9:59:59.000,9:59:59.000 How many people here would like to live[br]to be at least 80 years old? 9:59:59.000,9:59:59.000 Yeah. 9:59:59.000,9:59:59.000 I think we all have[br]this hopeful expectation 9:59:59.000,9:59:59.000 of living into old age. 9:59:59.000,9:59:59.000 Let's project out into the future, 9:59:59.000,9:59:59.000 to your future yous, 9:59:59.000,9:59:59.000 and let's imagine that we're all 85. 9:59:59.000,9:59:59.000 Now everyone look at two people. 9:59:59.000,9:59:59.000 One of you probably has[br]Alzheimer's disease. 9:59:59.000,9:59:59.000 Alright, alright. 9:59:59.000,9:59:59.000 And maybe you're thinking, well, 9:59:59.000,9:59:59.000 it won't be me. 9:59:59.000,9:59:59.000 Then, okay, you are a caregiver. 9:59:59.000,9:59:59.000 So in some way, 9:59:59.000,9:59:59.000 this terrifying disease[br]is likely to affect us all. 9:59:59.000,9:59:59.000 Part of the fear around Alzheimer's[br]stems from the sense 9:59:59.000,9:59:59.000 that there's nothing we can do about it. 9:59:59.000,9:59:59.000 Despite decades of research, we still[br]have no disease-modifying treatment 9:59:59.000,9:59:59.000 and no cure. 9:59:59.000,9:59:59.000 So if we're lucky enough[br]to live long enough, 9:59:59.000,9:59:59.000 Alzheimer's appears to be[br]our brain's destiny. 9:59:59.000,9:59:59.000 But maybe it doesn't have to be. 9:59:59.000,9:59:59.000 What if I told you we could[br]change these statistics, 9:59:59.000,9:59:59.000 literally change our brain's destiny, 9:59:59.000,9:59:59.000 without relying on a cure[br]or advancements in medicine? 9:59:59.000,9:59:59.000 Let's begin by looking at[br]what we currently understand 9:59:59.000,9:59:59.000 about the neuroscience of Alzheimer's. 9:59:59.000,9:59:59.000 Here's a picture[br]of two neurons connecting. 9:59:59.000,9:59:59.000 The point of connection,[br]this space circled in red, 9:59:59.000,9:59:59.000 is called the synapse. 9:59:59.000,9:59:59.000 The synapse is where[br]neurotransmitters are released. 9:59:59.000,9:59:59.000 This is where signals are transmitted, 9:59:59.000,9:59:59.000 where communication happens. 9:59:59.000,9:59:59.000 This is where we think, 9:59:59.000,9:59:59.000 feel, see, hear, desire, 9:59:59.000,9:59:59.000 and remember. 9:59:59.000,9:59:59.000 And the synapse[br]is where Alzheimer's happens. 9:59:59.000,9:59:59.000 Let's zoom in on the synapse 9:59:59.000,9:59:59.000 and look at a cartoon representation[br]of what's going on. 9:59:59.000,9:59:59.000 During the business[br]of communicating information, 9:59:59.000,9:59:59.000 in addition to releasing neurotransmitters[br]like glutamate into the synapse, 9:59:59.000,9:59:59.000 neurons also release a small peptide 9:59:59.000,9:59:59.000 called amyloid beta. 9:59:59.000,9:59:59.000 Normally, amyloid beta is cleared away[br]and metabolized by microglia, 9:59:59.000,9:59:59.000 the janitor cells of our brains. 9:59:59.000,9:59:59.000 While the molecular causes[br]of Alzheimer's are still debated, 9:59:59.000,9:59:59.000 most neuroscientists believe[br]that the disease begins 9:59:59.000,9:59:59.000 when amyloid beta begins to accumulate. 9:59:59.000,9:59:59.000 Too much is released,[br]or not enough is cleared away, 9:59:59.000,9:59:59.000 and the synapse begins[br]to pile up with amyloid beta. 9:59:59.000,9:59:59.000 And when this happens, it binds to itself, 9:59:59.000,9:59:59.000 forming sticky aggregates[br]called amyloid plaques. 9:59:59.000,9:59:59.000 How many people here[br]are 40 years old or older? 9:59:59.000,9:59:59.000 You're afraid to admit it now. 9:59:59.000,9:59:59.000 This initial step into the disease, 9:59:59.000,9:59:59.000 this presence of amyloid[br]plaques accumulating, 9:59:59.000,9:59:59.000 can already be found in your brains. 9:59:59.000,9:59:59.000 Now, the only way we could[br]be sure of this would be 9:59:59.000,9:59:59.000 through a PET scan, because at this point, 9:59:59.000,9:59:59.000 you are blissfully unaware. 