How many people here would like to live to be at least 80 years old? Yeah. I think we all have this hopeful expectation of living into old age. Let's project out into the future, to your future "you's," and let's imagine that we're all 85. Now, everyone look at two people. One of you probably has Alzheimer's disease.
A canta xente de aquí lle gustaría vivir ata ter polo menos 80 anos? Si. Penso que todos temos esta esperanza de vivir ata a vellez. Imos proxectarnos no futuro, nos "vostedes" futuros, e imos imaxinar que todos temos 85 anos. Agora mírense uns aos outros. Un de vostedes probablemente terá alzhéimer.
(Laughter)
(Risos)
Alright, alright. And maybe you're thinking, "Well, it won't be me." Then, OK. You are a caregiver. So --
Vale, vale. E se cadra están a pensar: "Ben, non serei eu". Entón é vostede un coidador. Así que...
(Laughter)
(Risos)
so in some way, this terrifying disease is likely to affect us all.
dalgún xeito, esta terrible doenza é probable que nos afecte a todos.
Part of the fear around Alzheimer's stems from the sense that there's nothing we can do about it. Despite decades of research, we still have no disease-modifying treatment and no cure. So if we're lucky enough to live long enough, Alzheimer's appears to be our brain's destiny.
Parte do medo que rodea o alzhéimer provén da idea de que non hai nada que poidamos facer. Malia décadas de investigación, aínda non temos tratamento contra esta doenza nin curación. Se temos sorte dabondo para vivirmos moitos anos, parece que o alzhéimer será o destino do noso cerebro.
But maybe it doesn't have to be. What if I told you we could change these statistics, literally change our brain's destiny, without relying on a cure or advancements in medicine?
Mais se cadra non ten por que ser. E se lles digo que podemos mudar as estatísticas, literalmente mudar o destino do noso cerebro, sen depender dunha curación ou dos avances da medicina?
Let's begin by looking at what we currently understand about the neuroscience of Alzheimer's. Here's a picture of two neurons connecting. The point of connection, this space circled in red, is called the synapse. The synapse is where neurotransmitters are released. This is where signals are transmitted, where communication happens. This is where we think, feel, see, hear, desire ... and remember. And the synapse is where Alzheimer's happens.
Comecemos por revisar o que se sabe actualmente sobre a neurociencia do alzhéimer. Aquí teñen un debuxo de dúas neuronas conectadas. O punto de conexión, este espazo cun círculo vermello, chámase sinapse. A sinapse é onde se liberan os neurotransmisores. Aquí é onde se transmiten os sinais, onde se produce a comunicación. Aquí é onde pensamos, sentimos, vemos, oímos, desexamos... e lembramos. E na sinapse é onde se produce o alzhéimer.
Let's zoom in on the synapse and look at a cartoon representation of what's going on. During the business of communicating information, in addition to releasing neurotransmitters like glutamate into the synapse, neurons also release a small peptide called amyloid beta. Normally, amyloid beta is cleared away metabolized by microglia, the janitor cells of our brains. While the molecular causes of Alzheimer's are still debated, most neuroscientists believe that the disease begins when amyloid beta begins to accumulate. Too much is released, or not enough is cleared away, and the synapse begins to pile up with amyloid beta. And when this happens, it binds to itself, forming sticky aggregates called amyloid plaques.
Imos ampliar a sinapse e mirar unha representación con debuxos do que acontece. Durante o proceso de comunicación da información, ademais de liberar neurotransmisores coma o glutamato na sinapse, as neuronas tamén liberan un pequeno péptido chamado amiloide beta. Normalmente o amiloide beta elimínase metabolizado polas microglías, as células conserxe do noso cerebro. Mentres que aínda están en debate as causas moleculares do alzhéimer, a maioría dos neurocientíficos cre que a doenza comeza cando os amiloides beta empezan a se acumularen. Libéranse demasiados ou non se eliminan os suficientes, e a sinapse comeza a acumular amiloides beta. Cando acontece isto, únense a si mesmos, formando adherencias chamadas placas amiloides.
How many people here are 40 years old or older? You're afraid to admit it now. This initial step into the disease, this presence of amyloid plaques accumulating, can already be found in your brains. The only way we could be sure of this would be through a PET scan, because at this point, you are blissfully unaware. You're not showing any impairments in memory, language, or cognition ... yet. We think it takes at least 15 to 20 years of amyloid plaque accumulation before it reaches a tipping point, then triggering a molecular cascade that causes the clinical symptoms of the disease. Prior to the tipping point, your lapses in memory might include things like, "Why did I come in this room?" or "Oh ... what's his name?" or "Where did I put my keys?"
