A previous review of the syndrome of Agenesis of the Corpus Callosum (ACC) identified three primary deficits: reduced interhemispheric transfer of sensory motor information, slowed cognitive processing, and deficits in complex problem solving (Brown & Paul, 2019). Interaction of these three deficits contributes to a variety of secondary cognitive and psychosocial deficiencies across domains. Recent research has also identified a possible fourth core deficit in ACC: restricted capacity for elaborative thought and creativity (Renteria et al., 2022; Bogen & Bogen 1988). We examined the syndrome of ACC using an exploratory factor analysis of neuropsychological test data (not including data regarding interhemispheric transfer) and hypothesized it would organize into factors of (1) reduced cognitive processing speed, (2) difficulty with complex problem solving, and (3) difficulty with creative tasks.

The present study analyzed archival data from individuals with ACC (N=60) acquired from common neuropsychological instruments: D-KEFS, WAIS-III, and WRAT-2. Among the participants, 13 had partial ACC, 1 was unspecified, and the remainder had complete ACC. The participants’ ages ranged from 7 to 55 years (M = 21.55, SD = 12.36), with an education level that ranged from 2 to 19 years (M = 11.59, SD = 3.77). All participants had complete data for at least one assessment and all available data was included. Missing values (49.85%) were excluded from analysis. Factor analysis (principal factor solution with promax rotation) was conducted with 33 commonly derived summary (standard) scores. Horn’s Parallel Analysis recommended a 4-factor solution, but we elected to generate a 3-factor model that would more closely follow previous literature.

Factor one involved processing speed and was comprised primarily of D-KEFS Color Word Interference Word Reading (1.02) and Color Naming (.78), D-KEFS Trail Making Test Visual Scanning (.86) and Number Sequencing (.74), and WAIS-III Processing Speed Index (.68). The second factor included several problem solving measures [e.g. D-KEFS Sorting Test Free Sorting (.90) and Sort Recognition (.90), and WAIS-III Perceptual Organization Index (.72)], as well as several additional measures including WAIS-III Working Memory Index (.84), WRAT-2 Arithmetic (.83), and WAIS-III Verbal Comprehension Index (.80). Finally, the third factor involved several measures requiring mental flexibility and cognitive control [e.g. D-KEFS Twenty Questions Test Achievement Score (.70), D-KEFS Design Fluency Switching Condition (.56), and D-KEFS Trail Making Test Number-Letter Switching Condition (.44)], as well as a measure of single word reading [WRAT-2 Reading (.66)].

The findings support inclusion of slowed cognitive processing speed as a core feature of the neurocognitive syndrome in ACC described by Brown and Paul (2019). The second factor is partially consistent with a deficit in complex problem solving, but is not restricted to that cognitive domain. Likewise, the third factor is largely related to mental flexibility and control (one aspect of creativity), but is not restricted to that domain. Future attempts to model the neurocognitive syndrome of ACC may provide greater clarity by including a wider range of cognitive and psychosocial indices and excluding individuals with comorbid neuropathology.

Agenesis of the corpus callosum(AgCC) is a disorder in which the connection between the two brain hemispheres is congenitally absent. Previous research has suggested that the auditory system can be affected in individuals with AgCC (Demopoulos et al., 2015). However, the nature of AgCC’s effect on musical perception skills is unclear. This study investigated the impact of AgCC on the music perception skills in high-functioining adults using a brief version of the Profile of Music Perception Skills (PROMS; Zentner, M. & Strauß, H. 2017). It was hypothesized that individuals with AgCC would have diminished music perception abilities when compared to a neurotypical control group.

Participants included 10 high-functioning adults with AgCC that had an intelligence quotation within the normal range (FSIQ>80) and 63 neurotypical controls who were recruited via Cloud Research. During the PROMS the participants were asked to listen to two different sound excerpts after which they were asked whether the second sound was the same or different from the first (correct answers= 2 points, uncertain answers= 1 point, and remaining answers not coded). The participants answered questions in four different areas of musical perception: Melody, Tuning, Accent, and Tempo.

