WHAT WAS THAT AGAIN?: A study led by a group at Harvard determined that degradation of white matter pathways that connect different brain regions may be behind fading memory associated with aging.
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As we age, it becomes harder and harder to recall names, dates—even where we put down our keys. Although we may fear the onset of Alzheimer's, chances are, our recollective powers have dulled simply because we're getting older—and our brains, like our bodies, are no longer in tip-top shape.

But what is it that actually causes memory and other cognitive abilities to go soft with senescence? Previous research has shown that bundles of axons (tubular projections sent out by neurons to signal other nerve cells) wither over time. These conduits, collectively referred to as white matter, help connect different regions of the brain to allow for proper information processing.

Now, researchers have found that these white matter pathways erode as we age, impairing communication or "cross talk'' between different brain areas.

"What we were looking at was the communication or cross talk between different regions of the brain," says study co-author Jessica Andrews-Hanna, a Harvard University graduate student. "The degree to which white matter regions are actually stable predicts the degree to which other regions are able to communicate with each other."

Andrews-Hanna and other Harvard researchers (along with collaborators at the University of Michigan at Ann Arbor and Washington University in St. Louis) concluded that white matter naturally degrades as we age—causing disrupted communication between brain regions and memory deficits—after conducting a battery of cognitive tests and brain scans on 93 healthy volunteers, ages 18 to 93. Participants fell into two age groups: one 18 to 34 and the other 60 to 93 years of age.

Scientists asked study subjects to perform several cognitive and memory exercises, such as determining whether certain words referred to living or nonliving objects. As they answered, researchers monitored activity in the fronts and backs of their brains with functional imaging magnetic resonance imaging (fMRI) to determine whether those areas were operating in sync. The results, published in Neuron: communication between brain regions appeared to have "dramatically declined" in the older group.

They fingered the potential reason for the dip by doing further brain scans using diffusion tensor imaging, an MRI technique that gauges how well white matter is functioning by monitoring water movement along the axonal bundles. If communication is strong, water flows as if cascading down a celery stalk, says Randy Buckner, a cognitive neuroscientist at Harvard; if it is disrupted, the pattern looks more like a drop of dye in a water bucket that has scattered in all directions. The latter was more evident in the older group, an indication that their white matter had lost some of its integrity.

The older crowd's performance on memory and cognitive skill tests correlated with white matter loss: The seniors did poorly relative to their younger peers. The researchers note that the white matter appears to fray more over time in the forebrain than in the brain's rear. They speculate that age-related depletion of neurotransmitters (the chemical signals sent between neurons) as well as the shrinking of gray matter (the tissue made up of the actual nerve cell bodies and supporting cells) also contribute to dimming memory and cognitive skills.

Buckner says that the team now plans to examine how aging affects white matter as well as gray matter and neurotransmitters. "We want to know," he says, "is this an important factor in why some people age gracefully and others age less gracefully?"