[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:01.12,0:00:05.53,Default,,0000,0000,0000,,How many people here would like to live\Nto be at least 80 years old?
Dialogue: 0,0:00:06.07,0:00:07.55,Default,,0000,0000,0000,,Yeah.
Dialogue: 0,0:00:07.57,0:00:10.37,Default,,0000,0000,0000,,I think we all have\Nthis hopeful expectation
Dialogue: 0,0:00:10.39,0:00:12.35,Default,,0000,0000,0000,,of living into old age.
Dialogue: 0,0:00:12.83,0:00:14.91,Default,,0000,0000,0000,,Let's project out into the future,
Dialogue: 0,0:00:14.94,0:00:16.50,Default,,0000,0000,0000,,to your future You's,
Dialogue: 0,0:00:16.52,0:00:19.38,Default,,0000,0000,0000,,and let's imagine that we're all 85.
Dialogue: 0,0:00:19.89,0:00:21.91,Default,,0000,0000,0000,,Now, everyone look at two people.
Dialogue: 0,0:00:23.15,0:00:26.68,Default,,0000,0000,0000,,One of you probably has\NAlzheimer's disease.
Dialogue: 0,0:00:27.36,0:00:30.79,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:00:30.81,0:00:32.41,Default,,0000,0000,0000,,Alright, alright.
Dialogue: 0,0:00:32.95,0:00:36.77,Default,,0000,0000,0000,,And maybe you're thinking,\N"Well, it won't be me."
Dialogue: 0,0:00:37.35,0:00:40.74,Default,,0000,0000,0000,,Then, OK. You are a caregiver.
Dialogue: 0,0:00:41.39,0:00:42.55,Default,,0000,0000,0000,,So --
Dialogue: 0,0:00:42.58,0:00:45.45,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:00:45.47,0:00:46.83,Default,,0000,0000,0000,,so in some way,
Dialogue: 0,0:00:46.85,0:00:50.50,Default,,0000,0000,0000,,this terrifying disease\Nis likely to affect us all.
Dialogue: 0,0:00:50.93,0:00:53.95,Default,,0000,0000,0000,,Part of the fear around Alzheimer's\Nstems from the sense
Dialogue: 0,0:00:53.97,0:00:56.38,Default,,0000,0000,0000,,that there's nothing we can do about it.
Dialogue: 0,0:00:56.41,0:01:01.53,Default,,0000,0000,0000,,Despite decades of research, we still\Nhave no disease-modifying treatment
Dialogue: 0,0:01:01.56,0:01:02.86,Default,,0000,0000,0000,,and no cure.
Dialogue: 0,0:01:03.32,0:01:05.79,Default,,0000,0000,0000,,So if we're lucky enough\Nto live long enough,
Dialogue: 0,0:01:05.81,0:01:08.92,Default,,0000,0000,0000,,Alzheimer's appears to be\Nour brain's destiny.
Dialogue: 0,0:01:09.37,0:01:11.25,Default,,0000,0000,0000,,But maybe it doesn't have to be.
Dialogue: 0,0:01:11.58,0:01:14.95,Default,,0000,0000,0000,,What if I told you we could\Nchange these statistics,
Dialogue: 0,0:01:14.97,0:01:17.66,Default,,0000,0000,0000,,literally change our brain's destiny,
Dialogue: 0,0:01:17.69,0:01:21.22,Default,,0000,0000,0000,,without relying on a cure\Nor advancements in medicine?
Dialogue: 0,0:01:21.98,0:01:24.51,Default,,0000,0000,0000,,Let's begin by looking at\Nwhat we currently understand
Dialogue: 0,0:01:24.53,0:01:26.89,Default,,0000,0000,0000,,about the neuroscience of Alzheimer's.
Dialogue: 0,0:01:27.73,0:01:30.74,Default,,0000,0000,0000,,Here's a picture\Nof two neurons connecting.
Dialogue: 0,0:01:30.76,0:01:34.12,Default,,0000,0000,0000,,The point of connection,\Nthis space circled in red,
Dialogue: 0,0:01:34.14,0:01:35.78,Default,,0000,0000,0000,,is called the synapse.
Dialogue: 0,0:01:35.81,0:01:38.100,Default,,0000,0000,0000,,The synapse is where\Nneurotransmitters are released.
Dialogue: 0,0:01:39.02,0:01:43.29,Default,,0000,0000,0000,,This is where signals are transmitted,\Nwhere communication happens.
Dialogue: 0,0:01:43.32,0:01:48.42,Default,,0000,0000,0000,,This is where we think,\Nfeel, see, hear, desire ...
Dialogue: 0,0:01:48.44,0:01:50.09,Default,,0000,0000,0000,,and remember.
Dialogue: 0,0:01:50.12,0:01:53.02,Default,,0000,0000,0000,,And the synapse\Nis where Alzheimer's happens.
