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.
Koliko vas koji ste ovde bi volelo da doživi bar 80 godina? Da. Mislim da svi mi gajimo tu nadu da ćemo doživeti duboku starost. Hajde da odemo u budućnost, gde se nalazite budući vi, i da zamislimo da svi imamo 85 godina. Sad neka svako od vas pogleda dve osobe. Jedna od njih verovatno ima Alchajmerovu bolest.
(Laughter)
(Smeh)
Alright, alright. And maybe you're thinking, "Well, it won't be me." Then, OK. You are a caregiver. So --
Dobro, dobro. Možda i mislite: „Pa, to nisam ja." U redu, onda ste vi staratelj. Tako da...
(Laughter)
(Smeh)
so in some way, this terrifying disease is likely to affect us all.
na neki način, će ova užasavajuća bolest verovatno pogoditi svakog od nas.
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.
Jednim delom strah od Alchajmera nastaje iz saznanja da se ništa ne može učiniti. Uprskos decenijskim istraživanjima, još uvek ne postoji tretman, niti lek. Tako da, ako budemo imali tu sreću da poživimo dugo, izgleda da će Alchajmer biti sudbina našeg mozga.
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?
Ali možda i ne mora da bude. Šta ako vam kažem da možemo da promenimo statistiku, da doslovno promenimo sudbinu mozga, a da se ne oslanjamo na lek, ni na napredovanja u medicini?
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.
Počnimo sa razmatranjem onoga što trenutno znamo o neurološkoj strani Alchajmera. Ovo je slika dva povezana neurona. Mesto gde se povezuju, označeno crvenim krugom, naziva se sinapsa. U sinapsu se ispuštaju neurotransmiteri. To je mesto gde se prenose signali, gde se odigrava komunikacija. Tu razmišljamo, osećamo, vidimo, čujemo, želimo... I pamtimo. I sinapsa je mesto na koje utiče Alchajmer.
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.
Hajde da zumiramo sinapsu, i da pogledamo grafički prikaz onoga što se događa. Kada se odigrava razmena informacija, pored ispuštanja neurotransmitera u sinapsu, kao što je glutamin, neuroni ispuštaju i mali peptid koji se zove amiloid beta. Obično bi amiloid beta bio uklonjen tako što ga metabolizuju mikroglije, ćelije koje su „domari" našeg mozga. Iako se o molekularnim razlozima Alchajmera još uvek raspravlja, većina neuronaučnika veruje da se bolest aktivira kada amiloid beta počne da se gomila. Previše se ispusti, ili se premalo ukloni, i u sinapsi počne da se nagomilava amiloid beta. A kada do toga dođe, vezuju se jedan za drugog, stvarajući lepljivu masu ili takozvane amiloidne naslage.
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?"
Koliko vas koji ste ovde ima 40 godina ili više? Sad se plašite da priznate. Prvi znak koji vodi ka bolesti, prisustvo amilodnih naslaga koje se nagomilavaju, već se može naći u vašem mozgu. To jedino možemo da potvrdimo ako se uradi PET snimak, jer sada živite u blaženom neznanju. Ne pokazujete znake oštećenja pamćenja, jezika ili razumevanja... Još uvek. Smatramo da je potrebno da prođe 15 do 20 godina nagomilavanja amiloidnih naslaga da bi se došlo do prelomne tačke, što bi aktiviralo molekularne reakcije, i dovelo do ispoljavanja kliničkih simptoma bolesti. Pre prelomne tačke, vaši gubici u memoriji mogu biti stvari kao što su: „Zašto sam došla u ovu sobu?" Ili „...Kako se on zove?" Ili „Gde sam ostavila ključeve?"
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?"
Pre nego što svi počnete da paničite, jer znam da se skoro svima dogodila makar jedna od ovih stvari u poslednja 24 časa, to su sve normalne vrste zaboravljanja. Zapravo, sigurna sam da se ovi primeri čak i ne tiču vašeg pamćenja, jer prvenstveno, niste obraćali pažnju gde ste spustili ključeve. Nakon prelomne tačke, propusti u pamćenju, jeziku i razumevanju su drugačiji. Umesto da pronađete ključeve u džepu kaputa, ili na stolu pored vrata, pronađete ih u frižideru ili ih pronađete i pomislite: „Za šta su ovi ključevi?"
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.
Šta se dešava kada se amiloidne naslage nagomilaju do prelomne tačke? Naši domari mikroglije postaju hiperaktivni, i oslobađaju hemikalije koje uzrokuju upale i ćelijska oštećenja. Mislimo da čak počinju da uklanjaju i same sinapse. Dolazi do hiperfosforilacije bitnog neuro transportnog proteina „tau", koji se savija u nešto što se zove čvor i ubija neurone iznutra. Kad Alchajmer stigne do srednje faze, dolazi do teških zapaljenja i čvorova, i sveopšteg napada na sinapsu, i odumiranja ćelija.