Results indicated that there was not a significant difference between the control group and the AgCC participants on music perception skills on the overall PROMS scores F(1,72)= .365, P-value= .548. Tested individually, none of the 4 individual domains showed a significant difference: Melody F(1,72)=2.67, P-value= .107; Tuning F(1,72)= .271, P-value= .606; Accent F(1,72)= .017, P-value= .897; or Tempo F(1,72)=.106, P-value= .746.

Contrary to the hypothesis of this study, the results showed that the participants with AgCC did not perform significantly differently in the PROMS total score when compared to neurotypical controls, nor were there significant differences in any of the four of the subtests (Melody, Tuning, Accent, and Tempo). Thus these high-functioning individuals with AgCC did not have deficient music perception abilities. These findings demonstrate that although the auditory system may be affected in some individuals with AgCC, we do not see differences in musical perception skills in high-functioning individuals with AgCC.

Previous research suggests that individuals with isolated Agenesis of the Corpus Callosum (AgCC) have cognitive and psychosocial deficiencies that include impaired recognition of the emotions of others (Symington et al., 2010) and a diminished ability to infer and describe the emotions of others (Paul et al., 2021; Turk et al., 2010). In addition, galvanic skin responses effectively discriminated between emotional images despite atypical emotion ratings (Paul et al, 2006), supporting a dissociation between cognitive and affective empathy in AgCC. Likewise, atypical patterns of visual attention to faces corresponded with impaired emotion recognition in AgCC (Bridgman et al, 2014), suggesting that atypical visual attention in AgCC negatively impacts the ability to identify others’ emotions. This study used the Multifaceted Empathy Test [MET] (Foell et al., 2018) to examine the impact of visual aesthetics (photo composition) on empathetic feelings (affective empathy) and situational emotion recognition (cognitive empathy) in persons with AgCC. Both cognitive and affective empathy scores are typically higher on MET stimuli composed according to the “Golden Spiral” (Callaway, 2022).

Results from 50 control participants recruited from Cloud Research were compared to responses from 19 participants with AgCC and normal-range FSIQ (>80). Data was gathered through an online version of the MET, which uses a series of photographs of individuals displaying an emotion, half of which adhere to the compositional technique known as “The Golden Spiral.” To measure cognitive empathy, the participants are asked to pick the correct emotion being displayed with three distractors for each item. To measure affective empathy, they are then asked on a sliding scale, “how much do you empathize with the person shown” (1 = Not at all, 7 = Very much).

Repeated measures mixed ANOVAs revealed no difference between AgCC and control groups on affective empathy, and as expected on the MET, both groups had significantly higher ratings for photos composed according to the Golden Spiral (AgCC, np2 = .071; control, np2 = .136). In contrast, the AgCC group scored significantly lower than controls overall on cognitive empathy, np2 =.065. Exploratory post-hoc found a significant group difference in cognitive empathy only on photos composed according to the Golden Spiral, np2 = .090, with the scores in the AgCC group unimpacted by composition type while the control group exhibiting significantly higher scores Golden Spiral images, np2 = .254.

Empathic deficits in AgCC were restricted to the cognitive component, while affective empathy was not impaired. Visual aesthetics of photo composition influenced affective empathy ratings in both AgCC and control groups. However, adults with AgCC had diminished ability to give cognitive labels to the emotional states of others, which was not enhanced by the formal aesthetics of stimuli. Thus the corpus callosum seems to facilitate the ability to cognitively label emotions by facilitating visual attention. It also suggests that the corpus callosum does not facilitate affective empathy, in part because it does not appear to determine whether formal aesthetics influences the processing of visual stimuli in AgCC or neurotypical controls.

Partial agenesis of the corpus callosum (PACC) is a rare brain birth defect characterized by incomplete development of the corpus callosum, the primary white matter bundle that connects the right and left hemispheres. PACC can be associated with other congenital abnormalities, including malformation of the brain’s ventricular system, such as colpocephaly or ventriculomegaly, and it is typically considered a pediatric diagnosis. Clinically, this condition may present with a broad continuum of cognitive and socioemotional difficulties ranging from significant day-to-day impairment to relative independence. Newly diagnosed PACC with ventriculomegaly in adults is very rare (0.0200.025%) and little is known about neuropsychological functioning in adults with this condition. The aim of this case study is to add to the literature base for better PACC neuropsychological conceptualization.

