Age-related Cognitive Decline May Be Reversed

Age-related Cognitive Decline May Be Reversed

Doris Howard, a 79-year-old former psychologist, has lived in the Heritage Retirement Community - set in a stately Tudor-style brick mansion in San Francisco's Marina District - for almost seven years. Fast-talking and quintessentially plucky, Howard is what the staff call a high-energy resident: a dedicated community volunteer, a member of the art committee, an avid reader, and editor of the in-house newsletter, Happenings. (In fact, she tells me, she barely has time to squeeze in this interview.) Which is why she was so unnerved, a few years ago, when she began to notice she was forgetting little things. "Short-term memory was my biggest problem," she says. "That's the first thing that goes. I had to become a compulsive list-maker."

Last spring, representatives from a local technology company called Posit Science came to the Heritage to see if any of the residents were interested in testing out a revolutionary computer-based program that could potentially revitalize their brains. "They said if we take this eight-week course, one hour a day, five days a week, we would learn to listen better, pay more attention, and relearn how to focus," says Howard. "It really sounded wonderful." A few weeks in, she began to notice small improvements. For one thing, she was no longer jumping out of bed at night to write something down for fear she would forget it. "I knew that if I thought of it while I was going to sleep," she says, "I would remember to do it the next day."

Also, her reading experience began to change. Before, when she would revisit a book she'd been reading, she would have to flip back to remind herself who all of the characters were and how they were connected. "After, I noticed that all the names stayed in my head," she says. "When I'd think 'who was that?' I'd take a moment and I'd remember."

But Howard's biggest triumph came months after she graduated from the program. It was time to renew her driver's licence, and she was nervous: the last time she'd had to take the written test, five years earlier, she'd failed it twice. "This time when I was studying it, I saw very clearly that I was memorizing all the details you don't normally remember," she says, referring to all of the signage and finicky rules of the road. "I was remembering them much better than I did when I was only 74." In just eight weeks - with no pills, no changes in diet or excercise, and no microchip implants - the Posit Science Brain Fitness program had literally shaved years off Doris Howard's brain age.

True, it sounds like something that might be advertised with a free set of Ginsu knives. But the Posit Science program is the result of decades of neurological research conducted by some of the world's leading brain scientists. Posit's chief scientific officer, Dr. Michael Merzenich, is a pioneer of neurophysiology who helped invent the cochlear ear implant. He leads a team of 50 brain scientists from top universities around the world, including Yale, Cambridge and the Massachusetts Institute of Technology, in developing non-invasive training programs to reverse age-related cognitive decline. Posit's mandate, as its slogan tells it, is to "extend brain span to match lifespan." To date, the company has set up brain fitness centres like the one at the Heritage in roughly 80 retirement homes across the U.S. and at one such facility in British Columbia. Early clinical trials are showing that its program reverses the cognitive effects of AGING by an average of 10 years, and sometimes much more. Posit's initial focus has been on adults over the age of 60. Ultimately, however, company executives expect their market to expand to include age-phobic baby boomers in their late 40s and 50s looking to fight early signs of memory loss. "We asked, 'What if we can take a 55-year-old and give her the processing speed of a 30-year-old?' " says Posit's CEO Jeff Zimman. "Well, now I'm taking the 'ifs' off."

With the Me GENERATION careening toward its 60s, the concept of brain fitness could not have materialized soon enough. Baby boomer anxiety is undoubtedly among the most powerful economic engines driving the 21st century. Boomers' collective dread of their own decay, of relinquishing cultural and economic dominance, has long sustained the beauty industry, the physical fitness industry, and the cosmetic surgery industry, not to mention dozens of tabloid magazines that feature close-ups of Demi Moore's frown lines or Madonna's incongruously decrepit hands and sell on the basis of pure schadenfreude. But while Botox and Restylane can keep skin taut and lips plump in perpetuity, on the inside, boomers are turning 50 at a rate of one every 7.5 seconds. On Jan. 1, 2006, the first boomer turned 60. Over the next two decades, 77 million more will follow. And what they'll find is that, like it or not, their internal machinery will slow down and simplify. Their brains will cut back on producing important chemicals. They'll be less likely to engage their minds in new, challenging ways. And they'll start to forget little things. Like where they left their car keys, or the name of their next-door neighbour, or why it was they came to the grocery store in the first place.

