Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia

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 < or = 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.

Figure. Neuropsychological Function: Age, Sex, and Education-Adjusted Mean Differences Based on Model

Mean difference indicates mean patient minus control differences. Wechsler Adult Intelligence Scale, third edition (WAIS-III) measures are index scores; Delis-Kaplan Executive Function System (D-KEFS) and Tests of Everyday Attention (TEA) measures are scaled scores. No attempt was made to normalize the mean differences or the 95% confidence intervals (CIs) to a common scale, so no attempt should be made to compare precision across tests without keeping in mind the natural scale of the raw data. Size of data markers indicates the weight of each measure in the study. For patients, sample size for all measures was n=146 except for D-KEFS number-letter switching and TEA map search (1 min), map search (2 min), telephone search time, and lottery (n=145); TEA elevator counting with distraction, visual elevator raw accuracy, and telephone search dual-task decrement (n=144); and TEA visual elevator timing and elevator counting with reversal (n=140). For controls, sample size for all measures was n=47 except for D-KEFS inhibition switching and TEA elevator counting with reversal and telephone search dual-task decrement (n=46); D-KEFS 20-question (20Q) initial abstraction, 20Q total questions, and 20Q total weighted achievement (n=45); and TEA map search (2 min) (n=44).