Abstract

Objective:Executive functioning (EF) and socioeconomic status (SES) are associated with functional outcomes (adaptive functioning and academic achievement) in healthy controls and pediatric populations with executive dysfunction. However, these relationships have yet to be investigated in survivors of childhood acute lymphoblastic leukemia (ALL), a population with EF impairment resulting from disease and treatment characteristics. The objective of this study was to examine the associations of functional outcomes with EF and SES (neighborhood-specific variables and academic support) in survivors of childhood ALL.Participants and Methods:Forty-four participants (38.6% female, 72.7% non-Hispanic White, ages 6-17) previously diagnosed with low-risk or standard-risk pre-B cell ALL and treated with chemotherapy-only were included. Participants were evaluated on performance-based measures of EF (cognitive flexibility, verbal fluency, working memory, and processing speed) and academic achievement (word reading and math calculation), and parent-ratings of EF and adaptive functioning. All measures were expressed as T-scores with lower scores indicating better performance. Neighborhood-specific variables were based on participants’ zip codes and census block group, and included area deprivation index (ADI) and child opportunity index (COI). Lower ADI and COI indicate lesser deprivation and greater opportunity. Individualized education plan (IEP) status was used as a proxy of academic support, coded dichotomously as with or without IEP. Percentages of participants showing impairments in functional outcomes were calculated using a cutoff of > 1 SD above the normative mean. Partial correlations were conducted while controlling for age at evaluation, age at diagnosis, sex, and verbal IQ, to examine whether participants with poorer performance-based and parent-rated EF would show reduced functional outcomes. Multiple regression analyses were conducted to evaluate whether neighborhood-specific variables and IEP status would predict functional outcomes while controlling for covariates.Results:Compared to population norms, survivors of childhood ALL showed worse functional outcomes. Within adaptive functioning, 45.5% of participants showed impairment in activities of daily living and leadership. Adaptive functioning was significantly positively correlated with parent-rated, but not performance-based, EF (r=0.694, p<0.001). Compared to female survivors, male survivors were at increased risk for adaptive functioning difficulties (r=-0.401, p<0.05). Impairments for word reading and math calculation were 25% and 41.7%, respectively. Greater math calculation was associated with better verbal fluency (r=0.378, p<0.05) and processing speed (r=0.439, p<0.05). Older participants at evaluation (/3=-0.580, p<0.001) and those without IEP support (ß=0.465, p<0.05) showed better word reading. Lower ADI predicted better verbal fluency (ß=0.282, p=0.041), however, neighborhood-specific variables were not associated with functional outcomes.Conclusions:Prior findings indicate that performance-based measures and parent-ratings assess different constructs of EF. Thus, adaptive functioning may relate more to the behavioral construct of EF than its cognitive construct. Current findings also suggest that male survivors are at increased risk for reduced adaptive functioning, consistent with recent reports that male survivors of ALL are at greater risk for specific neurocognitive outcomes. Overall, functional outcomes may be more strongly related to EF than neighborhood-specific variables. Long-term goals include early screening of adaptive and academic difficulties, targeted intervention, and neuropsychological monitoring to support pediatric survivors’ neurocognitive and psychosocial development.

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