WEBVTT 00:00:01.117 --> 00:00:05.531 How many people here would like to live to be at least 80 years old? 00:00:06.072 --> 00:00:07.547 Yeah. 00:00:07.571 --> 00:00:10.366 I think we all have this hopeful expectation 00:00:10.390 --> 00:00:12.350 of living into old age. 00:00:12.828 --> 00:00:14.914 Let's project out into the future, 00:00:14.938 --> 00:00:16.498 to your future You's, 00:00:16.522 --> 00:00:19.375 and let's imagine that we're all 85. 00:00:19.894 --> 00:00:21.912 Now, everyone look at two people. 00:00:23.151 --> 00:00:26.683 One of you probably has Alzheimer's disease. 00:00:27.365 --> 00:00:30.789 (Laughter) 00:00:30.813 --> 00:00:32.407 Alright, alright. 00:00:32.954 --> 00:00:36.771 And maybe you're thinking, "Well, it won't be me." 00:00:37.350 --> 00:00:40.735 Then, OK. You are a caregiver. 00:00:41.388 --> 00:00:42.552 So -- 00:00:42.576 --> 00:00:45.448 (Laughter) 00:00:45.472 --> 00:00:46.829 so in some way, 00:00:46.853 --> 00:00:50.497 this terrifying disease is likely to affect us all. NOTE Paragraph 00:00:50.933 --> 00:00:53.947 Part of the fear around Alzheimer's stems from the sense 00:00:53.971 --> 00:00:56.385 that there's nothing we can do about it. 00:00:56.409 --> 00:01:01.534 Despite decades of research, we still have no disease-modifying treatment 00:01:01.558 --> 00:01:02.865 and no cure. 00:01:03.321 --> 00:01:05.790 So if we're lucky enough to live long enough, 00:01:05.814 --> 00:01:08.922 Alzheimer's appears to be our brain's destiny. NOTE Paragraph 00:01:09.369 --> 00:01:11.249 But maybe it doesn't have to be. 00:01:11.585 --> 00:01:14.950 What if I told you we could change these statistics, 00:01:14.974 --> 00:01:17.664 literally change our brain's destiny, 00:01:17.688 --> 00:01:21.217 without relying on a cure or advancements in medicine? NOTE Paragraph 00:01:21.983 --> 00:01:24.508 Let's begin by looking at what we currently understand 00:01:24.532 --> 00:01:26.889 about the neuroscience of Alzheimer's. 00:01:27.730 --> 00:01:30.739 Here's a picture of two neurons connecting. 00:01:30.763 --> 00:01:34.120 The point of connection, this space circled in red, 00:01:34.144 --> 00:01:35.783 is called the synapse. 00:01:35.807 --> 00:01:38.999 The synapse is where neurotransmitters are released. 00:01:39.023 --> 00:01:43.291 This is where signals are transmitted, where communication happens. 00:01:43.315 --> 00:01:48.421 This is where we think, feel, see, hear, desire ... 00:01:48.445 --> 00:01:50.094 and remember. 00:01:50.118 --> 00:01:53.016 And the synapse is where Alzheimer's happens. NOTE Paragraph 00:01:53.040 --> 00:01:55.002 Let's zoom in on the synapse 00:01:55.026 --> 00:01:58.113 and look at a cartoon representation of what's going on. 00:01:58.799 --> 00:02:01.086 During the business of communicating information, 00:02:01.110 --> 00:02:05.108 in addition to releasing neurotransmitters like glutamate into the synapse, 00:02:05.132 --> 00:02:09.593 neurons also release a small peptide called amyloid beta. 00:02:10.617 --> 00:02:15.601 Normally, amyloid beta is cleared away metabolized by microglia, 00:02:15.625 --> 00:02:17.778 the janitor cells of our brains. 00:02:18.405 --> 00:02:22.264 While the molecular causes of Alzheimer's are still debated, 00:02:22.288 --> 00:02:25.542 most neuroscientists believe that the disease begins 00:02:25.566 --> 00:02:28.396 when amyloid beta begins to accumulate. 