Alzheimer's

There’s evidence that such activities do little to change the underlying drivers of Alzheimer’s, but doctors say they delay symptoms

Among the many frustrations surrounding an Alzheimer’s diagnosis is the fact that there is little that patients can do to halt or treat the disease. While promising drugs are under development, the only advice physicians give patients is to stay as mentally active as they can — by learning new languages, reading, piquing the brain with puzzles, and maintaining their social life. Such constant stimulation is supposed to keep the healthy parts of the brain as unaffected by the disease for as long as possible. There’s also evidence that a lifetime of such activity can build up so-called reserves, which can compensate for brain functions when Alzheimer’s sets in.

In a report published in the journal Neurology, Dr. Keith Johnson from Massachusetts General Hospital and Harvard Medical School and his colleagues reveal that people who report higher levels of intellectual stimulation throughout their lifetimes don’t actually exhibit lower levels of protein plaques and other signs of Alzheimer’s compared to those who don’t. But they also found that staying mentally and socially active can push back the appearance of memory problems and other symptoms of Alzheimer’s.

So while the results don’t show that mental activity can affect the biology of Alzheimer’s in any way, it can have a meaningful impact on symptoms. And that is “huge,” says Dr. David Knopman, professor of neurology at Mayo Clinic College of Medicine, who reviewed the paper and recommended it for publication. “If that resulted in a year or two delay in symptoms across the population, that would be a huge effect.”

MORE: Many Doctors Don’t Tell Patients They Have Alzheimer’s

The study involved 186 healthy volunteers with an average age of 74 years who agreed to report their current and past cognitive activities, as well as undergo a brain scan to measure levels of the Alzheimer’s-associated protein called amyloid and the volumes of specific regions of the brain responsible for memory. The group reporting more intellectual activity over their lifetimes did not show lower levels of Alzheimer’s progression as those who reported less cognitive stimulation. But the former group were able to delay the appearance of symptoms, presumably because their stronger intellectual base compensated for the effects of the disease for a longer period of time.

“If two people had the same amount of Alzheimer’s pathology, and one had higher education and engaged in more cognitively stimulating activities, and one had lower educational attainment and didn’t participate in as many mentally stimulating activities, then the symptoms [of Alzheimer’s] would appear earlier in the person with less cognitively stimulating activity,” says Knopman.

MORE: This Alzheimer’s Breakthrough Could Be a Game Changer

While earlier studies relied on studies on autopsy brains to draw connections between cognitive activity and Alzheimer’s disease, this is among the first to investigate the connection in healthy living people, by using state-of-the-art imaging techniques to pick up protein deposits in the brain and following the volunteers to see if any develop the disease. Next up will be studies looking at whether picking up more cognitive activities after an Alzheimer’s diagnosis can have the same effect of slowing memory problems as having a lifetime of such skills.

Here's how to get your brain blood flowing

A recent study alleviated fears that statins—taken by 1 in 4 adults over the age of 40—cause memory loss. But how do you strengthen recall in general? We asked Dr. Majid Fotuhi, chairman of the Memosyn Neurology Institute, to share the latest research-backed insights. “People don’t appreciate that such simple factors have an impact on your brain health, but they do,” he says. “They’re more powerful than any medicine you can take.”

1. Have a sense of purpose in life. In one study published earlier this year in the journal Stroke, scientists studied autopsied adult brains and found that the odds of having a stroke were reduced by half or older people who had a high sense of purpose, compared to people who reported a low sense of purpose.

2. Go dancing. It’s a brain-building triple threat, he says: physical activity protects the brain, learning lets it grow, and socialization helps it thrive. (Fotuhi recommends the tango.)

3. Learn something new. Pre-GPS, cabbies had to learn their cities’ streets and traffic patterns—a challenging mental exercise that over their career actually grew the part of the brain associated with spatial memory, one study found.

4. Take omega-3s fatty acids. The combo of DHA and EPA increase blood flow to the brain, reduce inflammation and help repair neurons, Fotuhi says. His research also suggests that DHA may slow cognitive decline.

