Symptoms of sickle-cell anemia often include severe pain and other major medical complications, but a new study shows that the disease might also decrease cognitive abilities in young and middle-aged adults.

About 70,000 people in the U.S. have sickle-cell anemia (SCA), but improved therapies are allowing most people with it to live well beyond the age of 50.

The disease causes the hemoglobin protein in oxygen-carrying red blood cells to be misshapen. This in turn makes the blood cells stiffer and more concave, shaped like a sickle rather than a round disc. These firmer, C-shaped cells are prone to jam together and block blood flow. The disease occurs most widely in people of African descent, and "its clinical presentation involves a multitude of complications involving all organs," Samir Ballas, of the Cardeza Foundation for Hematologic Research at Thomas Jefferson University's Jefferson Medical College, wrote in an editorial accompanying the new study, published online May 11 in JAMA, the Journal of the American Medical Association.

But "brain dysfunction may be the most important and least studied problem affecting individuals with this disease," the authors of the new study noted in their abstract. Anemia in general has been associated with poor brain oxygenation and perfusion, but a controlled study of cognitive function in adults with SCA had not yet been done.

To test the disease's relation to cognitive decline, 20 researchers, led by Elliott Vichinsky, of the Department of Hematology and Oncology at the Children's Hospital & Research Center Oakland, submitted 149 adults ages 19 to 55 with SCA (and no history of brain injury, stroke, major organ dysfunction or other chronic conditions that might impact cognitive fitness) and 49 healthy African-American controls to an IQ test and other tasks to assess overall cognitive capabilities. Vichinsky and his team found those with SCA had "significantly lower" IQ scores than the healthy subjects (86.69 compared with 95.19 for the controls). Tests of memory, attention, language and executive function also revealed that the SCA group was lacking in mental capabilities relative to controls.

"Neurocognitive deficits may be overlooked in adult patients with SCA or discounted as a manifestation of maladaptive behavior rather than recognized as the result of an organic process," Ballas noted in his editorial.

To ascertain any changes in the brain itself, the researchers performed MRI (magnetic resonance imaging) of some SCA patients and healthy subjects. They found no difference in the size of the hippocampus or gray matter. But with age, total brain volume did appear to decrease along with cognitive ability in the SCA patients. Lower hemoglobin levels—as well as lower education levels—were also associated with poorer cognitive performance in the patient group.

The researchers did not test patients with other forms of anemia to determine whether this cognitive decline was specifically tied to sickle-cell disease or would likely be manifest in other types as well. Ballas also noted that the SCA patients in Vichinsky's study were relatively healthy and more homogenous than the overall SCA patient population.

Vichinsky and the other authors are now working on a pilot study to see if a blood transfusion would help boost cognitive function among those with SCA who scored below 90 on the IQ test.

Image of sickle cells courtesy of Wikimedia Commons/NIH