00:02:28.967 --> 00:02:31.716 Too much is released, or not enough is cleared away, 00:02:31.740 --> 00:02:35.074 and the synapse begins to pile up with amyloid beta. 00:02:35.098 --> 00:02:37.317 And when this happens, it binds to itself, 00:02:37.341 --> 00:02:40.630 forming sticky aggregates called amyloid plaques. NOTE Paragraph 00:02:41.582 --> 00:02:44.535 How many people here are 40 years old or older? 00:02:45.184 --> 00:02:47.704 You're afraid to admit it now. 00:02:47.728 --> 00:02:49.954 This initial step into the disease, 00:02:49.978 --> 00:02:53.062 this presence of amyloid plaques accumulating, 00:02:53.086 --> 00:02:55.680 can already be found in your brains. 00:02:56.271 --> 00:02:59.741 The only way we could be sure of this would be through a PET scan, 00:02:59.765 --> 00:03:03.581 because at this point, you are blissfully unaware. 00:03:03.605 --> 00:03:07.894 You're not showing any impairments in memory, language, or cognition ... 00:03:07.918 --> 00:03:09.069 yet. 00:03:09.471 --> 00:03:14.008 We think it takes at least 15 to 20 years of amyloid plaque accumulation 00:03:14.032 --> 00:03:16.413 before it reaches a tipping point, 00:03:16.437 --> 00:03:18.672 then triggering a molecular cascade 00:03:18.696 --> 00:03:21.363 that causes the clinical symptoms of the disease. 00:03:21.810 --> 00:03:23.771 Prior to the tipping point, 00:03:23.795 --> 00:03:27.379 your lapses in memory might include things like, 00:03:27.403 --> 00:03:29.728 "Why did I come in this room?" 00:03:29.752 --> 00:03:31.980 or "Oh ... what's his name?" 00:03:32.479 --> 00:03:34.823 or "Where did I put my keys?" 00:03:35.553 --> 00:03:38.109 Now, before you all start freaking out again, 00:03:38.133 --> 00:03:43.531 because I know half of you did at least one of those in the last 24 hours -- 00:03:43.555 --> 00:03:46.792 these are all normal kinds of forgetting. 00:03:46.816 --> 00:03:49.129 In fact, I would argue that these examples 00:03:49.153 --> 00:03:51.130 might not even involve your memory, 00:03:51.154 --> 00:03:54.046 because you didn't pay attention to where you put your keys 00:03:54.070 --> 00:03:55.415 in the first place. 00:03:55.439 --> 00:03:57.117 After the tipping point, 00:03:57.141 --> 00:04:00.664 the glitches in memory, language and cognition are different. 00:04:00.688 --> 00:04:03.588 Instead of eventually finding your keys in your coat pocket 00:04:03.612 --> 00:04:05.614 or on the table by the door, 00:04:05.638 --> 00:04:08.352 you find them in the refrigerator, 00:04:08.376 --> 00:04:10.342 or you find them and you think, 00:04:10.366 --> 00:04:11.899 "What are these for?" NOTE Paragraph 00:04:12.843 --> 00:04:18.051 So what happens when amyloid plaques accumulate to this tipping point? 00:04:18.075 --> 00:04:21.394 Our microglia janitor cells become hyper-activated, 00:04:21.418 --> 00:04:25.552 releasing chemicals that cause inflammation and cellular damage. 00:04:25.576 --> 00:04:28.171 We think they might actually start clearing away 00:04:28.195 --> 00:04:29.899 the synapses themselves. 00:04:30.398 --> 00:04:34.846 A crucial neural transport protein called "tau" becomes hyperphosphorylated 00:04:34.870 --> 00:04:37.454 and twists itself into something called "tangles," 00:04:37.478 --> 00:04:40.513 which choke off the neurons from the inside. 