5. Exercise. In a study published in the journal PNAS, people who exercised every day for a year had 2% growth in their hippocampus—a part of the brain that plays a role in short- and long-term memory—while people who merely stretched saw shrinkage. Increasing blood flow to the brain helps it grow, Fotuhi says. “You need to be physically fit below your neck in order to have a fit brain above your neck.”

Poor sleep may be contributing to the buildup of the brain plaques that drive the disease

Doctors studying Alzheimer’s disease have known for a while now that their patients are poor sleepers. But does the disease result in disrupted sleep, or do unhealthy sleep habits contribute to the disease?

Reporting in Nature Neuroscience, researchers led by Matthew Walker at the University of California, Berkeley, describe for the first time a unique pattern of sleep brain waves that seems to be linked to a higher risk of building up the brain proteins that can lead to impaired memory.

When the team studied 26 cognitively normal older adults, they found that higher amounts of amyloid, the protein responsible for the hallmark plaques found in Alzheimer’s disease, were linked with more disrupted deep sleep patterns. More importantly, the higher amount of amyloid and the disturbed sleep were also associated with worse performance on simple paired-word memory tests, which the researchers gave the volunteers both before and after a night’s sleep.

MORE: Many Doctors Don’t Tell Patients They Have Alzheimer’s

“It wasn’t just all of deep sleep that was disrupted but a very specific electrical signature deficit that we found,” says Walker. “It’s very particular and very unique, so my hope is that it’s so specific that it may really offer quite a high degree of sensitivity and specificity for the changes we see associated with Alzheimer’s disease.”

He stresses that in the current study, all of the volunteers were cognitively normal, and that the researchers did not follow them to determine if they eventually developed mild cognitive impairment—which often precedes Alzheimer’s—or Alzheimer’s itself. But the fact that the build-up of amyloid was connected to worse performance on the memory task highlights how early the disease process of Alzheimer’s may start: well before people experience any change in their intellectual skills. And one of the factors that may contribute to the accumulation of amyloid may be poor sleep. “Sleep is a great early warning beacon, a distress call that we can latch onto, to potentially alert us to the beginnings of Alzheimer’s,” says Walker.

MORE: New Research on Understanding Alzheimer’s

“What we think we found is a new way that disruption of sleep contributes to the pathology that can disrupt the cementing of memories,” says Bryce Mander, a post doctoral fellow at University of California, Berkeley, and lead author of the paper. The findings also resolve one of the puzzling questions in Alzheimer’s disease: why buildup of amyloid starts initially in areas of the brain that don’t have anything to do with memory. Mander and Walker’s team found that the protein does deposit, however, in areas of the brain that generate the wave patterns of deep sleep.

The relationship between sleep and amyloid is likely a two-way street, they say, in which the more amyloid that builds up, the worse the sleep, and the more disrupted the sleep, the more amyloid that gets deposited. Other studies have shown that deep sleep can cement memories as well as clear away amyloid. Not getting enough deep sleep, then, perpetuates the poor memory cycle.

What that means is that it might be possible to slow down some of the damage done by piled-up amyloid. If poor, disrupted sleep is promoting buildup, then getting more deep sleep might be able to reduce the protein burden in the brain. “If my parents and friends in their 50s, 60s or 70s ask me if they should pay attention to sleep and prioritize sleep in terms of their health risk of developing Alzheimer’s, I would say at this stage very much, ‘yes,’” says Walker. “It’s very clear now that sleep is an under-appreciated factor contributing to cognitive decline later in life, and it seems, to the pathology behind Alzheimer’s.”

Scientists now know why some people rebound so well from setbacks. They also know how the rest of us can be more like them

Dr. Dennis Charney knows that each of his five children has hated him at some point or another–particularly when he dragged them along on one of his “semidangerous” adventure trips. He recalls a perilous hike with one of his daughters, who was 13 at the time. “Some weather came in, and there was some wildlife. When she said she despised me it came, like, from her soul,” says Charney, 64, who is now dean of the Icahn School of Medicine at Mount Sinai in New York City.

His son Alex knows the feeling. A decade ago, Charney took him on a kayaking trip to Patagonia with his best friend, Dr. Steven Southwick. It rained the entire time, the life jackets didn’t fit, and Alex had to share a broken-ruddered boat with his dad for 12-mile runs every day. When it was all over, Alex informed his father he never wanted to speak to him again.

