Neurocognitive outcome and associated factors in long-term, adult survivors of childhood acute lymphoblastic leukemia, treated without cranial radiation therapy.

OBJECTIVE: There is limited research on neurocognitive outcome and associated risk factors in long-term, adult survivors of childhood acute lymphoblastic leukemia (ALL), without treatment of cranial radiation therapy. Moreover, the impact of fatigue severity and pain interference on neurocognition has received little attention. In this cross-sectional study, we examined neurocognitive outcome and associated factors in this population. METHOD: Intellectual abilities, verbal learning/memory, processing speed, attention, and executive functions were compared to normative means/medians with one sample t tests or Wilcoxon signed-rank tests. Associations with risk factors, fatigue severity, and pain interference were analyzed with linear regressions. RESULTS: Long-term, adult survivors of childhood ALL (N = 53, 51% females, mean age = 24.4 years, SD = 4.4, mean = 14.7 years post-diagnosis, SD = 3.4) demonstrated above average intellectual abilities, but performed below average in attention, inhibition, processing speed, and shifting (p < 0.001). Executive functioning complaints were significantly higher than normative means, and positively associated with fatigue (p < 0.001). There was no interaction between sex and fatigue and no neurocognitive impairments were associated with pain interference, risk group, age at diagnosis, or sex. CONCLUSIONS: Long-term, adult survivors of ALL treated without cranial radiation therapy, demonstrate domain-specific performance-based neurocognitive impairments. However, continued research on the neurocognitive outcome in this population as they age will be important in the coming years. Executive functioning complaints were frequently in the clinical range, and often accompanied by fatigue. This suggests a need for cognitive rehabilitation programs.

Cognitive and behavioural rehabilitation interventions for survivors of childhood cancer with neurocognitive sequelae: A systematic review.

There is considerable interest in cognitive and behavioural interventions to manage and improve neurocognitive (dys)functions in childhood cancer survivors and the literature is rapidly growing. This systematic review aimed to examine the literature of such interventions and their impact on executive functions (EFs) and attention. A search of relevant manuscripts was performed in PubMed, PsycINFO, and Web of Science in March 2023 in accordance with the PRISMA statement. After screening 3737 records, 17 unique studies published between 2002 and 2022 were charted and summarized. Participants (N = 718) were mostly children (M = 12.2 years), who were long-term survivors (M = 5.0 years post treatment) of brain or CNS tumours (48%). Identified interventions included computerized cognitive training, physical activity, and cognitive interventions with compensatory strategy training. The highest quality RCT studies included computerized training (i.e., Cogmed), neurofeedback, and exergaming. Evidence suggests that Cogmed may improve the performance of certain working memory tasks (near transfer) and possibly improve visual attention tasks for individuals with working memory impairments. However, the evidence did not support far transfer of effects to real life. No significant effects (near or far-transfer) were found following neurofeedback and exergaming interventions. Finally, a knowledge gap was identified for interventions directed at long-term survivors in adulthood.

Atypical brain structure mediates reduced IQ in young adults born preterm with very low birth weight.

Preterm birth with very low birth weight (VLBW) confers heightened risk for perinatal brain injury and long-term cognitive deficits, including a reduction in IQ of up to one standard deviation. Persisting gray and white matter aberrations have been documented well into adolescence and adulthood in preterm born individuals. What has not been documented so far is a plausible causal link between reductions in cortical surface area or subcortical brain structure volumes, and the observed reduction in IQ. The NTNU Low Birth Weight in a Lifetime Perspective study is a prospective longitudinal cohort study, including a preterm born VLBW group (birthweight ≤1500 g) and a term born control group. Structural magnetic resonance imaging data were obtained from 38 participants aged 19, born preterm with VLBW, and 59 term-born peers. The FreeSurfer software suite was used to obtain measures of cortical thickness, cortical surface area, and subcortical brain structure volumes. Cognitive ability was estimated using the Wechsler Adult Intelligence Scale, 3rd Edition, including four IQ-indices: Verbal comprehension, Working memory, Perceptual organization, and Processing speed. Statistical mediation analyses were employed to test for indirect effects of preterm birth with VLBW on IQ, mediated by atypical brain structure. The mediation analyses revealed negative effects of preterm birth with VLBW on IQ that were partially mediated by reduced surface area in multiple regions of frontal, temporal, parietal and insular cortex, and by reductions in several subcortical brain structure volumes. The analyses did not yield sufficient evidence of mediation effects of cortical thickness on IQ. This is, to our knowledge, the first time a plausible causal relationship has been established between regional cortical area reductions, as well as reductions in specific subcortical and cerebellar structures, and general cognitive ability in preterm born survivors with VLBW.