9:59:59.000,9:59:59.000 You're not showing any impairments[br]in memory, language, or cognition 9:59:59.000,9:59:59.000 yet. 9:59:59.000,9:59:59.000 We think it takes at least 15 to 20 years[br]of amyloid plaque accumulation 9:59:59.000,9:59:59.000 before it reaches a tipping point, 9:59:59.000,9:59:59.000 then triggering a molecular cascade 9:59:59.000,9:59:59.000 that causes the clinical[br]symptoms of the disease. 9:59:59.000,9:59:59.000 Prior to the tipping point, 9:59:59.000,9:59:59.000 your lapses in memory[br]might include things like, 9:59:59.000,9:59:59.000 "Why did I come in this room?" 9:59:59.000,9:59:59.000 or "Oh, what's his name?" 9:59:59.000,9:59:59.000 or "Where did I put my keys?" 9:59:59.000,9:59:59.000 Yeah, now before you all[br]start freaking out again, 9:59:59.000,9:59:59.000 because I know half of you 9:59:59.000,9:59:59.000 did at least one of those[br]in the last 24 hours, 9:59:59.000,9:59:59.000 these are all normal kinds of forgetting. 9:59:59.000,9:59:59.000 In fact, I would argue that these examples 9:59:59.000,9:59:59.000 might not even involve your memory, 9:59:59.000,9:59:59.000 because you didn't pay attention 9:59:59.000,9:59:59.000 to where you put your keys[br]in the first place. 9:59:59.000,9:59:59.000 After the tipping point, 9:59:59.000,9:59:59.000 the glitches in memory,[br]language, and cognition are different. 9:59:59.000,9:59:59.000 Instead of eventually finding[br]your keys in your coat pocket, 9:59:59.000,9:59:59.000 or on the table by the door, 9:59:59.000,9:59:59.000 you find them in the refrigerator, 9:59:59.000,9:59:59.000 or you find them and you think, 9:59:59.000,9:59:59.000 "What are these for?" 9:59:59.000,9:59:59.000 Okay, so what happens[br]when amyloid plaques 9:59:59.000,9:59:59.000 accumulate to this tipping point? 9:59:59.000,9:59:59.000 Our microglia janitor cells[br]become hyper-activated, 9:59:59.000,9:59:59.000 releasing chemicals that cause[br]inflammation and cellular damage. 9:59:59.000,9:59:59.000 We think they might actually[br]start clearing away 9:59:59.000,9:59:59.000 the synapses themselves. 9:59:59.000,9:59:59.000 A crucial neural transport protein[br]called tau becomes hyperphosphorylated 9:59:59.000,9:59:59.000 and twists itself[br]into something called tangles 9:59:59.000,9:59:59.000 which choke off the neurons[br]from the inside. 9:59:59.000,9:59:59.000 By mid-stage Alzheimer's,[br]we have massive inflammation and tangles 9:59:59.000,9:59:59.000 and all-out war at the synapse 9:59:59.000,9:59:59.000 and cell death. 9:59:59.000,9:59:59.000 So if you are a scientist[br]trying to cure this disease, 9:59:59.000,9:59:59.000 at what point would you ideally[br]want to intervene? 9:59:59.000,9:59:59.000 Many scientists are betting big[br]on the simplest solution: 9:59:59.000,9:59:59.000 keep amyloid plaques[br]from reaching that tipping point, 9:59:59.000,9:59:59.000 which means that drug discovery[br]is largely focused on developing 9:59:59.000,9:59:59.000 a compound that will prevent, 9:59:59.000,9:59:59.000 eliminate, or reduce[br]amyloid plaque accumulation. 9:59:59.000,9:59:59.000 And so the cure for Alzheimer's 9:59:59.000,9:59:59.000 will likely be a preventative medicine. 9:59:59.000,9:59:59.000 We're going to have to take this pill[br]before we reach that tipping point, 9:59:59.000,9:59:59.000 before the cascade is triggered, 9:59:59.000,9:59:59.000 before we start leaving[br]our keys in the refrigerator. 9:59:59.000,9:59:59.000 We think this is why, to date, these kinds[br]of drugs have failed in clinical trials, 9:59:59.000,9:59:59.000 not because the science wasn't sound, 9:59:59.000,9:59:59.000 but because the people in these trials 9:59:59.000,9:59:59.000 were already symptomatic. 