But as a psychiatrist who, with Southwick, has studied the science of resilience for two decades, Charney knows there are benefits to forcing people out of their comfort zone. Resilience is essentially a set of skills–as opposed to a disposition or personality type–that make it possible for people not only to get through hard times but to thrive during and after them. Just as rubber rebounds after being squeezed or squished, so do resilient people.

It’s a tantalizing arena for neuroscientists, who are getting better at understanding why some people bounce back from difficult experiences–both those they seek out and those that blindside them–while others don’t fare quite so well. And thanks to modern imaging, scientists can peer inside the brain in real time to see how, and to what extent, stressful situations change the structure and functions of the brain. They are also learning that training for resilience can change the brain to, well, make it more resilient.

Much of the new evidence suggests that with a little practice, anyone can develop resilience, says Southwick, 67, a professor of psychiatry at the Yale School of Medicine. There are lots of ways to intervene so that stress or trauma doesn’t derail you, he says. No one size fits all.

That’s good news, because humans get stressed far more than they realize. The hot-and-cold boss, the traffic delays, the spat with their spouse, the monthly bills–these are all registered as stress in the brain. “The vast majority of us will be faced with one or more major traumatic stressors during a lifetime,” says Southwick. But the countless smaller stresses also take a toll. Resilience, research shows, can help with that, and it’s not a moment too soon, given that nearly all our modern ills, including heart disease and possibly even brain disorders like Alzheimer’s disease, have stress as a common risk factor.

With heart disease killing far more Americans than anything else and rates of Alzheimer’s expected to double in the coming decades, scientists are hard at work to find promising ways to prepare a large, aging population for healthier ways of dealing with stress. “Resilience training can help people deal effectively with chronic disease and improve their quality of life,” says Charney. “It helps people cope.”

Forget the old adage that you won’t know what you’re made of until you’re tested; the latest science shows that if you train your brain, how you act under pressure can, in large part, be up to you.

Understanding Resilience

Studying the capacity to successfully adapt to challenges wasn’t on researchers’ radar before World War II. Ann Masten, a resilience researcher and professor of child development at the University of Minnesota, notes that the war produced no shortage of traumatized and displaced people–many of them children who were orphaned, injured or sick, which is precisely the kind of thing that puts people at risk for trouble later on. But psychologists caring for these children noticed that some fared improbably well, despite their circumstances.

Researchers wondered why, and by the 1950s, Emmy E. Werner, a developmental psychologist and pioneer in resilience research, was inching toward an answer. In 1955 she and a team from the University of California, Berkeley, began what’s considered the most important longitudinal study in the field: a 40-year project following nearly 700 children in Kauai, Hawaii, many of whom had alcoholic parents. Her research showed that a third of the most vulnerable children adapted exceedingly well over time. Werner wanted to know what makes a person thrive in the aftermath of adversity. The study found that factors like having a tight-knit community, a stable role model and a strong belief in their ability to solve problems helped children succeed.

“As soon as people began to pay more attention to positive outcomes and positive development, they realized there were a lot of children doing well,” Masten says.

Most resilience research is still done on survivors of catastrophes–floods, fires, tsunamis, drought–as well as on soldiers. But while it’s tempting to think of resilience as a skill people won’t need until they’re locked in a cell or their home is sucked into a tornado, resilience experts say those extremes are a kind of psychological exaggeration of the things the rest of us go through.

After interviewing scores of Vietnam prisoners of war, Army Special Forces and survivors of horrific tragedies, Charney and Southwick became convinced that anyone could train him- or herself to be more resilient. POWs told Southwick and Charney that with only two resources–free time and their minds–they were able to do remarkable things they couldn’t do before; one developed a knack for multiplying huge numbers in his head, while another built a house in his imagination (and then later, on solid ground). “It said to us that there’s enormous untapped capacity of the human brain,” Charney says.

