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Feel helpless against Alzheimer’s disease? You can do something to help prevent it


2018-1-11 16:02 Science 65 0 0
Feel helpless against Alzheimer’s disease? You can do something to help prevent it

We should all feel empowered to take steps to keep our brains and bodies healthy, says neuroscientist and novelist Lisa Genova.


How many of you reading this would like to live to be at least 80 years old? I think we all have a hopeful expectation of living into old age. Now let’s project this thought out into the future, and imagine we’re all 85. Out of every two people, one of us probably has Alzheimer’s disease.


Maybe you’re thinking, “Well, it won’t be me.” OK, then, you’ll be a caregiver. In some way, this terrifying disease is likely to affect us all.


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.


But maybe it doesn’t have to be. What if I told you that we could change these statistics — perhaps change our brain’s destiny — without relying on a cure or advancements in medicine?


If you’re 40 or older, this initial step into the disease — the presence of accumulating amyloid plaques — can already be found in your brain.


Before we get into this, let’s go over what we currently understand about the neuroscience of Alzheimer’s. The point of connection between two neurons, or nerve cells, is called the synapse. The synapse is where neurotransmitters are released, transmitting signals and enabling communication. It’s where we think, feel, see, hear, desire and remember — and it’s where Alzheimer’s happens.


During the information communication process, 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 or metabolized by microglia, the janitor cells of our brains. While the molecular causes of Alzheimer’s are still debated, most neuroscientists believe the disease begins when amyloid beta begins to accumulate. If too much is released or not enough is cleared away, the synapse begins to pile up with amyloid beta. When this happens, it binds to itself, forming sticky aggregates called amyloid plaques.


If you’re 40 years old or older, this initial step into the disease — the presence of accumulating plaques — can already be found in your brain, but the only way to be sure of this would be through a PET scan. Otherwise, you’re not showing any impairments in memory, language or cognition … yet.


By mid-stage Alzheimer’s, your brain is full of massive inflammation, tangles and cell death.


Scientists think it takes at least 15 to 20 years of amyloid plaque accumulation before it reaches a tipping point, which then triggers a molecular cascade that causes the clinical symptoms of the disease. Prior to the tipping point, your lapses in memory may include things like,”Why did I come in this room?” or “Oh, what’s his name?” or “Where did I put my keys?” Before you freak out because you’ve asked at least one of those questions in the last 24 hours, those are all normal kinds of forgetting. In fact, these examples might not even involve your memory — maybe you just didn’t pay attention to where you put your keys in the first place.


After the tipping point actually occurs, those 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?”


What happens when amyloid plaques accumulate and reach this tipping point? Our microglia janitor cells become hyper-activated, releasing chemicals that cause inflammation and cellular damage. Scientists think they might actually start clearing away the synapses themselves. A crucial neural transport protein called tau becomes hyperphosphorylated and twists itself into tangles, which choke off the neurons from the inside. By mid-stage Alzheimer’s, your brain is full of massive inflammation, tangles and cell death.


Perhaps preventive Alzheimer’s drugs have failed in clinical trials not because the science wasn’t sound but because the people in these trials were already symptomatic.


If you were a scientist trying to cure this disease, at what point would you ideally want to intervene? Many researchers are betting big on the simplest solution: keeping amyloid plaques from reaching a tipping point. As a result, drug discovery is largely focused on developing a compound that will prevent, eliminate or reduce amyloid plaque accumulation. Which means the cure for Alzheimer’s will likely be a preventative medicine. We’ll need to take a pill before we reach the tipping point, before the cascade is triggered, before we start leaving our keys in the refrigerator. That may be 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 must blow out the match before the forest catches fire.


This is actually good news for us, because it turns out the way we live can influence the accumulation of amyloid plaques. There are things we can do to keep us from reaching the tipping point. Picture your risk of Alzheimer’s as a seesaw scale. Pile risk factors on one arm of your seesaw, and when that arm hits the floor, you are symptomatic and diagnosed with Alzheimer’s. So, 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 arm is tipped a little bit.


Some scientists even believe poor sleep hygiene may be a predictor of Alzheimer’s.


We’ve all inherited DNA from our moms and our dads, and some of our genes will increase our risk and others will decrease it. If you’re like the character Alice in my book Still Alice, you’ve inherited a rare genetic mutation that cranks out amyloid beta, which will tip your seesaw arm to the ground.