Dialogue: 0,0:01:53.04,0:01:55.00,Default,,0000,0000,0000,,Let's zoom in on the synapse
Dialogue: 0,0:01:55.03,0:01:58.11,Default,,0000,0000,0000,,and look at a cartoon representation\Nof what's going on.
Dialogue: 0,0:01:58.80,0:02:01.09,Default,,0000,0000,0000,,During the business\Nof communicating information,
Dialogue: 0,0:02:01.11,0:02:05.11,Default,,0000,0000,0000,,in addition to releasing neurotransmitters\Nlike glutamate into the synapse,
Dialogue: 0,0:02:05.13,0:02:09.59,Default,,0000,0000,0000,,neurons also release a small peptide\Ncalled amyloid beta.
Dialogue: 0,0:02:10.62,0:02:15.60,Default,,0000,0000,0000,,Normally, amyloid beta is cleared away\Nmetabolized by microglia,
Dialogue: 0,0:02:15.62,0:02:17.78,Default,,0000,0000,0000,,the janitor cells of our brains.
Dialogue: 0,0:02:18.40,0:02:22.26,Default,,0000,0000,0000,,While the molecular causes\Nof Alzheimer's are still debated,
Dialogue: 0,0:02:22.29,0:02:25.54,Default,,0000,0000,0000,,most neuroscientists believe\Nthat the disease begins
Dialogue: 0,0:02:25.57,0:02:28.40,Default,,0000,0000,0000,,when amyloid beta begins to accumulate.
Dialogue: 0,0:02:28.97,0:02:31.72,Default,,0000,0000,0000,,Too much is released,\Nor not enough is cleared away,
Dialogue: 0,0:02:31.74,0:02:35.07,Default,,0000,0000,0000,,and the synapse begins\Nto pile up with amyloid beta.
Dialogue: 0,0:02:35.10,0:02:37.32,Default,,0000,0000,0000,,And when this happens, it binds to itself,
Dialogue: 0,0:02:37.34,0:02:40.63,Default,,0000,0000,0000,,forming sticky aggregates\Ncalled amyloid plaques.
Dialogue: 0,0:02:41.58,0:02:44.54,Default,,0000,0000,0000,,How many people here\Nare 40 years old or older?
Dialogue: 0,0:02:45.18,0:02:47.70,Default,,0000,0000,0000,,You're afraid to admit it now.
Dialogue: 0,0:02:47.73,0:02:49.95,Default,,0000,0000,0000,,This initial step into the disease,
Dialogue: 0,0:02:49.98,0:02:53.06,Default,,0000,0000,0000,,this presence of amyloid\Nplaques accumulating,
Dialogue: 0,0:02:53.09,0:02:55.68,Default,,0000,0000,0000,,can already be found in your brains.
Dialogue: 0,0:02:56.27,0:02:59.74,Default,,0000,0000,0000,,The only way we could be sure of this\Nwould be through a PET scan,
Dialogue: 0,0:02:59.76,0:03:03.58,Default,,0000,0000,0000,,because at this point,\Nyou are blissfully unaware.
Dialogue: 0,0:03:03.60,0:03:07.89,Default,,0000,0000,0000,,You're not showing any impairments\Nin memory, language, or cognition ...
Dialogue: 0,0:03:07.92,0:03:09.07,Default,,0000,0000,0000,,yet.
Dialogue: 0,0:03:09.47,0:03:14.01,Default,,0000,0000,0000,,We think it takes at least 15 to 20 years\Nof amyloid plaque accumulation
Dialogue: 0,0:03:14.03,0:03:16.41,Default,,0000,0000,0000,,before it reaches a tipping point,
Dialogue: 0,0:03:16.44,0:03:18.67,Default,,0000,0000,0000,,then triggering a molecular cascade
Dialogue: 0,0:03:18.70,0:03:21.36,Default,,0000,0000,0000,,that causes the clinical\Nsymptoms of the disease.
Dialogue: 0,0:03:21.81,0:03:23.77,Default,,0000,0000,0000,,Prior to the tipping point,
Dialogue: 0,0:03:23.80,0:03:27.38,Default,,0000,0000,0000,,your lapses in memory\Nmight include things like,
Dialogue: 0,0:03:27.40,0:03:29.73,Default,,0000,0000,0000,,"Why did I come in this room?"
Dialogue: 0,0:03:29.75,0:03:31.98,Default,,0000,0000,0000,,or "Oh ... what's his name?"
Dialogue: 0,0:03:32.48,0:03:34.82,Default,,0000,0000,0000,,or "Where did I put my keys?"
