Study Finds Poorer Cognitive Performance Among Adults With Sickle Cell Anemia

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[18]:1823-1831.

2. JAMA. 2010;303[18]:1862-1863.