Central Coherence, Visuoconstruction and Visual Memory in Patients with Eating Disorders as Measured by Different Scoring Methods of the Rey Complex Figure Test.

OBJECTIVE: The aims of this study were to examine the performance of eating disorder (ED) patients on the Rey Complex Figure Test and to investigate the validity of the Q-score as a new method for measuring central coherence (CC). METHOD: Forty-one patients with anorexia nervosa, 40 patients with bulimia nervosa and 40 healthy controls completed the Rey Complex Figure Test, which was scored both quantitatively and qualitatively. RESULTS: Both ED groups scored lower than the healthy controls on copy, recall and the Q-score. For the anorexia nervosa group, performance on the Central Coherence Index was associated with the nadir body mass index. Performance on the recall measures was independently associated with the nadir body mass index and depressive symptoms for the bulimia nervosa group. There was a strong correlation between the Q-score and the Central Coherence Index (r = 0.77). DISCUSSION: The study reveals different levels of CC and suggests that the Q-score might be an applicable method for measuring CC in ED patients.

Neuropsychological function in patients with anorexia nervosa or bulimia nervosa.

OBJECTIVE: This study explored the neuropsychological performance of patients diagnosed with anorexia nervosa (AN) or bulimia nervosa (BN) compared with healthy controls (HCs). An additional aim was to investigate the effect of several possible mediators on the association between eating disorders (EDs) and cognitive function. METHOD: Forty patients with AN, 39 patients with BN, and 40 HCs who were comparable in age and education were consecutively recruited to complete a standardized neuropsychological test battery covering the following cognitive domains: verbal learning and memory, visual learning and memory, speed of information processing, visuospatial ability, working memory, executive function, verbal fluency, attention/vigilance, and motor function. RESULTS: The AN group scored significantly below the HCs on eight of the nine measured cognitive domains. The BN group also showed inferior performance on six cognitive domains. After adjusting for possible mediators, the nadir body mass index (lowest lifetime BMI) and depressive symptoms explained all findings in the BN group. Although this adjustment reduced the difference between the AN and HC groups, the AN group still performed worse than the HCs regarding verbal learning and memory, visual learning and memory, visuospatial ability, working memory, and executive functioning. DISCUSSION: Patients with EDs scored below the HCs on several cognitive function measures, this difference being most pronounced for the AN group. The nadir BMI and depressive symptoms had strong mediating effects. Longitudinal studies are needed to identify the importance of weight restoration and treatment of depressive symptoms in the prevention of a possible cognitive decline.

Intellectual function in patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: This study aimed to examine cognitive function in individuals with anorexia nervosa (AN) and bulimia nervosa (BN) on the basis of IQ measures, indexes and subtests of the Wechsler Adult Intelligence Scale ­ Third Edition (WAIS-III). METHODS: A total of 41 patients with AN, 40 patients with BN and 40 healthy controls (HC), matched for sex, age and education, were recruited consecutively to complete the WAIS-III. RESULTS: The AN group showed a significantly lower performance than the HC group on most global measures and on eight of the 13 administered subtests. Minor differences in verbal function were detected between the BN group and the HC group. CONCLUSION: The patients with eating disorders showed normal intellectual functions compared with the normative population. However, the AN group displayed a consistently lower performance than the matched HC group, which performed above normative means. The BN group performed at a level between that of the AN and HC groups.

Association of anxiety and depression to headache, abdominal- and musculoskeletal pain in children.

