Contribution of Fatigue to Cognitive Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors.

Late effects such as neurocognitive issues and fatigue have been reported in childhood acute lymphoblastic leukemia (cALL) survivors. Yet, their association is often poorly understood. In this study, we wished to (1) describe neurocognitive difficulties and fatigue in a well-characterized cohort of long-term cALL survivors and (2) explore the risk of having neurocognitive deficits as a function of fatigue. Childhood ALL survivors (N = 285) from three Canadian treatment centers completed the DIVERGT battery of cognitive tests and the PedsQL Multidimensional Fatigue Scale. We performed logistic regressions to assess the risk of a survivor to show cognitive deficits (<2.0 SD) depending on their fatigue levels. At least one cognitive deficit on the DIVERGT was present in 31% of participants. Domains primarily affected were working memory, fine motor skills, and verbal fluency. Sleep/rest fatigue in youths was higher than norms (d = 0.35). The risk for cognitive deficits increased independently with levels of fatigue in the domains of cognitive speed and flexibility, working memory, and verbal fluency. For every 10-point increase on general or sleep/rest fatigue on the 0-100 scale, there was a median +23-35% risk of showing a deficit among the 7 tasks significantly associated with fatigue. Fatigue may constitute a complementary target when searching to mitigate cognitive issues in this population.

Acceptability and Feasibility in a Pilot Randomized Clinical Trial of Computerized Working Memory Training and Parental Problem-Solving Training With Pediatric Brain Tumor Survivors.

OBJECTIVE: To evaluate the feasibility and acceptability of computerized working memory training in pediatric brain tumor survivors (PBTS) with cognitive deficits, as well as computerized working memory training that is enhanced with parental problem-solving skills training (PSST). METHODS: Twenty-seven PBTS (ages 7-16) recruited from a large, tertiary academic medical center were randomly assigned to computerized working memory training (Standard; n = 14) or computerized working memory training plus PSST (Combined; n = 13). PBTS completed a baseline assessment and parents completed acceptability surveys. Primary outcomes included number of intervention sessions completed and acceptability ratings. RESULTS: Fourteen of the 27 participants completed at least 20 sessions of the computerized training with average sessions lasting over an hour (M = 68.42 min, SD = 14.63). Completers had significantly better baseline auditory attention abilities than noncompleters. Parents reported both frustration and satisfaction related to the interventions and identified barriers to completing intervention sessions. CONCLUSIONS: This pilot randomized clinical trial raises significant questions related to the feasibility of computerized working memory training in PBTS with cognitive deficits. Findings also offer considerations for integrating family-based treatment approaches into cognitive remediation interventions for PBTS.

Family estimates of risk for neurocognitive late effects following pediatric cancer: From diagnosis through the first three years of survivorship.

BACKGROUND: Families often express a need for additional information about neurocognitive late effects (NCLE) after a pediatric cancer diagnosis. Therefore, we examined: (i) differences in parent, child, and oncologist estimates of risk for NCLE; (ii) whether the estimates of parents and/or children change over time; and (iii) whether estimates are different for children treated with central nervous system (CNS) directed therapies. PROCEDURE: Mothers, fathers, and children (initial age: 5-17, self-report: >10) from 258 families reported their perceived likelihood of the child developing "thinking/learning problems" on a visual analog scale (0-100%) at 2 months (T1), 1 year (T2), and 3 years (T3) following cancer diagnosis/relapse. Oncologists estimated the likelihood of NCLE at T1. Children were separated into groups based on CNS-directed treatment (n = 137; neurosurgery, intrathecal chemotherapy, and/or craniospinal radiation) or no CNS treatment. RESULTS: Mother, father, and child estimates of risk for NCLE were similar to oncologists and to one another around diagnosis (T1). Although there were no significant mean differences, a considerable subset of family members either underestimated their child's risk for NCLE (>40%) or overestimated the risk for NCLE (20%) in comparison to oncologists. At T2 and T3, the estimates of mothers were significantly higher than children. Linear growth curves indicated that mothers' estimates for children with CNS-directed treatment significantly increased throughout the first 3 years of survivorship. CONCLUSIONS: Considering that accurate understanding of NCLE is essential to seeking appropriate assessment and intervention, healthcare providers should focus on implementing family-based education early in treatment and throughout survivorship care.