This case study involves neuropsychological evaluation of cognitive and behavioral health functioning of a 37-year-old active duty service member (ADSM) with recently identified PACC and ventriculomegaly (via incidental imaging finding). The ADSM reported a history of learning difficulty, though she was able to earn rank of sergeant first class in a low density military occupation specialty (i.e., Mortuary Affairs) over an 18.5 year active duty career.

Cognitive testing was notable for consistently low to exceptionally low attention and processing speed scores. Mild executive dysfunction was also noted in the areas of planning and inhibition. Emotionally, she endorsed mild somatic and depression symptoms. Interpersonally, she was shy and avoidant with longstanding characterological traits characterized by worry, insecurity, and general tendency to catastrophize.

This case adds to the broad clinical presentation of PACC with ventriculomegaly, and highlights that even in the context of a significant congenital brain deformity and longstanding cognitive deficits, independent functioning can be achieved.

From diagnosis to remission, a patient’s journey with cancer can be long and tiresome, riddled with many adjustments and challenges. Because the stressors of the disease continue into remission, the battle is far from over when the cancerous cells are eradicated. The stress placed on cancer patients due to the disease and the treatments to control it causes many patients to experience cognitive impairment, also known as cancer-related cognitive impairment (CRCI). Researchers have long been baffled by CRCI and the mechanisms through which it takes place. Some explanations that have arisen include the cancer treatment, the cancer itself, the psychological distress, or a combination of all three. The objective of this study was to understand the mechanism through which CRCI occurs and what factors, including psychosocial, treatment, and demographic variables, exacerbate or reduce the cognitive symptoms.

Cancer survivors (n=39) with various types of cancer were recruited from support groups to complete an online survey, which was comprised of a series of self-report measures. These measures included perceived cognitive abilities, psychological distress, fatigue, social support, and demographic and treatment questionnaires.

Cognitive reserve (p < .05) and the presence of chemotherapy (p < .01) were the only variables that predicted perceived cognitive impairment. As expected, it was found that the length of time in remission led to lower levels of perceived cognitive impairment (p < .001). However, psychological distress was not found to be a significant predictor of perceived cognitive impairment as hypothesized. Remarkably, psychological distress was found to be a mediator in the relationship between perceived cognitive impairment and fatigue (p < .001).

This relationship indicates that how an individual copes with the cognitive impairment following cancer treatments can lead to the development and exacerbation of fatigue. A failure to manage psychological health can lead to the worsening of these secondary symptoms. Further research must examine the link between psychosocial factors as they relate to the subtle effects of CRCI.

Medulloblastoma is the most common pediatric malignant brain tumor. Approximately 29% of medulloblastoma patients experience postoperative posterior fossa syndrome (PFS) characterized by impairments in speech, motor, and mood. An interdisciplinary rehabilitation approach is associated with greater rehabilitation gains than a single discipline approach for brain injury patients with significant rehabilitation needs. However, literature regarding the feasibility and utility of this approach within a tertiary care pediatric hematology/oncology setting is lacking. The Acute Neurological Injury (ANI) service was developed to coordinate care for neurologically complex hematology/oncology patients receiving active cancer treatment, including those with PFS. ANI care coordination includes bimonthly interdisciplinary team meetings, interdisciplinary goal implementation for each patient, parent psychoeducation about applicable brain-behavior relationships (including PFS) at treatment initiation, neuropsychological assessment at transition times throughout treatment, cognitive remediation, and coordinated end of treatment transition planning. We gathered caregiver perspective on this approach within a tertiary care pediatric hematology/oncology setting.

Parents of children and young adults (ages 4-20) with PFS after medulloblastoma resection who received coordinated care as part of the ANI program (n=20) were interviewed at least 4 months following completion of cancer treatment. 75% experienced postoperative mutism while the remainder experienced significantly decreased speech without mutism. All received cranial-spinal irradiation and focal boosts to tumor sites followed by chemotherapy per multi-institutional treatment protocol. Caregivers were interviewed regarding perceived feasibility and utility of ANI program components including parent psychoeducation, neuropsychological assessment, cognitive remediation, and interdisciplinary team coordination/goal setting, as well as parental supports. Yes/no responses were gathered as well as responses regarding the perceived utility of aspects of the interdisciplinary ANI program approach via a five-point Likert scale.

