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White matter integrity and processing speed in sickle cell anaemia

By: Publication details: 2017Uniform titles:
  • Developmental Medicine and Child Neurology
Online resources: Summary: <span style="font-size: 10pt;">Background: Sickle cell anaemia is associated with silent cerebral infarction (SCI) and cognitive impairment. Cognitive impairment in the absence of SCI is poorly understood, but may relate to white matter abnormalities. Method: 37 patients with SCI (median age: 16.34, 8-36 years), 46 patients reported radiologically as normal (median age: 14.62, 8-37 years), and 32 sibling controls (median age: 15.26, 8-30 years), underwent cognitive assessment using the Wech-sler intelligence scales and 3T MRI with a multi-shell diffusion-weighted sequence. Tract-based spatial statistics analyses of diffusion tensor (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed. Results: Processing speed index (PSI) was lower in patients than controls by 9.34 standard scaled points (95% CI: 4.635-14.855, p=0.0002546), and there was a trend for lower full-scale intelligence (FSIQ) by 4.14 standard scaled points (95% CI:-1.067 to 9.551, p=0.1012), which diminished when PSI was included as a covariate. There were no differences between patients with and without SCI, and both groups had significantly lower PSI than controls (both p<0.001). In patients, severity of hypoxaemic exposure and socio-economic status were identified as independent predictors of PSI, and correlations were found between PSI and DTI (fractional ani-sotropy r=0.614, p<0.00001; r=-0.457, p<0.00001; mean diffu-sivity r=-0.341, p=0.0016; radial diffusivity r=-0.457, p<0.00001) and NODDI parameters (intracranial volume fraction r=0.364, p=0.0007) in widespread regions, including the corpus callosum, corona radiata, and inferior and superior longitudinal fasciculi, irrespective of the presence of SCI. Conclusions: These results confirm and extend previous reports of cognitive impairment in SCA that is independent of presence infarction and may worsen with age. The data identify processing speed as a particularly vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide the first evidence that reduced processing speed is related to the integrity of normal-appearing white matter using quantitative microstructure parameters from multi-shell diffusion MRI.&nbsp;</span>
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&lt;span style="font-size: 10pt;"&gt;Background: Sickle cell anaemia is associated with silent cerebral infarction (SCI) and cognitive impairment. Cognitive impairment in the absence of SCI is poorly understood, but may relate to white matter abnormalities. Method: 37 patients with SCI (median age: 16.34, 8-36 years), 46 patients reported radiologically as normal (median age: 14.62, 8-37 years), and 32 sibling controls (median age: 15.26, 8-30 years), underwent cognitive assessment using the Wech-sler intelligence scales and 3T MRI with a multi-shell diffusion-weighted sequence. Tract-based spatial statistics analyses of diffusion tensor (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed. Results: Processing speed index (PSI) was lower in patients than controls by 9.34 standard scaled points (95% CI: 4.635-14.855, p=0.0002546), and there was a trend for lower full-scale intelligence (FSIQ) by 4.14 standard scaled points (95% CI:-1.067 to 9.551, p=0.1012), which diminished when PSI was included as a covariate. There were no differences between patients with and without SCI, and both groups had significantly lower PSI than controls (both p&amp;lt;0.001). In patients, severity of hypoxaemic exposure and socio-economic status were identified as independent predictors of PSI, and correlations were found between PSI and DTI (fractional ani-sotropy r=0.614, p&amp;lt;0.00001; r=-0.457, p&amp;lt;0.00001; mean diffu-sivity r=-0.341, p=0.0016; radial diffusivity r=-0.457, p&amp;lt;0.00001) and NODDI parameters (intracranial volume fraction r=0.364, p=0.0007) in widespread regions, including the corpus callosum, corona radiata, and inferior and superior longitudinal fasciculi, irrespective of the presence of SCI. Conclusions: These results confirm and extend previous reports of cognitive impairment in SCA that is independent of presence infarction and may worsen with age. The data identify processing speed as a particularly vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide the first evidence that reduced processing speed is related to the integrity of normal-appearing white matter using quantitative microstructure parameters from multi-shell diffusion MRI.&amp;nbsp;&lt;/span&gt;

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