A quants de vostès els agradaria viure fins als 80 anys? Exacte. Crec que tots tenim l'esperança de viure fins a una edat avançada. Fem veure que som al futur, vostès d'aquí a uns anys, Imaginem que tots tenim 85 anys. Ara mirin a dues persones. Un de vostès probablement té Alzheimer.
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.
(Riure)
(Laughter)
D'acord, d'acord. I potser pensen, "no seré pas jo". Bé, d'acord. Vostè és el cuidador. Així que...
Alright, alright. And maybe you're thinking, "Well, it won't be me." Then, OK. You are a caregiver. So --
(Rialles)
(Laughter)
d'alguna manera, és possible que aquesta malaltia tan terrible ens afecti a tots.
so in some way, this terrifying disease is likely to affect us all.
Part de la por que genera l'Alzheimer prové de la idea que no podem fer-hi res. Tot i que s'ha investigat durant dècades, encara no hi ha cap tractament ni cura. Si tenim la sort de viure molts anys, sembla que l'Alzheimer sigui el destí del nostre cervell.
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.
Però potser no ha de ser així. I si us digués que es poden canviar aquestes estadístiques, literalment, canviar el destí del cervell, sense dependre d'una cura o avenços en la medicina?
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?
Comencem veient el que entenem ara per ara sobre la neurociència de l'Alzheimer. Us mostro una imatge de dues neurones connectades. El punt de connexió, l'espai en vermell, es diu sinapsi. La sinapsi és des d'on s'emeten els neurotransmissors. Aquí és on es transmeten els senyals, on té lloc la comunicació. Aquí és on pensem, sentim, veiem, escoltem, desitgem... i recordem. I la sinapsi és on té lloc l'Alzheimer.
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.
Apropem-nos a la sinapsi i mirem el que passa, en aquest gràfic. Durant el procés de comunicar informació, a més d'emetre neurotransmissors com glutamats a la sinapsi, les neurones també emeten un petit pèptid: el beta amiloide. Normalment, el beta amiloide s'elimina, metabolitzat per les micròglies, les cèl·lules protectores del cervell. Tot i que les causes mol·leculars de l'Alzheimer encara es debaten, la majoria de neurocientífics creuen que la malaltia comença quan els beta amiloides s'acumulen. Se n'emeten massa o no se n'eliminen prou, i la sinapsi es comença a omplir de beta amiloides. I quan això succeeix, s'enllaça, formant les plaques amiloides, uns agregats enganxifosos.
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.
Quants de vostès tenen 40 anys o més? Ara no ho volen admetre. Aquesta etapa inicial a la malaltia, la presència de plaques d'amiloides que s'acumulen ja es poden trobar als seus cervells. La manera de saber-ho del cert seria amb un escàner PET, ja que ara mateix en sou feliçment inconscients. No mostreu cap deteriorament de memòria, llenguatge o capacitats cognitives... encara. Creiem que cal una acumulació de plaques d'amiloides de 15 a 20 anys fins que s'arriba a un punt crític, es desencadena una cascada mol·lecular que causa els símptomes clínics de la malaltia. Abans d'arribar a aquest punt crític, els lapsus de la memòria poden incloure coses com "Per què he entrat a aquesta habitació?" o "Com es diu aquest?" o "On he deixat les claus?"
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?"
Però abans no s'espantin un altre cop, perquè la meitat n'ha fet una d'aquestes en les darreres 24 hores, són tipus d'oblits normals. De fet, diria que aquests exemples ni tan sols no impliquen la memòria, ja que no paraven atenció a on deixaven les claus per començar. Després d'aquest punt crític, els problemes de memòria, llenguatge i cognició són diferents. En comptes d'acabar trobant les claus a la butxaca, o a la tauleta del rebedor, les troba a la nevera, o les troba i pensa, "Per a què serveixen?"
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?"
Què passa quan les plaques d'amiloides s'acumulen fins a aquest punt crític? Les cèl·lules micròglies netejadores passen a estar hiperactivades, i emeten unes substàncies que causen inflamació i dany cel·lular. Pensem que potser comencen a eliminar les sinapsis. Una proteïna neuronal important, la tau, passa a estar hiperfosforilada s'entortolliga en un 'cabdell', que escanya les neurones des de dins. En la fase mitjana de l'Alzheimer tenim una gran inflamació, cabdells, una guerra a la sinapsi i mort cel·lular.
