photo in your hand.
0:44:15 > 0:44:19Sue returns every week to ensure Gareth is incorporating these
0:44:19 > 0:44:21techniques into his daily routine.
0:44:25 > 0:44:28Three months later, now it's time for Sue to find out
0:44:28 > 0:44:33whether Gareth's planning abilities and memory have improved.
0:44:33 > 0:44:35- Hiya, Sue!- Hi, Gareth.
0:44:35 > 0:44:38- Come on in. - How are you? Nice to see you.
0:44:38 > 0:44:41First up, can he remember not to burn his food?
0:44:41 > 0:44:44OK, Gareth, so you're going to show me how you're doing
0:44:44 > 0:44:48the cooking now, now you've been using the strategies for a bit?
0:44:48 > 0:44:52He's been putting them in action, helped by a new hi-tech oven.
0:44:52 > 0:44:57Right, all you do then is get that from there.
0:45:00 > 0:45:06Now cooking instructions, 20 to 25 minutes.
0:45:06 > 0:45:08Gareth has become so good at planning this task that he
0:45:08 > 0:45:11no longer needs the white board.
0:45:11 > 0:45:13He just uses the timer as a prompt.
0:45:13 > 0:45:15He sets it for 20 minutes.
0:45:15 > 0:45:18Right. And this is what I do, as a rule.
0:45:18 > 0:45:23This is where I usually put it, on there, and I usually take this seat.
0:45:23 > 0:45:26So, Gareth, have you managed to get an up-to-date picture of Rachel?
0:45:26 > 0:45:29That was one of the jobs I gave you last time, wasn't it?
0:45:29 > 0:45:31Yes, I got the photograph. There she is.
0:45:31 > 0:45:33There she is. Oh, that's a nice one.
0:45:33 > 0:45:36- At her right age.- Yeah.- Much better.
0:45:36 > 0:45:38TIMER RINGS
0:45:38 > 0:45:40Oh!
0:45:40 > 0:45:41Go on, then.
0:45:43 > 0:45:45The plan has worked.
0:45:45 > 0:45:47Gareth appears to have retrained his brain to connect
0:45:47 > 0:45:50the sound of the timer with the cooking.
0:45:51 > 0:45:52Right.
0:45:52 > 0:45:56- So, this turns itself off too, then? - Yeah.- Yeah?
0:45:56 > 0:45:58So, no risk of burning any more.
0:45:59 > 0:46:01They look good. So they're done?
0:46:01 > 0:46:03They are absolutely ready, yeah.
0:46:03 > 0:46:04Yeah? Excellent.
0:46:06 > 0:46:09And now for the ultimate test.
0:46:09 > 0:46:12Has his training improved his semantic memory?
0:46:18 > 0:46:21- Hiya, Rache!- Hiya, Grandad.
0:46:21 > 0:46:22Come on in.
0:46:24 > 0:46:27She's my grand-daughter, my Rachey-wachey.
0:46:27 > 0:46:31HE LAUGHS HAPPILY
0:46:31 > 0:46:34Oh, I'll never give in. I'll never ever give in.
0:46:34 > 0:46:40Might put me in my box, but I'll never...I'll never give in.
0:46:40 > 0:46:42I do believe I've improved tremendously.
0:46:42 > 0:46:45We'll go from this side across, yeah, and you can tell me
0:46:45 > 0:46:46who everyone is now.
0:46:46 > 0:46:49- That's Nathan.- That's Nathan. - Holly...
0:46:49 > 0:46:54These simple steps help people like Gareth to manage their lives better,
0:46:54 > 0:46:58but they can also improve the functioning of their brains.
0:46:58 > 0:47:00Dwayney, the decorator.
0:47:00 > 0:47:02People who had had the cognitive rehabilitation programme
0:47:02 > 0:47:05showed greater activation when they were doing a memory task
0:47:05 > 0:47:10in certain brain areas, particularly the bilateral frontal areas.
0:47:10 > 0:47:13Whereas people in the control group who hadn't had the programme
0:47:13 > 0:47:16showed reduced activation in those areas.
