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 ljudi ovdje bi htjelo doživjeti barem 80 godina? Da. Mislim da svi imamo ovakvo očekivanje puno nade od života u kasnoj dobi. Prebacimo se u budućnost, na vaše buduće 'vi', i zamislimo da svi imamo 85 godina. Sada neka svatko pogleda dvije osobe. Jedna od vas vjerojatno ima Alzheimerovu bolest.
(Laughter)
(Smijeh)
Alright, alright. And maybe you're thinking, "Well, it won't be me." Then, OK. You are a caregiver. So --
U redu. I možda mislite, "Pa, to neću biti ja." U redu. Onda ste njegovatelj. Dakle --
(Laughter)
(Smijeh)
so in some way, this terrifying disease is likely to affect us all.
na neki način, ova zastrašujuća bolest vjerojatno će pogoditi sve 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.
Dio straha vezanog za Alzheimera proizlazi iz osjećaja da ništa ne možemo učiniti po tom pitanju. Unatoč desetljećima istraživanja, još nemamo način utjecaja na bolest kao ni lijek. Pa ako imamo dovoljno sreće i dugo živimo, čini se da je naš mozak osuđen na Alzheimera.
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?
A možda i ne mora biti tako. Što kada bih vam rekla da možemo izmijeniti ovu statistiku, doslovno promijeniti sudbinu našeg mozga, bez oslanjanja na lijekove ili napretke 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 od promatranja onoga što trenutno razumijemo iz neuroznanosti vezano za Alzheimera. Ovo je slika dva povezana neurona. Točka spajanja, ovaj prostor zaokružen crveno, zove se sinapsa. Na sinapsi se oslobađaju neurotransmiteri. Tu se prenose signali i događa komunikacija. To je mjesto gdje razmišljamo, osjećamo, vidimo, čujemo, žudimo... i pamtimo. A upravo na sinapsi se javlja Alzheimer.
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.
Uvećajmo prikaz sinapse i pogledajmo crtani prikaz onoga što se ovdje događa. Za vrijeme procesa prijenosa informacija, uz otpuštanje neurotransmitera, poput glutamina, u sinapse, neuroni otpuštaju i mali peptid, nazvan beta amiloid. Redovno, beta amiloid se čisti i metabolizira od strane mikroglije, čistača stanica u našem mozgu. Dok se o molekularnim uzrocima Alzheimera još uvijek raspravlja, većina neuroznanstvenika vjeruje da bolest počinje kada se beta amiloid počinje nakupljati. Previše je otpušteno, ili je nedovoljno pročišćeno, i sinapsa počinje gomilati beta amiloid. I kada se to dogodi, veže ga za sebe, stvarajući ljepljive nakupine nazvane amiloidni plakovi.
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 ljudi ovdje ima 40 godina ili više? Bojite se to sada priznati. Taj početni korak u bolesti, to prisustvo amiloidnih plakova koji se nakupljaju već može biti u vašem mozgu. Jedini način da budemo sigurno u to bio bi putem PET pretrage, jer u ovom trenutku, vi ste posve nesvjesni toga. Ne pokazujete nikakva oštećenja u pamćenju, jeziku ili spoznaji... još. Mislimo da je potrebno najmanje 15 do 20 godina nakupljanja amiloidnog plaka prije negoli on dosegne prijelomnu točku, aktivirajući tada molekularni niz koji uzrokuje kliničke simptome bolesti. Prije te prekretnice, gubici u vašoj memoriji mogu uključivati stvari poput "Zašto sam došao/došla u ovu prostoriju?" ili "Oh... kako se on zove?" ili "Kamo sam stavio/stavila 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?"
Prije negoli svi ponovno počnete paničariti, jer znam da je polovina vas učinila bar jedno od ovoga u zadnja 24 sata... ovo su sve normalni oblici zaboravljanja. Zapravo, rekla bih da ovi primjeri ne moraju čak ni uključivati vašu memoriju, jer niste obraćali pažnju na to gdje ste ostavili ključeve na početku. Nakon prijelomne točke, zastoji u memoriji, jeziku i spoznaji su različiti. Umjesto da kasnije nađete ključeve u džepu svog kaputa, ili na stoliću pored vrata, nađete ih u hladnjaku, ili ih nađete i pomislite "Čemu ovo služi?"
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.
Što se, dakle, događa kada se amiloidni plakovi nakupe do te prijelomne točke? Naše mikroglija stanice, čistači, postaju prekomjerno aktivne, otpuštajući tvari koje uzokuju upalu i stanično oštećenje. Mislimo da možda počinju sa čišćenjem i samih sinapsi. Protein ključan za neuronski prijenos, zvan 'tau', postaje hiperfosforiliran i uvija se u nešto slično spirali, čvorovima, što pritišće neurone iznutra. U srednjoj fazi Alzheimera imamo brojne upale i čvorove, sveobuhvatni rat na sinapsi te odumiranje stanice.