Dialogue: 0,0:03:35.55,0:03:38.11,Default,,0000,0000,0000,,Now, before you all\Nstart freaking out again,
Dialogue: 0,0:03:38.13,0:03:43.53,Default,,0000,0000,0000,,because I know half of you did at least\None of those in the last 24 hours --
Dialogue: 0,0:03:43.56,0:03:46.79,Default,,0000,0000,0000,,these are all normal kinds of forgetting.
Dialogue: 0,0:03:46.82,0:03:49.13,Default,,0000,0000,0000,,In fact, I would argue that these examples
Dialogue: 0,0:03:49.15,0:03:51.13,Default,,0000,0000,0000,,might not even involve your memory,
Dialogue: 0,0:03:51.15,0:03:54.05,Default,,0000,0000,0000,,because you didn't pay attention\Nto where you put your keys
Dialogue: 0,0:03:54.07,0:03:55.42,Default,,0000,0000,0000,,in the first place.
Dialogue: 0,0:03:55.44,0:03:57.12,Default,,0000,0000,0000,,After the tipping point,
Dialogue: 0,0:03:57.14,0:04:00.66,Default,,0000,0000,0000,,the glitches in memory,\Nlanguage and cognition are different.
Dialogue: 0,0:04:00.69,0:04:03.59,Default,,0000,0000,0000,,Instead of eventually finding\Nyour keys in your coat pocket
Dialogue: 0,0:04:03.61,0:04:05.61,Default,,0000,0000,0000,,or on the table by the door,
Dialogue: 0,0:04:05.64,0:04:08.35,Default,,0000,0000,0000,,you find them in the refrigerator,
Dialogue: 0,0:04:08.38,0:04:10.34,Default,,0000,0000,0000,,or you find them and you think,
Dialogue: 0,0:04:10.37,0:04:11.90,Default,,0000,0000,0000,,"What are these for?"
Dialogue: 0,0:04:12.84,0:04:18.05,Default,,0000,0000,0000,,So what happens when amyloid plaques\Naccumulate to this tipping point?
Dialogue: 0,0:04:18.08,0:04:21.39,Default,,0000,0000,0000,,Our microglia janitor cells\Nbecome hyper-activated,
Dialogue: 0,0:04:21.42,0:04:25.55,Default,,0000,0000,0000,,releasing chemicals that cause\Ninflammation and cellular damage.
Dialogue: 0,0:04:25.58,0:04:28.17,Default,,0000,0000,0000,,We think they might actually\Nstart clearing away
Dialogue: 0,0:04:28.20,0:04:29.90,Default,,0000,0000,0000,,the synapses themselves.
Dialogue: 0,0:04:30.40,0:04:34.85,Default,,0000,0000,0000,,A crucial neural transport protein\Ncalled "tau" becomes hyperphosphorylated
Dialogue: 0,0:04:34.87,0:04:37.45,Default,,0000,0000,0000,,and twists itself\Ninto something called "tangles,"
Dialogue: 0,0:04:37.48,0:04:40.51,Default,,0000,0000,0000,,which choke off the neurons\Nfrom the inside.
Dialogue: 0,0:04:40.54,0:04:44.37,Default,,0000,0000,0000,,By mid-stage Alzheimer's,\Nwe have massive inflammation and tangles
Dialogue: 0,0:04:44.40,0:04:46.34,Default,,0000,0000,0000,,and all-out war at the synapse
Dialogue: 0,0:04:46.37,0:04:47.62,Default,,0000,0000,0000,,and cell death.
Dialogue: 0,0:04:48.24,0:04:51.33,Default,,0000,0000,0000,,So if you were a scientist\Ntrying to cure this disease,
Dialogue: 0,0:04:51.35,0:04:54.35,Default,,0000,0000,0000,,at what point would you ideally\Nwant to intervene?
Dialogue: 0,0:04:55.13,0:04:59.04,Default,,0000,0000,0000,,Many scientists are betting big\Non the simplest solution:
Dialogue: 0,0:04:59.06,0:05:02.90,Default,,0000,0000,0000,,keep amyloid plaques\Nfrom reaching that tipping point,
Dialogue: 0,0:05:02.92,0:05:06.95,Default,,0000,0000,0000,,which means that drug discovery is largely\Nfocused on developing a compound
Dialogue: 0,0:05:06.97,0:05:12.32,Default,,0000,0000,0000,,that will prevent, eliminate, or reduce\Namyloid plaque accumulation.
Dialogue: 0,0:05:12.86,0:05:18.05,Default,,0000,0000,0000,,So the cure for Alzheimer's will likely be\Na preventative medicine.
Dialogue: 0,0:05:18.07,0:05:21.50,Default,,0000,0000,0000,,We're going to have to take this pill\Nbefore we reach that tipping point,
Dialogue: 0,0:05:21.52,0:05:23.78,Default,,0000,0000,0000,,before the cascade is triggered,
Dialogue: 0,0:05:23.80,0:05:26.83,Default,,0000,0000,0000,,before we start leaving\Nour keys in the refrigerator.
