Altered cerebral blood flow and functional connectivity in sickle cell disease

Adults with sickle cell disease (SCD) often experience cognitive deficits and chronic pain, but the cerebral mechanisms underlying these symptoms remain unclear. Elevated cerebral blood flow (CBF) is a compensatory response to anemia, yet its impact on brain function and perception is not well understood.

To examine alterations in cerebral perfusion and resting-state brain function in adults with SCD and their associations with cognition and pain sensitivity.

Seven adults with SCD and 3 healthy controls underwent arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI). Metrics included global/regional CBF, resting-state functional connectivity (rsFC), and amplitude of low-frequency fluctuations (ALFF). Participants completed NIH Toolbox fluid cognition tests and the Pain Sensitivity Questionnaire (PSQ).

SCD patients exhibited significantly higher global CBF (72.1 vs. 47.2 mL/100g/min; P = .04), reduced cortical zALFF (P = .0013), and elevated white-matter zALFF (P = .0023). They also showed resting-state network hyperconnectivity, with diminished anti-correlations between the default mode and salience networks. SCD participants scored lower on processing speed (P = .02) and reported higher pain sensitivity (PSQ total, P = .0040). Higher CBF was associated with slower cognitive performance but not directly with pain sensitivity. Exploratory mediation models suggested that altered brain activity may partially mediate this relationship.

Adults with SCD demonstrate cerebral hyperperfusion, disrupted functional connectivity, and altered spontaneous brain activity, which may contribute to cognitive slowing and heightened pain sensitivity. These findings highlight the need for further research into brain-targeted therapies in SCD.