0:47:16 > 0:47:20We tentatively suggested that this might reflect
0:47:20 > 0:47:23some improvement in functioning in those areas of the brain.
0:47:23 > 0:47:24And, of course, that relates very much
0:47:24 > 0:47:26to the way the intervention works,
0:47:26 > 0:47:29where we're asking people to think about strategies
0:47:29 > 0:47:32and engage in particular strategies to manage everyday activities
0:47:32 > 0:47:33that help them to manage those better.
0:47:37 > 0:47:39Simple lifestyle changes seem to re-train
0:47:39 > 0:47:42and strengthen the functioning of the brain in people
0:47:42 > 0:47:45who are suffering from early-stage Alzheimer's.
0:47:46 > 0:47:49But in this new era of research,
0:47:49 > 0:47:52there is a much more dramatic ambition.
0:47:52 > 0:47:56This is a really exciting time for patients with Alzheimer's disease
0:47:56 > 0:47:59because we're starting to see trials that are starting
0:47:59 > 0:48:00to show evidence of efficacy.
0:48:00 > 0:48:03And I think there's a lot of excitement now,
0:48:03 > 0:48:06because there's some new data that looks very promising.
0:48:06 > 0:48:11This new data has launched worldwide drugs trials.
0:48:11 > 0:48:13One is taking place in Colombia.
0:48:18 > 0:48:23Here, the Alzheimer's gene mutation, which afflicts families like Flor's,
0:48:23 > 0:48:26offers a rare opportunity for research.
0:48:26 > 0:48:31In these families, the gene causes the amyloid to start building up
0:48:31 > 0:48:35in people as young as 30 and symptoms appear at 45,
0:48:35 > 0:48:38as has happened with Flor's sister Olga.
0:48:38 > 0:48:44Researchers want to find out if a drug can interrupt its progress.
0:48:44 > 0:48:48The prospect that Flor might have the early stages of the disease
0:48:48 > 0:48:50makes her a valuable participant.
0:49:20 > 0:49:24Every two weeks, Flor goes for physical and cognitive tests
0:49:24 > 0:49:27and she's given an injection which could be the brand-new
0:49:27 > 0:49:31Alzheimer's drug crenezumab or it could be a placebo.
0:49:33 > 0:49:36Crenezumab is an anti-amyloid treatment that had several
0:49:36 > 0:49:39characteristics we thought were especially
0:49:39 > 0:49:41suitable for prevention trials.
0:49:41 > 0:49:43It seemed to attack different forms of amyloid
0:49:43 > 0:49:47and there was a suggestion that it could reduce amyloid and
0:49:47 > 0:49:52might have a role if it was started in people at an earlier stage.
0:49:52 > 0:49:54IN SPANISH:
0:49:58 > 0:50:02For Dr Lopera, the trial offers a new future.
0:50:02 > 0:50:04IN SPANISH:
0:50:15 > 0:50:16Five one way.
0:50:16 > 0:50:21Meanwhile, 4,000km away in New England, Neil Corkery
0:50:21 > 0:50:26is part of another trial which already has promising early results.
0:50:28 > 0:50:31Ten years ago, the 75-year-old former head teacher
0:50:31 > 0:50:37and local politician first noticed he had the symptoms of Alzheimer's.
0:50:37 > 0:50:41We were going to an event for one of the state officials who was
0:50:41 > 0:50:44leaving and the Governor was supposed to speak.
0:50:44 > 0:50:47So he was late and they said, "Would you say a few words?"
0:50:47 > 0:50:50And I said, "Sure, I'll be glad to." And I got up and I started
0:50:50 > 0:50:53and I was fine and then I got to a point,
0:50:53 > 0:50:57I blanked out on a word and that's when I went for some tests.
0:50:57 > 0:51:02Doctors scanned his brain and diagnosed him with Alzheimer's.
0:51:02 > 0:51:06The news was devastating for Neil and his wife, Maureen.
0:51:06 > 0:51:10Initially - I've never told Maureen this - I did things like put
0:51:10 > 0:51:15music on that they could use when I, when they have the funeral.
