Abstract
Background
Neurological deficits after spontaneous intracerebral hemorrhage (ICH) are linked to treatment discontinuation in acute leukemia patients, but underlying mechanisms are unknown. We tested whether cognitive impairment mediates this relationship.
Methods
In this single-center retrospective cohort study (2016–2024), we included 102 acute leukemia patients who survived ≥6 months post-ICH and remained on hematologic treatment at the 6 month landmark. Neurological deficit at discharge [modified Rankin Scale (mRS), 0–2 vs. 3–5] was the exposure; MoCA score at 6 months was the mediator; time to permanent treatment discontinuation (non progression) was the outcome. We applied counterfactual mediation analysis with 1,000 bootstraps, reporting natural direct/indirect effects (NDE/NIE) as hazard ratios (HRs). We tested the proportional hazards assumption, quantified inter-rater agreement for outcome adjudication, and performed sensitivity analyses (continuous exposure, binary mediator, competing risks, and E-value).
Results
Mean MoCA was 22.0 (SD 5.2); 48.0% had impairment (MoCA
Conclusions
In this cohort of 6-month ICH survivors with acute leukemia, cognitive impairment was estimated to mediate 42.1% of the neurological deficit effect on hematologic treatment discontinuation. These findings are hypothesis-generating and suggest that post-ICH cognitive dysfunction may be a modifiable mechanism. Cognitive screening and early rehabilitation may warrant integration into post-ICH care; prospective trials are needed to test whether cognitive interventions improve treatment persistence.