Hypoxia and Inflammation in Children with Sickle Cell Disease: Implications for Hippocampal Functioning and Episodic Memory

Abstract

Children with sickle cell disease (SCD) suffer from systemic processes (e.g., chronic anemia, recurrent hypoxic-ischemic events, chronic inflammation) that have been associated with neurocognitive impairment in a range of clinical populations, but which have been largely understudied in relation to specific domains of cognitive functioning in children with SCD. This review focuses on episodic memory, as the hippocampus may be especially vulnerable to the systemic processes associated with SCD. The first part of the paper outlines the pathophysiology of SCD and briefly reviews the extant literature on academic and cognitive functioning in children with SCD, emphasizing the dearth of research on episodic memory. Next, the complex systemic processes of hypoxia and inflammation associated with SCD are reviewed, along with research that has associated these processes with hippocampal damage and memory impairment. The paper concludes with suggestions for future research that are informed, in part, by the literature on developmental amnesia.

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

“…Cognitive deficits in individuals with SCD are well documented . Prior research, however, has been mixed as to whether medical treatments influence cognition in individuals with SCD .…”

Cognitive and behavior deficits in sickle cell mice are associated with profound neuropathologic changes in hippocampus and cerebellum

“…In conclusion, several pathologic underpinnings of SCD, such as iron dyshomeostasis, chronic anemia, inflammation, recurrent episodes of tissue hypoxia and ischemia and reperfusion due to vaso-occlusion, acute and chronic pain, and sensitization of sensory nerve fibers, can potentially impact cerebral function(Andreotti et al, 2014; Iampietro et al, 2014; van Beers et al, 2015; Vichinsky et al, 2010). Here we described cognitive deficits, emotional behavior and mood changes, and reduced voluntary exercise capacity in two humanized SCD mouse strains.…”

Cognitive functioning in children from Nigeria with sickle cell anemia

“…While the adverse impact of both types of strokes on cognitive development in SCA has been reported in multiple studies, cognitive impairment may also occur in the absence of stroke, suggesting that other factors may contribute to its pathogenesis. Disease‐related risk factors such as hypoxia and lower hemoglobin levels have been demonstrated to be independent predictors, but they do not completely predict cognitive functioning in SCA . Nutritional status has been shown to be associated with cognitive functioning in children and adults in general, but not particularly in children with SCA.…”