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.
Dakle, ako biste bili znanstvenik koji pokušava izliječiti ovu bolest, na kojem točno dijelu biste intervenirali? Mnogi znanstvenici klade se u najjednostavnije rješenje: spriječiti amiloidne plakove da dosegnu prijelomnu točku, što znači da je pronalazak lijeka najviše fokusiran na razvoj sastojka koji će spriječiti, odstraniti ili smanjiti nakupljanje amiloidnog plaka. Stoga će lijek za Alzheimerovu bolest vjerojatno biti preventivna medicina. Morat ćemo uzeti tabletu prije nego dosegnemo tu prijelomnu točku, prije nego se molekularni niz aktivira, prije negoli počnemo ostavljati svoje ključeve u hladnjaku. Mislimo da zbog toga, do danas, ovakvi lijekovi nisu učinkoviti u kliničkim pokusima, ne zato što znanost nije na dobrom putu, već stoga što su ljudi u tim pokusima već imali simptome. Bilo je prekasno. Zamislite amiloidni plak kao šibicu. Na prijelomnoj točki, šibica prouzrokuje požar u šumi. Jednom kada je šuma u plamenu, nema nikakve koristi od gašenja šibice. Šibicu moraš ugasiti prije negoli šuma počne gorjeti.
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.
Čak i prije negoli znanstvenici ovo riješe, ova informacija je zapravo vrlo dobra vijest za nas, jer se ispostavlja da način na koji živimo može utjecati na nakupljanje amiloidnih plakova. I stoga možemo nešto učiniti kako ne bismo dosegnuli tu prijelomnu točku.
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.
Predočimo vaš rizik od Alzheimera kao na klackalici. Na jednoj ruci skupljat ćemo rizične čimbenike, i kada ta ruka udari u pod, imate simptome i dijagnozu Alzheimerove bolesti. Zamislimo da imate 50 godina. Niste više u cvijetu mladosti, i s godinama ste nakupili određenu količinu amiloidnih plakova. Vaša klackalica se malo nagnula.
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.
Pogledajmo sada vašu DNK. Svi smo mi naslijedili gene od svojih majki i očeva. Neki od tih gena povećat će naš rizik, a neki smanjiti. Ako ste poput Alice u filmu 'I dalje Alice', naslijedili ste rijetku genetsku mutaciju koja proizvodi beta amiloid i samo to će već nagnuti vašu klackalicu do poda. No za većinu nas, geni koje nasljeđujemo samo će malo nagnuti ruku na tu stranu. Na primjer, APOE4 je varijanta gena koja povećava amiloid, no možete naslijediti APOE4 od mame ili tate, a ipak ne dobiti Alzheimera, što znači da za većinu nas, sama naša DNK ne određuje hoćemo li dobiti Alzheimera. Što onda određuje? Ne možemo ništa učiniti u vezi starenja, ili gena koje nasljeđujemo. Za sada nismo izmijenili sudbinu našeg 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.
Što je sa spavanjem? Kod sporih valova u dubokom snu, naše glijalne stanice čiste cerebralnu spinalnu tekućinu po čitavom mozgu odstranjujući metabolički otpad koji se nakupljao u našim sinapsama dok smo bili budni. Duboki san je za mozak poput moćnog čistača. No, što se događa ako si uskraćujete san? Mnogi znanstvenici vjeruju da loša higijena spavanja zapravo može predskazati Alzheimera. Samo jedna noć uskraćivanja sna dovodi do povećanja beta amiloida. A pokazalo se kako nakupljanje amiloida ometa spavanje, što zauzvrat uzrokuje više amiloida koji se može nakupljati. I tako sada imamo tu pozitivnu povratnu vezu koja će ubrzati prevagu.
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.
Što još? Zdravlje srca i krvnih žila. Visoki krvni tlak, dijabetes, pretilost, pušenje, visoki kolesterol, svi su ukazali na povećanje našeg rizika od razvoja Alzheimera. Neke studije s obdukcija pokazale su da čak 80% ljudi koji su bolovali od Alzheimera, imali su i neku bolest krvožilnog sustava. Aerobna vježba pokazala se u mnogim studijama da smanjuje beta amiloid na životinjskim modelima bolesti. Dakle, mediteranski način života i prehrane, dobar za srce može pomoći i prevagnuti na suprotnu stranu.
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.
Dakle, ima mnogo toga što možemo učiniti da spriječimo ili odgodimo početak Alzheimera. No, recimo da niste učinili ništa od toga. Pretpostavimo da imate 65 godina; Alzheimerova bolest postoji u vašoj obitelji, i vjerojatno ste naslijedili koji gen, što čini malu prevagu na ovu stranu Godinama ste se naprezali, volite slaninu, i ne trčite osim ako vas netko ne lovi.