Dialogue: 0,0:05:27.38,0:05:31.05,Default,,0000,0000,0000,,We think this is why, to date,\Nthese kinds of drugs have failed
Dialogue: 0,0:05:31.08,0:05:32.32,Default,,0000,0000,0000,,in clinical trials --
Dialogue: 0,0:05:32.34,0:05:34.78,Default,,0000,0000,0000,,not because the science wasn't sound,
Dialogue: 0,0:05:34.81,0:05:38.94,Default,,0000,0000,0000,,but because the people in these trials\Nwere already symptomatic.
Dialogue: 0,0:05:38.97,0:05:40.70,Default,,0000,0000,0000,,It was too late.
Dialogue: 0,0:05:40.72,0:05:43.97,Default,,0000,0000,0000,,Think of amyloid plaques as a lit match.
Dialogue: 0,0:05:43.100,0:05:47.42,Default,,0000,0000,0000,,At the tipping point, the match\Nsets fire to the forest.
Dialogue: 0,0:05:47.88,0:05:49.83,Default,,0000,0000,0000,,Once the forest is ablaze,
Dialogue: 0,0:05:49.86,0:05:52.34,Default,,0000,0000,0000,,it doesn't do any good\Nto blow out the match.
Dialogue: 0,0:05:52.36,0:05:55.89,Default,,0000,0000,0000,,You have to blow out the match\Nbefore the forest catches fire.
Dialogue: 0,0:05:56.33,0:05:58.19,Default,,0000,0000,0000,,Even before scientists sort this out,
Dialogue: 0,0:05:58.22,0:06:01.09,Default,,0000,0000,0000,,this information is actually\Nreally good news for us,
Dialogue: 0,0:06:01.11,0:06:05.15,Default,,0000,0000,0000,,because it turns out that the way we live\Ncan influence the accumulation
Dialogue: 0,0:06:05.18,0:06:06.41,Default,,0000,0000,0000,,of amyloid plaques.
Dialogue: 0,0:06:06.43,0:06:08.01,Default,,0000,0000,0000,,And so there are things we can do
Dialogue: 0,0:06:08.03,0:06:10.65,Default,,0000,0000,0000,,to keep us from reaching\Nthat tipping point.
Dialogue: 0,0:06:11.12,0:06:15.00,Default,,0000,0000,0000,,Let's picture your risk\Nof Alzheimer's as a see-saw scale.
Dialogue: 0,0:06:15.03,0:06:17.08,Default,,0000,0000,0000,,We're going to pile\Nrisk factors on one arm,
Dialogue: 0,0:06:17.10,0:06:19.58,Default,,0000,0000,0000,,and when that arm hits the floor,\Nyou are symptomatic
Dialogue: 0,0:06:19.60,0:06:21.54,Default,,0000,0000,0000,,and diagnosed with Alzheimer's.
Dialogue: 0,0:06:22.06,0:06:24.78,Default,,0000,0000,0000,,Let's imagine you're 50 years old.
Dialogue: 0,0:06:24.80,0:06:26.54,Default,,0000,0000,0000,,You're not a spring chicken anymore,
Dialogue: 0,0:06:26.56,0:06:29.63,Default,,0000,0000,0000,,so you've accumulated\Nsome amyloid plaques with age.
Dialogue: 0,0:06:29.66,0:06:31.85,Default,,0000,0000,0000,,Your scale is tipped a little bit.
Dialogue: 0,0:06:32.32,0:06:34.06,Default,,0000,0000,0000,,Now let's look at your DNA.
Dialogue: 0,0:06:34.54,0:06:38.09,Default,,0000,0000,0000,,We've all inherited our genes\Nfrom our moms and our dads.
Dialogue: 0,0:06:38.11,0:06:42.19,Default,,0000,0000,0000,,Some of these genes will increase our risk\Nand some will decrease it.
Dialogue: 0,0:06:42.21,0:06:44.40,Default,,0000,0000,0000,,If you're like Alice in "Still Alice,"
Dialogue: 0,0:06:44.43,0:06:48.98,Default,,0000,0000,0000,,you've inherited a rare genetic mutation\Nthat cranks out amyloid beta,
Dialogue: 0,0:06:49.00,0:06:52.56,Default,,0000,0000,0000,,and this alone will tip\Nyour scale arm to the ground.
Dialogue: 0,0:06:52.58,0:06:56.74,Default,,0000,0000,0000,,But for most of us, the genes we inherit\Nwill only tip the arm a bit.
