Wentao Lai, Guanlin Huang, Min Zou, Jingdong Zhang, Jing Hu
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.
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 < 26). Over 12 month median follow up, 44.1% discontinued. Total effect of mRS 3-5 (vs. 0-2) was HR 3.42 (95% CI 2.05-5.72). Decomposition yielded NDE 2.08 (1.13-3.84) and NIE 1.64 (1.17-2.32), with 42.1% (15.4%-68.4%) mediated via cognition. Sensitivity analyses produced consistent estimates (NIE range 1.25-1.55; mediated proportion 35.8%-38.9%); E-value for NIE was 2.66 (lower CI 1.62).
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.