Compared with a group of healthy study participants, adults with sickle cell anemia showed poorer performance on neurocognitive tests, which was associated with anemia and age, according to a study in the May 12 issue of JAMA. 1
While the average life span for patients with sickle cell anemia (SCA) now exceeds 50 years, SCA has become a chronic illness associated with progressive deterioration in quality of life, according to background information in the article. “Neurocognitive dysfunction may be the most important and least studied problem affecting this aging population,” the authors write. “To our knowledge, controlled studies of neurocognitive function in adult patients have not been reported, and routine screening after childhood is not performed.”
Elliott P. Vichinsky, M.D., of Children’s Hospital & Research Center Oakland, Calif., and colleagues conducted a study to measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs. healthy control individuals. The study included a comparison of neuropsychological function and neuroimaging findings between adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA, ages 19 to 55 years, and of African descent (n = 149) or community controls (n = 47). Participants were stratified on age, sex, and education.
The primary outcome measured was nonverbal function, as assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index.
The researchers found that after adjusting for age, sex, and education level, the SCA patients had statistically significant lower average nonverbal function scores than controls. The WAIS-III PIQ score was more than 1 standard deviation below the normative average for 33 percent of patients and 15 percent of controls, compared with an expected 16 percent from the national norms. The authors suggest that patients with scores in the below-average range may have challenges in skills of daily life such as employment, financial management, medication adherence, use of community resources and social functioning.
SCA patients also had lower average scores for measures of processing speed, working memory, global cognitive function, and the majority of measures of executive function. Difficulties with selective attention in SCA patients were illustrated by lower average scores for tests regarding visual scanning and attention.
MRI findings did not explain the performance differences in the subset of patients with neuroimaging studies, as no differences in total gray matter or hippocampal volume were observed. Anemia was associated with poorer neurocognitive function in older patients.
“Adult patients with SCA who are neurologically asymptomatic are still at risk for neurocognitive performance deficits, because their anemia may be inducing neurocognitive impairment secondary to cerebral hypoxemia [deficient oxygen in the blood] undetectable by standard neuroimaging studies. Several practical steps can be taken. First, early identification of patients with difficulties on specific measures of neurocognitive function may allow these patients to enroll in and benefit from cognitive rehabilitation programs. Additionally, longitudinal studies are necessary to understand and evaluate disease progression. These studies can be linked to biological components to improve understanding of neurocognitive function in SCA,” the authors write.
“Overall, the results of this study suggest that neurocognitive performance is not adequately explained by findings on standard neuroimaging studies and support the need for intervention studies evaluating transfusion therapy, neuroprotective agents, hydroxyurea [a sickle cell anemia treatment], and oxygenation to determine whether such treatments will improve cognition.”
In an accompanying editorial, Samir K. Ballas, M.D., of Thomas Jefferson University, Philadelphia, comments on the findings of this study2.
“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. This study suggests that standardized and comprehensive neuropsychological assessment may be a valuable tool in the management of adult patients with sickle cell disease [SCD].”
“Like neurocognitive deficits, chronic sickle cell pain does not fit into either pathogenetic pathway and is difficult to diagnose. During the transition from acute to chronic pain, significant changes occur within the central nervous system, indicating that chronic pain evolves into a neurologic disorder. Neurocognitive deficits and chronic pain are both neurologic disorders of SCD, and both do not manifest with objective signs.”
1. JAMA. 2010;303:1823-1831.