Widening Memory Lane — Dr. Gary Small Interview

Circa 2007

Can’t remember what you ate for breakfast this morning, or where you put your car keys? Often blank on your mother-in-law’s name? Not to worry. These are probably not signs of Alzheimer’s disease. Yet aging Baby Boomers—those born between 1946 and 1964—do face a future in which they will experience a natural deterioration in their ability to recollect the past. But the game’s not over yet. Researchers such as Dr. Gary Small at the University of California at Los Angeles (UCLA) have evidence that a few simple life changes may help.

ABILITY Magazine’s editor-in-chief Chet Cooper and ABILITY’s health editor E. Thomas Chappell, MD, met with Dr. Small recently. As they entered his waiting room on UCLA’s medical campus, they spied his hot-selling memory enhancer Brain Games, now widely available in stores, on a table.

On the drive over the two interviewers had passed the time through LA traffic listening to Dr. Small’s The Healthy Brain Kit audio CD, made in collaboration with noted natural health guru Andrew Weil, MD. On the CD, Dr. Small demonstrates the memory trick for name and face association with the following example: listeners could remember his name by associating Gary with the city of Gary, Indiana, and then Small with a mental image of that state shrinking. So Cooper and Chappell jokingly asked for “Dr. Indiana Shrinking,” and then settled in for a conversation about aging and memory.

Chet Cooper: What can one do to improve memory?

Dr. Gary Small: Preliminary research suggests that rather simple lifestyle changes, such as eating five small meals a day to maintain levels of blood sugar, as well as regularly using relaxation techniques, may enhance memory.

Dr. Tom Chappell: What are some ways you’ve been able to show this scientifically?

Small: Well, one way is to look for improvement on a memory-skills test, for example. We test people before they make a lifestyle change and then test them again several weeks after.

Cooper: We noticed your office is next to an imaging center. What types of imaging are you using?

Small: Imaging refers to various diagnostic scans of the brain. These scans might be performed with a PET (Positron Emission Tomography) scanner or a special MRI (Magnetic Resonance Imaging) scanner.

Cooper: What role does this technology play in your research?

Small: These special types of brain scans show increases and decreases in activity in different areas of the brain. After just weeks of certain lifestyle changes, our research indicates improved efficiency in those areas of the brain known to control memory.

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Chappell: What else can you do for patients using this type of imaging?

Small: We just published a paper in the New England Journal of Medicine on a brain-scan technology we invented that helps us see changes in the brains of patients with Alzheimer’s.

Chappell: If there is currently no cure for Alzheimer’s, why is it important to be able to show it on a diagnostic image?

Small: Research on Alzheimer’s has come a long way in recent years. It’s not hard to imagine potential cures on the horizon. The way we’ve diagnosed the disease up to now has been by noting characteristic symptoms in a patient, such as atypical behavior and memory loss. One might imagine that this is not a highly reliable way to be certain of the diagnosis. But now we can we add to that an imaging technology—in this case a brain scan—which can give us more reliable information if a large group of patients diagnosed with Alzheimer’s are also found to have decreased function in a certain area of the brain.

We could also use this technology to scan new patients, and if they’re found to have decreased function in this same brain area, it would more strongly suggest that they truly do have Alzheimer’s, making it easier to confirm a diagnosis. Similarly, brain imaging can help us navigate the challenges of understanding brain function as it relates to memory. For example, if a new drug is being tested on Alzheimer’s patients and their symptoms improve, it would also be helpful to see signs of improved function on their brain scans.

Chappell: One of the interesting things about your research is that you often look at memory in people who have not yet developed what doctors would consider diagnosable memory problems. What else can you tell us about the research you recently published in The New England Journal of Medicine?

Small: We did a study where we gave people memory tasks while they were having their brain scans. These were people who are aging Baby Boomers with normal memory performance. We found that if they carried a gene called APOE-4—which is associated with increased risk for Alzheimer’s—their brains had to work harder to do the same memory task compared to a similar person without the gene. Not only that, but the people whose brains worked harder had more memory problems a few years later, even if they did not develop Alzheimer’s. It’s really cutting-edge, high-tech research… So, that’s my day job. (laughs)

Cooper: And what can you tell us about your moonlighting gigs, like your work on The Healthy Brain Kit and Brain Games?