00:04:40.537 --> 00:04:44.371 By mid-stage Alzheimer's, we have massive inflammation and tangles 00:04:44.395 --> 00:04:46.342 and all-out war at the synapse 00:04:46.366 --> 00:04:47.619 and cell death. NOTE Paragraph 00:04:48.238 --> 00:04:51.326 So if you were a scientist trying to cure this disease, 00:04:51.350 --> 00:04:54.347 at what point would you ideally want to intervene? 00:04:55.134 --> 00:04:59.038 Many scientists are betting big on the simplest solution: 00:04:59.062 --> 00:05:02.896 keep amyloid plaques from reaching that tipping point, 00:05:02.920 --> 00:05:06.948 which means that drug discovery is largely focused on developing a compound 00:05:06.972 --> 00:05:12.320 that will prevent, eliminate, or reduce amyloid plaque accumulation. 00:05:12.859 --> 00:05:18.048 So the cure for Alzheimer's will likely be a preventative medicine. 00:05:18.072 --> 00:05:21.501 We're going to have to take this pill before we reach that tipping point, 00:05:21.525 --> 00:05:23.777 before the cascade is triggered, 00:05:23.801 --> 00:05:26.829 before we start leaving our keys in the refrigerator. 00:05:27.381 --> 00:05:31.054 We think this is why, to date, these kinds of drugs have failed 00:05:31.078 --> 00:05:32.315 in clinical trials -- 00:05:32.339 --> 00:05:34.784 not because the science wasn't sound, 00:05:34.808 --> 00:05:38.942 but because the people in these trials were already symptomatic. 00:05:38.966 --> 00:05:40.698 It was too late. 00:05:40.722 --> 00:05:43.974 Think of amyloid plaques as a lit match. 00:05:43.998 --> 00:05:47.416 At the tipping point, the match sets fire to the forest. 00:05:47.884 --> 00:05:49.834 Once the forest is ablaze, 00:05:49.858 --> 00:05:52.340 it doesn't do any good to blow out the match. 00:05:52.364 --> 00:05:55.887 You have to blow out the match before the forest catches fire. NOTE Paragraph 00:05:56.331 --> 00:05:58.194 Even before scientists sort this out, 00:05:58.218 --> 00:06:01.086 this information is actually really good news for us, 00:06:01.110 --> 00:06:05.154 because it turns out that the way we live can influence the accumulation 00:06:05.178 --> 00:06:06.407 of amyloid plaques. 00:06:06.431 --> 00:06:08.007 And so there are things we can do 00:06:08.031 --> 00:06:10.650 to keep us from reaching that tipping point. NOTE Paragraph 00:06:11.117 --> 00:06:15.005 Let's picture your risk of Alzheimer's as a see-saw scale. 00:06:15.029 --> 00:06:17.078 We're going to pile risk factors on one arm, 00:06:17.102 --> 00:06:19.580 and when that arm hits the floor, you are symptomatic 00:06:19.604 --> 00:06:21.539 and diagnosed with Alzheimer's. 00:06:22.058 --> 00:06:24.777 Let's imagine you're 50 years old. 00:06:24.801 --> 00:06:26.536 You're not a spring chicken anymore, 00:06:26.560 --> 00:06:29.632 so you've accumulated some amyloid plaques with age. 00:06:29.656 --> 00:06:31.847 Your scale is tipped a little bit. 00:06:32.323 --> 00:06:34.062 Now let's look at your DNA. 00:06:34.536 --> 00:06:38.088 We've all inherited our genes from our moms and our dads. 00:06:38.112 --> 00:06:42.190 Some of these genes will increase our risk and some will decrease it. 00:06:42.214 --> 00:06:44.403 If you're like Alice in "Still Alice," 00:06:44.427 --> 00:06:48.978 you've inherited a rare genetic mutation that cranks out amyloid beta, 00:06:49.002 --> 00:06:52.555 and this alone will tip your scale arm to the ground. 