9:59:59.000,9:59:59.000 It was too late. 9:59:59.000,9:59:59.000 Think of amyloid plaques as a lit match. 9:59:59.000,9:59:59.000 At the tipping point, the match[br]sets fire to the forest. 9:59:59.000,9:59:59.000 Once the forest is ablaze, 9:59:59.000,9:59:59.000 it doesn't do any good[br]to blow out the match. 9:59:59.000,9:59:59.000 You have to blow out the match[br]before the forest catches fire. 9:59:59.000,9:59:59.000 Even before scientists sort this out, 9:59:59.000,9:59:59.000 this information is actually[br]really good news for us, 9:59:59.000,9:59:59.000 because it turns out that the way[br]we live can influence 9:59:59.000,9:59:59.000 the accumulation of amyloid plaques. 9:59:59.000,9:59:59.000 And so there are things we can do 9:59:59.000,9:59:59.000 to keep us from reaching[br]that tipping point. 9:59:59.000,9:59:59.000 Let's picture your risk of Alzheimer's 9:59:59.000,9:59:59.000 as a see-saw scale. 9:59:59.000,9:59:59.000 We're going to pile[br]risk factors on one arm, 9:59:59.000,9:59:59.000 and when that arm hits the floor,[br]you are symptomatic 9:59:59.000,9:59:59.000 and diagnosed with Alzheimer's. 9:59:59.000,9:59:59.000 Let's imagine you're 50 years old. 9:59:59.000,9:59:59.000 You're not a spring chicken anymore, 9:59:59.000,9:59:59.000 so you've accumulated[br]some amyloid plaques with age. 9:59:59.000,9:59:59.000 You're scale is tipped a little bit. 9:59:59.000,9:59:59.000 Now let's look at your DNA. 9:59:59.000,9:59:59.000 We've all inherited our genes[br]from our moms and our dads. 9:59:59.000,9:59:59.000 Some of these genes will increase our risk 9:59:59.000,9:59:59.000 and some will decrease it. 9:59:59.000,9:59:59.000 If you're like Alice in "Still Alice," 9:59:59.000,9:59:59.000 you've inherited a rare genetic mutation 9:59:59.000,9:59:59.000 that cranks out amyloid beta, 9:59:59.000,9:59:59.000 and this alone will tip[br]your scale arm to the ground. 9:59:59.000,9:59:59.000 But for most of us, the genes[br]we inherit will only tip the arm a bit. 9:59:59.000,9:59:59.000 For example, APOE4 is a gene variant 9:59:59.000,9:59:59.000 that increases amyloid, 9:59:59.000,9:59:59.000 but you can inherit a copy of APOE4[br]from mom and dad 9:59:59.000,9:59:59.000 and still never get Alzheimer's, 9:59:59.000,9:59:59.000 which means that for most of us, 9:59:59.000,9:59:59.000 our DNA alone does not determine[br]whether we get Alzheimer's. 9:59:59.000,9:59:59.000 So what does? 9:59:59.000,9:59:59.000 We can't do anything about getting older 9:59:59.000,9:59:59.000 or the genes we've inherited. 9:59:59.000,9:59:59.000 So far, we haven't changed[br]our brain's destiny. 9:59:59.000,9:59:59.000 What about sleep? 9:59:59.000,9:59:59.000 In slow-wave deep sleep,[br]our glial cells 9:59:59.000,9:59:59.000 rinse cerebral spinal fluid[br]throughout our brains 9:59:59.000,9:59:59.000 clearing away metabolic waste[br]that accumulated in our synapses 9:59:59.000,9:59:59.000 while we were awake. 9:59:59.000,9:59:59.000 Deep sleep is like[br]a power cleanse for the brain. 9:59:59.000,9:59:59.000 But what happens if you short-change[br]yourself on sleep? 9:59:59.000,9:59:59.000 Many scientists believe[br]that poor sleep hygiene 9:59:59.000,9:59:59.000 might actually be[br]a predictor of Alzheimer's. 9:59:59.000,9:59:59.000 A single night of sleep deprivation[br]leads to an increase in amyloid beta. 9:59:59.000,9:59:59.000 And amyloid accumulation[br]has been shown to disrupt sleep, 9:59:59.000,9:59:59.000 which in turn causes[br]more amyloid to accumulate. 9:59:59.000,9:59:59.000 And so now we have[br]this positive feedback loop 9:59:59.000,9:59:59.000 that's going to accelerate[br]the tipping of that scale. 9:59:59.000,9:59:59.000 What else? 9:59:59.000,9:59:59.000 Cardiovascular health. 