How exercise can help prevent Alzheimer’s | NOVA

Your brain loves it when you exercise. Of course, you yourself may not love every sweaty minute of your kickboxing class or Saturday afternoon run—but your brain revels in it. That’s because exercise doesn’t just increase muscle tone. It doesn’t just goose energy levels and enhance mood, fighting depression and anxiety. It also heightens problem-solving skills and memory. And, research has increasingly shown, it protects against Alzheimer’s disease—both delaying onset of the disease and slowing decline in patients who have already been diagnosed.

As baby boomers age and more Americans live longer, Alzheimer’s is on the rise. In 2020, some 5.8 million people in the US were living with this most common form of dementia, in which inflammation and tangles of misformed proteins in the brain accompany progressive memory loss and inability to perform day-to-day tasks.

Despite decades of research, effective treatments for Alzheimer’s have eluded researchers; even a full explanation of what happens inside an Alzheimer’s patient’s brain has remained out of reach. This is in part because the disease is incredibly knotty and multifaceted, says Fang Yu, a researcher at Arizona State University who specializes in applying new dementia science to human trials. Alzheimer’s affects myriad processes in the brain, our most complicated organ, but most treatments developed thus far have only been able to tackle one aspect of the disease at a time, she says. “Even if there is a medication that can help target certain pathways, there are many pathways needed.”

That’s why Yu’s Alzheimer’s studies have often focused on the power of moving our bodies. Exercise is unique in that it also affects the body and brain in many ways, she says, making it an important intervention for addressing the complexity of Alzheimer’s.

It’s “something quite special,” agrees Christiane Wrann, a neuroscientist at Harvard University and Massachusetts General Hospital. While you’re dancing, bicycling, or running, it may seem like “you’re doing something that doesn’t have anything to do with the brain,” she says. “But you’re actually getting improvement in cognitive function.”

How does it work?

Perhaps the most straightforward way in which exercise safeguards against Alzheimer’s is by improving cardiovascular health. The effects of a good sweat session don’t stop at our hearts—they help improve the condition of our other organs and blood vessels as well. Those healthier vessels deliver an upgrade in the connections among brain cells called neurons, Wrann says. With reinforced wiring, it’s easier for nourishing oxygen to get in, for waste products to get out, and for the neurons to talk to one another. And improved fitness of the heart and lungs also seems to help the brain take up glucose more efficiently, which helps keep neurons healthy.

Plus, research on mice—a common, if imperfect, source of new Alzheimer’s science, since it’s not possible to ethically conduct some kinds of research on living humans—has shown that exercise is a rare cause of “adult neurogenesis,” or the growth of new neurons in adulthood. Although it’s difficult to fully prove that the same happens in humans, it seems like one key player is irisin, a hormone manufactured in the muscles in response to exercise, Wrann explains. Irisin is special because it carries a pass to get through the blood-brain barrier, the barricade of tissue and blood vessels that keeps harmful substances from reaching the brain.

Once inside, irisin helps the brain create a neurotransmitter called BDNF, which is important to hippocampus health. The hippocampus is a center of learning and memory in the brain, and Alzheimer’s patients’ hippocampi tends to shrink as their health declines, Yu says. The ability to sprout new cells in the hippocampus, and to prune away connections that aren’t needed anymore—two processes that BDNF supports—is key to stabilizing and protecting it.

A series of studies at Wrann’s lab in Boston has also shown that, at least in mice, irisin produced during exercise has powerful anti-inflammatory effects in the brain. That could be an important insight because some new research points to inflammation, rather than previously implicated amyloid plaques, as a possible cause of neuron death in Alzheimer’s. Inflammation is caused by the immune response to negative stimuli—not just viruses or bacteria but also, for example, misfolded proteins in the brain. In an Alzheimer’s patient, the immune system may respond to the presence of these plaques by attacking them, Wrann explains, and in its enthusiasm, it may also attack the synapses that connect neurons. “If it gets completely out of control, you have this ‘friendly fire’ that causes damage to the neurons,” she says. But her research indicates irisin may bind to receptors on specialized cells deep within the brain, calming that inflammatory response.

And one last piece of the puzzle is sleep—not a type of exercise in itself, but caught up in something of a love triangle with exercise and Alzheimer’s disease. When it comes to dementia prevention, sleep and exercise may work together, says neuroscientist Miranda Chappel-Farley, a Ph.D. candidate at University of California, Irvine. Studies have shown that more exercise leads to better quality sleep, which is an important protective factor itself against Alzheimer’s. And people getting better sleep are more likely to feel up to exercising. Together, they create a powerful bulwark against dementia and represent a lifestyle factor ignored at your peril, says Chappel-Farley, who cautions against “targeting exercise but not paying attention to sleep.”

What kind of exercise is best?

Aerobic exercise seems to be the champion when it comes to protection against Alzheimer’s and maintaining executive function. Of course, most of the mice participating in Alzheimer’s trials run on their wheels, but that doesn’t mean you have to. Biking, dancing, swimming, or any activity that gets your heart rate up is a good candidate, Yu says. That’s because it has the potential to increase BDNF levels; spur blood flow and shore up blood vessels; and decrease “white matter hyperintensities,” abnormal changes that affect how the brain transmits electrical signals.

Newer research also indicates that resistance-based muscle-building exercise may support a broad spectrum of cognitive functions. That effect seems especially promising in patients who have already been diagnosed with Alzheimer’s, where it may help slow their decline, adds Yu, who often works with dementia patients. There, the goal is not improving but slowing deterioration. “And that’s basically what my research has shown: that exercise can level and stabilize,” she says.

Tai chi and other types of movement that incorporate mindfulness also decrease stress and inflammation and improve sleep, she adds. And some research suggests that a mix of many types of exercises may provide stronger improvement than a single activity. In a review of 71 studies of exercise and dementia, Yu and her colleagues found the most consistently effective exercise was “mixed component,” a blend of muscle-building and aerobic workouts.

Still, “it’s important to highlight that there’s a lot we don’t know yet,” says Chappel-Farley, since exercise comes in so many forms and can be adjusted by duration, intensity, frequency, and timing. “It’s not totally clear which might be best.” Does it take a certain amount of exercise for our brains to reap the benefits? Are there any findings in the extensive mouse research on this topic that can’t be transferred to humans?

Wrann says that data is encouraging so far, indicating that the more you exercise the more benefit you’ll experience. And really, what’s the risk? “My big message is that exercise is good for you,” Yu agrees. “Even if in the future we find that it doesn’t prevent Alzheimer’s for everyone, it’s still good for your health and quality of life.”

But Wrann also remains mindful of people who can’t exercise because of a disability or physical limitations, or who may develop Alzheimer’s despite getting plenty of exercise; there’s still no silver dementia bullet. While it’s unlikely that researchers could develop a drug that can affect the body in as many ways as exercise can, she’s hopeful about irisin’s potential as a source of new drug therapies. Because it’s a powerful anti-inflammatory that can already wriggle through the blood-brain barrier, she wonders if it might be possible to use irisin to create a drug that goes even beyond the positive effects of exercise. Inflammation in the brain seems to be central to many neurological conditions. That way, she says, “we could reach people with Alzheimer’s disease—or beyond.”

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