But for most of us, the genes we inherit will tip the arm only a bit. For example, the gene variant increases amyloid, but you can inherit a copy of APOE4 from Mom and Dad and still never get Alzheimer’s. That means for most of us, our DNA alone does not determine whether we get Alzheimer’s. So what does?


Sleep could be a factor. In slow-wave deep sleep, our glial cells rinse cerebrospinal 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, and a single night of sleep deprivation can lead to an increase in amyloid beta. At the same time, amyloid accumulation has been shown to disrupt sleep, which in turn causes more amyloid to accumulate. So there’s a positive feedback loop that’s going to accelerate the tipping of the seesaw. Some scientists even believe poor sleep hygiene may be a predictor of Alzheimer’s.


Cardiovascular health is another factor. High blood pressure, diabetes, obesity, smoking and high cholesterol have all been shown to increase the risk of developing Alzheimer’s. Some studies have shown that as many as 80 percent of people with Alzheimer’s also had cardiovascular disease. Aerobic exercise has been shown in numerous animal studies to decrease amyloid beta. A heart-healthy Mediterranean lifestyle and diet may be able to help counter the tipping of this scale.


The average brain has over 100 trillion synapses, and every time we learn something new, we are creating and strengthening new neural connections, new synapses.


There are many things we can do to try to prevent or delay the onset of Alzheimer’s, but maybe 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.


Let’s imagine that your amyloid plaques have reached that tipping point. Your scale arm has crashed to the floor. You’ve set 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. But you might not be.


There’s one more thing you can do to protect yourself from experiencing the symptoms of Alzheimer’s, and it has to do with neural plasticity and cognitive reserve. Remember, having Alzheimer’s is ultimately a result of losing synapses. The average brain has over 100 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 known as neural plasticity. Every time we learn something new, we are creating and strengthening new neural connections, new synapses.


In the Nun Study, 678 nuns, who were all over the age of 75 at the beginning of the study, were followed for more than two decades. They received regular physical checkups and cognitive tests, and when they died, they all donated their brains for autopsy. In some of these brains, scientists discovered something surprising. Despite the presence of plaques, tangles and brain shrinkage — what appeared to be unquestionable signs of Alzheimer’s — the nuns who possessed these brains had showed no symptoms of having the disease while they were alive.


Scientists think these nuns had a high level of cognitive reserve — meaning they had more functional synapses. People who have more years of formal education, who have a high degree of literacy, who regularly engage in mentally stimulating activities, all have more cognitive reserve. They have an abundance and a redundancy in neural connections. Even if they have a disease like Alzheimer’s compromising some of their synapses, they’ve got many extra backup connections, which buffers them from noticing that anything is amiss.


Building an Alzheimer’s-resistant brain could mean learning to speak Italian, meeting new friends, reading a book, or listening to a great TED Talk.


Why does this matter? I’ll give you a simplified example. Let’s say you only know one thing about a subject, and the subject is me. You know I wrote the novel Still Alice, and it’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, tangles, inflammation and microglia devouring that synapse. When someone asks you, “Hey, who wrote Still Alice?” you can’t remember, because that synapse is either failing or gone.


But what if you had learned more about me? Perhaps you learned four things about me. Now, imagine you have Alzheimer’s, and three of those synapses are damaged or destroyed. However, you still have a way to detour the wreckage; you can still remember my name.


We can be resilient to the presence of Alzheimer’s through the recruitment of yet-undamaged pathways. And we can start to 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, sound, associations and emotion.


This doesn’t mean doing crossword puzzles — you don’t want to simply retrieve information you’ve already learned. That’s like traveling down old, familiar streets, cruising neighborhoods you already know. You want to pave new neural roads. Building an Alzheimer’s-resistant brain could mean learning to speak Italian, meeting new friends, reading a book, or listening to a great TED Talk.


And if — despite all of your efforts — someday you are diagnosed with Alzheimer’s, there are lessons I’ve learned from my grandmother and the dozens of people living with this disease whom I’ve come to know. Being diagnosed with the disease does not mean you’re dying tomorrow, so keep living. You won’t lose your emotional memory. You’ll still be able to understand love and joy. You may not remember what you read five minutes ago, but you’ll remember how it made you feel. And you are more than what you can remember.



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