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.
Methods
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. Tract-based spatial statistics analyses of diffusion tensor imaging (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 points (95% confi-
dence 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.
Conclusion
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 DTI and NODDI