Discovering why some of us fare better than others has always been at the heart of resilience research. Now techniques like functional magnetic resonance imaging make it possible for scientists to look beyond their own observations of people and into the parts of their brains that govern emotion. By observing patterns of blood flow, they can measure brain activity and see, for instance, what stress looks like in different people–which is useful because how we respond to stress is a critical part of resilience. Like the animal whose pulse returns quickly to normal once it has successfully outrun a predator, resilient brains seem to shut off the stress response and return to baseline quickly. “Resilient people seem to have the capacity to appropriately regulate the subcortical fear circuits under conditions of stress,” says Charney.

It doesn’t take a predator to trigger a stress response in modern humans. Some research shows that even feelings of social pain–like rejection and loneliness–zoom along the same neural pathways as fear. “This notion that I’m going to be rejected or fail or won’t be accepted by the group activates the same circuits as if I saw a wolf,” Southwick says. It’s an evolutionary hanger-on from when our ancestors survived only in groups.

The problem is, even though we’re no longer bumping into wolves, we’re constantly activating the same neural pathways of fear with everyday stressors–worrying about the future, fretting about the past. The more we use this neuronal superhighway, the more efficient it grows, and this mode of thinking becomes our default. But new research shows humans can train their brains to build and strengthen different connections that don’t reinforce the fear circuit. Over time, if people use this new pathway enough, it can become the new response to stress.

Richard Davidson, a neuroscientist at the University of Wisconsin, Madison, thinks he’s found a connection in the brain that is especially important for resilience: the path from the prefrontal cortex–the seat of cognition and planning–to the amygdala, an emotional part of the brain that responds to threats. A stronger connection means the prefrontal cortex can more quickly tell the emotional amygdala to quiet down, Davidson writes in his book The Emotional Life of Your Brain.

Scientists can see how resilient brains respond to emotion differently, found Martin Paulus, scientific director and president of the Laureate Institute for Brain Research in Tulsa, Okla. In a series of brain-imaging experiments on resilient Navy SEALs, Paulus showed the SEALs a color cue that signaled they were about to see an emotional picture. Paulus saw that their brains anticipated the emotion more quickly than the average brain, letting them jump nimbly between different types of emotions. Paulus says that in his research he has seen differences in the brains of people with anxiety or depression that suggest they have a hard time letting go of emotions and are often too engaged in emotional processes. The Navy SEALs, on the other hand, weren’t glued to the emotional experiences. Why? “They’re more resilient,” he says. And just like working your biceps or your abs, say experts, training your brain can build up strength in the right places–and at the right times–too.

The Workout for Your Brain

A good way to gauge how close you are to resilience is to consider how you react when things don’t go your way, Davidson says. His research shows that the way we cope with little stressors strongly predicts how we’ll do once the big stuff hits. Personality is not as big a factor as one might think: Pollyannas are not always more resilient than pessimists, and even stubborn curmudgeons can pick up traits associated with resilience.

What’s more, scientists have identified at least a dozen ways that people can up their resilience game, which Charney and Southwick detail in their 2012 book, Resilience: The Science of Mastering Life’s Greatest Challenges, to be updated this year with reams of new research on the topic. “For resilience, there’s not one prescription that works,” Charney says. “You have to find what works for you.”

So far, researchers have found that facing the things that scare you relaxes the fear circuitry, making that a good first step in building resilience. They have also found that developing an ethical code to guide daily decisions can help. Studies have shown that traits scientists once thought of as nice but unnecessary–like having a strong network of social support–are critical to resilience. “Very few highly resilient individuals are strong in and by themselves,” Southwick says. “You need support.” There are even neurobiological elements to social support. When people are exposed to a stressor in a lab, their heart rate and blood pressure don’t go up quite as much if a friend is in the room as they do if they’re alone.

In an interesting twist, scientists have learned that working the body’s muscles makes people’s minds more resilient as well. That’s because exercise also spurs the development of new neurons, which are quite literally damaged by stress, Southwick says. Over time, regular exercise can tamp down a person’s stress response.

The most compelling new research about resilience focuses on mindfulness–an area in which most people would do well to improve, since people spend 47% of their days thinking about things other than what they’re actually doing, a 2010 Harvard study found.