Canta xente de aquí ten 40 anos ou máis? Teñen medo de recoñecelo agora. Este paso inicial da doenza, esta presenza de placas amiloides que se acumulan, xa se pode atopar nos seus cerebros. O único xeito de estarmos seguros disto sería facer un escáner TEP, porque neste momento vivimos nunha feliz ignorancia. Non amosamos ningunha deterioración da memoria, linguaxe ou coñecemento... aínda. Pensamos que se tarda entre 15 e 20 anos en acumular placa amiloide antes de que alcance o punto crítico, logo desencadea un cadoiro molecular que provoca os síntomas da doenza. Antes do punto crítico, os lapsos da memoria poden incluír cousas coma: "Por que entrei neste cuarto?" ou "Oh... Como se chama?" ou "Onde botei as chaves?"
Now, before you all start freaking out again, because I know half of you did at least one of those in the last 24 hours -- these are all normal kinds of forgetting. In fact, I would argue that these examples might not even involve your memory, because you didn't pay attention to where you put your keys in the first place. After the tipping point, the glitches in memory, language and cognition are different. Instead of eventually finding your keys in your coat pocket or on the table by the door, you find them in the refrigerator, or you find them and you think, "What are these for?"
Agora, antes de que todos se asusten de novo (porque sei que polo menos a metade tivo algún destes nas últimas 24 horas) trátase de esquecementos normais. De feito, eu sostería que estes exemplos poderían non involucrar a súa memoria, porque non prestou atención a onde botou as chaves en primeiro lugar. Tras o punto crítico, os problemas de memoria, linguaxe e coñecemento son diferentes. No canto de atopar as chaves no peto do abrigo ou na mesa que está onda a porta, atópaas no frigorífico, ou atópaas e pensa: "Isto para que é?"
So what happens when amyloid plaques accumulate to this tipping point? Our microglia janitor cells become hyper-activated, releasing chemicals that cause inflammation and cellular damage. We think they might actually start clearing away the synapses themselves. A crucial neural transport protein called "tau" becomes hyperphosphorylated and twists itself into something called "tangles," which choke off the neurons from the inside. By mid-stage Alzheimer's, we have massive inflammation and tangles and all-out war at the synapse and cell death.
Que acontece cando as placas amiloides se acumulan ata este punto crítico? As nosas células conserxe microglías tórnanse hiperactivas e liberan substancias químicas que causan dano celular e inflamación. Pensamos que poderían en realidade comezar a eliminar a sinapses elas mesmas. Unha proteína neurotransportadora crucial denominada "tau" vólvese hiperfosforilada e retórcese en vultos denominados "nobelos", que cortan as neuronas desde o interior. Na fase intermedia do alzhéimer, temos inflamación masiva e nobelos, unha guerra sen cuartel na sinapse e morte celular.
So if you were a scientist trying to cure this disease, at what point would you ideally want to intervene? Many scientists are betting big on the simplest solution: keep amyloid plaques from reaching that tipping point, which means that drug discovery is largely focused on developing a compound that will prevent, eliminate, or reduce amyloid plaque accumulation. So the cure for Alzheimer's will likely be a preventative medicine. We're going to have to take this pill before we reach that tipping point, before the cascade is triggered, before we start leaving our keys in the refrigerator. We think this is why, to date, these kinds of drugs have failed in clinical trials -- not because the science wasn't sound, but because the people in these trials were already symptomatic. It was too late. Think of amyloid plaques as a lit match. At the tipping point, the match sets fire to the forest. Once the forest is ablaze, it doesn't do any good to blow out the match. You have to blow out the match before the forest catches fire.
Se vostede fose un científico que tenta curar esta doenza, cal sería o punto ideal no que desexaría intervir? Moitos científicos están apostando alto pola solución máis simple: manter as placas amiloides lonxe de alcanzar o punto crítico, polo que a investigación farmacéutica céntrase en desenvolver un composto que evite, elimine ou reduza a acumulación de placa amiloide. Así que a cura do alzhéimer probablemente será a medicina preventiva. Imos ter que tomar esta pastilla antes de alcanzar o punto crítico, antes de que se desencadee o cadoiro, antes de que empecemos a deixar as chaves no frigorífico. Pensamos que esta é a razón de que, ata agora, fallasen este tipo de fármacos en ensaios clínicos... non por non contar cunha ciencia sólida senón porque as persoas destes ensaios xa manifestaban síntomas. Era demasiado tarde. Imaxinen que as placas amiloides son mistos acendidos. No punto crítico, o misto incendia o monte. Cando o monte está a arder, non serve de nada soprarlle ao misto. Hai que soprarlle ao misto antes de que o monte se incendie.