Neurocognitive and psychosocial outcomes in survivors of childhood leukemia with Down syndrome.

OBJECTIVE: The primary aim of this study was to assess the feasibility of a developmentally tailored neurocognitive assessment in survivors of childhood acute leukemia with Down syndrome (DS-leukemia). A secondary aim was to compare outcomes in the DS-leukemia group to a historical comparison group of individuals with DS and no history of childhood cancer. METHODS: Survivors of DS-leukemia (n = 43; 56% male, mean [SD] age at diagnosis = 4.3 [4.5] years; age at evaluation = 15 [7.9] years) completed a neurocognitive assessment battery that included direct measures of attention, executive function, and processing speed, and proxy ratings of attention problems and executive dysfunction. Direct assessment outcomes were compared to a historical comparison cohort of individuals with DS and no history of childhood cancer (DS-control; n = 117; 56% male, mean [SD] age at evaluation = 12.7 [3.4] years). RESULTS: Rates of valid task completion ranged from 54% to 95%, suggesting feasibility for most direct assessment measures. Compared to the DS-control group, the DS-leukemia group had significantly lower completion rates on measures of executive function (p = 0.008) and processing speed (p = 0.018) compared to the DS-control group. There were no other significant group differences in completion rates. Compared to the DS-control group, the DS-leukemia group had significantly more accurate performance on two measures of executive function (p = 0.032; p = 0.005). Compared to the DS-control group, the DS-leukemia group had significantly more problems with executive function as identified on proxy ratings (6.5% vs. 32.6%, p = <0.001). CONCLUSION: Children with Down syndrome (DS) are at increased risk for developing acute leukemia compared to the general population but are systematically excluded from neurocognitive outcome studies among leukemia survivors. This study demonstrated the feasibility of evaluating neurocognitive late effects in leukemia survivors with DS using novel measures appropriate for populations with intellectual developmental disorder.

Are Young Adult Survivors of Pediatric Cancer Being Overlooked? Cognitive Testing Results and Referrals in Child, Adolescent, and Young Adult Survivors.

Treatment gaps in meeting the neuropsychological needs of young adult (YA) cancer survivors can be attributed to several clinical and systemic reasons. Access to neurocognitive care can be increased through the effective integration of neuropsychological monitoring and intervention in survivorship care. In this brief report, we aim to compare the efficacy of a brief neuropsychological screener (DIVERGT) in meeting the assessment and referral needs of pediatric and YA cancer survivors (n = 40) as part of a wellness and survivorship clinic. Participants (n = 40) were patients who presented to a pediatric oncology survivorship clinic over the span of 15 months.

Comparing the Relaxing Effects of Different Virtual Reality Environments in the Intensive Care Unit: Observational Study.

BACKGROUND: After a prolonged intensive care unit (ICU) stay, approximately 50%-75% of all critically ill patients suffer from neurocognitive late effects and a reduction of health-related quality of life. It is assumed that the noisy and stressful ICU environment leads to sensory overload and deprivation and potentially to long-term cognitive impairment. OBJECTIVE: In this study, we investigated three different virtual reality environments and their potentially restorative and relaxing effects for reducing sensory overload and deprivation in the ICU. METHODS: A total of 45 healthy subjects were exposed to three different environments, each 10 minutes in length (dynamic, virtual, natural, and urban environments presented inside the head-mounted display, and a neutral video on an ICU TV screen). During the study, data was collected by validated questionnaires (ie, restoration and sickness) and sensors to record physiological parameters (240 hertz). RESULTS: The results showed that the natural environment had the highest positive and restorative effect on the physiological and psychological state of healthy subjects, followed by the urban environment and the ICU TV screen. CONCLUSIONS: Overall, virtual reality stimulation with head-mounted display using a dynamic, virtual and natural environment has the potential, if directly used in the ICU, to reduce sensory overload and deprivation in critically ill patients and thus to prevent neurocognitive late effects.