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.
Ako ste vi naučnik koji pokušava da izleči ovu bolest, tokom koje faze bi bilo najbolje da intervenišete? Mnogi naučnici se klade na najjednostavnije rešenje: sprečiti amiloidne pločice da dođu do prelomne tačke, što znači da je istraživanje za lek fokusirano na razvijanje jedinjenja koje će sprečiti, ukloniti ili smanjiti gomilanje amiloidnih pločica. Tako da će to verovatno biti preventivni lek za Alchajmer. Moraćemo da uzimamo tabletu pre nego što dođemo do prelomne tačke, pre nego što se pokrene urušavanje, pre nego što počnemo da ostavljamo ključeve u frižideru. Mislimo da zato lekovi koji se koriste danas nemaju dejstva u kliničkim ispitivanjima, ne zato što nauka nije ispravna, nego zato što su ljudi koji su ispitivani već pokazivali simptome bolesti. I već je bilo kasno. Mislite o amiloidnim pločicama kao o zapaljenoj šibici. Na prelomnoj tački, šibica je zapalila šumu. Kada se šuma zapali, više nema potrebe gasiti šibicu. Ona mora da se ugasi pre nego što šumu zahvati plamen.
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.
Dok naučnici to razreše, ovo je zapravo dobra informacija za nas, jer se ispostavilo da naš način života utiče na nagomilavanje amiloidnih pločica. Tako da ima stvari koje možemo uraditi kako ne bismo stigli do prelomne tačke.
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.
Hajde da predstavimo rizik od Alchajmera na klackalici. Na jednu stranu ćemo staviti rizične faktore, i kada ona dođe do zemlje, ispoljavate simptome, i imate Alchajmera. Recimo da imate 50 godina. Niste više tako mladi, i sa godinama su se nagomilale amiloidne pločice. Klackalica se malo nagla.
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.
Sad pogledajmo vaš DNK. Svi smo nasledili gene od majki i očeva. Neki od njih povećavaju rizik, a neki ga umanjuju. Ako ste kao Alis u „I dalje Alis", nasledili ste retku genetsku mutaciju koja ispušta mnogo amiloid bete, i samo zbog toga će vaša klackalica dotaći pod. Ali za većinu, geni koje smo nasledili će je samo malo nagnuti. Na primer, APOE4 je varijanta gena koja povećava amiloide, ali možete naslediti kopiju APOE4 od majke i oca, a da nikada ne obolite od Alchajmera, što znači da za većinu nas, DNK nije jedini koji određuje da li ćemo oboleti od Alchajmera. Šta onda određuje? Ne možemo da uradimo ništa povodom starenja ili gena koje smo nasledili. Još uvek nismo izmenili sudbinu našega mozga.
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.
Šta je sa snom? U dubokom snu sporih talasa, naše glijalne ćelije ispiraju naš mozak tečnošču iz kičmene moždine i čiste sav metabolički otpad koji se nagomilao u našim sinapsama dok smo bili budni. Duboki san je za mozak kao čišćenje pod pritiskom. Ali šta se dešava ako sami sebe zakidate na snu? Mnogi naučnici veruju da loš san zapravo može biti rani znak nastajanja Alchajmera. Jedna noć manjka sna dovodi do povećanja amiloida beta. Dokazano je da nagomilavanje amiloida izaziva poremećaje spavanja, što dalje prouzrokuje još skupljanja amiloida. Sada imamo ovu pozitivnu petlju koja se nastavlja i koja ubrzava neravnotežu.
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.
Šta još? Kardiovaskularno zdravlje. Visok krvni pritisak, dijabetes, gojaznost, pušenje, visok holesterol, za sve je dokazano da povećavaju rizik nastanka Alchajmera. Neke autopsije pokazale su da čak do 80% ljudi sa Alchajmerom takođe ima kardiovaskularne bolesti. Dokazano je da aerobičke vežbe smanjuju amiloid beta u istraživanjima sa životinjama. Mediteranski stil života i ishrana sa zdravim srcem mogu pomoći da se uspori razvoj bolesti.
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.
Postoje mnoge stvari koje možemo da uradimo kako bismo sprečili ili odložili nastanak Alchajmera. Ali recimo da niste uradili bilo šta od toga. Recimo da imate 65 godina, u vašoj porodici ima bolesti, verovatno ste nasledili gen ili dva koji će malo iskriviti klackalicu, gorite sveću sa oba kraja već godinama; obožavate slaninu; ne trčite osim ako vas neko juri.
(Laughter)
(Smeh)
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.