Even before scientists sort this out, this information is actually really good news for us, because it turns out that the way we live can influence the accumulation of amyloid plaques. And so there are things we can do to keep us from reaching that tipping point.
Incluso antes de que os científicos o solucionen, esta información en realidade son boas novas para nós, porque resulta que o noso xeito de vivir pode ter influencia sobre a acumulación de placas amiloides. Así que podemos facer algo para estarmos lonxe de alcanzar o punto crítico.
Let's picture your risk of Alzheimer's as a see-saw scale. We're going to pile risk factors on one arm, and when that arm hits the floor, you are symptomatic and diagnosed with Alzheimer's. Let's imagine you're 50 years old. You're not a spring chicken anymore, so you've accumulated some amyloid plaques with age. Your scale is tipped a little bit.
Poñamos o risco de que sufran alzhéimer coma nunha balanza. Imos acumular factores de risco nun brazo e, cando ese brazo choque no chan, vostede ten síntomas e diagnostícanlle alzhéimer. Imaxine que ten 50 anos. xa non é un rapaz, así que leva acumuladas placas amiloides coa idade. A súa balanza inclínase un pouquiño.
Now let's look at your DNA. We've all inherited our genes from our moms and our dads. Some of these genes will increase our risk and some will decrease it. If you're like Alice in "Still Alice," you've inherited a rare genetic mutation that cranks out amyloid beta, and this alone will tip your scale arm to the ground. But for most of us, the genes we inherit will only tip the arm a bit. For example, APOE4 is a gene variant that increases amyloid, but you can inherit a copy of APOE4 from mom and dad and still never get Alzheimer's, which means that for most of us, our DNA alone does not determine whether we get Alzheimer's. So what does? We can't do anything about getting older or the genes we've inherited. So far, we haven't changed our brain's destiny.
Agora observemos o seu ADN. Herdamos os nosos xenes das nosas nais e dos nosos pais. Algúns destes xenes aumentarán o risco e outros diminuirano. Se vostede é como Alice en <i>Still Alice</i>, herdou unha mutación xenética rara que produce amiloides beta, e isto só inclinará a súa balanza ata o chan. Pero na maioría de nós, os xenes herdados só inclinarán un pouco o brazo. Por exemplo, o APOE4 é unha variante xenética que aumenta o amiloide, pero pódese herdar unha copia da APOE4 da nai e do pai e nunca ter alzhéimer, o que significa que na maioría de nós o noso ADN só non determina se imos padecer alzhéimer. Entón que o determina? Non podemos evitar envellecer nin os xenes que herdamos. Ata agora, non cambiamos o destino do noso cerebro.
What about sleep? In slow-wave deep sleep, our glial cells rinse cerebral spinal fluid throughout our brains, clearing away metabolic waste that accumulated in our synapses while we were awake. Deep sleep is like a power cleanse for the brain. But what happens if you shortchange yourself on sleep? Many scientists believe that poor sleep hygiene might actually be a predictor of Alzheimer's. A single night of sleep deprivation leads to an increase in amyloid beta. And amyloid accumulation has been shown to disrupt sleep, which in turn causes more amyloid to accumulate. And so now we have this positive feedback loop that's going to accelerate the tipping of that scale.
Que pasa co sono? No sono profundo, as nosas células gliais limpan o fluído espinal cerebral por todo o cerebro, eliminando os refugallos metabólicos que se acumulan nas nosas sinapses mentres estamos espertos. O sono profundo é coma un potente limpador para o cerebro. Pero que ocorre se non se aproveita ben o sono? Moitos científicos cren que unha mala hixiene de sono pode realmente predicir o alzhéimer. Unha soa noite de privación do sono provoca un incremento de amiloides beta. E demostrouse que a acumulación de amiloides altera o sono, que á súa vez provoca máis acumulación de amiloides. Entón agora temos esta retroalimentación positiva que vai acelerar a inclinación da balanza.
What else? Cardiovascular health. High blood pressure, diabetes, obesity, smoking, high cholesterol, have all been shown to increase our risk of developing Alzheimer's. Some autopsy studies have shown that as many as 80 percent of people with Alzheimer's also had cardiovascular disease. Aerobic exercise has been shown in many studies to decrease amyloid beta in animal models of the disease. So a heart-healthy Mediterranean lifestyle and diet can help to counter the tipping of this scale.