Dialogue: 0,0:06:56.77,0:07:01.58,Default,,0000,0000,0000,,For example, APOE4 is a gene variant\Nthat increases amyloid,
Dialogue: 0,0:07:01.61,0:07:04.88,Default,,0000,0000,0000,,but you can inherit a copy of APOE4\Nfrom mom and dad
Dialogue: 0,0:07:04.90,0:07:07.29,Default,,0000,0000,0000,,and still never get Alzheimer's,
Dialogue: 0,0:07:07.32,0:07:09.43,Default,,0000,0000,0000,,which means that for most of us,
Dialogue: 0,0:07:09.45,0:07:13.29,Default,,0000,0000,0000,,our DNA alone does not determine\Nwhether we get Alzheimer's.
Dialogue: 0,0:07:13.98,0:07:15.46,Default,,0000,0000,0000,,So what does?
Dialogue: 0,0:07:15.48,0:07:19.27,Default,,0000,0000,0000,,We can't do anything about getting older\Nor the genes we've inherited.
Dialogue: 0,0:07:19.30,0:07:22.30,Default,,0000,0000,0000,,So far, we haven't changed\Nour brain's destiny.
Dialogue: 0,0:07:23.14,0:07:24.61,Default,,0000,0000,0000,,What about sleep?
Dialogue: 0,0:07:25.28,0:07:29.36,Default,,0000,0000,0000,,In slow-wave deep sleep, our glial cells\Nrinse cerebral spinal fluid
Dialogue: 0,0:07:29.38,0:07:30.60,Default,,0000,0000,0000,,throughout our brains,
Dialogue: 0,0:07:30.62,0:07:34.20,Default,,0000,0000,0000,,clearing away metabolic waste\Nthat accumulated in our synapses
Dialogue: 0,0:07:34.22,0:07:36.12,Default,,0000,0000,0000,,while we were awake.
Dialogue: 0,0:07:36.14,0:07:38.95,Default,,0000,0000,0000,,Deep sleep is like\Na power cleanse for the brain.
Dialogue: 0,0:07:39.65,0:07:42.83,Default,,0000,0000,0000,,But what happens if you shortchange\Nyourself on sleep?
Dialogue: 0,0:07:43.42,0:07:44.95,Default,,0000,0000,0000,,Many scientists believe
Dialogue: 0,0:07:44.98,0:07:49.23,Default,,0000,0000,0000,,that poor sleep hygiene might actually\Nbe a predictor of Alzheimer's.
Dialogue: 0,0:07:49.61,0:07:54.54,Default,,0000,0000,0000,,A single night of sleep deprivation\Nleads to an increase in amyloid beta.
Dialogue: 0,0:07:55.41,0:07:58.84,Default,,0000,0000,0000,,And amyloid accumulation\Nhas been shown to disrupt sleep,
Dialogue: 0,0:07:58.86,0:08:01.35,Default,,0000,0000,0000,,which in turn causes\Nmore amyloid to accumulate.
Dialogue: 0,0:08:01.37,0:08:03.85,Default,,0000,0000,0000,,And so now we have\Nthis positive feedback loop
Dialogue: 0,0:08:03.87,0:08:06.74,Default,,0000,0000,0000,,that's going to accelerate\Nthe tipping of that scale.
Dialogue: 0,0:08:07.31,0:08:08.73,Default,,0000,0000,0000,,What else?
Dialogue: 0,0:08:08.75,0:08:10.38,Default,,0000,0000,0000,,Cardiovascular health.
Dialogue: 0,0:08:11.04,0:08:14.79,Default,,0000,0000,0000,,High blood pressure, diabetes,\Nobesity, smoking, high cholesterol,
Dialogue: 0,0:08:14.81,0:08:18.95,Default,,0000,0000,0000,,have all been shown to increase our risk\Nof developing Alzheimer's.
Dialogue: 0,0:08:18.97,0:08:20.86,Default,,0000,0000,0000,,Some autopsy studies have shown
Dialogue: 0,0:08:20.89,0:08:23.56,Default,,0000,0000,0000,,that as many as 80 percent\Nof people with Alzheimer's
Dialogue: 0,0:08:23.58,0:08:26.34,Default,,0000,0000,0000,,also had cardiovascular disease.
Dialogue: 0,0:08:26.37,0:08:31.37,Default,,0000,0000,0000,,Aerobic exercise has been shown\Nin many studies to decrease amyloid beta
Dialogue: 0,0:08:31.40,0:08:33.13,Default,,0000,0000,0000,,in animal models of the disease.
Dialogue: 0,0:08:33.62,0:08:37.20,Default,,0000,0000,0000,,So a heart-healthy\NMediterranean lifestyle and diet
Dialogue: 0,0:08:37.22,0:08:39.88,Default,,0000,0000,0000,,can help to counter\Nthe tipping of this scale.
