Why are super-agers fitter than average?

Dr. Anne Maass conducts research on super agers. These are people whose memory functions excellently into old age. An interview about risk factors, her current research - and what researchers on Alzheimer can learn from super agers.

Dr. Maass, have you ever investigated whether you yourself have what it takes to be a super-ager?

(laughs) To be honest, I don't think much about aging yet. Whether someone can become a super-ager depends - as far as the findings of previous studies go - on the one hand on genetic and on the other hand on environmental and behavioral conditions. And I generally try to live a healthy life, so I can minimize this one risk factor. But I don't do it with an eye on old age - I want to be healthy even now.

Super agers are something like the embodiment of a dream: to still be really fit in old age.

And we actually have criteria for this: We define super agers as people who are more than 80 years old, but who still have the same memory capacity as 50- to 60-year-olds. In the normal aging process, memory performance declines from the age of 60, and this also affects people who do not suffer from dementia. The exciting thing is that these normal aging processes do not seem to affect super agers.

What do you know about the causes of this?

I myself have been working on this topic since my PhD studies, and at that time we did an exciting study: we examined older test subjects who had completed a fitness program - they exercised regularly on a treadmill for 3 months. We studied whether their brains were still plastic, whether blood flow to the brain improved, and whether cognitive performance improved. The results were promising: even such a comparatively small training intervention stimulates blood flow in the hippocampus, a central part of the brain. This shows that anyone can achieve something very positive with quite little effort.

What insights do you hope to gain from working with super agers?

I would like to understand which factors play a role in super agers: Why are they fitter than average? Is it environmental factors, do they simply do more sport, or are they very active socially? How important are the genetic preconditions? From these insights into the special features of super agers, we can then deduce how other people also can grow old in a better way: What do they need to pay attention to, which behaviors support a healthier cognitive aging.

Which methods do you use to find the answers to these questions?

We are building up a cohort in which we characterize the test subjects comprehensively, i.e. with molecular biological measurements and imaging methods. In this cohort, we are examining them, for example, with regard to Alzheimer's proteins such as tau and amyloid, which in old age are deposited in the brain. In addition, there is comprehensive cognitive testing with specific memory tests and a fitness test in which we examine cardiovascular fitness. Using magnetic resonance imaging, we look closely at how good the blood flow in the brain is, we examine the connectivity of the brain, the activation of the brain - in other words, really everything you can imagine in order to gain a picture as comprehensive as possible.

How many people do you include in this cohort?

We're trying to recruit 50 super agers and 50 subjects who are also over 80 years old and cognitively healthy, but not super agers. Then we'll add another 300 subjects between the ages of 60 and 79. We'd like to follow all these 400 study participants over four years.

So far, the gold standard for identifying super agers has not been molecular testing, but memory tests. How do they work?

This is the so-called verbal learning and memory test: The test subjects are presented with a list of words, have to memorize them and be able to recall them later. This is used to measure long-term verbal memory.

Do more highly educated people have an advantage in such tests - do they tend to become super agers?

That's probably the case. There is a theory that education builds up something like a cognitive reserve, with which you can compensate for memory loss to a certain degree even if you develop pathologies.

So do you become a super-ager if you have positive traits, such as a trained brain - or if you don't have negative traits, such as Alzheimer's pathologies?

That's an interesting question that we're also looking at. There are two different theories or concepts about this that might underlie the maintenance of cognitive performance. One is that some people are resistant and don't deposit tau or amyloid - and these proteins are, after all, associated with the development of dementia. The other hypothesis is that super agers also deposit tau and amyloid, but they are able to better cope with it (i. e., they are resilient) or they can compensate by having a larger brain or better circuitry. Some studies have shown that super agers have a larger anterior cingulate cortex, which is a part of the brain responsible for decision making, social interaction and problem solving. This brain region consistently appears in the results of various studies of super-agers; there is evidence that it is larger. We hope to gain further insights from our cohort study. For example, we want to determine whether super-agers actually have fewer Alzheimer's proteins in their brains - when we know that, I hope I can answer your question more precisely.

Is it actually possible that someone is considered a super-ager only because they just had a particularly good day on the cognitive test?

We asked ourselves that question, too. When I was a postdoc at Berkeley, we did a cohort study on this and looked at the subjects we identified as super-agers over up to ten years. The results were clear: They had better memory not only on the first test, but also over time. In some, we found that memory didn't deteriorate at all. And that's really a good perspective.