Que máis? Saúde cardiovascular. Tensión arterial alta, diabetes, obesidade, tabaquismo e colesterol alto... está demostrado que incrementan o noso risco de padecer alzhéimer. Algunhas autopsias demostraron que un 80 por cento de persoas con alzhéimer tamén ten trastornos cardiovasculares. Moitos estudos demostraron que o exercicio aeróbico diminúe os amiloides beta en modelos animais da doenza. Así que o estilo de vida e a dieta mediterránea, saudable para o corazón, poden axudar a contrarrestar a inclinación da balanza.
So there are many things we can do to prevent or delay the onset of Alzheimer's. But let's say you haven't done any of them. Let's say you're 65; there's Alzheimer's in your family, so you've likely inherited a gene or two that tips your scale arm a bit; you've been burning the candle at both ends for years; you love bacon; and you don't run unless someone's chasing you.
Así que hai moitas cousas que podemos facer para previr ou atrasar a aparición do alzhéimer. Pero poñamos que non fixeron nada diso. Digamos que teñen 65 anos; hai alzhéimer na súa familia, así que é probable que herdasen un xene ou dous que inclina o brazo da balanza un pouco; estiveron anos queimando a candea polos dous extremos; encántalles o touciño; e non corren a non ser que alguén os persiga.
(Laughter)
(Risos)
Let's imagine that your amyloid plaques have reached that tipping point. Your scale arm has crashed to the floor. You've tripped the cascade, setting fire to the forest, causing inflammation, tangles, and cell death. You should be symptomatic for Alzheimer's. You should be having trouble finding words and keys and remembering what I said at the beginning of this talk. But you might not be.
Imaxinemos que as súas placas amiloides alcanzaron o punto crítico. O brazo da balanza chegou ata o chan. Desencadeouse o cadoiro, prendeu lume no monte, provocando inflamación, nobelos e morte celular. Deben ter síntomas de alzhéimer. Deben ter problemas para atopar palabras e as chaves e lembrar o que dixen ao comezo desta charla. Pero poida que non.
There's one more thing you can do to protect yourself from experiencing the symptoms of Alzheimer's, even if you have the full-blown disease pathology ablaze in your brain. It has to do with neural plasticity and cognitive reserve. Remember, the experience of having Alzheimer's is ultimately a result of losing synapses. The average brain has over a hundred trillion synapses, which is fantastic; we've got a lot to work with. And this isn't a static number. We gain and lose synapses all the time, through a process called neural plasticity. Every time we learn something new, we are creating and strengthening new neural connections, new synapses.
Hai unha cousa máis que poden facer para se protexer de experimentar os síntomas do alzhéimer, mesmo se teñen toda a patoloxía da doenza desencadeada no seu cerebro. Ten que ver coa neuroplasticidade e a reserva cognitiva. Lembren que a experiencia de padecer alzhéimer é o resultado final da perda de sinapses. Un cerebro medio ten máis de cen billóns de sinapses, o que é fantástico; temos moito co que traballar. E non se trata dun número estático. Gañamos e perdemos sinapses continuamente, a través dun proceso denominado neuroplasticidade. Cada vez que aprendemos algo novo, estamos a crear e fortalecer novas conexións neurais, novas sinapses.
In the Nun Study, 678 nuns, all over the age of 75 when the study began, were followed for more than two decades. They were regularly given physical checkups and cognitive tests, and when they died, their brains were all donated for autopsy. In some of these brains, scientists discovered something surprising. Despite the presence of plaques and tangles and brain shrinkage -- what appeared to be unquestionable Alzheimer's -- the nuns who had belonged to these brains showed no signs of having the disease while they were alive.
Nun estudo con monxas, 678 monxas, todas de máis de 75 anos cando comezou o estudo, sometéronse a un seguimento durante máis de dúas décadas. Facíanlles regularmente revisións físicas e tests cognitivos, e cando faleceron, doaron os cerebros para realizar unha autopsia. Nalgúns destes cerebros, os científicos descubriron algo sorprendente. Malia a presenza de placas, nobelos e perda cerebral, o que semellaba ser alzhéimer de xeito incuestionable, as monxas ás que pertencían eses cerebros non manifestaban signos de padecer a doenza mentres estaban vivas.
How can this be? We think it's because these nuns had a high level of cognitive reserve, which is a way of saying that they had more functional synapses. People who have more years of formal education, who have a high degree of literacy, who engage regularly in mentally stimulating activities, all have more cognitive reserve. They have an abundance and a redundancy in neural connections. So even if they have a disease like Alzheimer's compromising some of their synapses, they've got many extra backup connections, and this buffers them from noticing that anything is amiss.