Small: I think those projects get me more involved in reaching out to a larger audience, trying to translate science into a language that is more understandable to everybody. It’s also somewhat of a family affair—my wife has been very helpful with her ability as a professional writer. I think I’m a better writer for having worked with her, and she’s a better scientist.

Chappell: So how do you turn a scientific theory into a product that will be as catchy and marketable as Brain Games?

Small: Brain Games was actually someone else’s idea based on our work. They wanted to create a hand-held game that not only helps people improve their memories, but is also fun to play. You can build up your memory skills and train without straining your brain, and you can set the level of difficulty where you want it.

Cooper: How are the sales going?

Small: Pretty well. The game just came out last month, and people like it. It’s supposed to be for Baby Boomers, but I can’t get it away from my 12-year-old son. Brain Games II is under development now, and I’m excited about that because it’s not only going to have the mental aerobics of Brain Games, but also tips about stress reduction and diet. It should help people with the 14-day program, so that they can really jump-start their longevity and brain health.

Chappell: Brain exercise, physical exercise, diet, stress reduction—it seems that improving one’s memory is multi-faceted. What other factors might affect memory?

Small: We just submitted a grant application to the NIH (National Institutes of Health) to study whether memory training plus Tai Chi has a better impact on memory scores and brain function than just memory training alone. We’re also interested in how inflammation and immune function relate to memory. We know that cardiovascular conditioning and stress reduction will boost the immune system. If boosting the immune system also helps memory, then physical conditioning and stress reduction may improve memory by enhancing the immune system.

Cooper: Do you have a private practice in psychiatry as well? Small: I’m full-time faculty here at UCLA, so I do see some patients. But most of my time is devoted to research, teaching and administration.

Chappell: Do you have several grants to support your research?

Small: Lots of grants. We have a lot of support from the National Center on Aging, and we have foundations that support us, as well as private donors. We also do fundraising to make it all happen.

Chappell: What’s your hottest research right now?

Small: Currently our brain-scan technology is extremely hot. It’s got worldwide recognition because ours is the only technology like it in the world. As a matter of fact, I was recently invited to go to Congress to talk with staffers and legislators about our research. They occasionally bring in scientists to brief them on important topics.

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Cooper: Is that important for getting research funding from the government?

Small: There’s a lot of work that goes into educating policymakers and lawmakers. The NIH is very interested in influencing public policy to improve funding of scientific research. So my efforts are just part of that endeavor to educate. The NIH is happy when an article, such as our recent one, appears in a high-profile publication like The New England Journal of Medicine. Stories in there often get picked up by mainstream media, and senators and congressmen read them in USA Today and The Wall Street Journal, which gets their attention.

Cooper: Dr. Chappell, how does this special brain scan for Alzheimer’s affect your work as a neurosurgeon? Chappell: Well, it lets us neurosurgeons off the hook. For many years the medical community talked about actually performing biopsies of patients’ brains to find out if they had Alzheimer’s. Most of us are adamantly against that. The procedure has risks and there is no cure for the disease. Why risk getting a biopsy diagnosis for something you can’t reverse anyway? But the landscape is now changing—the diagnosis can be made without invasive techniques, a brain scan will confirm it, and soon there may be treatment!

Small: If we can push this forward, what will happen ultimately is you will deal with your brain the way you deal with your cholesterol: You will get a brain check-up. If you have the disease or the possibility of developing it, you will get your vaccine or your medicine to stave off the problem. Pharmaceutical and biotech companies currently are testing new drugs and vaccines that can prevent or remove the abnormal proteins that cause Alzheimer’s. We can diagnose these same proteins with our special brain scans, so they would provide a logical means for monitoring.

Chappell: Do you have some federally funded grants for your imaging work, too?