The comorbidity between recurrent pain, anxiety, and depression among children is frequent and well documented. However, only a few studies of the predictive effect of anxiety and depression on pain have adjusted for symptoms of the other disorder when examining the respective relations to different pain locations, rendering the unique contribution from anxiety and depression undetermined. In the current investigation we explore the strength of associations between pain at different locations with symptoms of anxiety and depression in a community sample of 10-year-old children (n = 703). The children were interviewed about the frequency of pain during the last 3 months. Parents and children were interviewed separately about symptoms of anxiety and depression using a semi-structured diagnostic interview. Results of three multivariate regression models for each of headache, abdominal and musculoskeletal pain revealed that depression was associated with musculoskeletal pain and headache, whereas anxiety was not. The associations for depression were not significantly stronger compared to anxiety. Gender-specific models found that depression was related to headache only among girls, but the association was not statistically different compared to boys. These results may, in turn, influence our interpretation of different forms of pain in children, with less weight given to abdominal symptoms viewed as a strong correlate with psychological problems, compared to for instance headache. The results provided no clear support for neither a differential relationship between anxiety and pain and depression and pain nor gender differences.

The effect of high-intensity interval training on cognitive function in patients with substance use disorder: Study protocol for a two-armed randomized controlled trial.

Introduction: Substance use disorder (SUD) is characterized by cognitive impairment, especially executive dysfunction. Executive function is recognized as an important determinant of treatment outcome as it is associated with dropout rate, attendance to therapy and potential relapse after treatment termination. Physical activity can have beneficial effects on cognitive function, but there is still a lack of knowledge regarding potential benefits of aerobic exercise for executive function in SUD treatment. The aim of this study is to examine the effect of aerobic high-intensity interval training (HIIT) on cognitive function and the subsequent effect on treatment outcome in patients with SUD. Methods and analysis: This study is a randomized controlled trial, including men and women ≥18 years with diagnosed SUD by ICD-10. The patients will be recruited from the department for inpatient treatment at Blue Cross - Lade Addiction Treatment Center, Trondheim, Norway. Participants will be randomized 1:1 into either HIIT (3x/week) + treatment as usual (TAU), or TAU alone. Study outcomes will be assessed at baseline, after eight weeks of intervention, and at 3- and 12-months follow-up. The primary outcome is to compare the change in executive function (via altered BRIEF-A score, Behavior Rating Inventory of Executive Function-Adult) measured between the two study groups after eight weeks. Secondary outcomes include mapping of cognitive function in different subgroups (e.g. type of substance, age, fitness level), collecting self-reported information about quality of life, craving, sleep quality, etc., as well as assessing compliance to TAU and long-term treatment outcome. Ethics and dissemination: The project was approved by the Regional Ethical Committee and will be performed in accordance with this protocol and the Declaration of Helsinki. Written informed consent will be obtained from all participants prior to inclusion. This project will explore a novel approach to how exercise can be applied in SUD treatment, beyond the well-known effects on physical health. We expect to achieve new knowledge in regard to what extent HIIT can improve cognitive abilities and subsequent treatment outcome in SUD. Trial registration number: https://www.clinicaltrials.gov/NCT05324085.

Neurocognitive function and associations with mental health in adults born preterm with very low birthweight or small for gestational age at term.

Objectives: To assess neurocognitive function in adults born with low birthweight compared with controls and to explore associations between neurocognitive function and psychopathology in these groups. Methods: In this prospective cohort study, one group born preterm with very low birthweight (VLBW: birthweight <1,500 g, n = 53), one group born small for gestational age at term (SGA: birthweight <10th percentile, n = 63) and one term-born control group (birthweight ≥10th percentile, n = 81) were assessed with neurocognitive tests, diagnostic interviews, and self-report questionnaires at 26 years of age. Results: The VLBW group scored significantly below the control group on several neurocognitive measures, including IQ measures, psychomotor speed, verbal fluency, aspects of visual learning and memory, attention, social cognition, working memory and fine motor speed. The SGA group consistently scored at an intermediate level between the VLBW and the control group and had significantly lower scores than controls on Performance IQ and psychomotor speed, including switching. In the VLBW group, associations were found between lower spatial working memory and the presence of anxiety disorders, internalizing and attention problems, and autistic traits. Furthermore, lower Full scale IQ was associated with attention problems when adjusting for sex and parental socioeconomic status. Conclusion: Adults born preterm with VLBW or born term SGA displayed neurocognitive difficulties. Spatial working memory was associated with difficulties with attention, anxiety, and social function of VLBW adults. The finding and its clinical applicability should be further explored.

