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Winning the Memory Game

By Karen Houppert
Memory loss over time is natural, but researchers have found that you can take action now to build a better brain. Here are ways to offset some of the cognitive decline as you age, as well as new research into memory’s most vigilant foe, Alzheimer’s.
Most of us have done it. We climbed to the second floor of our house, for example, and paused on the landing to wonder why we’d made the journey. Had we come to fetch the phone charger? To collect towels for the washer? As we stand there casting about for a reason, we might also wonder: Is this just a normal hiccup in memory or could it be something more? 
 
Memory loss and difficulty with recall are natural consequences of aging. They can start as early as our 30s and make simple tasks, like remembering a word or a person’s name, take a little longer. While normal, these lapses of recall can be scary. We wonder if it portends something more serious. 
 
In fact, surveys have shown that more people are afraid of losing their memory through Alzheimer’s or some other form of dementia than they are of dying from cancer, according to Constantine Lyketsos, director of the Johns Hopkins Memory and Alzheimer’s Treatment Center. “What makes us people are those higher functions [like memory],” he says. “It cuts close to the bone to think we are going to lose our personhood by losing those very unique capacities.”
 
Memories form the very essence of self. “Our memories are unique records of our personal histories,” says Jason Brandt, a professor of psychiatry, behavioral sciences, and neurology at Johns Hopkins. “It’s what gives us a sense of who we are.” When personal history goes missing, we feel at a loss. Brandt has patients who suffer severe amnesia, and while they are still bright and articulate, they describe feeling “disconnected” from their lives. “When you reteach them facts from their personal past,” he says, “they feel like they are learning someone else’s biography.”
 
There are important distinctions, however, between usual memory decline due to aging, which is characterized by a slowing in the retrieval of information, and the complexities of brain trauma or forms of dementia, like Alzheimer’s. These conditions can be conflated, even in our daily lexicon. We forget where we put the car keys and quip: “It’s the Alzheimer’s setting in.” There are so many common misconceptions about memory that doctors who deal with these issues routinely begin by explaining the differences. “Memory loss,” in fact, is a misnomer at times. “It implies that memories that were previously stored are suddenly gone,” Brandt explains. Rather, a natural decline in memory with aging is more about inefficiencies in memory than literal loss.
 
First, some decline in memory with aging is normal. The brain shrinks with age and certain cognitive abilities decrease. Neurons are not dying, but the connections between them are fraying, and other mechanisms scientists still don’t fully understand are changing our ability to process information and recall events.
 
On the other hand, dementia is a general category for a variety of disorders that cause more extreme memory loss or affect thinking and reasoning abilities. For example, one or more strokes can lead to vascular dementia, which is when damaged blood vessels restrict the flow of blood to your brain. Parkinson’s disease can also cause dementia. Alzheimer’s is the most common cause of dementia, affecting 60 to 80 percent of people with dementia. It is a degenerative disease of the brain marked by the accumulation of two proteins, beta-amyloid and twisted fibers called tau. These alterations ultimately cause nerve cells in the brain to die and block the free flow of information between cells.
 
While we can’t yet prevent Alzheimer’s, research shows that there are things we can do to help fend off mem­ory loss in general and to maintain our wits as we age (and it has nothing to do with shelling out money for so-called “brain games.”) Meanwhile, new studies into Alzheimer’s have found ways to provide better care now for people with the disease, while compelling research is yielding insight into how the disease itself works.
 

Researchers have found that you can take action now to build a more robust brain that can delay the future onset of some disease. “If you lose some nerve cells as a function of normal aging, but you have a lot of ‘cerebral reserves,’ you have brain power to spare,” Brandt says. “On the other hand, if you have a brain with little reserve, you are going to notice age-related cognitive losses and find yourself in trouble.”

 
Building those reserves happens in large part through both mental and physical exercise. While the exact mechanics are not fully understood, it is believed that this allows the neurons to make more connections with other cells.
 
Marilyn Albert, who directs the Division of Cognitive Neuroscience at Johns Hopkins, collaborates with an interdisciplinary group of researchers to study the earliest phases of Alzheimer’s. “We understand the biology much better now for Alzheimer’s,” Albert says. 
 
