An Interview with Claudia H. Kawas, M.D.
Professor of Neurology, Neurobiology & Behavior
Associate Director, Institute for Brain Aging
University of California, Irvine
Q: You are the principal investigator of the so-called 90+ Study, which is possibly the largest study ever to prospectively track people in this age group. What are your primary goals and why is such a study needed?
A: The 90+ Study currently enrolls 1,000 people who were over age 90 as of January 1, 2003. The participants are part of a much larger study, the Leisure World Cohort, which has tracked the health status and lifestyle characteristics of almost 14,000 elderly people since 1980. The primary goal is to better understand factors that are relevant to the health and longevity of people in their 90s. We are particularly interested in factors having to do with brain health and cognition, but we are also looking at factors that affect other abilities, such as mobility or functional status.
The reason we need this study is because people over 90 are the fastest-growing segment of the population in much of the world right now. Right now in the U.S., there are fewer than two million people in this age range, but in a few decades there are going to be 10 to 12 million. They are the primary consumers of healthcare, yet we know almost nothing about them.
For example, we don’t even know if the risk of dementia continues to increase after age 90, if the longer you live the more likely you are to get it, or if dementia risk levels off or even declines, as some researchers have suggested. This question is not settled. We don’t know if a third of them are going to have dementia, or half, or three-quarters. When you’re talking about the difference between one-third to three-quarters of 10 to 12 million people, you’re potentially talking about a lot of dementia. We face the possibility of having more individuals suffering from dementia in that age group alone than we currently have in all ages.
Q: Consistent with some earlier studies, your research has found correlations between cognitive status and levels of a protein associated with synapses (synaptophysin). What are your findings and what do they suggest in terms of compensatory responses to incipient pathology?
A: Synaptophysin is simply a way to measure pre-synaptic function. It has long been shown to correlate with cognition in a variety of settings. In the late 1980s, Robert Terry and colleagues published data showing an association between cognition and synaptophysin even in Alzheimer’s patients. We know that you need synapses to function and that in a lot of brain diseases and probably even in aging, there are likely to be declines in synaptophysin. This presumably means that you are losing synapses, or at least synaptic function, which is how nerve cells communicate with one another.
Our results show a definite relationship between cognition and synaptophysin. Specifically, we found significantly lower levels in people with clinically diagnosed dementia, and higher levels in people who have some cognitive impairment but are not demented. We also have preliminary data that synaptophysin is increased in people whose cognition was normal when measured in the months before death, but who, on autopsy, had high levels of Alzheimer’s-like pathology.
But there was a relatively small number of subjects in that group: the latest published paper includes data on about 30 brains. We’re now doing the same studies with 100 additional brains to see if we can confirm that somewhat preliminary finding.
If the finding is verified, I would say it could suggest that the brain either already had some kind of compensatory reserve or was making a compensatory effort to try to get around the pathology. We can’t tell which it is, but the data could be interpreted that way.
Q: How does this data fit with “cognitive reserve” theories of aging?
A: People toss around this term a lot, but what do they mean? Part of the problem is that we’re not sure what we mean. On one level, we use the term to imply a “better brain” that is somehow able to withstand insults associated with disease or aging and continue to perform, perhaps even at a higher level.
As a researcher, if you look at a brain that has pathology but continues to function normally, you tend to think: “There’s something else going on in this brain, and if I could find out what it is, maybe I could use it to help other people.” We know, for example, that younger people often have amyloid without being demented. We presume those people have preclinical Alzheimer’s disease, but we don’t know if it’s preclinical by two months, two years, or 25 years. It looks as if 25 years might be closer to the truth.
The key question is, what is going on in that brain that underlies the feature that we are calling cognitive reserve? We don’t know the answer yet. I do think that stronger synapses and more synapses are very good things, and that people who have those tend to be called people with cognitive reserve. What I don’t know is how they get those. I don’t know if it’s the “chicken” or the “egg.” I don’t even know how much is genetic vs. environmental or to what extent.
Q: You’re also examining how diet is related to cognitive functioning in the “oldest olds” enrolled in your 90+ Study. What can we say with confidence regarding dietary factors and cognitive health?
A: There is only one thing I can say with confidence regarding dietary factors and cognitive health: a good, well-balanced diet with an emphasis on fruits and vegetables—the things we’re all told are good for us—is a good thing for health in general, and most likely also a good thing for cognition. I think that a “good diet,” especially in the elderly, should include a lot of variety. There needs to be a lot of different fruits and vegetables in your diet, not just the same ones every day.
Personally I am not convinced—and this is a minority opinion—that we can say with confidence that any specific dietary factor is ultimately protective when it comes to cognitive health, or aging. There is some data in specific disorders, such as folate during pregnancy to prevent neural tube defects, but not in terms of general cognitive aging.
I think the idea of a message such as “eat more fruits and vegetables” may be overly simplistic to people. Everyone wants it to be “vitamin X.” I don’t think the answer is vitamin X; I think the answer is vitamin A, C, D, and all the different B complexes and all the lycopenes and all the fish oils. Scientifically, it’s hard to separate all those things out. People who have diets with good levels of one of those nutrients tend to have diets that are good in a lot of those nutrients. I think that’s why they generally do better in a variety of ways. But we tend to study only one at a time to try to figure out which vitamin X is the answer, because people want a simple choice.
Q: There seems to be increasing emphasis on the science of “cognitive fitness,” or what can be done on a day-to-day basis to maintain brain health throughout life. How do you view these types of studies?
A: It’s true that there is more science coming out in this area, especially in relation to exercise and non-exercise leisure activities. In the 90+ Study, we found both were associated with how long people lived. We’re now looking at how exercise and leisure activity relate to cognition, and expect to have those results in one or two years. The level of exercise was correlated very strongly with longevity. An average of 15 minutes a day provided benefit, 30 provided more, 45 provided the most, and after that it leveled off: three hours was just as good as 45 minutes. It didn’t have to be done daily; we measured the average done daily over the course of a week.
One of the things about this that I can’t help noticing is that these are things that most of our mothers tried to teach us. This is not exactly, in some ways, a new idea. Now people are going in the laboratory and showing that if you let mice or dogs have a better diet, their cognition is better. If you let them exercise as opposed to not letting them exercise, their cognition is better. And if you then sacrifice the mice that you’ve let exercise, you will find differences in their brain growth factors and synaptic levels. If you put rodents in a cage with things to play with, they make more synapses as they grow up. It is all coming together. As scientists are looking at the kinds of things our mother told us, they’re seeing that there is actually something there. It’s interesting that this is what it takes to get us to listen to our mothers.