Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease

Abstract

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non-SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3-7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, 2 (1) = 17.8, P < .0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD.

Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease

“…Although SCD affects general intelligence, [3][4][5]43 executive function abilities are particularly sensitive to the impact of SCD. 43,44 Executive function abilities encompass the cognitive aspects of goal-directed behavior, including the ability to sustain and shift attention, changing one's response to boundaries (set-shifting), and manipulating information with a delayed response (working memory). 45 Such complex cognitive abilities arise from functional relationships within higher-level cortical association networks.…”

“…59 Ongoing metabolic stress in the brains of children with SCD could potentially hinder microstructural white matter development, ultimately impacting functional network architecture and cognition. Alternatively, metabolic stress in the white matter could reversibly disrupt functional connectivity, as Hood et al reported an improvement in executive function abilities immediately after transfusion of red blood cells, 44 a therapeutic intervention that has been shown to decrease metabolic stress, as measured by OEF. 12 Multimodal imaging techniques provide complementary information, improving our understanding of the pathophysiology of cognitive decline in SCD and potentially improving risk prediction algorithms.…”

“…Earlier cognitive testing showing differences between SCD and controls did not utilize the NIHTB‐CB 3–5,43 . However, the NIHTB was developed with the goal of standardizing research‐based cognitive testing, enabling better comparison across disease states, 45 and the NIHTB‐CB has previously been utilized in SCD 44 . Additionally, 90% of our SCD cohort was receiving primary disease modifying therapy with HU, which differentiates our cohort from earlier investigations into the cognitive effects of SCD that were published prior to recommendations that all patients with HbSS and HbSβthal 0 genotypes receive HU 68 .…”

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

“…Interestingly, global gray and white matter CBF were similar among all groups, and there were no differences in total hemoglobin or SpO 2 between HU-treated and transfused patients, suggesting that the between-group differences in OEF are not explainable by differences in global oxygen delivery. Of note, given that imaging was conducted on the day before scheduled transfusion, and other studies have shown reductions in global CBF and OEF 24 h post-transfusion (191), these findings may suggest that the hemodynamic effects of transfusion are greater near transfusion, compared to far from transfusion, as has been demonstrated for cognitive impairment (292). Nevertheless, the apparent inferiority of HU, even when compared with “late” transfusion effects, may be accounted for by the increased affinity of hemoglobin F for oxygen (293).…”

Brief Screening Measures Identify Risk for Psychological Difficulties Among Children with Sickle Cell Disease

“…Recruitment occurred through the sickle cell clinic at St. Louis Children s Hospital as part of a larger study assessing cognitive functioning (Hood et al, 2019). Inclusion criteria for children with SCD were age 4 to 18 years, diagnosis of SCD identified through newborn screening or laboratory testing, and treatment with either CTT or HU for at least 6 months prior to study.…”