Dialogue: 0,0:08:40.70,0:08:43.05,Default,,0000,0000,0000,,So there are many things we can do
Dialogue: 0,0:08:43.07,0:08:45.44,Default,,0000,0000,0000,,to prevent or delay\Nthe onset of Alzheimer's.
Dialogue: 0,0:08:45.47,0:08:47.70,Default,,0000,0000,0000,,But let's say\Nyou haven't done any of them.
Dialogue: 0,0:08:48.21,0:08:50.66,Default,,0000,0000,0000,,Let's say you're 65;
Dialogue: 0,0:08:50.69,0:08:54.36,Default,,0000,0000,0000,,there's Alzheimer's in your family,\Nso you've likely inherited a gene or two
Dialogue: 0,0:08:54.38,0:08:56.40,Default,,0000,0000,0000,,that tips your scale arm a bit;
Dialogue: 0,0:08:56.43,0:08:59.16,Default,,0000,0000,0000,,you've been burning the candle\Nat both ends for years;
Dialogue: 0,0:08:59.18,0:09:00.69,Default,,0000,0000,0000,,you love bacon;
Dialogue: 0,0:09:00.71,0:09:02.93,Default,,0000,0000,0000,,and you don't run unless\Nsomeone's chasing you.
Dialogue: 0,0:09:02.96,0:09:04.26,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:09:04.28,0:09:07.89,Default,,0000,0000,0000,,Let's imagine that your amyloid plaques\Nhave reached that tipping point.
Dialogue: 0,0:09:07.92,0:09:09.97,Default,,0000,0000,0000,,Your scale arm has crashed to the floor.
Dialogue: 0,0:09:09.99,0:09:11.67,Default,,0000,0000,0000,,You've tripped the cascade,
Dialogue: 0,0:09:11.70,0:09:13.26,Default,,0000,0000,0000,,setting fire to the forest,
Dialogue: 0,0:09:13.28,0:09:16.38,Default,,0000,0000,0000,,causing inflammation, tangles,\Nand cell death.
Dialogue: 0,0:09:17.14,0:09:19.80,Default,,0000,0000,0000,,You should be symptomatic for Alzheimer's.
Dialogue: 0,0:09:19.82,0:09:23.14,Default,,0000,0000,0000,,You should be having trouble\Nfinding words and keys
Dialogue: 0,0:09:23.16,0:09:26.31,Default,,0000,0000,0000,,and remembering what I said\Nat the beginning of this talk.
Dialogue: 0,0:09:26.92,0:09:28.63,Default,,0000,0000,0000,,But you might not be.
Dialogue: 0,0:09:29.18,0:09:31.66,Default,,0000,0000,0000,,There's one more thing you can do\Nto protect yourself
Dialogue: 0,0:09:31.68,0:09:34.27,Default,,0000,0000,0000,,from experiencing\Nthe symptoms of Alzheimer's,
Dialogue: 0,0:09:34.29,0:09:38.78,Default,,0000,0000,0000,,even if you have the full-blown disease\Npathology ablaze in your brain.
Dialogue: 0,0:09:38.81,0:09:42.71,Default,,0000,0000,0000,,It has to do with neural plasticity\Nand cognitive reserve.
Dialogue: 0,0:09:43.26,0:09:45.64,Default,,0000,0000,0000,,Remember, the experience\Nof having Alzheimer's
Dialogue: 0,0:09:45.66,0:09:48.87,Default,,0000,0000,0000,,is ultimately a result of losing synapses.
Dialogue: 0,0:09:49.34,0:09:52.72,Default,,0000,0000,0000,,The average brain has\Nover a hundred trillion synapses,
Dialogue: 0,0:09:52.74,0:09:55.45,Default,,0000,0000,0000,,which is fantastic;\Nwe've got a lot to work with.
Dialogue: 0,0:09:55.48,0:09:57.15,Default,,0000,0000,0000,,And this isn't a static number.
Dialogue: 0,0:09:57.17,0:09:59.57,Default,,0000,0000,0000,,We gain and lose synapses all the time,
Dialogue: 0,0:09:59.59,0:10:02.40,Default,,0000,0000,0000,,through a process\Ncalled neural plasticity.
Dialogue: 0,0:10:02.42,0:10:04.49,Default,,0000,0000,0000,,Every time we learn something new,
Dialogue: 0,0:10:04.52,0:10:08.64,Default,,0000,0000,0000,,we are creating and strengthening\Nnew neural connections,
Dialogue: 0,0:10:08.67,0:10:10.28,Default,,0000,0000,0000,,new synapses.
Dialogue: 0,0:10:10.99,0:10:12.56,Default,,0000,0000,0000,,In the Nun Study,
Dialogue: 0,0:10:12.59,0:10:17.48,Default,,0000,0000,0000,,678 nuns, all over the age of 75\Nwhen the study began,
Dialogue: 0,0:10:17.50,0:10:19.81,Default,,0000,0000,0000,,were followed for more than two decades.
