Silent cerebral infarctions (SCIs) were not associated with cognitive performance or impairment among patients with sickle cell anemia (SCA), according to the results of a study published in Frontiers in Neurology.

Patients with SCA are at risk of SCI, with this risk increasing as patients age. Presence of SCI by low resolution sequences has been associated with cognitive impairment and the use of SCI as a biomarker of cognitive impairment has been discussed. The aim of this study was to evaluate the potential clinical utility of SCI as a biomarker of cognition.

“These findings expose the challenges associated with the widespread use of SCI presence as a biomarker of white-matter injury and cognitive dysfunction in cross-sectional high-resolution MRI studies in patients with SCA,” the authors wrote in their report.

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The study included 106 patients with SCI and 48 controls of siblings or race-matched peers aged 8 to 30 who underwent 3T MRI with high-resolution fluid attenuated inversion recovery (FLAIR) sequence. IQ was measured using Wechsler subtests.

The prevalence of SCI among patients ranged from 24% to 42% and from 4% to 23% among controls, with differences due to varying definitions of lesion metrics.

IQ differed between the groups, with patients with SCA demonstrating scores lower by 7 WMI points (P <.005), 8 PSI points (P <.005), and 4 IQ points (P =.06) resulting in moderate to large effect sizes on cognition. There were 11.3% of patients with SCA who had cognitive impairment compared with 4.2% of patients in the control group.

However, cognition was not affected by any global metric of SCI and regional SCI metrics were associated with cognitive effects of small magnitude.

“Contrary to hypotheses, neither the presence, nor the total number, nor the total volume of lesions based on any SCI definition predicted general cognitive performance or impairment,” the authors wrote.

The authors concluded, “Our results highlight the challenges surrounding SCI definition and quantification and suggest limited utility of SCI metrics as biomarkers of cognitive dysfunction.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Stotesbury H, Kawadler JM, Clayden JD, et al. Quantification of silent cerebral infarction on high-resolution FLAIR and cognition in sickle cell anemia. Front Neurol. 2022;13:867329. doi: 10.3389/fneur.2022.867329