00:06:52.579 --> 00:06:56.745 But for most of us, the genes we inherit will only tip the arm a bit. 00:06:56.769 --> 00:07:01.584 For example, APOE4 is a gene variant that increases amyloid, 00:07:01.608 --> 00:07:04.876 but you can inherit a copy of APOE4 from mom and dad 00:07:04.900 --> 00:07:07.291 and still never get Alzheimer's, 00:07:07.315 --> 00:07:09.428 which means that for most of us, 00:07:09.452 --> 00:07:13.292 our DNA alone does not determine whether we get Alzheimer's. NOTE Paragraph 00:07:13.984 --> 00:07:15.458 So what does? 00:07:15.482 --> 00:07:19.274 We can't do anything about getting older or the genes we've inherited. 00:07:19.298 --> 00:07:22.295 So far, we haven't changed our brain's destiny. NOTE Paragraph 00:07:23.144 --> 00:07:24.609 What about sleep? 00:07:25.278 --> 00:07:29.360 In slow-wave deep sleep, our glial cells rinse cerebral spinal fluid 00:07:29.384 --> 00:07:30.600 throughout our brains, 00:07:30.624 --> 00:07:34.196 clearing away metabolic waste that accumulated in our synapses 00:07:34.220 --> 00:07:36.121 while we were awake. 00:07:36.145 --> 00:07:38.951 Deep sleep is like a power cleanse for the brain. 00:07:39.646 --> 00:07:42.832 But what happens if you shortchange yourself on sleep? 00:07:43.421 --> 00:07:44.953 Many scientists believe 00:07:44.977 --> 00:07:49.227 that poor sleep hygiene might actually be a predictor of Alzheimer's. 00:07:49.613 --> 00:07:54.539 A single night of sleep deprivation leads to an increase in amyloid beta. 00:07:55.410 --> 00:07:58.836 And amyloid accumulation has been shown to disrupt sleep, 00:07:58.860 --> 00:08:01.347 which in turn causes more amyloid to accumulate. 00:08:01.371 --> 00:08:03.847 And so now we have this positive feedback loop 00:08:03.871 --> 00:08:06.744 that's going to accelerate the tipping of that scale. NOTE Paragraph 00:08:07.306 --> 00:08:08.729 What else? 00:08:08.753 --> 00:08:10.379 Cardiovascular health. 00:08:11.043 --> 00:08:14.788 High blood pressure, diabetes, obesity, smoking, high cholesterol, 00:08:14.812 --> 00:08:18.948 have all been shown to increase our risk of developing Alzheimer's. 00:08:18.972 --> 00:08:20.863 Some autopsy studies have shown 00:08:20.887 --> 00:08:23.559 that as many as 80 percent of people with Alzheimer's 00:08:23.583 --> 00:08:26.345 also had cardiovascular disease. 00:08:26.369 --> 00:08:31.374 Aerobic exercise has been shown in many studies to decrease amyloid beta 00:08:31.398 --> 00:08:33.128 in animal models of the disease. 00:08:33.619 --> 00:08:37.199 So a heart-healthy Mediterranean lifestyle and diet 00:08:37.223 --> 00:08:39.877 can help to counter the tipping of this scale. NOTE Paragraph 00:08:40.697 --> 00:08:43.046 So there are many things we can do 00:08:43.070 --> 00:08:45.442 to prevent or delay the onset of Alzheimer's. 00:08:45.466 --> 00:08:47.695 But let's say you haven't done any of them. 00:08:48.211 --> 00:08:50.665 Let's say you're 65; 00:08:50.689 --> 00:08:54.355 there's Alzheimer's in your family, so you've likely inherited a gene or two 00:08:54.379 --> 00:08:56.403 that tips your scale arm a bit; 00:08:56.427 --> 00:08:59.159 you've been burning the candle at both ends for years; 00:08:59.183 --> 00:09:00.686 you love bacon; 00:09:00.710 --> 00:09:02.933 and you don't run unless someone's chasing you. 00:09:02.957 --> 00:09:04.258 (Laughter) 00:09:04.282 --> 00:09:07.894 Let's imagine that your amyloid plaques have reached that tipping point. 00:09:07.918 --> 00:09:09.966 Your scale arm has crashed to the floor. 