Cerebral Blood Flow in Children and Adults With Sickle Cell Anemia

Understanding age-related changes in cerebral blood flow (CBF, rate of blood delivery to brain tissue) in sickle cell anemia (SCA) is a prerequisite to incorporating CBF as a marker of brain health. CBF decreases from school-age through adulthood in nonanemic people. In SCA, CBF is generally increased to compensate for anemia, but knowledge of age-related norms is limited. We hypothesized that age-related CBF trajectories differ for SCA vs nonanemic healthy persons: CBF increases from childhood to early adulthood in SCA to compensate for reduced blood oxygen content and then plateaus because of reduced vasodilatory capacity with older age.

Children and adults with SCA and race-matched controls (hemoglobin [Hb] AA) aged 6-45 years were enrolled in an observational cross-sectional study from 2014 to 2023 at an academic and community health center. History of overt stroke or arterial stenosis >50% were exclusions. Brain MRIs were performed at 3T with arterial-spin-labeling measurements of gray matter CBF. Regression analyses assessed how age, imaging markers of ischemia, Hb, and arterial oxygen saturation (SpO₂) related to CBF.

In 192 Black participants with SCA (N = 126; mean age = 18.7 ± 9.0 years, 52.4% female) or without SCA (N = 66; mean age = 22.4 ± 9.7 years, 54.5% female), total Hb was lower in SCA (mean Hb = 8.9 ± 1.3 g/dL) vs control (mean Hb = 13.4 ± 1.5 g/dL) participants (p < 0.001) and did not differ with age in the SCA group. SpO₂ was reduced in SCA (median SpO₂ = 96%; interquartile range [IQR] = 94-97.4%) vs controls (median SpO₂ = 98%, IQR = 97-99%, p < 0.001). In SCA participants, SpO₂ was lower in adults (median SpO₂ = 95%, IQR = 94%-97%, p = 0.001) compared with children (SpO₂ = 96.5%, IQR = 95%-98.2%). Regression analyses, including an interaction between age and group (SCA vs control), showed that CBF increases in SCA by 5.03 mL/100 g/min per decade (95% CI 1.70-8.37) and plateaus at approximately age 30-35 years. In controls, CBF decreased by -5.20 mL/100 g/min per decade (95% CI -8.96 to -1.94).

The divergent age dependency of CBF between SCA and non-anemic persons may be explained by a gradient of increasing CBF with age required to compensate for reductions in blood oxygen content in SCA, with possible exhaustion of cerebral vasodilatory abilities in the fourth decade of life. Longitudinal studies are needed.