(Laughter)
(Smijeh)
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 vaši amiloidni plakovi dosegnuli prijelomnu točku. Vaša ruka prevagom je tresnula o pod, aktivirali ste molekularni niz, zapalili vatru u šumi, što je dovelo do izgaranja, čvorova te odumiranja stanica. Trebali biste imati simptome Alzheimera. Trebalo bi vam biti teško pronaći ispravnu riječ, ključeve, ili zapamtiti što sam rekla na početku ovog govora. No, možda i nije.
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.
Ima još nešto što možete učiniti kako biste se zaštitili od proživljavanja simptoma Alzheimera, čak i ako u svom mozgu imate patologiju bolesti u punom zamahu. To je vezano za neuralnu plastičnost i kognitivne rezerve. Zapamtite, iskustvo koje imate bolujući od Alzheimera rezultat je gubitka sinapsi. Prosječan mozak ima preko stotinu trilijuna sinapsi, što je fantastično, imamo mnogo toga s čime možemo raditi. I to nije samo statičan broj. Mi neprestano stječemo i gubimo sinapse, kroz proces koji se zove neuralna plastičnost. Svaki puta kada naučimo nešto novo, stvaramo i jačamo nove neuralne 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 jednoj studiji o redovnicama, njih 678, sve su bile stare preko 75 godina kada je studija počela, i promatrane su preko dva desetljeća. Redovito su bile podvrgnute sistematskim pregledima i kognitivnim testovima, i kada su umrle, mozgovi svih njih bili su donirani za potrebe obdukcije. U nekim od tih mozgova, znanstvenici su otkrili nešto iznenađujuće. Unatoč postojanju plakova, čvorova, te smanjivanju mozga, što je neupitno ukazivalo na Alzheimera, mozgovi tih redovnica nisu pokazivali znakove postojanja bolesti 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 to moguće? Mislimo da je to stoga što su imale visoki stupanj kognitivne rezerve, što bi značilo da su imale funkcionalnije sinapse. Osobe koje imaju više godina formalnog obrazovanja, koje imaju visok stupanj pismenosti, koje su redovito zaokupljene mentalno stimulativnim aktivnostima, sve te osobe imaju veće kognitivne rezerve. One imaju obilje i višak neuralnih veza. Pa čak i ako imaju bolest poput Alzheimera, koja ugrožava neke od njihovih sinapsi, one imaju i još mnogo dodatnih rezervnih veza, koje ublažavaju dojam da nešto nije u redu.
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.
Zamislimo pojednostavljeni primjer. Recimo da znate samo jedan podatak o nekoj temi. Recimo da se radi o meni. Znate da je Lisa Genova napisala 'I dalje Alice', i to je jedino što znate o meni. Imate tu jedinu neuralnu vezu, tu jednu sinapsu. Sada zamislite da bolujete od Alzheimera. Imate plakove, čvorove i upale te mikrogliju koja guta tu sinapsu. I sada, kada vas netko pita, "Hej, tko je napisao 'I dalje Alice?'" vi se ne možete sjetiti, jer je ta sinapsa ili zakazala ili odumrla. Zauvijek ste me zaboravili.
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 što ako ste o meni znali nešto više? Recimo da ste naučili četiri stvari o meni. Sada zamislite da bolujete od Alzheimera, i tri od tih sinapsi su oštećene ili uništene. I dalje imate način da zaobiđete prepreku. I dalje se sjećate mog imena. Znači, možemo biti prilagodljivi na prisustvo patologije Alzheimera aktiviranjem još neoštećenih puteva. I mi stvaramo te puteve, te kognitivne rezerve, kada učimo nove stvari. U idealnom slučaju, želimo da te nove stvari budu što bogatije značenjem, aktivirajući vid, zvuk, 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.
Dakle, to zaista ne znači rješavanje križaljki. Ne želite samo izvlačiti informacije koje ste već naučili, jer to je poput vožnje starim, poznatim cestama, kružeći četvrtima koja već poznajete. Vi želite stvoriti nove neuralne puteve, stvarati mozak koji će biti otporan na Alzheimera znači naučiti govoriti talijanski, steći nove prijatelje, pročitati knjigu, ili odslušati neki odličan 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.
I ako unatoč svemu ovome, jednog dana dobijete dijagnozu Alzheimera, tri su lekcije koje sam naučila od svoje bake i deseci ljudi koje sam upoznala i koji žive s ovom bolešću. Dijagnoza ne znači da ćete sutra umrijeti. Nastavite živjeti. Nećete izgubiti svoju emocionalnu memoriju. I dalje ćete moći razumjeti ljubav i radost. Možda se nećete sjećati što sam rekla prije pet minuta, ali ćete se sjećati kakav osjećaj sam izazvala u vama. I vi ste mnogo više od onoga čega se možete sjetiti.
Thank you.
Hvala vam.
(Applause)
(Pljesak)