00:09:09.990 --> 00:09:11.671 You've tripped the cascade, 00:09:11.695 --> 00:09:13.261 setting fire to the forest, 00:09:13.285 --> 00:09:16.383 causing inflammation, tangles, and cell death. 00:09:17.137 --> 00:09:19.796 You should be symptomatic for Alzheimer's. 00:09:19.820 --> 00:09:23.136 You should be having trouble finding words and keys 00:09:23.160 --> 00:09:26.306 and remembering what I said at the beginning of this talk. 00:09:26.917 --> 00:09:28.631 But you might not be. 00:09:29.180 --> 00:09:31.658 There's one more thing you can do to protect yourself 00:09:31.682 --> 00:09:34.268 from experiencing the symptoms of Alzheimer's, 00:09:34.292 --> 00:09:38.783 even if you have the full-blown disease pathology ablaze in your brain. 00:09:38.807 --> 00:09:42.714 It has to do with neural plasticity and cognitive reserve. 00:09:43.261 --> 00:09:45.638 Remember, the experience of having Alzheimer's 00:09:45.662 --> 00:09:48.868 is ultimately a result of losing synapses. 00:09:49.339 --> 00:09:52.716 The average brain has over a hundred trillion synapses, 00:09:52.740 --> 00:09:55.453 which is fantastic; we've got a lot to work with. 00:09:55.477 --> 00:09:57.146 And this isn't a static number. 00:09:57.170 --> 00:09:59.568 We gain and lose synapses all the time, 00:09:59.592 --> 00:10:02.395 through a process called neural plasticity. 00:10:02.419 --> 00:10:04.491 Every time we learn something new, 00:10:04.515 --> 00:10:08.642 we are creating and strengthening new neural connections, 00:10:08.666 --> 00:10:10.283 new synapses. NOTE Paragraph 00:10:10.988 --> 00:10:12.563 In the Nun Study, 00:10:12.587 --> 00:10:17.480 678 nuns, all over the age of 75 when the study began, 00:10:17.504 --> 00:10:19.813 were followed for more than two decades. 00:10:19.837 --> 00:10:23.297 They were regularly given physical checkups and cognitive tests, 00:10:23.321 --> 00:10:27.369 and when they died, their brains were all donated for autopsy. 00:10:27.393 --> 00:10:31.768 In some of these brains, scientists discovered something surprising. 00:10:31.792 --> 00:10:36.368 Despite the presence of plaques and tangles and brain shrinkage -- 00:10:36.392 --> 00:10:39.261 what appeared to be unquestionable Alzheimer's -- 00:10:39.285 --> 00:10:42.964 the nuns who had belonged to these brains showed no signs 00:10:42.988 --> 00:10:45.555 of having the disease while they were alive. NOTE Paragraph 00:10:46.181 --> 00:10:47.630 How can this be? 00:10:48.009 --> 00:10:52.136 We think it's because these nuns had a high level of cognitive reserve, 00:10:52.160 --> 00:10:56.083 which is a way of saying that they had more functional synapses. 00:10:56.107 --> 00:10:58.681 People who have more years of formal education, 00:10:58.705 --> 00:11:00.940 who have a high degree of literacy, 00:11:00.964 --> 00:11:04.543 who engage regularly in mentally stimulating activities, 00:11:04.567 --> 00:11:07.048 all have more cognitive reserve. 00:11:07.072 --> 00:11:11.199 They have an abundance and a redundancy in neural connections. 00:11:11.223 --> 00:11:13.903 So even if they have a disease like Alzheimer's 00:11:13.927 --> 00:11:15.981 compromising some of their synapses, 00:11:16.005 --> 00:11:18.990 they've got many extra backup connections, 00:11:19.014 --> 00:11:22.349 and this buffers them from noticing that anything is amiss. NOTE Paragraph 00:11:22.977 --> 00:11:25.239 Let's imagine a simplified example. 