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.
Si fossin científics intentant curar aquesta malaltia, quan pensen que seria ideal intervenir? Molts científics aposten per la solució més senzilla: impedir que les plaques amiloides arribin al punt crític, vol dir que el descobriment de fàrmacs se centra en crear una combinació que previngui, elimini o redueixi l'acumulació de plaques amiloides. La cura de la malaltia sembla que serà una medicina de prevenció. Pendrem una pastilla abans d'arribar al punt crític, abans que es desencadeni la cascada, abans que comencem a deixar les claus a la nevera. Per això, creiem que els medicaments han fallat en estudis clínics - no perquè la ciència no sigui correcta, sinó perquè les persones en les proves ja mostraven símptomes. Ja era massa tard. Pensin en les plaques amiloides com un llumí. En el punt crític, el llumí cala foc al bosc. Quan el bosc està en flames, ja no soluciona res apagar el llumí. S'ha d'apagar abans que el bosc s'incendiï.
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.
Abans que se solucioni això, aquesta informació ja és una bona notícia perquè sembla que la manera de viure pot influenciar l'acumulació de plaques amiloides. Hi ha coses que podem fer per evitar d'arribar al punt crític.
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.
Imaginem el seu risc d'Alzheimer en una balança. Apilem els factors de risc en un braç, i quan el braç toca a terra, ja són simptomàtics i se'ls diagnostica l'Alzheimer. Imaginem que tenen 50 anys. Ja no són jovenets, i amb l'edat ja s'han acumulat les plaques amiloides. La seva balaça s'inclina una mica.
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.
Ara mirem el seu ADN. Hem heretat els gens de les nostres mares i pares. Alguns d'aquests gens augmentaran el risc i d'altres el disminuiran. Si són l'Alice, de "Sempre Alice", han heretat una mutació genètica rara que produeix beta amiloides sense parar, i això sol inclinarà la balança cap a terra. Per la majoria, els gens que hem heretat només desviaran una mica el braç. Per exemple, l'ApoE4 és un gen variant que augmenta els amiloides, però es pot heretar una còpia del ApoE4 de la mare i el pare i no desenvolupar mai Alzheimer, que significa que, per a la majoria, el nostre ADN sol no determina si tindrem la malaltia. I què ho fa, doncs? No podem impedir fer-nos grans, ni els gens heretats. Fins ara, no hem canviat el destí del cervell.
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.
I quan dormim? En el son profund, les cèl·lules glials esbandeixen líquid cefalorraquidi per tot el cervell, netegen residus metabòlics que s'han acumulat a les sinapsis quan estàvem desperts. El son profund és una neteja a fons del cervell. Què passa si no es dorm el necessari? Molts científics creuen que una mala higiene del son podria ser un predictor de l'Alzheimer. Privar el son una sola nit condueix a un augment de beta amiloides. I l'acumulació d'amiloides s'ha demostrat que altera el son, la qual cosa comporta més acumulació d'amiloides. Ara tenim aquest cercle positiu que es retroalimenta i accelerarà la desviació de la balança.
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.
I què més? La salut cardiovascular. Hipertensió, diabetis, obesitat, fumar i el colesterol alt s'ha demostrat que augmenten el risc de desenvolupar Alzheimer. Estudis d'autopsia han mostrat que fins a un 80 per cent de gent amb Alzheimer també tenien problemes cardiovasculars. Estudis confirmen que l'exercici l'aeròbic redueix la beta amiloide en models animals de la malaltia. Un cor sa, una vida i dieta mediterrànies
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
ajuden a contrarrestar la desviació de la balança. Hi ha moltes coses que podem fer per prevenir o retardar l'inici de l'Alzheimer. Però diguem que n'heu fet cap. Imaginem que teniu 65 anys; i teniu Alzheimer a la família. Algun gen heu pogut heretar i pot desviar la balança una mica, fa anys que us excediu; us encanta la cansalada;
can help to counter the tipping of this scale. 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;
i només correu quan us persegueixen.
and you don't run unless someone's chasing you.