Family Functioning Mediates the Association Between Neurocognitive Functioning and Health-Related Quality of Life in Young Adult Survivors of Childhood Brain Tumors.

PURPOSE: Childhood brain tumor (BT) survivors experience significant neurocognitive sequelae that affect health-related quality of life (HRQOL). A model of neurodevelopmental late effects and family functioning in childhood cancer survivors suggests associations between survivor neurocognitive functioning, family functioning, and survivor HRQOL. This study examines the concurrent associations between survivor neurocognitive functioning, family functioning, and survivor emotional HRQOL, and the indirect effects of neurocognitive functioning on survivor emotional HRQOL through family functioning. METHODS: Participants included young adult-aged childhood BT survivors (18-30 years old; N=34) who were on average 16 years post-diagnosis, and their mothers. A brief neuropsychological battery assessed working and verbal memory, processing speed, and executive functioning. Survivors and mothers completed measures of family functioning, and mothers completed a proxy-report measure of survivor HRQOL. RESULTS: Spearman bivariate correlations examined the associations between indices of survivor neurocognitive functioning and concurrent family functioning and survivor emotional HRQOL. Poorer survivor processing speed, working memory, verbal memory, and executive function were significantly associated with worse survivor- and mother-reported family functioning (r's range: 0.36-0.58). Additionally, worse survivor processing speed and executive function were significantly associated with poorer survivor emotional HRQOL (r's range: 0.44-0.48). Bootstrapping analyses provided evidence for the indirect effects of neurocognitive functioning on survivor emotional HRQOL through family functioning. CONCLUSION: These findings suggest that family functioning is an important variable that might mitigate the negative influence of neurocognitive late effects on survivors and is a potential target in future interventions.

Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate.

Childhood cancer survivors frequently experience long-lasting consequences of chemotherapy on health outcomes. Neurocognitive late effects of chemotherapy occur in 40 - 60% of acute lymphoblastic leukemia (ALL) survivors. These deficits affect mental health, school performance, job success, and are associated with poor quality of life, therefore presenting a clinical challenge for psychiatrists. However, not all cancer survivors are impacted by treatment in the same manner and emerging evidence suggests that genetic variation may modulate neurocognitive outcomes. Much like other complex psychopathologies, neurocognitive deficits in cancer survivors are the result of complex interactions between genetic and environmental variables. This review describes adverse neurocognitive outcomes observed in survivors of acute lymphoblastic leukemia (ALL) and discusses genetic variability in biochemical pathways targeted by chemotherapeutic agents as a possible mechanism contributing to psychopathology in ALL survivors.

Les survivants d'un cancer pédiatrique éprouvent souvent des conséquences durables de la chimiothérapie sur leurs résultats de santé. Les effets tardifs neurocognitifs de la chimiothérapie surviennent chez 40% à 60% des survivants de la leucémie lymphoblastique aiguë (LLA). Ces déficits touchent la santé mentale, le rendement scolaire, la réussite professionnelle et sont associés à une piètre qualité de vie, et présentent donc un défi clinique pour les psychiatres. Cependant, les survivants du cancer ne sont pas tous affectés de la même manière par le traitement et de nouvelles données probantes suggèrent que la variation génétique puisse moduler les résultats neurocognitifs. À l'instar d'autres psychopathologies complexes, les déficits neurocognitifs chez les survivants du cancer sont le résultat d'interactions complexes entre les variables génétiques et environnementales. Cette revue décrit les résultats neurocognitifs indésirables observés chez les survivants de la leucémie lymphoblastique aiguë (LLA) et discute de la variabilité génétique des trajectoires biochimiques ciblées par les agents chimiothérapeutiques comme mécanisme possible contribuant à la psychopathologie chez les survivants de la LLA.