"We have a horrible situation now where we've figured out how to prolong the health of the body without prolonging the health of the mind," says Merzenich, from his San Francisco office. "Right now, if you've passed your 65th birthday, there's almost a 50-50 chance you'll eventually be identified as senile. And if you're not, there's a pretty good chance you'll be so impaired that you can't really take care of yourself. So we have longevity, but the end is crap."

Compounding this anxiety is the fact that boomers' parents are living longer than any generation ever has - well into their 80s and 90s - making boomers the first cohort to witness that cognitive decline in such large numbers. An estimated 23 per cent of people over 65 have mild cognitive impairment (MCI), and every year, roughly one-fifth of those are diagnosed with Alzheimer's disease. By 2030, according to the Alzheimer's Association, nearly eight million adults will suffer from the disease in the U.S. alone.

Meanwhile, there aren't enough twenty- and thirtysomethings to support baby boomers in their retirement. To maintain the standard of living to which they've become accustomed, many will have to keep working indefinitely. And they'll need to find ways to keep themselves mentally agile as they compete against ever-younger people in an evermore complex workplace. "Baby boomers pride themselves on creating new paradigms for each new life stage, and old age won't be any different," says Zimman. "We're a generation that grew up with Sputnik. Some of us were on the front edge of computers. So we have a belief in the ability of technology to make our lives better." A 60-year-old would have a significant advantage if she could think at the speed of someone in his 20s, he says: "With all the industry knowledge she'd have from 30 years in the industry, that's who I'd bet on to compete with any young hotshot you want to show me."

As luck and science would have it, a great deal of attention has been focused on this matter. The '90s was deemed the Decade of the Brain by the George H.W. Bush administration, and billions of funding dollars were poured into brain research. "We saw the advent of brain imaging technologies like MRIs and CAT scans," says Zimman. In short, we learned a great deal about how we learn. "It has changed the way we think about the brain and, some say, created massive hope for the future prospect of aging."

Until now, the brain fitness industry, such as it is, has consisted of a mishmash of products and services that promise to build up the brain like a muscle. There are bestselling Sudoku puzzles, crosswords, and dozens of brain-related self-help titles: The Memory Bible: An Innovative Strategy for Keeping Your Brain Young and Get Your Brain in the Fast Lane. Pharmacies carry vitamin supplements and herbal brain tonics with names like "Mind Power" and "Deep Thought" specifically formulated for smarts. The "grey gaming" market is burgeoning. Nintendo's Brain Age game, which makes no scientific claims but promises to "keep people's minds active with fun mental workouts," has sold millions of copies worldwide. Sony, Sega and Bandai all have brain software in the works.

But the average person's understanding of brain science is rudimentary at best, and sales of these products - much like expensive skin creams - are driven largely by hope on a grand scale. Neuroscientists are now saying that exercise, diet, brainteasers and video games like Nintendo - while certainly helpful - are not enough. "Nintendo says, 'We've run scans, and this increases blood flow to the brain.' " says Zimman. "But standing on your head increases blood flow to the brain. We're looking for a little bit more than that."

As it turns out, it's how you use your brain that counts. "The brain isn't just a muscle that you pump up," says Donald Stuss, a Univeristy of Toronto professor and neuropsychologist with the Baycrest Research Centre for Aging and the Brain. "It's a series of processes which you can adapt and learn. You can teach the brain to do things efficiently." Stuss and his colleagues recently developed their own rehabilitation program designed to help older adults fight cognitive decline by teaching them to think efficiently. The results of their clinical trials were published in the January 2007 issue of the Journal of the International Neuropsychological Society. Participants showed "significant improvement" in memory, practical task planning and psychosocial function - a finding with implications that are nothing less than revolutionary.