Surveys were completed by 66% of families contacted. Mean age at first contact with neuropsychology as part of the ANI program was 9.45 years (SD=4.4 years). Mean time between end of treatment and parent interview was 3.20 years (SD=2.01 years). Most parents reported that initial psychoeducation about PFS helped to decrease their concerns (81%) and increased their understanding of their child’s functioning in the context of PFS (88%). They reported benefit from neuropsychological assessment reports prior to initiating adjuvant treatment (92%), at end of treatment (90%), and one year following initiation of cancer treatment (100%), though they perceived less benefit from assessments intended to inform provider interventions during treatment (81% and 66%). Reports were shared most often with schools (75%), behavioral therapists (50%), physicians (50%), and rehabilitation specialists (25%). Parents indicated that the interdisciplinary ANI program approach was helpful (94%) and the coordinated interdisciplinary goal was beneficial (92%). Most parents favored the weekly frequency of cognitive remediation sessions (83%). Much interest was voiced in establishing a formal mentoring program to offer peer support by parents whose children have previously experienced PFS to those acutely managing a new PFS diagnosis (95%). Of note, all participants indicated that they would be willing to serve in a peer mentor role (100%).

The interdisciplinary ANI program approach is feasible with perceived benefits to families managing new PFS and medulloblastoma diagnoses and receiving active cancer treatment.

Chimeric antigen receptor (CAR) T-cell therapy is a novel treatment approach for refractory hematological malignancies. Risk factors for cognitive changes have been identified with CAR-T cell therapy, including severe cognitive problems due to neurotoxicity. Given the novelty of this treatment, research on this topic remains limited. Only one known study has examined cognitive performance following CAR T-cell therapy among patients diagnosed with non-Hodgkin’s lymphoma and observed a pattern of initial decline in executive functioning and visuospatial skills with improvement towards baseline one year following treatment. Additional research is needed to understand cognitive functioning in the context of CAR T-cell therapy. Our study presents preliminary descriptive longitudinal cognitive data among a small cohort of patients with mixed cancers undergoing CART cell therapy.

Adult patients undergoing CAR T-cell therapy (N=16) completed the NIH-Toolbox core cognitive battery prior to treatment, and at 100-, 180-, and one-year post-treatment. Subtests of the Weschler Abbreviated Scale of Intelligence (WASI-II; block design, vocabulary) and the Wide Range Achievement Test (WRAT-5; word reading, math computation) were administered at baseline and one year follow up. Mean age of participants was 51.6 (SD = 14.4). Most patients had completed high school or more education (89.7%) identified as male (56.3%) and were white (75%). Diagnoses included lymphoblastic leukemia (n=2), diffuse large B-cell lymphoma (n=7), follicular lymphoma (n=3), mantle cell lymphoma (n=1), metastatic sarcoma (n=1), myxoid liposarcoma (n=1), and synovial sarcoma (n=1).

Mean cognitive scores (adjusted for age) were calculated. At baseline, mean cognitive performance was average across domains, except for inhibitory control, which was in the low average range. At day 100, mean cognitive performance showed the same pattern as baseline. At day 180, mean scores in all domains were within the average range. At one year, all scores were within the average range or higher, although only two participants have completed the one-year follow-up, as data collection is ongoing. One participant died due to neurotoxicity following treatment, thus did not complete follow-up evaluations.

Overall, cognitive performances were broadly within normal limits in the sample and demonstrated relatively stable performance over time. Interestingly, baseline and day 100 mean inhibitory control was an area of relative weakness across participants, which is consistent with prior research. CAR T-cell therapy is reserved for refractory malignancies; thus, patients may have executive functioning deficits at baseline due to prior treatments. One patient died due to neurotoxicity. Overall, although severe cognitive changes and neurotoxicity have been observed as a risk of CAR T-cell therapy, this may be a distinct adverse event rather than the norm, as surviving patients in our sample remained cognitively stable following treatment. Although a unique and important population of study, our sample is limited due to its size. Results should be considered preliminary, and data collection is ongoing.