0:51:15 > 0:51:17Like Glen...
0:51:17 > 0:51:23who's, Glen, Glen Campbell, who's a noted singer.
0:51:23 > 0:51:26He has, he's got a song that they had him sing
0:51:26 > 0:51:29and it's just a beautiful song.
0:51:29 > 0:51:34# I'm still here but yet I'm gone... #
0:51:35 > 0:51:40So I was kind of romancing the kind of negative side of it,
0:51:40 > 0:51:44I guess, but I've been through that, I hope, you know.
0:51:44 > 0:51:49I think we both felt depressed after the diagnosis,
0:51:49 > 0:51:52because you know there's no cure.
0:51:52 > 0:51:55The future for the Corkerys looked bleak.
0:51:55 > 0:51:56Luckily for them,
0:51:56 > 0:52:00tests had just started on a new drug to fight Alzheimer's.
0:52:02 > 0:52:07In 2014, the man behind the drug was on the way to his office
0:52:07 > 0:52:11when his chief executive called with the results of its Phase 1 trial.
0:52:11 > 0:52:13I was driving down the street.
0:52:13 > 0:52:15When he started to tell me the results, I had to pull over,
0:52:15 > 0:52:17because they were so exciting.
0:52:17 > 0:52:18And he was telling me
0:52:18 > 0:52:23that the drug had unexpectedly shown an effect on cognitive decline.
0:52:23 > 0:52:26Our drug was slowing cognitive decline in patients
0:52:26 > 0:52:28with Alzheimer's disease.
0:52:28 > 0:52:31I'm glad I pulled over, because I was so excited
0:52:31 > 0:52:34and I...I was smiling from ear to ear.
0:52:34 > 0:52:40The drug, called aducanumab, was what everyone had been hoping for.
0:52:40 > 0:52:41The results sent share prices
0:52:41 > 0:52:45in the pharmaceutical company Biogen rocketing.
0:52:46 > 0:52:49The trial showed that the drug was having a remarkable
0:52:49 > 0:52:52impact on the brains of people with Alzheimer's.
0:52:52 > 0:52:55So what we're looking at here is a slice of a human brain
0:52:55 > 0:52:57in the living patient with Alzheimer's disease.
0:52:57 > 0:53:01And what we see here is a red colour and yellow.
0:53:01 > 0:53:04And the red colour shows where the amyloid plaques are in the brain.
0:53:04 > 0:53:08And the more red it is, the more plaque there is.
0:53:10 > 0:53:13This shows what happens after treatment with our drug.
0:53:13 > 0:53:16We see that the redness has been reduced and that
0:53:16 > 0:53:21means that the amyloid plaques have been removed from this brain.
0:53:21 > 0:53:24The scan on the right shows just how effective
0:53:24 > 0:53:28the drug has been in removing amyloid plaque from the brain,
0:53:28 > 0:53:31but a major complication has now been discovered.
0:53:31 > 0:53:35The main side effect that we saw with this drug in the clinical trial
0:53:35 > 0:53:37was a thing called ARIA.
0:53:37 > 0:53:40And what we see here is a picture of ARIA.
0:53:40 > 0:53:43And what we see is a whiteness here in this...in the brain,
0:53:43 > 0:53:46which signifies oedema or swelling in the brain.
0:53:46 > 0:53:48And that's not a good thing,
0:53:48 > 0:53:50because the brain is in an enclosed space
0:53:50 > 0:53:54and swelling can be harmful to patients.
0:53:54 > 0:53:57Researchers hope to stop the swelling by initially giving
0:53:57 > 0:54:01a low dose of the drug and then gradually increasing it.
0:54:01 > 0:54:03Extensive phase III trials
0:54:03 > 0:54:06are being rolled out across Europe and America.
0:54:06 > 0:54:10There is even a possibility that the drug will combat the tau tangles,
0:54:10 > 0:54:13that other great hallmark of Alzheimer's disease.
0:54:13 > 0:54:16But the results won't be known for four years.
0:54:16 > 0:54:18- How are you today?- Very good.