One of the studies she is leading allows people to be evaluated with imaging tools that measure the structure and the function of the brain. Albert hopes to get a sense of what is going on in the brain much earlier, before Alzheimer’s symptoms are too advanced and when treatment could be more effective. Albert sees these tools as a valuable way of searching for pre-dementia. “Me, I don’t even want to wait until we see symptoms in patients, I want to ID them when they’re normal,” she says. The goal is to intervene as early as possible.
 
These studies are also looking at protective factors that might help the brain, like exercise. What researchers believe is that variety matters: It’s not simply how much energy you expend, but also how you mix it up. It is better to burn 500 calories jogging and 500 swimming than to torch 1,000 calories by jogging alone, Constantine Lyketsos says. “Think of the brain as a muscle,” he says. You have to stimulate the circuits you want to maintain. “If you do some jogging and some swimming, then you are stimulating two circuits.”
 
“You don’t have to be running miles or going to the gym every day,” Albert says, “but moderate activity really helps.” She cautions that specifics about exactly what kind of physical exercise and how long to engage in it are still being researched.
 
Better yet, Lyketsos says, are activities that cross over from mere physical stimulation to social and mental engagement. Things like ballroom dancing or sightseeing on foot combine social, mental, and physical exercise at the same time. “So the more of that you do, the more of your brain you are engaging,” Lyketsos says.
 
Since strokes can affect a person’s memory, regular exercise and a good diet serve a dual function as we age. “What’s good for your heart is good for your brain,” Lyketsos says. Lyketsos is a proponent of the Mediterranean diet, which, he says, consistently produces better brain health later in life. Rich in olive oil, fish, and vegetables and light on carbohydrates and red meat, this healthy diet is also better than simply opting for dietary supplements or vitamins, he says. 
 
A daily mental workout might also reap age-defying brain benefits. “Learn a new language; take adult ed classes; work your brain hard,” says Brandt, who also works with elderly persons at the Copper Ridge Institute, an affiliate of the Johns Hopkins School of Medicine. “We always encourage patients and others concerned about their potential for dementia to stay active cognitively.”
 
There is no scientific evidence that intellectually engaging tasks will prevent Alzheimer’s, but there is research indicating that mind exercises help keep the brain healthy and may delay dementia. This does not mean that you have to start playing the increasingly popular “brain games,” which promise improved cognition. In fact, research shows that many of the brain game companies’ claims are overblown. Brandt says you should save your money.
 
“In general, doing something is better than doing nothing, but what that something is really doesn’t matter, as long as it is novel, interesting, and challenging,” says Brandt. “There’s no indication that any one product is better than any other; or, in fact, better than doing the New York Times Crossword Puzzle. Don’t go for these expensive programs when there are plenty of things you can do for free that challenge your brain.” 
 
The key is doing something that you truly enjoy. “If you really love to play bridge, do it. If you like to play along with Jeopardy on TV, do that. Or if you prefer reading novels or nonfiction, fine. Just keep your brain active at a high level,” Brandt says.
 

Humans are social animals. At least, we’re wired to be. So if you want to cut out of work early to make dinner for friends, you can dispel the voice in your head that chides you for being a slacker. Such socializing has a positive, long-term impact on your memory.

 
Scientists still aren’t sure why this is the case, but so far they’ve seen an impressive connection. “Most of the studies that have looked at this have been observational,” says Albert. In such a study, “we take a thousand people, measure a bunch of things about them when you know they are doing reasonably well, and then follow them over time to see who is maintaining a high level of function.” 
 
Regular social engagement comes up repeatedly among those who maintain better memories as they age. “We don’t really understand yet what that means at a biological level,” Albert says, describing this area as the one most in need of more studies.
 
Ongoing research now focuses on whether such social engagement decreases stress—and that’s why it’s helpful—or whether it is connected more directly to the mental activities above, since keeping an active social life means a brain workout as we navigate social dynamics, revisit memories with our friends, meet new people, and thus learn new things. 
 
It’s also important to remember that forgetting is a part of life, and we should employ tools to help keep track of our busy, modern lives. In fact, some of the memory experts themselves struggle to navigate this very terrain. “I’m one of the most forgetful people I know,” says Brandt. “I carry a pencil and index cards in my pocket all the time.” 
 