Zamislimo da su vaše naslage amiloida dostigle tu kritičnu tačku. Kazaljka na vagi pala je na pod. Pokrenuli ste slap, zapalili šumu i doveli do upale, mršenja i umiranja ćelija. Trebalo bi da imate simptome Alchajmera. Trebalo bi da imate problema da pronađete reči i ključeve i setite se onoga što sam rekla na početku ovog govora. Ali možda i ne.
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.
Postoji još nešto što možete uraditi kako biste se zaštitili od simptoma Alchajmera, čak i ako imate razvijenu patologiju bolesti u svom mozgu. Ima veze sa neuronskom plastičnošću i kognitivnim rezervama. Prisetite se da je doživljaj Alchajmera na kraju samo posledica gubljenja sinapsi. Prosečan mozak ima preko sto triliona sinapsi, što je fantastično, imamo dosta toga sa čime možemo da radimo. A ovo nije fiksiran broj. Stalno dobijamo i gubimo sinapse, kroz proces zvani neuronska plastičnost. Svaki put kada naučimo nešto novo, stvaramo i ojačavamo nove neuronske veze, nove sinapse.
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.
U istraživanju sa kaluđericama, 678 kaluđerica, sve starije od 75 godina u vreme početka istraživanja, praćene su više od dve decenije. Redovno su imale lekarske preglede i kognitivna ispitivanja i kada su umrle, njihovi mozgovi donirani su za autopsiju. U nekim od ovih mozgova, naučnici su otkrili nešto iznenađujuće. Uprkos prisustvu naslaga i čvorova i smanjenju mozga - što je bez pogovora bio Alchajmer - kaluđerice koje su imale ove mozgove nisu pokazivale nikakve znakove toga da su imale bolest dok su bile žive.
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.
Kako je ovo moguće? Mislimo da je zato što su ove kaluđerice imale velike kognitivne rezerve, što je drugi način da se kaže da su imale funkcionalnije sinapse. Ljudi koji imaju više godina formalnog obrazovanja, koji imaju viši nivo pismenosti, koji se redovno bave aktivnostima koje stimulišu mentalno, svi imaju veće kognitivne rezerve. Imaju obilje i višak nervnih veza. Tako da čak i ako imaju bolest poput Alchajmera koja kompromituje neke od njihovih sinapsi, imaju mnogo dodatnih rezervnih veza i ovo ih sprečava da primete da se nešto loše dešava.
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.
Uzmimo pojednostavljen primer. Recimo da znate samo jednu stvar o nečemu. Recimo da je to o meni. Znate da je Lisa Đenova napisala "I dalje Alis", i to je jedina stvar koju znate o meni. Imate tu jednu nervnu vezu, jednu sinapsu. Sada zamislite da imate Alchajmera. Imate naslage i čvorove i upale i mikroglije koji napadaju tu sinapsu. Sada kada vas neko pita: "Hej, ko je napisao 'I dalje Alis?'", ne možete da se setite, jer ta sinapsa ili propada, ili je nestala. Zaboravili ste me zauvek.
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.
Ali šta kada biste saznali više o meni? Recimo da ste naučili četiri stvari o meni. Sada zamislite da imate Alchajmera i da se oštete ili unište tri te sinapse. Još uvek imate način da ispravite štetu. Još se sećate mog imena. Možemo biti otporni na prisustvo patologije Alchajmera kroz regrutovanje onih putanja koje još nisu oštećene. Mi stvaramo te putanje, te kognitivne rezerve, tako što učimo nove stvari. Idealno bi bilo da te nove stvari budu što bogatije u značenju i da angažuju vid i sluh i asocijacije i emocije.
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.
Ovo ne podrazumeva da rešavamo ukrštenice. Ne želite da prosto posežete za već naučenim informacijama jer je ovo poput putovanja starim, poznatim ulicama, prolaženja krajevima koje već znate. Želite da stvarate nove nervne puteve. Pravljenje mozga otpornog na Alchajmera podrazumeva da učite italijanski, upoznajete nove prijatelje, čitate knjige ili slušate sjajan TED govor.
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.
Ako uprkos svemu ovome jednog dana imate dijagnozu Alchajmera, postoje tri lekcije koje sam naučila od moje bake i desetine ljudi koje sam upoznala koji žive sa ovom bolešću. Dijagnoza ne znači da ćete sutra umreti. Nastavite da živite. Nećete izgubiti svoje emotivno pamćenje. Moći ćete da razumete ljubav i radost. Možda se nećete sećati onoga što sam rekla pre pet minuta, ali ćete se sećati toga kako sam vas naterala da se osećate. Vi ste više od onoga čega možete da se prisetite.
Thank you.
Hvala vam.
(Applause)
(Aplauz)