White matter integrity and processing speed in sickle cell anemia

Neurology. 2018 Jun 5;90(23):e2042-e2050. doi: 10.1212/WNL.0000000000005644. Epub 2018 May 11.


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% 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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / diagnostic imaging
  • Cerebral Infarction / diagnostic imaging
  • Cerebral Infarction / etiology*
  • Child
  • Cognition Disorders / etiology
  • Cross-Sectional Studies
  • Diffusion Magnetic Resonance Imaging
  • Disease Progression
  • Female
  • Humans
  • Imaging, Three-Dimensional
  • Male
  • Retrospective Studies
  • Social Class
  • White Matter / diagnostic imaging*
  • White Matter / physiopathology
  • Young Adult