Cognitive and physical disability after traumatic brain injury in patients with sickle cell disease: A national cohort study from the all of us research program

Abstract Background: Traumatic brain injury (TBI) in patients with sickle cell disease (SCD) has never been studied despite potential biological plausibility for overlapping mechanisms for damage between TBI and SCD. Murine models of SCD demonstrate impaired motor recovery and metabolic derangements post-TBI, but human data validating these deficits are lacking. We investigated whether patients with SCD-TBI experience worsened long-term functional outcomes compared to TBI-only patients using national cohort data. Methods: We utilized the All of Us Research Program (AoURP), a large national biobank with linked surveys and electronic health records, to identify patients with a history of TBI, defined by ICD-9/10 criteria. We assessed baseline demographics, injury characteristics, and functional outcomes five years post-injury using patient-reported survey data. Functional domains included cognitive limitations, mobility, self-care, health literacy, access to care, and ability to manage work responsibilities. Chi-squared and t-tests were used to compare groups; p<0.05 was considered significant. Results: A total of 5270 patients were identified with TBI, of which 243 (4.6%) had SCD. Compared to TBI-only patients, the SCD-TBI cohort was younger (42.3 ± 14.7 vs 45.6 ± 15.3 years, p=0.028), more likely to be Black (75.3% vs 18.1%, p<0.001), but was similar in gender distribution and insurance status. SCD-TBI patients reported significantly higher rates of difficulty concentrating or deciding (30.6% vs 23.3%, p=0.0047), reading health-related materials (45.7% vs 38.1%, p=0.0072), and accessing transportation (17.3% vs 10.8%, p=0.0412). They were also more likely to live in areas with poor care access (9.0% vs 3.8%, p=0.019) and report difficulty getting time off work (11.9% vs 5.4%, p=0.008). Trends toward greater difficulty dressing/bathing (10.8% vs 7.7%, p=0.0753), walking or climbing stairs (25.9% vs 21.2%, p=0.0598), and doing errands alone (17.5% vs 13.7%, p=0.0779) were also observed. Conclusions: This is the first study to quantify long-term functional disability in SCD patients following TBI using a national cohort. SCD-TBI patients experienced higher rates of cognitive, physical, and care access limitations five years after injury despite similar insurance status. These findings mirror murine models of SCD-TBI, which demonstrate impaired recovery and systemic dysfunction post-injury. Our data highlight an urgent need for longitudinal surveillance, tailored rehabilitation, and improved health system navigation strategies for this uniquely vulnerable population. Future studies should investigate mechanisms of delayed neurorecovery and identify interventions to mitigate long-term disability in patients with SCD following head trauma.