Successful Aging Requires Personal Resolve and Cognitive Reserve


by Guy McKhann, M.D.

January 9, 2008

I don’t know many people over 75 who are not worried about their memory. The Washington Post article "To Screen, or Not to Screen" addresses the issue of what happens to our brains as we age. There are several patterns of cognitive change.

At one end of the spectrum are people who do extremely well, maintaining their intellectual functions and interests, and often develop new ones. They often look and act many years younger than their age. When I meet people like this I like to ask them: “On a good day, how old do you see yourself?” Even when in their 90s, the answer is usually “somewhere in my 60s.” Often the people they associate with are in their 60s, with no idea of the person’s age.

My father was fortunate to be like that into his late 80s. A retired professor of pediatrics, he still read medical journals, books and newspapers avidly. While perusing the obituaries, he would occasionally make the comment: “That poor old man finally died.” I would be unkind enough to point out that the person in question was years younger than he was. His reaction was actually one of surprise.

Why do some people do so well? It is in part genetic—they lack the “bad” genes that would make them more likely to develop Alzheimer’s or cerebrovascular disease. They may also have “good” genes that are protective or involved in maintaining brain functions. We don’t spend enough time thinking about this latter possibility, our focus being so heavily directed toward disease-associated genetics.

There are also lifestyle factors. Numerous studies have shown that those who age successfully are more likely to be physically active, mentally active and socially involved. They also pay more attention to modifying cardiovascular risk factors such as high blood pressure, cholesterol or diabetes.

Continuing along the spectrum, another group continues to do well, but is slipping a little. They can’t multitask as well, can’t handle multiple subjects as they once did. Names of people or places don’t come as easily—so-called “senior moments” are more frequent. According to research reported on in the New York Times “Mental Reserves Keep Brains Agile”, this is part of the spectrum of normal aging and depends on a person’s “cognitive reserve,” the inherent ability of the brain to develop and maintain new connections between nerve cells. It is maintenance of this cognitive reserve that those who age successfully are achieving with their lifestyles.

A third group is those who are on the threshold of real trouble. They are in the early stages of dementia—the loss of memory and other cognitive functions. This is the group toward which the screening proposal is aimed. Can we pick up the changes in cognition early, before the pathological process, usually Alzheimer’s disease, has irreversibly wrecked the brain?

The major goal of research for treatment of Alzheimer’s disease is to slow or stop the progression of the disease—to preserve normal brain functions as long as possible. To do this we need to identify the disease process early, to predict who will progress and how fast, and to introduce protective or reversing medications. We aren’t able to do that yet, but many pharmaceutical companies are trying.

The population that will eventually have to be used for testing new agents is not those with advanced disease, but those in the early stages. These stages are identified by changes in cognitive performance over repeated screenings, along with changes in other parameters identified by brain imaging.

We can learn from flipper

When I need to escape, I go sailing. In the ocean, dolphins come and play around the bow of my boat. I can watch and admire them play on the surface before they plunge under water for many minutes only to pop back up to play some more. Some seals can stay under for an hour or more. How do they do that? We humans can hold our breaths for only a minute or so and would be unconscious after 4 or 5 minutes.

Researchers in the marine lab at the University of California–Santa Cruz have an answer, as reported in the Telegraph story “Marine Mammals Study Offers Brain-Damage Hope.” All species of mammals have an oxygen-carrying protein called hemoglobin in their blood. Diving marine mammals have additional oxygen-carrying proteins neuroglobin and cytoglobin in their brain cells, which allow them to store oxygen.

The discovery of these cellular globins is three or four years old, and the implications of their potential role in recovery from stroke and other brain injuries is just beginning to be explored. Stay tuned!