The Functional Assessment of Cancer Therapy-Cognitive scale (FACT-Cog) is one of the most frequently used patient-reported outcome (PRO) measures of cancer-related cognitive impairment (CRCI) and of CRCI-related impact on quality of life (QOL). Previous studies using the FACT-Cog found that >75% of women with breast cancer (BCa) experience CRCI. Distress tolerance (DT) is a complex construct that encompasses both the perceived capacity (i.e., cognitive appraisal) and the behavioral act of withstanding uncomfortable/aversive/negative emotional or physical experiences. Low DT is associated with psychopathology and executive dysfunction. We previously found that women with BCa with better DT skills reported less CRCI on the FACT-Cog. However, this relationship has not been tested using a performance-based cognitive measure. Therefore, the aims of this study were to: (1) assess the relationship between the FACT-Cog and the Telephone Interview for Cognitive Status (TICS), a performance-based cognitive measure; and (2) test whether the association between DT and CRCI (using the FACT-Cog) was replicated with the TICS.

Participants completed the Distress Tolerance Scale (DTS), the FACT-Cog, and the TICS after undergoing BCa surgery and prior to starting adjuvant therapy [101 women, age >50 years, M(SD)= 61.15(7.76), 43% White Non-Hispanic, 34.4% White Hispanic, 10.8% Black, with nonmetastatic BCa, 55.4% lumpectomy, 36.6% mastectomy; median 29 days post-surgery].

Although there was a significant correlation between the TICS total score and the FACT-CogQOL subscale (r = 0.347, p < 0.001), the TICS total score was not correlated with scores on the FACT-Cog perceived cognitive impairment (CogPCI), perceived cognitive abilities (CogPCA), or comments from others (CogOth) subscales. However, the TICS memory item, a 10-word list immediate recall task, had a weak statistically significant correlation with CogPCI (r = 0.237, p < 0.032), CogOth (r = 0.223, p < 0.044), and CogPCA (r = 0.233, p < 0.036). Next, the sample was divided based on the participant’s score on TICS memory item (i.e., < vs. > sample mean of 5.09). Results of independent samples t-tests demonstrated significant differences in mean scores for CogPCI, f(80) = -2.09, p = 0.04, Mdt = -7.65, Cohen’s d = 0.483, and CogQOL, f(80) = -2.57, p = 0.01, Mditt = -2.38, Cohen’s d = 0.593. A hierarchical linear regression found that DTS subscale and total scores did not significantly predict performance on the TICS. However, DTS continued to be a significant predictor of poorer FACT-Cog PCI scores while controlling for TICS scores.

We found a weak relationship between self-reported cognitive impairment and objective cognitive performance (TICS). However, greater self-reported PCI and its impact on QOL was found in participants who scored below the sample mean on a recall task from the TICS. Although perceived ability to tolerate distress continued to predict self-reported PCI on the FACT-Cog, it did not predict overall performance on the TICS. Therefore, responses on the FACT-Cog may be more representative of an individual’s ability to tolerate distress related to perceived CRCI than actual overall cognitive ability or impairment.

Survivors of childhood brain tumor are historically thought to perform worse on measures of executive functioning, including cognitive flexibility (CF; e.g., set-shifting), when compared to their peers. Commonly utilized measures, such as subtests from the Delis-Kaplan Executive Function System (D-KEFS), have baseline conditions that attempt to measure performances independent of but critical for CF tasks (e.g., motor speed on trail making, letter fluency on verbal fluency). However, in research, conditions measuring CF are often included in analyses without accounting for these important baseline conditions. The aim of the current study is to explore differences in CF performance between survivors and their healthy peers when controlling for baseline conditions. The variance explained by each baseline condition on CF condition performance in survivors is also explored.

