Cognitive defects found in sickle cell worsen with age.

ATLANTA -- Neuropsychological dysfunction and undetected brain injury affect the majority of adults with sickle cell disease, even though they are neurologically intact, according to research presented at the annual meeting of the American Society of Hematology.

"These defects worsen with age and will become a bigger problem for society as more and more children with sickle cell disease survive into adulthood," said Dr. Elliott P. Vichinsky, director of the department of hematology/oncology at Children's Hospital and Research Center, Oakland, Calif, and professor of medicine at the University of California, San Francisco.

The pediatric brain in sickle cell disease has been widely studied in the past 20 years, and it is known that up to 30% of these children have neurocognitive abnormalities. Unfortunately, Dr. Vichinsky said, those studies are "abruptly stopped at age 18, and the continuation of what happens to these patients when they reach adulthood has never really been investigated."

Dr. Vichinsky presented preliminary findings from the first prospective study on neurocognitive and brain imaging abnormalities in adults with sickle cell disease on behalf of his coinvestigators from the National Heart, Lung, and Blood Institute's Comprehensive Sickle Cell Centers.

The study evaluated 138 adults (aged 21-29 years) with sickle cell disease and 37 controls, using a variety of cognitive tests, including the Wechsler Adult Intelligence Scale (WAIS-III), the Wechsler Memory Scales (WMS-III), the Woodcock-Johnson Tests of Achievement, the Test of Everyday Attention (TEA), and the WAIS Processing Speed Index, which assesses attention and the ability to plan and coordinate visual information and motor activities.

Study participants were also evaluated with brain MRI to test for atrophy and lesions, and with volumetric MRI to quantitate white and gray matter.

Overall, 63% of the 138 patients with sickle cell disease had neuropsychological dysfunction according to the tests, or abnormal findings on MRI. A total of 38% had brain imaging abnormalities, including evidence of silent infarcts and hippocampal atrophy, and 18% had ischemic lesions.

Among the patients with sickle cell disease, 32% showed significant impairment in their overall WAIS-III test, scoring below 86 on the scale. In comparison, 15% of the controls scored below 86 on the WAIS-III.

Similarly, 26% of sickle cell patients scored below 86 on the WMS-III memory scale, compared with 16% of controls. Subtests of attention and flexibility of thought, as measured on the TEA, decreased significantly with age in sickle cell patients, but not in controls, Dr. Vichinsky said.

The TEA "is a good assessment of executive functioning. The one aspect of the test that stood out was the ability to be flexible with cognitive thinking, that is, to switch from one question to another with ease. This inability was striking in the sickle cell population," Dr. Vichinsky said.

The mean hemoglobin level in the sickle cell patients was 8.2 g/dL, which was below the normal range and lower than the level of 13.9 g/dL in the controls. "Patients who had lower hemoglobin had lower IQ scores, and hemoglobin was a significant independent predictor of verbal IQ, math, and executive functioning, so the more anemic you were, the more likely you were to have significant neurocognitive abnormalities," he added.

Sickle cell patients also had significant loss in both right and left hippocampal volume, compared with controls. This was increasingly apparent as the patients aged. "We saw a progressive loss of hippocampal volume from age 20 to 29, but there was no loss in the age-matched controls," Dr. Vichinsky said. "I predict that as we follow these patients out longer, they are going to develop more volume loss," he added.

Hippocampal volume also correlated "very strongly" with performance and verbal IQ and other indexes of intellectual functioning. "This may very well be the tip of the iceberg for adults with sickle cell. Remember, the patients in our study had no history of brain abnormalities or history of brain injury. So this is a very neurologically intact group, and yet 38% had MRI findings consistent with ischemic injury, either significant atrophy or overt ischemic lesions."

The second phase of the NHLBI-sponsored study is testing whether transfusing these patients can reverse the neurocognitive abnormalities in those who do not have overt neurologic deficits.

BY FRAN LOWRY

Orlando Bureau

Adults With Sickle Cell Disease More Likely to Have Cognitive Impairment

                                         Sickle cell disease  Control
                                         (n = 138)            (n = 37)

Wechsler Adult Intelligence Scale Score  32%                  15%
  <86
Wechsler Memory Scale score <86          26%                  16%

Note: Based on a study of adults aged 21-29 years.
Source: Dr. Vichinsky
ELSEVIER GLOBAL MEDICAL NEWS

Note: Table made from bar graph.