Memory and concentration diminish as organ's wiring sustains damage

By Janet Raloff

Web edition: March 25, 2011
Print edition: April 23, 2011; Vol.179 #9 (p. 8)

Obesity subtly diminishes memory and other features of thinking and reasoning even among seemingly healthy people, an international team of scientists reports. At least some of these impairments appear reversible through weight loss. Researchers also report one likely mechanism for those cognitive deficits: damage to the wiring that links the brain’s information-processing regions.

A number of studies in recent years have shown that individuals with diseases linked to obesity, including cardiovascular disease, hypertension and type 2 diabetes, don’t score as well on cognitive tests as less hefty individuals do. To test whether weight alone — and not disease — might be partially responsible, John Gunstad of Kent State University in Ohio and his colleagues recruited 150 obese individuals for a series of cognitive tests. These people weighed on average just under 300 pounds, although some were substantially heavier. Two-thirds would shortly undergo weight-loss surgery.

Scores on the tests were assessed against those of people in the Brain Resource International Database, a large multicenter project with data on very healthy people. Obese individuals in the new study initially performed on the low end of the normal range for healthy individuals from the database on average, Gunstad says, although nearly one-quarter of the obese participants’ scores on memory and learning actually fell within what researchers consider the impaired range.

Tested again 12 weeks after bariatric surgery — when most had shed some 50 pounds — the lighter but still heavy patients scored substantially better. Most now performed “within the average or greater-than-average range for all cognitive tests,” the researchers reported online in October in Surgery for Obesity and Related Diseases.

Study participants who didn’t have surgery — or lose weight — performed worse on the second test. “That was a bit surprising,” Gunstad says.

Neurologist Stefan Knecht of the University of Münster in Germany, who is not involved in the new research, says he is not surprised that the untreated participants experienced rapid, continuing drops in cognitive performance. Among the morbidly obese, he says, “You can actually watch them getting worse from one three-month period to the next if you have sufficiently sensitive measures, which [Gunstad’s group] did.”

The second new study by Gunstad’s group used a form of magnetic resonance imaging, or MRI, to probe the wiring that connects nerve cells to move information throughout the brain. The bundled fibers are sheathed in a protective layer of white insulation, giving rise to the tissue’s name: white matter.

In obese individuals — but not normal-weight or overweight people — this sheathing shows signs of damage. “It’s not as though a cable has been cut,” Gunstad says. “It’s just that its integrity is diminished,” jeopardizing the strength or clarity of signals that must traverse these cognitive highways. His group’s findings appear in the March Obesity.

This white matter study “is interesting, and the methodology looks sensible,” says brain-imaging expert Mark Bastin of the University of Edinburgh Western General Hospital, who is also studying white matter integrity. But he argues it must be viewed as preliminary owing to “the very small numbers of subjects” — just 17 obese individuals among the 103 people studied.

Using the same MRI technique last year, Knecht’s team linked C-reactive protein — a blood marker of systemic inflammation — with white matter integrity in a group of 447 older adults. Both type 2 diabetes and obesity can chronically elevate CRP levels in the blood.

As CRP levels in blood increased, Knecht and his colleagues found, so did the likelihood that white matter’s insulation would be impaired. This suggests “that low-grade inflammation, which is strongly correlated with obesity, could be an important mediator,” Knecht says.

 In that study, the researchers reported in the March 30, 2010 Neurology, higher levels of CRP also correlated with “with worse performance in executive function, including tests of psychomotor speed and attention.”