In a study published last year, Paulus and researchers at the University of California, San Diego, trained four Marine infantry platoons in an eight-week mindfulness course, and four platoons trained as usual. The Marines then spent a day at the Infantry Immersion Trainer facility, an elaborate mock Iraqi village the Marines use to prepare for deployment, where they were ambushed and otherwise stressed. A subset of both groups had their brains scanned before and after the intervention. When the experiment was over, researchers found that the Marines who trained in mindfulness returned to baseline levels of heart rate and breathing rate faster than those who hadn’t been trained.

They also showed lower activation in the region of the brain associated with emotional reactions. By the end of training, their brains actually looked more resilient, Paulus says. “We were able to show, at least in the brain, that we can train people to modify their brain processes toward the direction of resilience.”

Even though the Marines’ brains changed to reflect those of more resilient people, they didn’t report feeling more resilient. So researchers did another experiment, using Olympic BMX athletes. This time, they told them how their mindfulness course could be affecting their brains. “That’s particularly helpful for people who may initially not be as susceptible to mindfulness,” says Paulus, who led the research. “They may say, ‘Well, this may not be for me.’ But when we showed them that we can actually change their brains, it becomes much more interesting to them.”

Like the mindful Marines, the mindful BMX cyclers showed less emotional reactivity to a stressful task than they had before they took the course. Unlike the Marines, however, they also said they felt more resilient–likely because they had been primed to associate the exercise with that benefit. Shortly after the study ended, the athletes competed in a major BMX competition and swept the gold, silver and bronze medals. (Two years before, at the London Olympics, they hadn’t placed.) There’s no control group in real life, of course, and they might have done just as well without the training. “But they at least told us that it was particularly noticeable to them,” Paulus says.

The Meditation Miracle?

It might seem too touchy-feely to believe that becoming tougher has everything to do with tuning into the mind, the body and the present moment. But that’s precisely what Davidson from the University of Wisconsin is finding. In 1992 he wrote a letter to the Dalai Lama asking if he could study Tibetan Buddhist monks to see how meditation changes the structure or function of their brains. To his surprise, the Dalai Lama wrote back with a request that Davidson devote as much time to studying the effects of kindness and compassion on the brain as depression, anxiety and fear.

Since then, Davidson has used brain imaging to watch the brains of all kinds of people while they’re in meditation states, from novices to Buddhist monks. He’s found that consistent practice changes how the brain looks as well as how it operates. The more experienced the meditator, the more quickly the brain recovers from stress. Another recent study shows that meditation can even help decrease expression of pro-inflammatory genes.

“The changes we see aren’t just changes during the meditation state itself, but they’re changes that persist beyond the meditation state,” Davidson says. “They transform our baseline.” And a solid baseline state is what we really need when the waters get rough, he says.

That’s why Charney and Southwick emphasize again and again the importance of finding resilience-building skills you’ll stick with. When Charney lost his granddaughter and Southwick’s mother died, each leaned on the other to get through it–a case of resilience-building social support in action.

And while you won’t find Charney joining Southwick in meditation, and you won’t spot Southwick bench-pressing next to Charney in the med students’ gym at Mount Sinai, you’ll almost certainly find them building resilience together and apart. Because as they’ve learned, this stuff really pays off when you need it.

"People think it's a curable disease"

Seth Rogen may be one of America’s favorite funny guys, but when it comes to Alzheimer’s research, he’s not kidding around. Rogen’s mother-in-law was diagnosed with early-onset Alzheimer’s not long after he started dating his now-wife, Lauren Miller. He’s become a public face of advocacy for awareness about Alzheimer’s, even testifying before the Senate Committee on Appropriates last year in a bid to get more funding for research. The couple also work to raise money with their movement Hilarity for Charity, which has an event this weekend at the University of Vermont to congratulate students there for raising the most money of any college for the second year in a row. Their prize is a live narration of the Superbad soundtrack by Rogen and “McLovin” actor Christopher Mintz-Plass. We caught up with Rogen and Miller before the event.

TIME: What’s the concept behind Hilarity for Charity?

Miller: My mom was diagnosed at 55 years old with early onset Alzheimer’s. My grandfather had had it, and my grandmother. So it’s something that’s always been part of my life and affected me at an age when I was very young. After we formed Hilarity for Charity, we had all these young people reaching out to us who wanted a way to use their voices and take action, so we came up with this idea as sort of a charity-in-a-box program: we’d make it really simple for college students—fraternities, sororities, groups of friends, whatever—to throw these events, and we’d give them everything they need.