A sample of 107 long-term survivors of childhood brain tumor (Mage=21.81, SD=5.99, 50.5% female) and 142 healthy controls (Mage= 23.25, SD=6.61, 61.3% female) were administered the Trail Making Test (TMT), Color-Word Interference (CWI), and Verbal Fluency (VF) subtests from the D-KEFS. For the TMT, baseline conditions include visually scanning for a target, motor speed, and letter and number sequencing. For the CWI subtest, baseline conditions include rapid color naming, word reading, and reading words in a different colored ink. On the VF subtest, baseline conditions include rapidly naming words with a specific letter and from a specific category. An analysis of covariance was conducted for each subtest to determine if groups differed in performance on the CF condition (i.e., Number-Letter Switching, Inhibition/Switching, Category Switching Accuracy) when controlling for baseline conditions. In survivors only, linear regressions investigated the amount of variance explained by each baseline condition on the CF conditions of each subtest.

Groups did not differ in CF performance of each subtest when controlling for baseline conditions (ps>.10). Across subtests, baseline conditions significantly predicted CF performance in survivors. On the TMT, Letter Sequencing (p=.003, unique-R2=.05), but not Visual Scanning, Number Sequencing, or Motor Speed, was a significant predictor of Number-Letter Sequencing performance (p<.001, R2=.50). On the CWI subtest, Word Reading (p<.001, unique-R2=.09) and Inhibition (p<.001, unique-R2=.05), but not Color Naming, were significant predictors of Inhibition/Switching performance (p<.001, R2=.67). On the VF subtest, Letter Fluency (p=.009, unique-R2=.06) and Category Fluency (p<.001, unique-R2=.08) were significant predictors of Category Switching Accuracy performance (p<.001, R2=.37).

Findings suggest that CF may not differ between survivors and their healthy peers, but that other factors of executive functioning, such as processing speed, drive performance differences on measures of CF. As these tasks rely heavily on speed, survivors may be slower than their healthy counterparts, but may not perform worse on set-shifting. In addition, these results highlight the importance of controlling for lower-order processes in analyses to help isolate CF performance and more accurately characterize potential differences between groups. While replication of findings in survivors and other clinical groups (e.g., congenital heart disease, traumatic brain injury) is still needed, this work can help inform which processes are most important to account for, which is not yet established.

Erdheim-Chester disease (ECD) is a rare disorder characterized by excessive production and accumulation of histiocytes within multiple tissues and organs. ECD primarily affects adults, and symptoms vary depending upon the specific location and severity. Etiology is not always known, but some patients with ECD may have a non-inherited genetic change that allows histiocytes to reproduce uncontrollably. Currently, the cognitive outcomes of ECD are not well understood, and there are no previous neuropsychological findings in the literature. Thus, the objective of this case study was to describe the neuropsychological presentation and findings of an ECD case to inform diagnosis and treatment better.

The patient was a 64-year-old white, non-Hispanic, right-handed man diagnosed with ECD in 2017. ECD accounted for a constellation of medical problems, including diabetes insipidus, hypogonadism, and interstitial lung disease. A brain MRI in 2018 revealed orbital nodularities and pituitary infiltration thought to be consistent with ECD. The patient first noticed cognitive functioning difficulties in 2020 primarily related to short-term memory. Approximately two years later, he noted significant cognitive changes, including difficulties recalling recent events, dates, and conversations, problem-solving, and planning. He had difficulty driving and had two recent car accidents when leaving his driveway. Physically, he reported increased fatigue, unsteadiness, and occasional falls. In 2022, he had a brain MRI that demonstrated a progression of multiple diffuse cerebral, cerebellum, and brainstem lesions and cerebral volume loss compared to prior imaging. He was referred for a neuropsychological assessment to rule out a neurodegenerative disorder.

Neuropsychological data demonstrated moderate-to-severe deficits on tests of basic spatial working memory, visually based processing speed, visual memory, letter verbal fluency, and semantic verbal fluency. He demonstrated mild-to-moderate deficits on tests of basic auditory attention, verbal memory, higher-level visuospatial processing, abstract nonverbal reasoning, multistep, organization and planning, self-monitoring of performance quality, and fine hand and motor dexterity. He demonstrated variable initial learning of new information across modalities, although he did benefit from structured verbal material. Recognition was variable, with difficulty demonstrated in discriminating visual information presented, from similar competing information, along with availability recalling visual information. He showed average auditory-based divided attention, confrontational object naming, and abstract verbal reasoning. Regarding his emotional functioning, he reported mild depressive and anxiety symptoms.

