Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Anemia
- Elliott P. Vichinsky, MD;
- Lynne D. Neumayr, MD;
- Jeffrey I. Gold, PhD;
- Michael W. Weiner, MD;
- Randall R. Rule, PhD;
- Diana Truran, BA;
- Jeffrey Kasten, BA;
- Barry Eggleston, MS;
- Karen Kesler, PhD;
- Lillian McMahon, MD;
- Eugene P. Orringer, MD;
- Thomas Harrington, MD;
- Karen Kalinyak, MD;
- Laura M. De Castro, MD;
- Abdullah Kutlar, MD;
- Cynthia J. Rutherford, MD;
- Cage Johnson, MD;
- Joel David Bessman, MD;
- Lanetta B. Jordan, MD, MPH;
- F. Daniel Armstrong, PhD
- for the Neuropsychological Dysfunction and Neuroimaging Adult Sickle Cell Anemia Study Group
- Author Affiliations: Department of Hematology/Oncology, Children's Hospital & Research Center Oakland, Oakland, California (Drs Vichinsky, Neumayr, and Rutherford); Keck School of Medicine, University of Southern California, and Departments of Anesthesiology and Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California (Dr Gold); Veterans Administration Medical Center and Departments of Radiology, Medicine, Psychiatry, and Neurology, University of California, San Francisco (Drs Weiner and Rule, Ms Truran, and Mr Kasten); Rho Inc, Research Triangle Park, North Carolina (Dr Kesler and Mr Eggleston); Boston Medical Center, Boston, Massachusetts (Dr McMahon); Department of Medicine, Division of Hematology and Oncology, University of North Carolina, Chapel Hill (Dr Orringer); Department of Medicine, Division of Hematology and Oncology (Dr Harrington) and Department of Pediatrics (Dr Armstrong), University of Miami, Miami, Florida; Cincinnati Children's Hospital Medical Center and University Hospital Cincinnati, Cincinnati, Ohio (Dr Kalinyak); Duke University Medical Center, Durham, North Carolina (Dr De Castro); Medical College of Georgia, Augusta (Dr Kutlar); University of Texas Southwestern Medical Center at Dallas (Dr Rutherford); Department of Medicine, Division of Hematology, University of Southern California, Los Angeles (Dr Johnson); University of Texas Medical Branch, Galveston (Dr Bessman); and Memorial Cancer Institute, Hollywood, Florida (Dr Jordan).
Abstract
Context Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease.
Objective To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals.
Design, Setting, and Participants Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level ≤10 mg/dL) aged 19 to 55 years and of African descent (n = 149) or community controls (Hb AA and normal hemoglobin level) (n = 47). Participants were stratified on age, sex, and education.
Main Outcome Measures The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae.
Results The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, −5.50; 95% confidence interval {CI}, −9.55 to −1.44]; P = .008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, −5.19; 95% CI, −9.24 to −1.13]; P = .01), working memory (90.75 vs 95.25 [mean difference, −4.50; 95% CI, −8.55 to −0.45]; P = .03), processing speed (86.50 vs 97.95 [mean difference, −11.46; 95% CI, −15.51 to −7.40]; P < .001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function.
Conclusion Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.
