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.
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.
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.
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.
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.
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% 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. 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.
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.
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. 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.
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.
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. But what if you had learned more about me? Let’s say you learned four things about me.