9:59:59.000,9:59:59.000 High blood pressure, diabetes,[br]obesity, smoking, high cholesterol, 9:59:59.000,9:59:59.000 have all been shown to increase[br]our risk of developing Alzheimer's. 9:59:59.000,9:59:59.000 Some autopsy studies have shown[br]that as many as 80 percent 9:59:59.000,9:59:59.000 of people with Alzheimer's[br]also had cardiovascular disease. 9:59:59.000,9:59:59.000 Aerobic exercise has been shown[br]in many studies 9:59:59.000,9:59:59.000 to decrease amyloid beta 9:59:59.000,9:59:59.000 in animal models of the disease. 9:59:59.000,9:59:59.000 So a heart-healthy Mediterranean[br]lifestyle and diet 9:59:59.000,9:59:59.000 can help to counter[br]the tipping of this scale. 9:59:59.000,9:59:59.000 Okay, so there are many things[br]we can do to prevent 9:59:59.000,9:59:59.000 or delay the onset of Alzheimer's, 9:59:59.000,9:59:59.000 but let's say you haven't[br]done any of them. 9:59:59.000,9:59:59.000 Let's say you're 65, 9:59:59.000,9:59:59.000 there's Alzheimer's in your family,[br]so you've likely inherited a gene or two 9:59:59.000,9:59:59.000 that tips your scale arm a bit, 9:59:59.000,9:59:59.000 you've been burning the candle[br]at both ends for years, 9:59:59.000,9:59:59.000 you love bacon, 9:59:59.000,9:59:59.000 and you don't run unless[br]someone's chasing you. 9:59:59.000,9:59:59.000 Let's imagine that your amyloid plaques[br]have reached that tipping point. 9:59:59.000,9:59:59.000 Your scale arm has crashed to the floor. 9:59:59.000,9:59:59.000 You've tripped the cascade, 9:59:59.000,9:59:59.000 setting fire to the forest, 9:59:59.000,9:59:59.000 causing inflammation, tangles,[br]and cell death. 9:59:59.000,9:59:59.000 You should be symptomatic for Alzheimer's. 9:59:59.000,9:59:59.000 You should be having trouble[br]finding words and keys 9:59:59.000,9:59:59.000 and remember what I said[br]at the beginning of this talk. 9:59:59.000,9:59:59.000 But you might not be. 9:59:59.000,9:59:59.000 There's one more thing you can do[br]to protect yourself 9:59:59.000,9:59:59.000 from experiencing[br]the symptoms of Alzheimer's 9:59:59.000,9:59:59.000 even if you have the full-blown disease[br]pathology ablaze in your brain. 9:59:59.000,9:59:59.000 It has to do with neural plasticity[br]and cognitive reserve. 9:59:59.000,9:59:59.000 Remember, the experience[br]of having Alzheimer's 9:59:59.000,9:59:59.000 is ultimately a result of losing synapses. 9:59:59.000,9:59:59.000 The average brain has[br]over a hundred trillion synapses, 9:59:59.000,9:59:59.000 which is fantastic. We've got[br]a lot to work with. 9:59:59.000,9:59:59.000 And this isn't a static number. 9:59:59.000,9:59:59.000 We gain and lose synapses[br]all the time through a process 9:59:59.000,9:59:59.000 called neural plasticity. 9:59:59.000,9:59:59.000 Every time we learn something new, 9:59:59.000,9:59:59.000 we are creating and strengthening[br]new neural connections, 9:59:59.000,9:59:59.000 new synapses. 9:59:59.000,9:59:59.000 In the nun study, 9:59:59.000,9:59:59.000 678 nuns, 9:59:59.000,9:59:59.000 all over the age of 75[br]when the study began, 9:59:59.000,9:59:59.000 were followed for more than two decades. 9:59:59.000,9:59:59.000 They were regularly given[br]physical checkups and cognitive tests 9:59:59.000,9:59:59.000 and when they died, their brains[br]were all donated for autopsy. 9:59:59.000,9:59:59.000 In some of these brains, scientists[br]discovered something surprising. 9:59:59.000,9:59:59.000 Despite the presence of plaques[br]and tangles and brain shrinkage, 9:59:59.000,9:59:59.000 what appeared to be[br]unquestionable Alzheimer's, 9:59:59.000,9:59:59.000 the nuns who had belonged to these brains 9:59:59.000,9:59:59.000 showed no signs of having the disease[br]while they were alive. 9:59:59.000,9:59:59.000 How can this be? 9:59:59.000,9:59:59.000 We think it is because these nuns[br]had a high level of cognitive reserve, 9:59:59.000,9:59:59.000 which is a way of saying that they had[br]more functional synapses. 