It used to be held as religion among neurology experts that the brain was plastic, or malleable, in our infancy; after that, its infrastructure was set. "Within the last five to 10 years, I used to teach - we all used to teach - that when you're older, your brain is finished, kaputsky," says Stuss. "[This idea] was actually the basis of a Nobel Prize that was awarded to two scientists from Harvard - David Hubel and Torsten Wiesel - and it was largely horses--t," says Merzenich. "Their notion was that the brain developed into mature functionality by the end of this critical period and beyond that period, it was like a computer - every neuron knew what to do." A person had a finite number of brain cells and once they were gone, they were gone. But if this were true, says Merzenich, how do you account for learning? "You can learn to play the piano if you're 70 if you really want to, through driving your brain to master that ability. The brain is plastic through a lifetime.You never lose your ability to acquire ability."

This lifelong ability to adapt, called brain plasticity, and the ability to generate new brain cells, called neurogenesis, are now heralded as the twin pillars of aging smart. Research conducted by Merzinich and others in the '80s and '90s was among the first to prove they work. In early studies, they observed the deterioration of aging rats. "They gradually lost their ability to control their paws," says Merzenich. "They struggled to feed themselves by manipulating food and ultimately, they lost control of hind limbs, dragging them around." Using brain imaging technologies, scientists found that part of the problem was the poor quality of sensory information the rats were receiving at this stage of life. When the rats were directed to perform certain activities in a particular manner and order, Merzenich and his colleagues found they could help them recuperate their motor skills and prolong their lives by 15 to 20 per cent. "The rats didn't lose their mobility for an extra three months," says Merzenich. "And when you looked inside the brain of the rat, you had actually restored substantially the quality of information that was coming from the paw. The point is, these kind of experiments demonstrated that you could take these very old brains - rats, not humans of course - and you could drive them to learn things and acquire new skills."

In the mid-'90s, neurologists began exploring the possibility of developing brain plasticity in people. Dr. Richard Frackowiak, a professor of cognitive neurology at the Institute of Neurology, University College London (and a member of Posit Science's scientific advisory board), studied the brains of London cab drivers. He chose them because of the rigorous nature of the training they must complete, known as The Knowledge, before they're permitted to drive one of London's iconic black taxis. Cabbies-in-training spend roughly two years learning 320 routes, which encompass about 25,000 streets within a six-mile radius. Frackowiak theorized that their extensive, specialized navigational experience would render their brains structurally different from an average person's. He was right: in the cabbie group, the posterior hippocampi - the long ridges embedded in each cerebral hemisphere - were significantly larger than in the control group. He concluded that the hippocampus plays a specific role in spatial memory and that the brains of London cabbies had literally changed shape as a result of their focused mental activity.

Around the same time, Merzenich decided to take what he'd learned about brain plasticity in the labs and develop practical tools that could be useful to people. In 1996, he co-founded a company called Scientific Learning in Oakland, Calif., through which he developed brain-training programs for older children with learning disabilities. The key to helping such kids read and learn, he determined, was to identify the flaws in how they're receiving information and correct them. The programs focused on how the brain processes sound, since the majority of the crucial information we consume daily is delivered through speech. Merzenich figured that if kids' brains could learn to receive sound in a higher-quality form, this would improve the speed with which the information was processed and the quality with which it was imprinted in the child's memory.

By way of explanation, he uses the example of a child born with a cleft palate. Forty years ago, he says, this condition was not uncommon and it was terribly stigmatizing. "You knew that child had inherited low intelligence," he says. "You knew that child would never have normal speech, and you knew that child would struggle to learn to read." Today, cleft palates still exist, but the notion that a child with this condition will automatically have learning disabilities has disappeared. "Turns out, it wasn't inherited at all," he says. "Turns out that if you fix it early enough, none of that happens. How could that be?" A really simple way to think about it, he says, is that when you have a cleft palate, your auditory system is blocked by fluids - in the womb and until its fixed, it's all underwater. "What that means," he says, "is that your native language is not English. Your native language is noisy English or muffled English. So this poor kid has to develop a construction of their native language on the basis of that crap." When the condition is fixed, he says, the resolution of sound improves and the learning disabilities eventually disappear. There are any number of inherited conditions that will cause this sort of "noisy" processing. Based on this idea, Scientific Learning developed computer-based training programs designed to improve the quality of the sound such kids take in. "We've enabled hundreds of thousands of children to successfully initiate reading and improve their cognitive abilities," he says.