Small: Yes. Last year we got a Program Project Grant from the NIH, so we have several projects going. We are doing experiments in which we use a small PET scanner made for experimental animals like rats. The experiments involve giving the Alzheimer’s gene to them, which gives them the disease. We can then use our chemical marker for Alzheimer’s that shows up on the brain scans, and follow up by giving the rats test drugs that we hope will treat the disease. This way we can see if there are changes in the rats’ brains by using the scanner instead of killing the rats and then looking at their brains under a microscope.

Chappell: So this technique may also make research on humans safer and easier as well?

Small: Yes. In fact we are not just studying experimental drugs. We can study drugs that have been on the market for years—drugs used for other physical illnesses, such as anti-inflammatory drugs, that may protect the brain as well. We did some studies where we put the abnormal protein plaques that cause Alzheimer’s in a test tube. Then we added drugs like naproxen (Aleve) and ibuprofen (Motrin), and they actually dissolved the plaques in the test tube. So we’re looking at these drugs as potential treatments for Alzheimer’s. So far the studies have been negative, but that might be because of the way the studies are designed. It may also be that by the time somebody has Alzheimer’s, they’re too far down the road. We may have to start the treatment in people who are just beginning to show signs of the disease. I think it’s easier to protect a healthy brain than to repair a sick one.

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Chappell: Is this the type of approach your study in the New England Journal of Medicine suggests?

Small: We found in that study that we could see the abnormal protein plaques in people’s brains before they got full-blown Alzheimer’s. These were patients with mild forms of impairment, and you could see an obvious signal on their brain scans if they were going to go on to develop Alzheimer’s disease. So I have tremendous optimism that we have the technology, if we can focus our efforts and get enough funding. We’ve already got the talent and the ideas.

Chappell: Lots of interesting research is now being done with a relatively new kind of MRI called functional MRI (fMRI); unlike regular MRI scans that only show brain structure, fMRIs, somewhat similar to PET scans, show brain activity, capturing even moment-to-moment changes. Are you using fMRI in your studies of Alzheimer’s?

Small: We do functional MRI (fMRI), the new kind of PET scan and the traditional PET. We do multiple scans on people, multiple tests, including genetic tests, so we can get a comprehensive profile. With fMRI, it’s exciting. We’re developing new kinds of ways of stressing the brain, or activating the different brain circuits. That’s really fun. Imagine the paradigms you can come up with… for example, we did a study where we found that people who had more educational achievement had a different profile on their PET scan than those with less achievement. So using a scan, we could estimate the number of years of college they’d had. Just think—in the future, we may be able to do a scan and say, “Hey, you didn’t really get the A in that course that you claimed you got!” (laughter)

Chappell: I actually didn’t know until listening to your CD that people with higher education were at reduced risk for Alzheimer’s, or at least have a lower incidence of the disease.

Small: We don’t know the explanation for that. It could be the Brain Games idea—you’re exercising your brain, and that’s protecting it. Or it could be that people who have good brain genes get on the college track.

Cooper: Did you have people actually doing the Brain Games during the PET scan?

Small: That’s a good question. That’s actually a study I was thinking of doing, but we haven’t gotten around to it. It’s a little tricky to do those studies in the MRI machine, because when people are in there they can’t really see the game, and you also don’t want them to be moving a lot. As a result, we have to create certain devices to simplify the movement and then present them to the subject with a computer screen that simulates the cognitive activity. So we’re not doing that game per se, but the next best thing.

The study we could more easily do with that game—and really we sort of already did the study to some extent— is to tell people, “Play Brain Games for an hour a day for a couple of weeks, and we’ll do scans before and after to see how it changes your brain.” And that study would probably show something.

Cooper: You mentioned something in your CD about brain effects for chess players and chess games?

Small: Yes, we know from many studies that you can train the brain for specific cognitive tasks. You can train people in reasoning skills, and you can show that if they continue to use those skills, they’ll do better at them. But they won’t necessarily do better with other mental skills you haven’t trained, like verbal memory or visualspatial memory. So there tends to be some specificity.

