Executive dysfunction is associated with poorer health-related quality of life in pediatric brain tumor survivors.

Children with a brain tumor (BT) are at risk for a number of physical and cognitive problems that may lower their health-related quality of life (HRQoL). Executive functioning (EF) and intellectual ability are hypothesized to associate with HRQoL and deficits in these areas may be amenable to interventions. This study aimed to investigate intellectual function, EF, and HRQoL following conformal radiation therapy (CRT) for pediatric BT. Forty-five BT survivors (age 12.68 ± 2.56) treated with CRT participated. Thirty-six siblings of BT patients (age 12.36 ± 2.13) and 33 survivors of non-CNS solid tumors (ST; age 12.18 ± 2.88) were comparison groups. IQ estimate (Wechsler Abbreviated Scale of Intelligence; WASI), EF ratings (Behavior Rating Inventory of Executive Function; BRIEF), and HRQoL ratings (KINDL-R) were obtained. BT survivors reported lower overall HRQoL than ST survivors (p = .012). Parents reported lower overall HRQoL for BT survivors than siblings (p = .014). Parent-report on individual areas of HRQoL was higher than self-report for most subscales. IQ and HRQoL ratings were not related (Parent r = .17, p = .27; Child r = .11, p = .49). EF ratings correlated with Parent (r = -.15 to -.73) but not Child HRQoL ratings. Children with BT experienced poorer HRQoL than controls. Children's HRQoL was consistently rated higher by parent- than self-report across all domains. HRQoL was associated with EF, but not with IQ. These findings identify interventions targeting EF (e.g., cognitive rehabilitation, medication) as a possible avenue for improving HRQoL in childhood BT survivors.

Adaptive functioning of childhood brain tumor survivors following conformal radiation therapy.

Adaptive functioning is not often examined in childhood brain tumor (BT) survivors, with the few existing investigations relying on examiner interviews. Parent questionnaires may provide similar information with decreased burden. The purpose of this study was: (1) to examine adaptive behaviors in BT survivors relative to healthy peer and cancer survivor groups, and (2) to explore the validity of a parent questionnaire in relation to an examiner administered interview. Participants (age 13.11 ± 2.98 years) were BT survivors treated with conformal radiation therapy (n = 50), healthy siblings of BT survivors (n = 39) and solid tumor (ST) survivors who did not receive CNS-directed therapy (n = 40). Parents completed the Adaptive Behavior Assessment System­2nd Edition (ABAS-II). For a subset of the BT cohort (n = 32), examiners interviewed the parents using the Vineland Adaptive Behavior Scales (VABS) within 12 months. Groups differed significantly on each of the ABAS-II indices and the general adaptive composite, with the BT group scoring lower than the sibling and ST groups across indices. Executive functioning, but not IQ, was associated with adaptive skills; no clear pattern of clinical and demographic predictors was established. VABS scores were correlated with ABAS-II scores on nearly all indices. BT survivors showed significantly lower adaptive functioning when compared to healthy and cancer controls. The ABAS-II proved sensitive to these behavioral limitations and was consistent with scores on the VABS. The use of a parent questionnaire to assess adaptive functioning enhances survivorship investigations by increasing flexibility of assessment and decreasing examiner burden.

The impact of attention on social functioning in survivors of pediatric acute lymphoblastic leukemia and brain tumors.

BACKGROUND: The cognitive late effects experienced by many survivors of pediatric acute lymphoblastic leukemia (ALL) and brain tumors are well-established. The most commonly reported deficit is difficulty with attention. Problems with social functioning have also been identified, but their relationship with cognitive functioning is not well understood. This multi-site, cross-sectional study aimed to examine the impact of attention on social functioning. PROCEDURE: Four hundred sixty nine survivors of ALL and brain tumors (55% ALL; 57% male) completed study procedures, including parent- and teacher-report measures of attention (Conners' Rating Scales, Revised) and parent-report of social functioning [Social Skills Rating System (SSRS)] as part of their screening evaluation for a large clinical trial. Survivors were 12.1 years of age and 4.9 years from the end of treatment at the time of study. RESULTS: Results revealed that survivors' parent-reported attention problems were uniquely associated with their social functioning, relative to known demographic- and treatment-related risk factors. Teacher-reported attention problems, in contrast, were not, despite a significant correlation between the two. Deficits in intelligence and female gender were also significantly associated with poor social functioning. CONCLUSIONS: Attention problems uniquely impact difficulties with social functioning in survivors of pediatric cancer. Future studies will need to further examine the relationship between attention and social functioning in survivors, particularly when assessed by teacher report. Pediatr Blood Cancer 2012; 59: 1290-1295. © 2012 Wiley Periodicals, Inc.