9:59:59.000,9:59:59.000 People who have more years[br]of formal education, 9:59:59.000,9:59:59.000 who have a high degree of literacy, 9:59:59.000,9:59:59.000 who engage regularly[br]in mentally stimulating activities, 9:59:59.000,9:59:59.000 all have more cognitive reserve. 9:59:59.000,9:59:59.000 They have an abundance[br]and a redundancy in neural connections. 9:59:59.000,9:59:59.000 So even if they have a disease[br]like Alzheimer's 9:59:59.000,9:59:59.000 compromising some of their synapses, 9:59:59.000,9:59:59.000 they've got many extra backup connections, 9:59:59.000,9:59:59.000 and this buffers them from noticing[br]that anything is amiss. 9:59:59.000,9:59:59.000 Let's imagine a simplified example. 9:59:59.000,9:59:59.000 Let's say you only know one thing[br]about a subject. 9:59:59.000,9:59:59.000 Let's say it's about me. 9:59:59.000,9:59:59.000 You know that Lisa Genova[br]wrote "Still Alice," 9:59:59.000,9:59:59.000 and that's the only thing[br]you know about me. 9:59:59.000,9:59:59.000 You have that single neural connection, 9:59:59.000,9:59:59.000 that one synapse. 9:59:59.000,9:59:59.000 Now imagine you have Alzheimer's. 9:59:59.000,9:59:59.000 You have plaques and tangles[br]and inflammation 9:59:59.000,9:59:59.000 and microglia devouring that synapse. 9:59:59.000,9:59:59.000 Now, when someone asks you,[br]"Hey, who wrote 'Still Alice?'" 9:59:59.000,9:59:59.000 you can't remember, because[br]that synapse is either failing or gone. 9:59:59.000,9:59:59.000 You've forgotten me forever. 9:59:59.000,9:59:59.000 But what if you had learned more about me? 9:59:59.000,9:59:59.000 Let's say you learned[br]four things about me. 9:59:59.000,9:59:59.000 Now imagine you have Alzheimer's, 9:59:59.000,9:59:59.000 and three of those synapses[br]are damaged or destroyed. 9:59:59.000,9:59:59.000 You still have a way[br]to detour the wreckage. 9:59:59.000,9:59:59.000 You can still remember my name. 9:59:59.000,9:59:59.000 So we can be resilient[br]to the presence of Alzheimer's pathology 9:59:59.000,9:59:59.000 through the recruitment of[br]yet undamaged pathways, 9:59:59.000,9:59:59.000 and we create these pathways, 9:59:59.000,9:59:59.000 this cognitive reserve, 9:59:59.000,9:59:59.000 by learning new things. 9:59:59.000,9:59:59.000 Now ideally we want these new things[br]to be as rich in meaning as possible, 9:59:59.000,9:59:59.000 recruiting sight and sound[br]and associations and emotion. 9:59:59.000,9:59:59.000 So this really doesn't mean[br]doing crossword puzzles. 9:59:59.000,9:59:59.000 You don't want to simply retrieve[br]information you've already learned, 9:59:59.000,9:59:59.000 because this is like traveling[br]down old, familiar streets, 9:59:59.000,9:59:59.000 cruising neighborhoods you already know. 9:59:59.000,9:59:59.000 You want to pave new neural roads. 9:59:59.000,9:59:59.000 Building an Alzheimer's-resistant brain 9:59:59.000,9:59:59.000 means learning to speak Italian, 9:59:59.000,9:59:59.000 meeting new friends, 9:59:59.000,9:59:59.000 reading a book, 9:59:59.000,9:59:59.000 or listening to a great TEDTalk. 9:59:59.000,9:59:59.000 And if despite all of this, you are[br]someday diagnosed with Alzheimer's, 9:59:59.000,9:59:59.000 there are three lessons I've learned[br]from my grandmother 9:59:59.000,9:59:59.000 and the dozens of people I've come[br]to know living with this disease. 9:59:59.000,9:59:59.000 Diagnosis doesn't mean[br]you're dying tomorrow. 9:59:59.000,9:59:59.000 Keep living. 9:59:59.000,9:59:59.000 You won't lose your emotional memory. 9:59:59.000,9:59:59.000 You'll still be able to understand[br]love and joy. 9:59:59.000,9:59:59.000 You might not remember what I said[br]five minutes ago, 9:59:59.000,9:59:59.000 but you'll remember[br]how I made you feel. 9:59:59.000,9:59:59.000 And you are more than what[br]you can remember. 9:59:59.000,9:59:59.000 Thank you. 9:59:59.000,9:59:59.000 (Applause)