Using Multiple Biological Markers to Measure Sickle-Cell Disease Severity and Cognitive Risk

Sickle-cell disease (SCD) is associated with neurological complications including brain perfusion deficits and tissue infarction, which can lead to cognitive deficits early in life. Timely assessment and detection of these deficits is critical for effective intervention. Biological measures of disease severity may serve as clinical markers of neurological complications; however the relationship between such markers and cognitive deficits in this population remains unclear. Mixed evidence for the relationship may have resulted due to the use of too few measures to assess a broad and complicated construct. Moreover, most studies have considered each measure in isolation rather than in combination with other clinical markers. Lastly, recent evidence suggests that SCD may consist of two clinical sub-phenotypes, whereas previous studies have treated SCD severity as a unitary construct. This study aimed to examine the relationship between biological measures of disease severity and cognitive deficits in children with SCD. We employed a classical measurement approach to construct a disease severity scale for each sub-phenotype, and assessed whether a two-dimensional model of disease severity could better account for the relationship with cognitive deficits than a one-dimensional model. In two samples, scores on the disease severity scale appeared to be more strongly associated with cognitive outcomes than individual biological measures and better predictors of whether one has cognitive deficits. A unitary view of disease severity appeared to be as a good as a two-dimensional model and more parsimonious