Attention and working memory abilities in children treated for acute lymphoblastic leukemia

Abstract

To extend investigation beyond global cognitive measures prevalent in the literature, this study examined attention and working memory (WM) abilities of survivors of childhood acute lymphoblastic leukemia (ALL), the separate contributions of attention and WM to intelligence quotient (IQ), and their association with neuroimaging changes. Ninety-seven children with ALL received risk-directed therapy based on presenting clinical and biological factors. During consolidation therapy, low-risk patients received half the dose of intravenous methotrexate that standard-risk/high-risk patients received, and fewer doses of triple intrathecal therapy. Patients were classified according to end of consolidation magnetic resonance imaging scans (normal or leukoencephalopathy), and continuous measures of white matter structure were computed. As part of the protocol study, children completed cognitive assessment 2 years later (completion of therapy), using Digit Span Forward (DSF) for attention and Digit Span Backward (DSB) for WM. For the total sample and the standard-/high-risk group, Total Digit Span (TDS), DSF, and DSB were impaired relative to norms (P<.05). In the low-risk group, only DSB was impaired (P<.0001). Across groups, a higher percentage of patients performed below the average range (scale score<7) on DSB (66%) compared with the DSF (14%) or TDS (18%). Regression analysis indicated that DSB predicted estimated IQ (P<.05), after accounting for DSF. Leukoencephalopathy was predictive of lower TDS (P<.05). WM appears to be especially sensitive to treatment-related changes in ALL survivors, detecting difficulties potentially missed by global intelligence measures. These findings may facilitate the identification of vulnerable neural pathways and the development of targeted cognitive interventions.