Dialogue: 0,0:10:19.84,0:10:23.30,Default,,0000,0000,0000,,They were regularly given\Nphysical checkups and cognitive tests,
Dialogue: 0,0:10:23.32,0:10:27.37,Default,,0000,0000,0000,,and when they died, their brains\Nwere all donated for autopsy.
Dialogue: 0,0:10:27.39,0:10:31.77,Default,,0000,0000,0000,,In some of these brains, scientists\Ndiscovered something surprising.
Dialogue: 0,0:10:31.79,0:10:36.37,Default,,0000,0000,0000,,Despite the presence of plaques\Nand tangles and brain shrinkage --
Dialogue: 0,0:10:36.39,0:10:39.26,Default,,0000,0000,0000,,what appeared to be\Nunquestionable Alzheimer's --
Dialogue: 0,0:10:39.28,0:10:42.96,Default,,0000,0000,0000,,the nuns who had belonged\Nto these brains showed no signs
Dialogue: 0,0:10:42.99,0:10:45.56,Default,,0000,0000,0000,,of having the disease\Nwhile they were alive.
Dialogue: 0,0:10:46.18,0:10:47.63,Default,,0000,0000,0000,,How can this be?
Dialogue: 0,0:10:48.01,0:10:52.14,Default,,0000,0000,0000,,We think it's because these nuns\Nhad a high level of cognitive reserve,
Dialogue: 0,0:10:52.16,0:10:56.08,Default,,0000,0000,0000,,which is a way of saying that they had\Nmore functional synapses.
Dialogue: 0,0:10:56.11,0:10:58.68,Default,,0000,0000,0000,,People who have more years\Nof formal education,
Dialogue: 0,0:10:58.70,0:11:00.94,Default,,0000,0000,0000,,who have a high degree of literacy,
Dialogue: 0,0:11:00.96,0:11:04.54,Default,,0000,0000,0000,,who engage regularly\Nin mentally stimulating activities,
Dialogue: 0,0:11:04.57,0:11:07.05,Default,,0000,0000,0000,,all have more cognitive reserve.
Dialogue: 0,0:11:07.07,0:11:11.20,Default,,0000,0000,0000,,They have an abundance\Nand a redundancy in neural connections.
Dialogue: 0,0:11:11.22,0:11:13.90,Default,,0000,0000,0000,,So even if they have a disease\Nlike Alzheimer's
Dialogue: 0,0:11:13.93,0:11:15.98,Default,,0000,0000,0000,,compromising some of their synapses,
Dialogue: 0,0:11:16.00,0:11:18.99,Default,,0000,0000,0000,,they've got many extra backup connections,
Dialogue: 0,0:11:19.01,0:11:22.35,Default,,0000,0000,0000,,and this buffers them from noticing\Nthat anything is amiss.
Dialogue: 0,0:11:22.98,0:11:25.24,Default,,0000,0000,0000,,Let's imagine a simplified example.
Dialogue: 0,0:11:25.26,0:11:27.99,Default,,0000,0000,0000,,Let's say you only know one thing\Nabout a subject.
Dialogue: 0,0:11:28.01,0:11:29.54,Default,,0000,0000,0000,,Let's say it's about me.
Dialogue: 0,0:11:29.57,0:11:31.87,Default,,0000,0000,0000,,You know that Lisa Genova\Nwrote "Still Alice,"
Dialogue: 0,0:11:31.90,0:11:34.33,Default,,0000,0000,0000,,and that's the only thing\Nyou know about me.
Dialogue: 0,0:11:34.36,0:11:36.75,Default,,0000,0000,0000,,You have that single neural connection,
Dialogue: 0,0:11:36.77,0:11:38.72,Default,,0000,0000,0000,,that one synapse.
Dialogue: 0,0:11:38.74,0:11:40.90,Default,,0000,0000,0000,,Now imagine you have Alzheimer's.
Dialogue: 0,0:11:40.92,0:11:43.26,Default,,0000,0000,0000,,You have plaques and tangles\Nand inflammation
Dialogue: 0,0:11:43.28,0:11:46.02,Default,,0000,0000,0000,,and microglia devouring that synapse.
Dialogue: 0,0:11:46.60,0:11:50.83,Default,,0000,0000,0000,,Now when someone asks you,\N"Hey, who wrote 'Still Alice?'"
Dialogue: 0,0:11:50.86,0:11:52.10,Default,,0000,0000,0000,,you can't remember,
Dialogue: 0,0:11:52.13,0:11:55.31,Default,,0000,0000,0000,,because that synapse\Nis either failing or gone.
Dialogue: 0,0:11:55.33,0:11:57.09,Default,,0000,0000,0000,,You've forgotten me forever.