0:54:18 > 0:54:22Neil Corkery is now participating in the trial.
0:54:22 > 0:54:25He doesn't know whether he's on a placebo or the drug,
0:54:25 > 0:54:28but taking part has made all the difference.
0:54:29 > 0:54:34Recently, he was even able to speak off the cuff at his son's wedding.
0:54:34 > 0:54:37I was like my old self. I really...
0:54:37 > 0:54:39Yeah, it was extemporaneous
0:54:39 > 0:54:43and there wasn't any rehearsal or written words or anything.
0:54:43 > 0:54:47He just got up and he spoke and it flowed.
0:54:47 > 0:54:49It was nice, it was really nice.
0:54:49 > 0:54:51She's been by me all the time.
0:54:51 > 0:54:53She's, she...
0:54:53 > 0:54:55She knows what's right.
0:54:55 > 0:54:58It has made me feel better, yeah, absolutely.
0:54:58 > 0:55:00I mean, I don't know what else to attribute it to,
0:55:00 > 0:55:03you know, unless it's a miracle I'm unaware of.
0:55:03 > 0:55:07Neil is convinced he is benefiting from the drug trial,
0:55:07 > 0:55:09although it could be the famous placebo effect.
0:55:09 > 0:55:13TANGO MUSIC PLAYS
0:55:14 > 0:55:18For Flor, who's taking part in the Colombia trial,
0:55:18 > 0:55:21the curse of Alzheimer's which has hung over her family for
0:55:21 > 0:55:24so long could at last be lifted.
0:55:26 > 0:55:28IN SPANISH:
0:55:37 > 0:55:39The first results from this trial
0:55:39 > 0:55:42will also become available in around four years.
0:55:46 > 0:55:49These trials, and others around the world,
0:55:49 > 0:55:52are bringing hope to millions.
0:55:53 > 0:55:56We believe it marks the dawn of a new era
0:55:56 > 0:55:59in Alzheimer's-prevention research.
0:55:59 > 0:56:03And that gives us now the opportunity to rapidly evaluate
0:56:03 > 0:56:07the range of promising but unproven prevention therapies.
0:56:07 > 0:56:11And maybe, just maybe, find and support the approval
0:56:11 > 0:56:15of effective prevention therapies within the next ten years.
0:56:16 > 0:56:19There's a lot of hope for Alzheimer's patients.
0:56:19 > 0:56:22We're in the final stages of clinical trials with a drug
0:56:22 > 0:56:23that looks very promising.
0:56:23 > 0:56:26We can remove the amyloid from the brains of patients
0:56:26 > 0:56:27with Alzheimer's disease.
0:56:27 > 0:56:32My hope is that if we treat early enough, we may stave off Alzheimer's
0:56:32 > 0:56:35disease completely and we may never have to worry about it again.
0:56:37 > 0:56:42Up until now, a treatment for Alzheimer's has eluded scientists.
0:56:42 > 0:56:46We can all make changes to our lifestyles and help
0:56:46 > 0:56:50stave off the disease, like eating well and getting enough sleep.
0:56:50 > 0:56:55But innovative scanning techniques and a new generation of drugs
0:56:55 > 0:56:59are giving people with Alzheimer's, and those at risk of developing it,
0:56:59 > 0:57:04new hope that they will hold on to their memories and their lives.
0:57:06 > 0:57:11# I'm still here but yet I'm gone
0:57:13 > 0:57:18# I don't play guitar or sing my song
0:57:21 > 0:57:25# It never defined who I am
0:57:28 > 0:57:33# The man that loves you till the end
0:57:37 > 0:57:41# You're the last person I will love
0:57:44 > 0:57:49# You're the last face I will recall
0:57:49 > 0:57:52# And best of all
0:57:56 > 0:57:59# I'm not gonna miss you
0:58:03 > 0:58:07# I'm not gonna miss you
0:58:14 > 0:58:18# I'm never gonna hold you like I did
0:58:21 > 0:58:26# Or say "I love you" to the kids
0:58:29 > 0:58:34# You're never gonna see it in my eyes. #