Brandt says he relies on little notes to himself to prompt his memory and he asks his patients if they do the same. Do they use day planners, datebooks, or cellphones for notes to themselves? “Many of them say, ‘No.’ When I ask them why, they say, ‘That would be cheating.’ I say, ‘That’s not cheating! This isn’t a game. This is your life!’ ”
 

The causes of Alzheimer’s disease are still unknown. Research suggests the disease is influenced by genetic makeup, oxidative damage to neurons, serious head injuries, brain inflammation, and environmental factors. With no clear bulls-eye to target, scientists have tested multiple approaches to prevent Alzheimer’s or to slow the disease’s progression. Researchers are digging in deep—in a variety of directions—supported in part by a $122 million increase in funding for Alzheimer’s research and care, which President Barack Obama signed into law last year. This is, though, a drop in the bucket of funding needed for such complex research.

 
“Everyone wants to know: When are we going to cure Alzheimer’s?” says Lyketsos. “We are 30 or 50 years off.”  Statistics show that 130 million people will develop dementia of some kind in the next 30 to 40 years, he explains, and “we aren’t going to have cures for them.” 
 
But not having a one-size-fits-all cure on the horizon doesn’t mean patients should lose hope, as a number of treatments are showing potential to enhance quality of life. “As a field, we have taken 
a big bet on amyloid-busting drugs,” Lyketsos says, explaining that such studies haven’t shown much promise for those with advanced dementia. However, new studies are investigating whether amyloid-preventing drugs might be effective if administered to patients who haven’t shown symptoms but may be carrying deterministic genes or have PET scans showing they have some damage to the hippocampus. 
 
Another line of research is offering hope for patients with what’s called amnestic mild cognitive impairment, or aMCI. Patients who suffer from aMCI have memory problems that are worse than would be expected for their age, and the condition can signal risk for Alzheimer’s. One study, led by Johns Hopkins neuroscientist Michela Gallagher, found that low doses of the epilepsy drug levetiracetam may help the brain by calming hippocampal hyperactivity in patients’ brains. In their study, which involved 84 patients, the researchers found that low doses of the drug improved memory performance in some. They hope next to study the drug in a larger-scale, longer-term clinical trial. “What we want to discover now is whether treatment over a longer time will prevent further cognitive decline and delay or stop progression to Alzheimer’s dementia,” Gallagher says.
 
Another ongoing study at Hopkins takes a different approach and is also showing some success. A possible cause of Alzheimer’s in some people is the disruption or resistance to insulin in the brain. But insulin, injected the way a diabetic does, doesn’t reach the brain. Researchers in a large, multicenter trial, including Hopkins, are experimenting with patients inhaling insulin through their noses. 
 
“Don’t go for these expensive programs when there are plenty of things you can do for free that challenge your brain.”
 
Lyketsos is a principal investigator in a study looking into whether a mechanical device can stimulate the brain and counteract some effects of memory impairment in Alzheimer’s disease. “We implanted 42 brave people around the country with a pacemaker-style device,” Lyketsos explains. The device sends a series of small, continuous shocks into the fornix, a C-shaped bundle of fibers in the brain that carries signals from the hippocampus. As with a cardiac pacemaker, the patient feels nothing, but the hope is that by stimulating the brain in this way, it will halt or slow the memory loss Alzheimer’s patients experience. This study targets the same area of the brain as Gallagher’s research above, Lyketsos says, and while one stimulates the brain and the other calms it, it’s not uncommon to see varying approaches when researching Alzheimer’s. “There is a scientific foundation that both, or one or the other, or neither, might work,” he explains, which is why multiple approaches are being tested. Results from Lyketsos’ “deep brain stimulator” study will come out later this year. 
 
The momentum to find a cure and eliminate the disease, Lyketsos says, builds each year. And scientists are working hard to develop better ways to care for affected people and support their families, friends, and caregivers. “I have an optimism that is mostly focused on my sense that the current standard of care is actually pretty good,” he says, explaining that an individually tailored “package of interventions” ranging from antidepressants to caregiver training has improved the quality of life for patients, allowing them to stay in their homes longer, and staving off many of their attendant medical complications. These interventions were part of an experimental care program developed at Hopkins known as Maximizing Independence at Home, and its success in keeping people with dementia at home longer has garnered significant attention from organizations like the National Institute on Aging.
 
In the next two to five years, he says, there will be a big boost in the dissemination of research and best practices thanks to federal funding and an organized, concerted effort by researchers. “It’s not curative, but it will make a real difference in people’s lives.”  
Winning the Memory Game
Marcos Chin
Regular social engagement comes up repeatedly among those who maintain better memories as they age.

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