Abstract
ObjectiveThe purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia.MethodsThirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed.ResultsProcessing speed index (PSI) was lower in patients than controls by 9.34 points (95% confidence interval: 4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval: −1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions.ConclusionOur results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI.
Highlights
Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls underwent cognitive assessment using the Wechsler scales and 3-tesla MRI
Our results extend previous reports of impairment that is independent of presence of infarction and may worsen with age
We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI)
Summary
Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Participants were recruited and assessed between 2015 and 2016. Cognitive variables Full Scale IQ (FSIQ) was measured using the Wechsler Abbreviated Scale of Intelligence (WASI-II subscale IQ; POMS patients), Wechsler Intelligence Scale for Children (WISCIV; SAC patients and controls younger than 16 years), or the Wechsler Adult Intelligence Scale (WAIS-IV; SAC patients and controls 16 years or older). Strong correlations have been demonstrated between editions (WASI/WAIS/WISC) and between the child and adult versions (WISC/WAIS), justifying their inclusion in the same analyses.[24,25] Assessments were double-scored by trained assessors (J.M.K., M.K., H.S., P.B.) that were blinded to disease status. In the event of disagreement or ambiguity, the opinion of a third assessor was sought
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