Parent and teacher ratings of attention during a year-long methylphenidate trial in children treated for cancer.

OBJECTIVE: Longitudinally examine attention performance in childhood cancer survivors prescribed methylphenidate (MPH) to ameliorate cognitive late effects, comparing measures for inter-rater and inter-method discrepancies. METHODS: Survivors of acute lymphoblastic leukemia (n = 33) or brain tumor (n = 35), mean age 11.11 ± 0.37 years, completed a 12-month, open-label trial of MPH. Conners' Parent and Teacher Rating Scales were completed at baseline, 1, 3, 6, and 12 months. The Conners' Continuous Performance Test (CPT) was completed at baseline and 12 months. RESULTS: Improved attention was reported after 1 month of MPH (p < .05), with relative stability throughout the trial. Inter-rater agreement was low-to-moderate (ICC = -.06 to .46). Observer ratings correlated with select CPT indices at baseline (p < .05), but not at 12 months. CONCLUSIONS: Childhood cancer survivors' attention improved after 1 month on MPH. Modest agreement between parents and teachers, and low-to-moderate correlations between behavior ratings and performance-based attention measures highlight a need for multimodal assessment.

Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma.

PURPOSE: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. METHODS AND MATERIALS: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. RESULTS: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. CONCLUSIONS: There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before the initiation of irradiation suggested that other factors influence functional outcomes above and beyond the effects of irradiation.

A 5-year investigation of children's adaptive functioning following conformal radiation therapy for localized ependymoma.

PURPOSE: Conformal and intensity modulated radiation therapies have the potential to preserve cognitive outcomes in children with ependymoma; however, functional behavior remains uninvestigated. This longitudinal investigation prospectively examined intelligence quotient (IQ) and adaptive functioning during the first 5 years after irradiation in children diagnosed with ependymoma. METHODS AND MATERIALS: The study cohort consisted of 123 children with intracranial ependymoma. Mean age at irradiation was 4.60 years (95% confidence interval [CI], 3.85-5.35). Serial neurocognitive evaluations, including an age-appropriate IQ measure and the Vineland Adaptive Behavior Scales (VABS), were completed before irradiation, 6 months after treatment, and annually for 5 years. A total of 579 neurocognitive evaluations were included in these analyses. RESULTS: Baseline IQ and VABS were below normative means (P<.05), although within the average range. Linear mixed models revealed stable IQ and VABS across the follow-up period, except for the VABS Communication Index, which declined significantly (P=.015). Annual change in IQ (-.04 points) did not correlate with annual change in VABS (-.90 to +.44 points). Clinical factors associated with poorer baseline performance (P<.05) included preirradiation chemotherapy, cerebrospinal fluid shunt placement, number and extent of surgical resections, and younger age at treatment. No clinical factors significantly affected the rate of change in scores. CONCLUSIONS: Conformal and intensity modulated radiation therapies provided relative sparing of functional outcomes including IQ and adaptive behaviors, even in very young children. Communication skills remained vulnerable and should be the target of preventive and rehabilitative interventions.

Amnestic mild cognitive impairment: diagnostic outcomes and clinical prediction over a two-year time period.

Amnestic mild cognitive impairment (MCI) has been defined as a precursor to Alzheimer's disease (AD), although it is sometimes difficult to identify which persons with MCI will eventually convert to AD. We sought to predict MCI conversion to AD over a two-year follow-up period using baseline demographic and neuropsychological test data from 49 MCI patients. Using a stepwise discriminant function analysis with Dementia Rating Scale (DRS) Initiation/Perseveration and Wechsler Memory Scale, third edition (WMS-III) Visual Reproduction Percent Retention scores, we correctly classified 85.7% of the sample as either AD converters or MCI nonconverters, with 76.9% sensitivity and 88.9% specificity. Adding race, the presence of vascular risk factors, or cholinesterase inhibitor use to the analysis did not greatly change the classification rates obtained with neuropsychological test data. Examining neuropsychological test cutoff scores revealed that DRS Initiation/Perseveration scores below 37 and Visual Reproduction Percent Retention scores below 26% correctly identified AD converters with 76.9% sensitivity and 91.7% specificity. These results demonstrate that commonly administered neuropsychological tests identify persons with MCI at baseline who are at risk for conversion to AD within 1-2 years. Such methods could aid in identifying MCI patients who might benefit from early treatment, in providing prognostic information to patients, and identifying potential clinical trial participants.