White matter structural connectivity could modify altered blood oxygenation that predisposes patients with sickle cell disease (SCD) to impaired cognitive function, according to a study recently published in Blood Advances.

“Our data suggest that cognitive dysfunction is mediated by potentially reversible hypoxic–ischemic effects on networks in normal appearing white matter, and highlight the need to move beyond a focus on the presence or absence of silent cerebral infarction in this vulnerable population,” the authors wrote. 

This research included 92 patients with SCD and 54 healthy controls. All participants underwent intelligence quotient (IQ) assessments and monitoring of oxygen saturation with fingertip pulse oximeters during the daytime on the same day.

Individuals also underwent brain magnetic resonance imaging with a graph-theoretical analysis to observe areas of possible past silent cerebral infarctions and structural connectivity of the brain.

As expected, progressive decreases in oxygen saturation correlated with lower streamline weighted efficiency, negatively affecting the processing speed index.

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Furthermore, blood oxygenation negatively correlated with cognition, and path analysis revealed that this mechanism could be under the mediation of network characteristics. For example, the efficiency of structural connectivity showcased indirect associations with decreased oxygen saturation and the processing speed index. These network pathways observed in patients with SCD differed from those of individuals in the control group.

Similar to the processing speed index, the working memory index exhibited negative effects related to streamline-weighted subnetwork efficiency, fractional anisotropy-weighted full network, and subnetwork efficiency. Finally, silent cerebral infarcts did not seem to be affected in terms of number or volume.

This study demonstrated debilitated white matter connectivity among patients with SCD compared to that healthy individuals and that this situation further mediates the effects of oxygen saturation on processing speed, as explained by Kirkham and colleagues. 

“Measures of structural brain connectivity may serve as useful biomarkers to monitor disease trajectories and study therapeutic interventions,” the researchers concluded.


Kirkham FJ, Clayden JD, Stotesbury H, et al. Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia. Blood Adv. Published online August 10, 2022. doi:10.1182/bloodadvances.2021006751