What I like to do with The Healthy Brain Kit and my other materials is to give people strategies so they can generalize the mental skills they develop. For example, they might ask, “So what if I can learn a list of 10 unrelated words? How’s that going to help me?” In my trainings, I’ll explain, “Well, here’s how you can apply that to those five errands you have to do today that you don’t have time to write down.” Or, “Here’s how you can use that for remembering names and faces, so you don’t have to get embarrassed when you see your mother-inlaw and can’t remember her name.” (laughter)

The thing about memory techniques, like the name-andface association technique we discussed earlier, is that the memory cues that will work for any given individual are very personal. Most people don’t get this immediately. So when I teach them these techniques, I tell them, “Just use the first thing that comes to mind. If there is something meaningful in your life that helps you remember a name, a person or a word, that’s great. Other people don’t have to remember it that way.”

Cooper: When you’re writing books or developing products for the general public, what helps you determine how to best get your message across to the average person?

Small: I think, “How do I present this? What would be a snappy way to say it?” The techniques I’m talking about have been discussed in many different forums. I think we have an edge in presenting them because we simplify the ideas and make them easy for people to understand and use.

I first started thinking about this in medical school when I was trying to remember a lot of material myself. I read a memory book with all these techniques, and I thought, “If I could really learn these, maybe I could get medical school down to one word!” Of course, I’d probably forget that word and have to start over again. (laughs) But all memory techniques are just a process for organizing ideas. That’s really what we’re talking about—simplifying the information, creating a mental template so it works for you, and putting it into some context so it makes sense.

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Cooper: Were you expecting all the popular recognition you’ve received? For instance, what was your thought when you first saw Brain Games in the store?

Small: (laughs) I was amused… it tickled me.

Cooper: How many of the games are you directly responsible for? Or did the game company produce them by extrapolating from your principles?

Small: The process involves talking with a company that’s interested in what we do. Then we negotiate the contract of what the game should contain, and next meet with the programmers. The Dallas-based company we worked with, Radica Games, is very clever. I told them, “Look, here are the issues, here are my three books, here’s what I think ought to be in these games, and here’s what I’d like you to do.” There were a lot of things I wanted in the product, but they wanted to get something out quickly, so there were inevitable compromises. For the first game out of the box, I think they did a pretty good job. It’s a lot of fun, and I think the next one is going to be even better.

Chappell: So they have gamers write the games?

Small: Oh, yeah. When we did it, I went to a large techgame convention called the E3 to get a sense of the industry, and it was a hoot. That’s a whole world that I was unfamiliar with.

Chappell: Your kids don’t play electronic games?

Small: Well, that’s interesting question, because the book that my wife Gigi and I are working on right now is about how digital technology affects the brain and behavior. We actually monitor and try to limit the amount of time our kids use computers and games.

My son is way into this virtual gaming thing. He’s got some World of Warcraft game that he loves. My daughter—forget it! For her, it’s MySpace. So we try to monitor these types of activities and set reasonable boundaries. It’s a big problem, because a lot of our kids’ social activities now are being transferred to this electronic digital technology.

The perplexity lies in the fact that our brains are malleable, and they’re constantly responding to stimuli. The way the brain does this is by growth of dendrites [small extensions of brain cells to other brain cells], sprouting of neurons [brain cells], changes in neurotransmitters [the chemicals that brain cells use to communicate] and alterations in synapses [the actual connections between brain cells]… So the brain is continually re-shaping itself, and the neural circuitry is sort of a moving target. We see it in our PET-scan studies. You can train the brain and strengthen the circuits, but for every circuit you strengthen, you weaken others. So the concern I have is that too much virtual technology, Internet and email and too little face-to-face interaction is not good for our brains. There have been studies showing that increased hours of TV time raise the risk for Attention Deficit Hyperactivity Disorder (ADHD) in kids at young ages. So there’s lots of evidence, especially for children, whose brains are still being shaped, that what they are exposed to in their day-to-day environment is critical. We’ve got to teach them face-to-face skills, how to have empathy. That’s really what we’re writing about.

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