Como é posible? Pensamos que se debe a que estas monxas tiñan un alto nivel de reserva cognitiva, que é un xeito de dicir que tiñan máis sinapses funcionais. As persoas que teñen máis anos de formación académica, que teñen un alto grao de alfabetización, que se implican habitualmente en actividades que estimulan a mente, dispoñen de máis reserva cognitiva. Teñen unha abundancia e redundancia de conexións neurais. Así que aínda que teñan unha doenza coma o alzhéimer, que afecta algunhas das súas sinapses, teñen moitas conexións extra de reserva, e isto protéxeas de notar que existe unha perda.
Let's imagine a simplified example. Let's say you only know one thing about a subject. Let's say it's about me. You know that Lisa Genova wrote "Still Alice," and that's the only thing you know about me. You have that single neural connection, that one synapse. Now imagine you have Alzheimer's. You have plaques and tangles and inflammation and microglia devouring that synapse. Now when someone asks you, "Hey, who wrote 'Still Alice?'" you can't remember, because that synapse is either failing or gone. You've forgotten me forever.
Imaxinemos un exemplo simplificado. Poñamos que só saben unha cousa sobre un tema. Digamos que é sobre min. Saben que Lisa Genova escribiu <i>Still Alice</i>, e iso é o único que saben sobre min. Teñen esa única conexión neural, esa única sinapse. Agora imaxinen que padecen Alzheimer. Teñen placas, nobelos, inflamación e as microglías que devoran esa sinapse. Agora cando alguén lles pregunta se saben quen escribiu <i>Still Alice</i> non se lembran, porque esa sinapse está a fallar ou desapareceu. Esquecéronme para sempre.
But what if you had learned more about me? Let's say you learned four things about me. Now imagine you have Alzheimer's, and three of those synapses are damaged or destroyed. You still have a way to detour the wreckage. You can still remember my name. So we can be resilient to the presence of Alzheimer's pathology through the recruitment of yet-undamaged pathways. And we create these pathways, this cognitive reserve, by learning new things. Ideally, we want these new things to be as rich in meaning as possible, recruiting sight and sound and associations and emotion.
Pero que acontece se teñen máis información sobre min? Digamos que aprenderon catro cousas de min. Imaxinemos que padecen alzhéimer, e tres desas sinapses están deterioradas ou destruídas. Aínda teñen un xeito de desviar o desastre. Aínda poden lembrar o meu nome. Así que podemos ser resilientes á presenza da enfermidade de alzhéimer a través da captación de vías aínda non deterioradas. E creamos estas vías, esta reserva cognitiva, aprendendo cousas novas. O ideal é que estas cousas novas sexan tan ricas en significado como for posible, captando vista e oído, así como asociacións e emoción.
So this really doesn't mean doing crossword puzzles. You don't want to simply retrieve information you've already learned, because this is like traveling down old, familiar streets, cruising neighborhoods you already know. You want to pave new neural roads. Building an Alzheimer's-resistant brain means learning to speak Italian, meeting new friends, reading a book, or listening to a great TED Talk.
Así que isto en realidade non significa facer encrucillados. Non se trata de simplemente recuperar información que xa aprenderon, porque iso é como viaxar ao pasado, a rúas familiares, atopándose con veciños que xa coñecen. Trátase de asfaltar novas vías neurais. Crear un cerebro resistente ao alzhéimer significa aprender a falar italiano, coñecer novos amigos, ler un libro ou escoitar unha gran charla TED.
And if, despite all of this, you are someday diagnosed with Alzheimer's, there are three lessons I've learned from my grandmother and the dozens of people I've come to know living with this disease. Diagnosis doesn't mean you're dying tomorrow. Keep living. You won't lose your emotional memory. You'll still be able to understand love and joy. You might not remember what I said five minutes ago, but you'll remember how I made you feel. And you are more than what you can remember.
E se, malia todo isto, algún día lle diagnostican alzhéimer, hai tres leccións que aprendín da miña avoa e da ducia de persoas que coñecín que viven con esta doenza. O diagnóstico non significa que vaian morrer mañá. Sigan vivindo. Non han perder a súa memoria emocional. Aínda poderán entender o amor e a alegría. Poden non lembrar o que dixeron hai cinco minutos, mais lembrarán como os fixo sentir. E vostedes son máis do que lembran.
Thank you.
Grazas.
(Applause)
(Aplausos)