Dialogue: 0,0:11:57.76,0:12:00.39,Default,,0000,0000,0000,,But what if you had learned more about me?
Dialogue: 0,0:12:00.41,0:12:02.50,Default,,0000,0000,0000,,Let's say you learned\Nfour things about me.
Dialogue: 0,0:12:02.52,0:12:04.37,Default,,0000,0000,0000,,Now imagine you have Alzheimer's,
Dialogue: 0,0:12:04.39,0:12:07.39,Default,,0000,0000,0000,,and three of those synapses\Nare damaged or destroyed.
Dialogue: 0,0:12:08.08,0:12:10.54,Default,,0000,0000,0000,,You still have a way\Nto detour the wreckage.
Dialogue: 0,0:12:10.56,0:12:12.58,Default,,0000,0000,0000,,You can still remember my name.
Dialogue: 0,0:12:13.28,0:12:17.21,Default,,0000,0000,0000,,So we can be resilient\Nto the presence of Alzheimer's pathology
Dialogue: 0,0:12:17.23,0:12:20.34,Default,,0000,0000,0000,,through the recruitment\Nof yet-undamaged pathways.
Dialogue: 0,0:12:20.36,0:12:24.14,Default,,0000,0000,0000,,And we create these pathways,\Nthis cognitive reserve,
Dialogue: 0,0:12:24.16,0:12:25.86,Default,,0000,0000,0000,,by learning new things.
Dialogue: 0,0:12:26.46,0:12:30.98,Default,,0000,0000,0000,,Ideally, we want these new things\Nto be as rich in meaning as possible,
Dialogue: 0,0:12:31.00,0:12:35.74,Default,,0000,0000,0000,,recruiting sight and sound\Nand associations and emotion.
Dialogue: 0,0:12:36.40,0:12:39.53,Default,,0000,0000,0000,,So this really doesn't mean\Ndoing crossword puzzles.
Dialogue: 0,0:12:39.56,0:12:43.65,Default,,0000,0000,0000,,You don't want to simply retrieve\Ninformation you've already learned,
Dialogue: 0,0:12:43.68,0:12:47.02,Default,,0000,0000,0000,,because this is like traveling\Ndown old, familiar streets,
Dialogue: 0,0:12:47.04,0:12:49.63,Default,,0000,0000,0000,,cruising neighborhoods you already know.
Dialogue: 0,0:12:50.11,0:12:52.95,Default,,0000,0000,0000,,You want to pave new neural roads.
Dialogue: 0,0:12:52.97,0:12:55.48,Default,,0000,0000,0000,,Building an Alzheimer's-resistant brain
Dialogue: 0,0:12:55.51,0:12:57.69,Default,,0000,0000,0000,,means learning to speak Italian,
Dialogue: 0,0:12:57.71,0:12:59.22,Default,,0000,0000,0000,,meeting new friends,
Dialogue: 0,0:12:59.24,0:13:00.41,Default,,0000,0000,0000,,reading a book,
Dialogue: 0,0:13:00.44,0:13:02.80,Default,,0000,0000,0000,,or listening to a great TED Talk.
Dialogue: 0,0:13:03.28,0:13:08.60,Default,,0000,0000,0000,,And if, despite all of this, you are\Nsomeday diagnosed with Alzheimer's,
Dialogue: 0,0:13:08.62,0:13:11.77,Default,,0000,0000,0000,,there are three lessons I've learned\Nfrom my grandmother
Dialogue: 0,0:13:11.80,0:13:15.53,Default,,0000,0000,0000,,and the dozens of people I've come to know\Nliving with this disease.
Dialogue: 0,0:13:16.12,0:13:19.30,Default,,0000,0000,0000,,Diagnosis doesn't mean\Nyou're dying tomorrow.
Dialogue: 0,0:13:19.32,0:13:21.04,Default,,0000,0000,0000,,Keep living.
Dialogue: 0,0:13:21.07,0:13:23.44,Default,,0000,0000,0000,,You won't lose your emotional memory.
Dialogue: 0,0:13:23.46,0:13:26.96,Default,,0000,0000,0000,,You'll still be able\Nto understand love and joy.
Dialogue: 0,0:13:26.99,0:13:29.99,Default,,0000,0000,0000,,You might not remember\Nwhat I said five minutes ago,
Dialogue: 0,0:13:30.02,0:13:32.30,Default,,0000,0000,0000,,but you'll remember how I made you feel.
Dialogue: 0,0:13:32.94,0:13:36.22,Default,,0000,0000,0000,,And you are more than what\Nyou can remember.
Dialogue: 0,0:13:36.24,0:13:37.53,Default,,0000,0000,0000,,Thank you.
Dialogue: 0,0:13:37.56,0:13:42.88,Default,,0000,0000,0000,,(Applause)