title: White matter integrity and core cognitive function in children diagnosed with sickle cell disease.
abstract: Children diagnosed with sickle cell disease (SCD) have an increased risk of stroke, often associated with white matter damage and neurocognitive morbidity. Growing evidence suggests that subtle changes in white matter integrity, which do not pass the threshold to be visible on a clinical magnetic resonance image and classified as stroke, may contribute to decreased cognitive performance. We used archived diffusion-weighted imaging and neurocognitive assessment data to identify associations between microstructural changes in normal-appearing white matter and cognitive performance in children with SCD. Study participants included 10 healthy children and 15 pediatric SCD patients (5 with identified lesions and 10 without lesion). After excluding lesioned tissue from analyses, we detected significant increases in apparent diffusion coefficient across the brains of patients in comparison with control children, suggesting compromise to the structure of normal-appearing white matter. Deficits in working memory and processing speed were also apparent in patients. Increased apparent diffusion coefficient and deficiencies in processing speed were again detected in a subanalysis including only the patients without lesion. Correlation analyses evidenced associations between the microstructure of the right frontal lobe and cerebellum, and processing speed. This outcome suggests a relationship between tissue integrity and cognitive morbidity in SCD patients.
authors.affiliation: Program in Neuroscience and Mental Health Department of Psychology, Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Scantlebury
authors.forename: Donald
authors.initials: D
authors.lastname: Mabbott
authors.forename: Laura
authors.initials: L
authors.lastname: Janzen
authors.forename: Conrad
authors.initials: C
authors.lastname: Rockel
authors.forename: Elysa
authors.initials: E
authors.lastname: Widjaja
authors.forename: Garland
authors.initials: G
authors.lastname: Jones
authors.forename: Melanie
authors.initials: M
authors.lastname: Kirby
authors.forename: Isaac
authors.initials: I
authors.lastname: Odame
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000473:pathology* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology*; D002648:Child; D003071:Cognition; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008297:Male; D012044:Regression Analysis; D012189:Retrospective Studies