Abstract
BACKGROUND: Dexamethasone is used in acute lymphoblastic leukemia (ALL) treatment, though long-term impact on central nervous system (CNS) function is unclear. As glucocorticoids influence hippocampal function, we investigated memory networks in survivors of childhood ALL treated with dexamethasone or prednisone. PROCEDURE: Neurocognitive assessment and functional magnetic resonance imaging (fMRI) were conducted in 38 adult survivors randomly recruited from cohorts treated on one of two standard treatment protocols, which differed primarily in the glucocorticoid administered during continuation therapy (dexamethasone [n = 18] vs. prednisone [n = 20]). Groups did not differ in age at diagnosis, age at evaluation, or cumulative intravenous or intrathecal methotrexate exposure. RESULTS: Survivors treated with dexamethasone demonstrated lower performance on multiple memory-dependent measures, including story memory (P = 0.01) and word recognition (P = 0.04), compared to survivors treated with only prednisone. Dexamethasone treatment was associated with decreased fMRI activity in the left retrosplenial brain region (effect size = 1.3), though the small sample size limited statistical significance (P = 0.08). Story memory was associated with altered activation in left inferior frontal-temporal brain regions (P = 0.007). CONCLUSIONS: Results from this pilot study suggest that adult survivors of ALL treated with dexamethasone are at increased risk for memory deficits and altered neural activity in specific brain regions and networks associated with memory function.