00:11:25.263 --> 00:11:27.989 Let's say you only know one thing about a subject. 00:11:28.013 --> 00:11:29.542 Let's say it's about me. 00:11:29.566 --> 00:11:31.872 You know that Lisa Genova wrote "Still Alice," 00:11:31.896 --> 00:11:34.332 and that's the only thing you know about me. 00:11:34.356 --> 00:11:36.746 You have that single neural connection, 00:11:36.770 --> 00:11:38.716 that one synapse. 00:11:38.740 --> 00:11:40.901 Now imagine you have Alzheimer's. 00:11:40.925 --> 00:11:43.258 You have plaques and tangles and inflammation 00:11:43.282 --> 00:11:46.017 and microglia devouring that synapse. 00:11:46.603 --> 00:11:50.833 Now when someone asks you, "Hey, who wrote 'Still Alice?'" 00:11:50.857 --> 00:11:52.102 you can't remember, 00:11:52.126 --> 00:11:55.309 because that synapse is either failing or gone. 00:11:55.333 --> 00:11:57.092 You've forgotten me forever. 00:11:57.760 --> 00:12:00.386 But what if you had learned more about me? 00:12:00.410 --> 00:12:02.499 Let's say you learned four things about me. 00:12:02.523 --> 00:12:04.368 Now imagine you have Alzheimer's, 00:12:04.392 --> 00:12:07.387 and three of those synapses are damaged or destroyed. 00:12:08.077 --> 00:12:10.538 You still have a way to detour the wreckage. 00:12:10.562 --> 00:12:12.581 You can still remember my name. 00:12:13.283 --> 00:12:17.209 So we can be resilient to the presence of Alzheimer's pathology 00:12:17.233 --> 00:12:20.336 through the recruitment of yet-undamaged pathways. 00:12:20.360 --> 00:12:24.139 And we create these pathways, this cognitive reserve, 00:12:24.163 --> 00:12:25.863 by learning new things. 00:12:26.455 --> 00:12:30.976 Ideally, we want these new things to be as rich in meaning as possible, 00:12:31.000 --> 00:12:35.739 recruiting sight and sound and associations and emotion. NOTE Paragraph 00:12:36.398 --> 00:12:39.533 So this really doesn't mean doing crossword puzzles. 00:12:39.557 --> 00:12:43.654 You don't want to simply retrieve information you've already learned, 00:12:43.678 --> 00:12:47.021 because this is like traveling down old, familiar streets, 00:12:47.045 --> 00:12:49.630 cruising neighborhoods you already know. 00:12:50.113 --> 00:12:52.947 You want to pave new neural roads. 00:12:52.971 --> 00:12:55.483 Building an Alzheimer's-resistant brain 00:12:55.507 --> 00:12:57.687 means learning to speak Italian, 00:12:57.711 --> 00:12:59.221 meeting new friends, 00:12:59.245 --> 00:13:00.412 reading a book, 00:13:00.436 --> 00:13:02.805 or listening to a great TED Talk. NOTE Paragraph 00:13:03.283 --> 00:13:08.596 And if, despite all of this, you are someday diagnosed with Alzheimer's, 00:13:08.620 --> 00:13:11.773 there are three lessons I've learned from my grandmother 00:13:11.797 --> 00:13:15.534 and the dozens of people I've come to know living with this disease. 00:13:16.115 --> 00:13:19.299 Diagnosis doesn't mean you're dying tomorrow. 00:13:19.323 --> 00:13:21.045 Keep living. 00:13:21.069 --> 00:13:23.435 You won't lose your emotional memory. 00:13:23.459 --> 00:13:26.965 You'll still be able to understand love and joy. 00:13:26.989 --> 00:13:29.992 You might not remember what I said five minutes ago, 00:13:30.016 --> 00:13:32.301 but you'll remember how I made you feel. 00:13:32.944 --> 00:13:36.220 And you are more than what you can remember. NOTE Paragraph 00:13:36.244 --> 00:13:37.533 Thank you. NOTE Paragraph 00:13:37.557 --> 00:13:42.880 (Applause)