Sublingual Microvascular Findings in Sickle Cell Disease and Correlation with Cognition: A Pilot Study

Background: In sickle cell disease (SCD), microvascular disease affects all organs, including the brain, and can result in cognitive impairment. We conducted a pilot study using sublingual imaging (SI) to examine differences in sublingual microvasculature between patients with SCD and controls, and whether these differences were associated with cognition. Methods: Eligibility included age 18-65 with or without SCD. We used GlycoCheck™, a non-invasive device that assesses microvascular health, to measure the following SI-derived measures: vessel density (VD), the number of capillaries filled with blood; perfused boundary region (PBR; higher is worse), the part of the endothelial glycocalyx (EGX) accessible to the blood film; and red blood cell filling percentage (RBCFP), the median percentage of time that RBCs are present at each measurement point. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Delis-Kaplan Executive Function System (D-KEFS). We used Cohen’s d (d) to test the standardized difference between means, and Kendall’s rank correlation coefficient (τ) to test for correlations. Results: We enrolled 16 participants (n=9 with SCD, n=7 controls; age, 50.1±11.0; 43.8% female; 87.0% with at least some college education). Among participants screened, 85% enrolled in the study. PBR was higher in patients (2.2 µm vs 2.0 µm, d=0.7, p=0.20). Patients had lower mean VD (417.0 vs 515.1, d=-0.7, p=0.35) and RBCFP (69.0% vs 72.1%, d=-0.4, p=0.40). Average D-KEFS scores were similar (9.8 vs 9.3, d=0.2, p=0.71) as were the total RBANS scores (95.1 vs 93.0, d=0.2, p=0.86). There were weak to no correlations between PBR and the RBANS total scale for both patients (τ=0.03, p=0.92) and controls (τ=0.2, p=0.72) as well as between PBR and D-KEFS score (τ= 0.03, p= 0.92 vs τ=0.2, p=0.54). Conclusion: Patients with SCD had lower but nonsignificant EGX, VD, and RBCFP and SI was feasible in this patient group. There were weak or no correlations between EGX and cognition in SCD. Future larger studies with enough power to detect these differences should be carried out to confirm these results. This study paves way for improved screening of microvessel disease in SCD to promote public health.