- The Washington Times - Wednesday, May 17, 2006

Good mental and physical exercises are thought to help with brain functioning as we age. But the devil is in the details and inside the brain itself, which has a mind of its own — in a manner of speaking — that is difficult to read.

Researchers have many theories about how our brains change as we grow older. Their discoveries have overturned some old assumptions, but scientists necessarily are cautious about applying to humans the findings from experiments done on animals. The brain still is largely a frontier.

Studies under way to learn about normal changes associated with age, as opposed to diseased or pathologically driven states, are encouraging overall. Findings are so encouraging, in fact, that one authority, Dr. Gene Cohen, a psychiatrist who heads the Center on Aging, Health & Humanities at George Washington University, has titled his latest book “The Mature Mind: The Positive Power of the Aging Brain.”

The “mechanism that links a behavior such as physical activity to cognitive health” still is unknown, says David Brown, a senior behavioral scientist with the Centers for Disease Control and Prevention.

Decades ago, it was thought people were born with all the neurons they would have and, though it might be possible to generate new ones, they inevitably would lose a certain percentage as they grew older.

“Both those pieces of dogma have been discredited in the past few years,” says Molly Wagster, director of the Neuropsychology of Aging program in the National Institute on Aging, part of the Bethesda-based National Institutes of Health.

She says that “we still do lose some — particularly in areas important for learning and memory — but not so many as a factor of aging” and notes a growing interest in the development of what she calls “cognitive enhancers” — both behavioral and pharmacological. These would include dietary supplements as well as drugs that could improve function by affecting the chemistry of the brain.

Thinking improves with aging, Dr. Cohen asserts. “Maturity matters,” he says. “Certain skills or capacities diminish, but others can increase. We may have trouble [with forgetfulness], but our vocabulary continues to improve, and vocabulary is important in managing our environment.”

He is especially interested in what he identifies as developmental intelligence — defined as “a broader way of thinking that is a tremendous advantage in a judge or diplomat. … People have overvalued negative changes. If the speed of response is slower, they overlook that life perspective is changing.”

Dr. Cohen, 61, who was the first chief of the Center on Aging at the National Institute of Mental Health, points to a growing body of research in the past 20 years into what is called brain plasticity. The term is used widely to refer to activities occurring at the deepest level of the brain. Scientists once thought brain functioning was laid down shortly after birth, but now they focus on learning the organ’s adaptability quotient.

“Every time you challenge your brain, it rewires [itself] because it is forming new synapses and dendrites, and this continues throughout the entire life cycle,” Dr. Cohen says. Further, he asserts that “you can’t prevent normal onset of Alzheimer’s, but challenging the mind delays the onset.”

The new challenge, being taken up by such companies as the Posit Science Corp. of San Francisco, is developing methods that help reverse serious physical disorders and enhance cognitive performance.

Key research on brain function is derived from animal studies, but also from MRI (magnetic resonance imaging) and PET (position-emission tomography) scans, and autopsies in a few cases. The latter, Dr. Cohen says, have shown the greatest number of dendrites in the hippocampus —the part of the brain essential for information processing — in people from their early 50s to the late 70s. He cites a 2002 finding derived from MRI studies indicating that young adults typically use one side of the brain, while those entering middle age are using both sides.

Ms. Wagster speaks more cautiously about this particular finding, calling it “an area of scrutiny [still] at the theory stage.”

Denise Park, professor of psychology and co-director of the Center for Healthy Minds at the University of Illinois at Urbana-Champaign, has found through scanning and other research techniques done on humans that such activity is most likely “compensatory.” By that she means the older brain is compensating for functions that younger brains normally handle in other ways.

“Older adults tend to engage more frontal cortex than younger adults and engage both sides of the brain,” she explains. Observing people doing tasks, she and others in her lab see “where young adults use both sides of the brain, older adults will recruit additional tissue [to perform them].”

In line with many other psychologists and neuroscientists, the Web site for Ms. Park’s Productive Aging Laboratory concludes “there is evidence that the brain continuously reorganizes with age.” In exploring neural routes that older adults use to perform a given cognitive task, the lab has found a difference from those used by younger people. They see “a hippocampal-frontal circuit that differs as a function of age.”

Michela Gallagher, chairwoman of the department of psychological and brain sciences at Johns Hopkins University, uses animals to study the cellular molecular basis of cognitive aging. She agrees that much can be known about the kinds of changes occurring in aged animals who end up with a degenerative disease or impairment of some kind. Normal brain health is another matter. Her research shows that “memory problems in the absence of Alzheimer’s are not due to loss of brain cells, but a functional condition of cells that are there.”

The finding is encouraging because it likely makes the condition easier to manage, she says, and therefore easier to correct.

In work with older rats that maintain what she calls “high functioning,” Ms. Gallagher sees parallels with some recent neuroimaging work being done on humans.

“Old rats that are coming out well at an older age are showing more adaptive changes without us causing them. Those adaptations seem to be protecting the brain against some of the changes,” she says. The “successfully aging” older rats, which have brains different from young rat brains, may find ways of adapting at the cellular level.

However, she admits that with older humans, because there is “just so much going on in terms of their life histories,” it’s difficult to set up controlled experiments to prove definitively what accounts for individual difference.

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