Column: Studying the Brains of the ‘Super Old’

by Guy McKhann, M.D.

June 19, 2009

Several recent news stories have emphasized the fact that baby boomers are reaching their 60s—an age at which dementia starts to appear in increasing numbers of people.

Much less attention has been directed toward another age-related phenomenon: more and more people are living longer, into their 90s and beyond. In fact, this is the fastest-growing segment of our society. In the New York Times article “At the Bridge Table, Clues to a Lucid Old Age,” reporter Benedict Carey highlights the work of Claudia Kawas. Kawas has focused on these “super old,” taking advantage of the fact that a large number of people over 90 years old live at the site of her studies, Laguna Woods Village.

These subjects, many of whom have unimpaired memory skills, are available for repeated memory tests, genetic tests, documentation of physical and social activities and, in many cases, autopsy studies of the brain. The study featured in the Times article, referred to as the “90+ study,” is quite a unique longitudinal study, documenting what keeps an old brain functioning like a young brain.

A memory-protecting allele

We all know of families in which older people seem to do very well. Why? Rather than focus on finding genetic mechanisms of diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis or autism, Kawas and her colleagues are asking an unusual question regarding this super old population: Are there genetic mechanisms that keep us from getting the dementia of Alzheimer’s disease?

The results are somewhat surprising. One of the genetic factors associated with Alzheimer’s disease is the APOE4 form (allele) of the gene for a protein called apolipoprotein E (APOE). In contrast, another allele, APOE2, seems to be protective. Super old people who are doing cognitively well may have the pathology we associate with Alzheimer’s disease, but if they have APOE2 they stay cognitively normal.

Kawas speculates that APOE2 is working not through what we presume to be the mechanism for Alzheimer’s disease, but rather through a different pathway

This is only a first cut at the problem. However, the table has been set for the identification of other protective genetic factors.

What else do the super old do that preserves their memory and other cognitive functions? Those featured in the Times article play highly competitive bridge, an activity that includes challenges not only to one’s memory, but also to one’s patience, emotional control and ability to strategize. It also involves social interactions, which Kawas thinks may be as important as the memory challenges.

The 90+ study was started by other investigators more than 25 years ago. Now it is finally paying off in terms of our understanding of the brain of the super old.

Explaining a ‘senior moment’

We all have experienced the phenomenon known as a “senior moment,” and it occurs more frequently as we get older. We can’t come up with a name. We know all about the person—he lives in a white house, he drives a red car, his wife’s name is Alice, he has a black dog whose name is Charcoal—but no name for him. Frantically we try to come up with a first letter—and are usually wrong. In despair we turn our attention to something else. Then, seemingly out of the blue, the name pops up. The prototypical senior moment! What is the brain doing on its own to make this happen?

As described in the VOA News article “Study Shows Brain’s Problem-Solving Function at Work while We Daydream,” Kalina Christoff of the University of British Columbia may have come up with the start of an answer. In ingenious experiments using brain scans, Christoff tried to find out what your brain does when your mind wanders away from a specific task. She showed that, even though you have shifted to another problem or state, your brain is not quiet. In fact it is more active.

Furthermore, brain systems that usually do not act together, including some which were even thought to oppose each other, act in synchrony in such circumstances. Somehow the brain is bringing more resources to the problem without any conscious direction from you. This observation doesn’t solve the problem of how your brain functions during one of these lapses, but it does suggest new questions to ask and possible ways to answer them. For example, maybe this problem gets worse as we get older because communication pathways in the brain become slower, and the brain adapts by recruiting other pathways to help solve the problem. That is a testable hypothesis!

Now, tell me again what your name is?