Rogen: Yep, and we thought, as much as we’d like to think a bunch of college kids would do a charity event out of the goodness of their hearts, some incentive might help in some capacity, so we tried to come up with prizes. Like me, I went and visited the school last year, met everyone and we showed an early screening of Neighbors, and this year we’re doing a live audio commentary of Superbad with me and Chris Mintz-Plass. Just stuff that you would hope they’d enjoy even if it wasn’t affiliated with a charity event in any way.

What do you hope fundraising like this can accomplish for Alzheimer’s research and treatment?

Rogen: From my perspective, it’s more about changing the conversation so that the government actually does something about it. I think the government is reactive to people’s desires as opposed to leading the way for people’s best interest. I think that people want to get elected and they want to stay in power, and if it seems like people care about something, then they appeal to that thing, you know? So that’s our real goal, is to make it that Alzheimer’s is the type of thing that people in government have to support to make the general population happy.

Do you think part of why it’s not a more strongly championed cause is because people think of it as something that affects older people?

Miller: That’s definitely one of them. It’s tough, we don’t have an adorable baby to put on our campaign posters, we don’t have success stories of people who have been cured of Alzheimer’s to get up and give a great, inspiring speech about how if you support us, people will be cured. It is an uphill battle, we’re very much at the beginning, but progress has been made. It’s just about rallying the voices. There are close to 6 million people living in this country with Alzheimer’s disease. So it’s about showing the caregivers for those people with the disease that they can use their voices, and if they do they’ll be heard, and change will come.

Rogen: And considering it’s costing the government more than any other disease, it’s especially odd that they don’t put more resources into trying to cure it.

Do you think a movie like Still Alice was helpful to the cause of raising awareness?

Rogen: Yeah!

Miller: Oh, very. For Julianne Moore to portray someone with early onset Alzheimer’s was extremely helpful, and definitely educational. So many people saw it and came to me and said, “I didn’t know!” It was a huge step in the right direction. If you look at diseases like cancer, 30 years ago people whispered it because you didn’t say “cancer,” it wasn’t in TV shows and movies.

Rogen: And then it started to be. Movies like Love Story started to normalize it and make it something you don’t have to be ashamed of. It’s portrayed in the culture, and so it seems less like something you should be secretive about.

Miller: There’s also the stigma. A lot of people, when they’re diagnosed with Alzheimer’s, my mom included—she wouldn’t let us tell anyone. For a couple years, until she was so far advanced that it was so obvious and she didn’t know we were telling people, she wouldn’t let us tell anyone. Which is really sad. We just want to try to end that stigma.

I read that some doctors don’t even tell their patients they have Alzheimer’s.

Miller: That’s a huge issue. A lot of doctors don’t tell, because a lot of patient’s don’t want to know. They say, “Well if I have dementia, just leave it, I don’t want to know. And that’s not okay! People need to know. You can only attack something in the correct way if you know. And often it’s not being reported as a cause of death in an autopsy, which is a huge issue, because more people are dying from this disease than are currently recorded.

What is your hope for the future of Alzheimer’s research and treatment?

Rogen: I mean, people think it’s a curable disease.

Miller: There’s a lot of promising studies out there, and if the government would just get behind and fund a heckuva lot more of them, I know we’d be a lot closer.

One facility is using a technique from "50 First Dates"

One home for people suffering from Alzheimer’s disease and dementia is using a method inspired by an Adam Sandler movie to help jog residents’ memories at the start of each day.

In the 2004 film 50 First Dates, actor Adam Sandler’s character creates a video that actress Drew Barrymore (whose character loses her memory each day) plays each morning to remind her who she is and what happened to her. The Hebrew Home at Riverdale in New York City has family members of its residents doing the same thing as Sandler’s character, the Associated Press reports, recording videos of themselves providing messages and anecdotes for the patients to watch every morning.

“[The film] was fluff, but it made me think,`How could that translate to our residents with memory loss?'” Charlotte Dell, director of social services at the home told the AP.

The Associated Press notes that people with Alzheimer’s present differently and that one technique may not work for everyone.

[AP]