In 2003, Merzenich co-founded Posit Science, to develop a similar series of programs for older brains. Only this was a little more complicated - and more of a long shot. As we age, our brains deteriorate for a whole host of reasons, including disuse and natural processes. Also, every year, the brain's production of neuromodulators - key brain chemicals for learning and remembering - drops sharply. Studies suggest that after age 40, with each passing decade people produce an average of 13 per cent less dopamine. The resulting memory loss is compounded by negative learning behaviours - our tendency to develop techniques for compensating for those changes, such as list-making, which ultimately serves to reinforce them. All this noisy processing means the brain is having a harder time creating an accurate representation of the sensory information it is receiving. The hazier things get, the harder the brain has to work to process them. When this happens, everything slows down, which is why, generally speaking, the older we get, the more difficult it is to follow a conversation.

"When people have thought of this historically, they think of the onset of pathology as inexorable," says Merzenich. "They think of it as just sort of the end stage of this machine which is killing itself off. It's like an old motor whose valves are shot." The latest findings suggest that that well-worn motor would benefit quite a bit from a blast of WD-40, if someone would only buy a can.

At first glance, Posit Science's brain fitness programs seem like any other brainteaser video game. But they are designed to stimulate very specific chemical reactions in the brain, and are intensive, repetitive and progressively challenging. As Posit describes it, in pushing the brain into new territory, it builds and refines neural pathways, making information transmit more freely. When that happens, brain function speeds up, the accuracy with which sound is received strengthens, and the brain's ability to record information is improved. The program has six activities - including "match it!", a sound-matching game designed to improve the clarity of memory, and "tell us apart," in which the brain has to distinguish very similar-sounding phonemes delivered at high speed - which are designed to release brain chemicals called neuromodulators that are crucial for learning and memory. One, called acetylcholine, is released when people learn under conditions of sharp focus - it helps us "tune in." Another, dopamine, is released when a person expects to be rewarded - which is why the program comes equipped with carefully timed animation and "dings" to denote a correct answer. Finally, norepinephrine is released whenever a person encounters something new or surprising - when you make a mistake in the game, you get a hollow "thunk." It's the brain's way of calling you to attention.

Posit has conducted a series of studies using neuropsychological tests and three types of brain imaging to assess how - and how well - its program works. In August 2006, the company and its collaborators at the Keck Center for Integrative Neurosciences at the University of California published an article in the medical journal Proceedings of the National Academy of Sciences. It revealed that, in a study of 182 healthy adults ages 60 to 87, 93 per cent of people using the Brain Fitness program significantly increased their auditory processing speed, with 10 years or more improvement on average. They also found "generalization" - that the benefits apply broadly to people's lives. Currently, they are working on developing programs for improving visual processing and executive function (problem-solving). Not only that, they're exploring potential for other applications: for treating Alzheimer's, OCD, Parkinson's, schizophrenia and chronic pain.

Their biggest challenge will be in overcoming the average person's confusion where brain health is concerned. Nevertheless, scientists involved in this research say there is no doubt that what we now know about brain plasticity will change the way people age. Zimman speculates that brain fitness is in the same spot today that the physical fitness industry was in the '70s. In 20 years, he predicts, people will visit online brain gyms through devices such as BlackBerries and cellphones. "I think most people will have a program like this in the way they have a gym membership," he says. And, he says, as with gyms, where you can customize your workout to target specific parts of the body - abs, pecs, etc. - brain fitness centres will allow you to customize your workout. "You'll be able to work out your speech and language cortex or your frontal cortex." In time, Merzenich says, the pharmaceutical industry will inevitably introduce drugs that boost and accelerate these processes. "But ideally, if the body or brain could fix itself organically, using its own resources, what could be better?"

See also NEUROSCIENCE.

Maclean's April 9, 2007