Sickle cell disease (SCD) is an inherited hemoglobin disorder that affects an estimated 1 out of every 365 African-American newborns in the United States . SCD is characterized by chronic hemolytic anemia, increased susceptibility to infections, end organ damage, and intermittent episodes of vascular occlusion that result in acute and chronic pain. Additionally, SCD is associated with cognitive impairments across multiple domains, most notably intellectual functioning , attention, and executive function , with attention and working memory being especially vulnerable .
The etiology of cognitive deficits in SCD patients is complex and multifaceted. The etiology may be primary to the disease itself or may be related to complications secondary to the disease, such as CNS-related transient ischemic attacks, seizures, and increased intracranial pressure . While the incidence of stroke in the general pediatric population is rare, findings indicate that 1 in 10 children with SCD will experience a stroke by the age of 20, resulting in broad and pervasive neuropsychological impairment depending on the location of the insult [4, 6]. Other research has suggested that compromised executive dysfunction and attentional abnormalities may be the result of compromised fronto-cortical circuitry and explain the deficits seen across many cognitive domains . Further complicating the clinical picture, SCD is often associated with socioeconomic disadvantage compounded with recurrent hospitalizations and poor school attendance from an early age .
Overall, given the multiple medical and neuropsychiatric difficulties associated with and secondary to the disease, a diverse cognitive profile may be observed with deficits across one or several domains . It is recommended that clinical neuropsychologists employ an informed approach to the neuropsychological evaluation that is determined by pertinent illness-related factors, consideration of general developmental level and timing of evaluation, relationship to medical treatment, and transition to adulthood . While cognitive rehabilitation or remediation training may be effective in improving attention, executive functions, and memory, the research is limited by small samples sizes and lack of randomized control groups . Similarly, more research is needed to determine potential benefits of newer medical interventions, such as hydroxyurea, on the neurocognitive functioning of children and adults with SCD.
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 Schatz, J., Finke, R. L., Kellett, J. M., & Kramer, J. H. (2002). Cognitive functioning in children with sickle cell disease: a meta-analysis. Journal of Pediatric Psychology, 27, 739-748. doi:10.1093/jpepsy/27.8.739
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 Berkelhammer, L. D., Williamson, A. L., Sanford, S. D., Dirksen, C. L., Sharp, W. G., Margulies, A. S., & Prengler, R. A. (2007). Neurocognitive sequelae of pediatric sickle cell disease: a review of the literature. Child Neuropsychology, 13, 120-131. doi: 10.1080/09297040600800956
 Edwards, C. L., Raynor, R. D., Feliu, M., McDougald, C., Schmechel, D., Saurona, P., ... & Abrams, M. (2007). Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD). Neuropsychiatric Disease and Treatment, 3, 705-709. doi:10.2147/NDT.S518
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 Schatz, J., Finke, R., & Roberts, C. W. (2004). Interactions of biomedical and environmental risk factors for cognitive development: a preliminary study of sickle cell disease. Journal of Developmental & Behavioral Pediatrics, 25, 303-310.
 Daly, B., Kral, M. C., & Tarazi, R. A. (2011). The role of neuropsychological evaluation in pediatric sickle cell disease. The Clinical Neuropsychologist, 25(6), 903-925. doi: 10.1080/13854046.2011.560190
Abstract: This literature review summarizes all studies relating neuropsychological performance to neuroimaging findings in pediatric sickle cell disease (N=28; published 1991–2005). Although inconsistencies exist within and across domains, deficits in intelligence (IQ), attention and executive functions, memory, language, visuomotor abilities, and academic achievement have been identified. Overall neurocognitive compromise was revealed to be related to the level of neurological injury and the location of silent infarct. Attentional and executive dysfunction is prevalent and related to frontal lobe abnormalities.Berkelhammer, L. D., Williamson, A. L., Sanford, S. D., Dirksen, C. L., Sharp, W. G., Margulies, A. S., & Prengler, R. A. (2007). Neurocognitive sequelae of pediatric sickle cell disease: a review of the literature. Child Neuropsychology, 13, 120-131. doi: 10.1080/09297040600800956
Mechanisms Underlying Pain in Sickle Cell Disease.
Video features Cheryl Stucky, Medical College of Wisconsin, delivering a talk describing the problem of sickle cell pain, mechanisms underlying the disease, and the latest research in this area.
Caring for Children with Sickle Cell Disease. https://www.youtube.com/watch?v=3yTKV8VnWW0&t=01s
Video features Deepika Darbari, MD, of Children's National Health System as she reviews age-appropriate screenings and immunizations for children with sickle cell disease, as well as tips for co-managing the care of children with sickle cell disease.
Sickle Cell Disease Q&A – Episode 134
Podcast features Dr. John Roberts discussing sickle cell disease. Dr. Roberts’ current research focuses upon improving delivery of care to people with sickle cell disease
Daly, B., Kral, M. C., & Tarazi, R. A. (2011). The role of neuropsychological evaluation in pediatric sickle cell disease. The Clinical Neuropsychologist, 25, 903-925.
Mackin, R. S., Insel, P., Truran, D., Vichinsky, E. P., Neumayr, L. D., Armstrong, F. D., ... & Weiner, M. W. (2014). Neuroimaging abnormalities in adults with sickle cell anemia Associations with cognition. Neurology, 82, 835-841. https://www.researchgate.net/profile/Philip_Insel/publication/262046615_Neuroimaging_abnormalities_in_adults_with_sickle_cell_anemia_Associations_with_cognition/links/0046353a39d8aa6409000000.pdf
Sanger, M., Jordan, L., Pruthi, S., Day, M., Covert, B., Merriweather, B., ... & Kassim, A. (2016). Cognitive deficits are associated with unemployment in adults with sickle cell anemia. Journal of clinical and experimental neuropsychology, 38(6), 661-671. doi: 10.1080/13803395.2016.1149153 http://www.tandfonline.com/doi/abs/10.1080/13803395.2016.1149153
Schatz, J., Finke, R. L., Kellett, J. M., & Kramer, J. H. (2002). Cognitive functioning in children with sickle cell disease: a meta-analysis. Journal of Pediatric Psychology, 27, 739-748. doi: 10.1093/jpepsy/27.8.739 https://academic.oup.com/jpepsy/article/27/8/739/887555/Cognitive-Functioning-in-Children-With-Sickle-Cell
Vichinsky, E. P., Neumayr, L. D., Gold, J. I., Weiner, M. W., Rule, R. R., Truran, D., ... & Orringer, E. P. (2010). Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia. JAMA, 303, 1823-1831. doi:10.1001/jama.2010.562 http://jamanetwork.com/journals/jama/fullarticle/185851