To the best of our knowledge, this is the first report documenting detailed neuropsychological data on this rare disease. The case study documents widespread cognitive deficits with greater difficulty with visually based abilities than verbal abilities. Specifically, patients with ECD may present with cognitive difficulties in visual learning and memory, processing speed, visuospatial processing, select areas of executive/frontal systems, letter and semantic verbal fluency, and fine motor dexterity.

A growing body of research demonstrates that social determinants of health (SDOH) are important predictors of neurocognitive and psychological outcomes in survivors of pediatric brain tumor (PBT). Existing research has focused primarily on individual level SDOH (e.g., family income, education, insurance status). Thus, more information is needed to understand community level factors which may contribute to health inequities in PBT survivors. This study aimed to examine the effects of specific aspects of neighborhood opportunity on cognitive and emotional/behavioral outcomes among PBT survivors.

The sample included clinically-referred PBT survivors who completed a neuropsychological evaluation (N=199, Mage=11.63, SD= 4.63, 56.8% male, 71.8% White). Data included an age-appropriate Wechsler Scale and parent-report questionnaires (Behavior Rating Inventory of Executive Function, Child Behavior Checklist). Nationally-normed Child Opportunity Index (COI) scores were extracted for each participant from electronic medical records based on home address using Census tract geocoding. The COI measures neighborhood-level quality of environmental and social conditions that contribute to positive health. It includes three component scores assessing distinct aspects of opportunity, which include educational opportunity (e.g., educational quality, resources, and outcomes), health/environmental opportunity (e.g., access to healthy food, healthcare, and greenspace) and social/economic opportunity (e.g., income, employment, poverty). Stepwise linear regression models were examined to identify significant predictors of cognitive/psychological outcomes associated with PBT; the three COI indices were entered as predictors and retained in the model if they significantly contribute to variance in the outcome.

Lower educational opportunity was associated with lower processing speed performance (Wechsler Processing Speed Index: t = 2.47, p = 0.02) and increased parent-reported executive functioning problems (BRIEF GEC: t = -2.25, p = 0.03; BRIEF Working Memory: t = -2.45, p = 0.02) and externalizing problems (CBCL Externalizing: t = -2.19, p = 0.03). Lower social/economic opportunity was associated with lower working memory performance (Wechsler Working Memory Index: t = 2.63, p < 0.01) and increased parent-reported internalizing problems (CBCL Internalizing: t = -2.38, p = 0.02). Health/environmental opportunity did not emerge as a primary predictor of any of the examined cognitive/psychological outcomes. Exploratory analyses examining the impact of age on associations between COI and cognitive/psychological outcomes found a significant moderation effect of age on the relationship between educational opportunity and processing speed (t = 2.35, p = 0.02) such that this association was stronger at older ages. There were no other moderation effects by age.

Consistent with a growing body of literature demonstrating the impact of social and environmental contexts to health outcomes, these results show inequities in neurocognitive and psychosocial outcomes in PBT survivors related to neighborhood-level SDOH. Examination of specific neighborhood factors highlight educational and social/economic factors as particularly important contributors to neurocognitive/psychological risk for survivors. The identification of these specific and potentially modifiable risk factors is crucial to inform individual-level problem-prevention following oncological treatment, as well as community-level policy and advocacy efforts.

Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.

Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores >1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.

The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p < 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p < 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p < 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p < 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p<.001) and semantic fluency (ß=7.59, p=.007).

These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

High-grade gliomas are aggressive and infiltrate surrounding brain parenchyma, making gross total resection difficult, and despite aggressive treatment, its recurrence is inevitable (Zhou et al., 2016). Repeated tumor resections have been shown to increase survival (Chaichana et al., 2013) but the cost of doing so on quality of life (QoL) and functioning is not known. To address this gap, we compared changes in QoL using the Functional Assessment of Cancer Therapy-Brain questionnaire (FACT-Br; Weitzner et al., 1995) in high-grade glioma patients undergoing first versus repeat surgical resection.