(Rialles) Imaginem: les plaques amiloides són al punt crític. La balança s'ha precipitat al terra S'ha activat la cascada, s'ha calat foc al bosc, i causa inflamació, cabdells i mort cel·lular. Començaríeu amb els símptomes de la malaltia. Tindríeu problemes per trobar les paraules i les claus, per recordar el què he dit a l'inici de la xerrada.
(Laughter) 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.
O podria no ser així. Encara podeu fer una cosa per protegir-vos d'experimentar els símptomes de l'Alzheimer, encara que la patologia de la malaltia us cremi al cervell. Té a veure amb la plasticitat neuronal i la reserva cognitiva. Recordeu, el fet de tenir Alzheimer és el resultat de perdre les sinapsis. Un cervell normal té més de cent bilions de sinapsis. Fantàstic. Tenim molt de material. No és un nombre estàtic. Guanyem i perdem sinapsis constantment, a través de la plasticitat neuronal. Quan aprenem una cosa nova, creem i enfortim noves connexions,
But you might not be. 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,
noves sinapsis. A l'"Estudi de les monges" es va fer el seguiment de 678 monges de més de 75 anys al principi de l'estudi, durant més de dues dècades. Se'ls feien exàmens físics i tests cognitius regularment, i quan morien, es donaven els cervells per a autòpsia. En alguns dels cervells es va descobrir una cosa inesperada. Tot i la presència de plaques, cabdells i reducció del cervell que semblava indubtablement Alzheimer. Les monges no havien mostrat senyals
new synapses. 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
d'Alzheimer en vida. Com és possible? Creiem que aquestes monges tenien un alt nivell de reserva cognitiva, que vol dir que tenien més sinapsis funcionals. Les persones amb més anys d'educació formal, amb un nivell més alt de coneixements, que fan activitats d'estimulació mental, tenen més reserva cognitiva. Tenen abundància i redundància de connexions neuronals. Tot i tenir una malaltia com l'Alzheimer, que els afecta algunes sinapsis, tenen connexions extres de reserva,
of having the disease while they were alive. 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,
que fa que no s'adonin que alguna cosa va malament Imaginem un exemple senzill. Imaginem que només saben una cosa d'un tema. Sobre mi. Saben que Lisa Genova va escriure 'Sempre Alice', i és l'únic que saben sobre mi. Tenen una sola connexió neuronal, una sola sinapsis. Imaginin que tenen Alzheimer. Tenen plaques i cabdells i inflamació i micròglies que devoren la sinapsi. Si algú els pregunta "Qui ha escrit aquest llibre?" No ho recorden perquè la sinapsis falla o ja no hi és.
and this buffers them from noticing that anything is amiss. 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.
M'han oblidat per sempre. I si haguessin après més coses sobre mi? Diguem que han après quatre coses. Ara tenen Alzheimer, i tres de les sinapsis s'han espatllat o destruit. Encara tenen una manera per evitar el desastre. Encara poden recordar el meu nom. Podem ser resistents a la presència de patologia de la malaltia si busquem camins encara no fets malbé. Creem camins, reserva cognitiva, aprenent coses noves. Haurien de ser coses molt riques en significat,
You've forgotten me forever. 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,
que impliquin vista i oïda, associacions i emocions. No vol dir que fem mots encreuats. No volem només recuperar el que ja hem après, perquè això és com viatjar per llocs familiars, com anar per barris que ja coneixem. S'han d'asfaltar nous camins de neurones Crear un cervell resistent a l'Alzheimer és aprendre a parlar Italià, fer nous amics, llegir un llibre,
recruiting sight and sound and associations and emotion. 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,
o escoltar una bona xerrada de TED. I si, tot i això, un dia us diagnostiquen Alzheimer, us deixo amb tres lliçons de la meva àvia i de molta altra gent que he conegut amb aquesta malaltia. El diagnòstic no vol dir morir-se demà. Continueu vivint. No perdreu la vostra memòria emocional. Encara podreu entendre l'amor i l'alegria. Pot ser que no recordeu el que he dit fa cinc minuts, però recordareu com us he fet sentir.
or listening to a great TED Talk. 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.
I, al final, som més del que recordem.
And you are more than what you can remember.
Gràcies. (Aplaudiments)
Thank you. (Applause)