Stotesbury, Hanne, Kirkham, Fenella, Koelbel, Melanie, Balfour, Philippa, Clayden, Jonathan D., Sahota, Sati, Sakaria, Simrat, Saunders, Dawn E, Howard, Jo, Kesse-Adu, Rachel, Inusa, Baba, Pelidis, Maria, Chakravorty, Subarna, Rees, David C, Awogbade, Moji, Wilkey, Olu, Layton, Mark, Clark, Christopher A and Kawadler, Jamie M (2018) White matter integrity and processing speed in sickle cell anemia. Neurology, 90 (23), e2042-e2050. (doi:10.1212/WNL.0000000000005644).
Abstract
Objective: The 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 (SCA). Method: 37 patients with silent cerebral infarction (SCI), 46 patients with normal MRI, and 32 sibling controls (age range 8-37 years), underwent cognitive assessment using the Wechsler scales and 3T MRI. Tract-based spatial-statistics analyses of diffusion tensor (DTI) and neurite orientation dispersion and density imaging parameters (NODDI) were performed. Findings: Processing speed index (PSI) was lower in patients than controls by 9.34 points (95% CI: 4.635-14.855, p=0.0003). FSIQ was lower by 4.14 scaled points (95% CI: -1.066-9.551, 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 SCI, and both groups had lower PSI than controls (both p<0.001). In patients, arterial oxygen content, socio-economic 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. Conclusion: Our results extend previous reports of impairment that is independent of presence infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provideevidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI.
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