Thirty-three patients with high-grade gliomas (mean age=52, 54.5% female) that underwent tumor resection and completed comprehensive neuropsychological evaluations that included FACT-Br pre-operative and at 2-week follow up were included in this study. FACT-Br assesses four QoL domains: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), and functional well-being (FWB). A subscale total score was computed for each domain, and these subscale scores were summed to compute a total score for overall QoL. Difference scores were computed for each subscale score and total score by subtracting patients’ pre-operative rating from post-operative rating. More positive scores indicate lesser perceived changes of QoL post-operatively. One-way MANOVA analysis was run to compare the difference scores between patients that underwent first resection and those that underwent repeated resection.

There was no significant difference in perceived changes of overall QoL between the two groups of patients. However, patients with previous resection reported larger decline in perceived physical well-being compared to patients without previous resection (F(1,30)=99.93, p<.05,partial n2=.16). There were no significant differences in other QoL domains between the two groups.

We showed no differences in perceived changes across most QoL domains in patients undergoing repeat versus first surgical resection for treatment of high-grade glioma, suggesting that repeated resections may be a viable strategy in managing tumor recurrences. Specifically, there were no group differences in social, emotional, and functional well-being pre-to postoperatively. However, patients with previous resection reported significantly larger decline in their perceived physical well-being than those without any previous resection. A possible explanation is that patients with previous resection underwent adjuvant therapies (e.g., radiation therapy, chemotherapy) and experienced tumor progression necessitating reoperation, which could have made them more vulnerable to the physical impacts of surgery. Our findings are encouraging and may provide useful insight to guide treatment strategies and patient’s decision making to optimize both surgical and functional outcomes.

Phonemic fluency, an important cognitive skill for everyday functioning, has been shown to decline in comparison to same-aged peers following pediatric cancer diagnosis and treatment, despite intact semantic fluency. More generally, socioeconomic status (SES) has recently been shown to be one of the strongest predictors of neuropsychological outcomes among pediatric oncology patients, with lower SES predicting worse intellectual and academic functioning. However, the association between SES and phonemic fluency within this population has yet to be explored. The main objective of this project was to determine whether SES (specifically estimated household income) significantly predicts phonemic fluency performance among patients with PBT, and it was hypothesized that higher SES would be associated with better phonemic fluency outcomes.

136 participants with PBT ages 7-20 (x=14.15 years, SD=3.87), were administered phonemic fluency trials (either from the NEPSY - Second Edition or Delis-Kaplan Executive Function System, with no significant differences in performance between measures). The sample was 58.8% male and half Latino (50.0%), followed by Caucasian (30.1%), Asian American (7.4%), Black (6.6%), and Other (5.9%) ethnicity. All patients identified English as their primary and preferred language regardless of predominant household language, reducing the potential confounding impact of language. Given documented associations between PBT and lower intelligence following diagnosis and treatment, estimated intellectual functioning was included in the first block of hierarchical regression to isolate and further elucidate the potential contributing influence of SES on phonemic fluency. Median household income for specific neighborhoods was used as a proxy for SES, while Wechsler Matrix Reasoning (MR) was used as an estimate of general intellectual functioning given the high correlation between MR and full scale IQ.

Consistent with prior literature, phonemic fluency was lower than normative age expectations [t(135)=-3.653, p=.0002], though still within the average range clinically (x=8.93). As hypothesized, SES was positively correlated with phonemic fluency [r(136)=.219, p=.005]. Furthermore, SES significantly predicted phonemic fluency performance above and beyond estimated intelligence, accounting for a significant increase in variance (p=.020). Post-hoc analyses also revealed poorer phonemic fluency among participants with infratentorial brain tumors as compared to supratentorial brain tumors after controlling for SES, t(108)=-1.748, p=.042.

Consistent with the known impact of SES on neuropsychological late effects among patients with pediatric cancer, phonemic fluency was positively correlated with SES among participants with PBT above and beyond estimated intelligence, suggesting the distinct role of SES on rapid verbal retrieval within this population. This has important implications for identifying patients at higher risk, helping to ensure timely provision of services and supports. Poorer phonemic fluency was also noted among patients with infratentorial (vs. supratentorial) brain tumors after controlling for SES, which may influence studies combining tumor location as the vast majority of PBTs are infratentorial. This supports prior literature demonstrating the need for increased cerebellar activation during phonemic (vs. semantic) retrieval. Additional research is needed to further explore these findings.