Cognitive Rehabilitation for Neurocognitive Late Effects in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Feasibility and Case-Series Study.

Neurocognitive late effects following the diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) commonly include impaired executive functions (EFs), with negative consequences for one's health-related quality of life and mental health. However, interventions for EF impairments are scarce. Thus, the aims of this study were to (1) explore the feasibility and acceptability of the cognitive rehabilitation program Goal Management Training (GMT) and (2) examine whether GMT is associated with positive outcomes across cases of ALL survivors with EF complaints. Four participants (median age 31.5 years) underwent nine GMT modules in a total of five group sessions. Rehabilitation was focused on compensatory strategies to improve real-life EFs. Participants were evaluated at 2-week and 6-month follow-ups. Evaluation of feasibility and acceptability included adherence, a semi structured interview, self-reports, and safety. Additionally, therapists' experience with implementation was evaluated. Outcome measures included self-reports and neurocognitive tests of attention, EF, and processing speed. All participants completed GMT and rated the intervention as useful, suitable, and satisfactory. The reliable change index showed improved daily life EFs (two participants) and neurocognitive performance (three participants) at 6-month follow-up. Additionally, all participants improved on a "real-life" task involving EF. A future randomized controlled trial is recommended.

The outcome at follow-up after inpatient eating disorder treatment: a naturalistic study.

BACKGROUND: Patients with eating disorders may experience a severe and enduring course of illness. Treatment outcome for patients provided with inpatient treatment is reported as poor. Research to date has not provided consistent results for predictors of treatment outcome. The aims of the study were to investigate rates of remission at follow-up after inpatient treatment, symptom change from admission to follow-up, and predictors of treatment outcome. METHODS: The follow-up sample consisted of 150 female adult former patients (69.4% of all eligible female patients) with eating disorders. Mean age at admission was 21.7 (SD = 4.9) years. Diagnostic distribution: 66% (n = 99) anorexia nervosa, 21.3% (n = 32) bulimia nervosa and 12.7% (n = 19) other specified feeding or eating disorder, including binge eating. Data were collected at admission, discharge and follow-up (mean 2.7 (SD = 1.9) years). Definition of remission was based on the EDE-Q Global score, body mass index and binge/purge behavior. Paired T-tests were performed to investigate change over time. Univariate and multivariate logistic regressions were estimated to investigate predictors of remission. RESULTS: At follow-up, 35.2% of the participants were classified as in remission. Significant symptom reduction (in all patients) (p <  0.001) and significant increase in body mass index (BMI) (in underweight participants at admission) (p <  0.001) was found. Increased BMI (p <  0.05), the level of core eating disorder symptoms at admission (p <  0.01) and reduced core eating disorder symptoms (p <  0.01) during inpatient treatment were found significant predictors of outcome in the multivariate model. CONCLUSIONS: All participants had an eating disorder requiring inpatient treatment. Approximately one-third of all participants could be classified as in remission at follow-up. However, most participants experienced significant symptom improvement during inpatient treatment and the improvements were sustained at follow-up. Increased probability of remission at follow-up was indicated by lower core ED symptoms at admission for all patients, raised BMI during admission for patients with AN, and reduced core ED symptoms during inpatient treatment for all patients. This finding contributes important information and highlights the importance of targeting these core symptoms in transdiagnostic treatment programs.

Neurocognitive Outcome and Compensating Possibilities in Children and Adolescents Treated for Acute Lymphoblastic Leukemia With Chemotherapy Only.

Aim: To examine the neurocognitive outcomes in children and adolescents with acute lymphoblastic leukemia (ALL) in remission who were treated with systemic chemotherapy only (CTO). Methods: Neurocognitive performances in 36 children and adolescents, aged 8.4-15.3 years, in long-term remission from ALL 4.3-12.4 years post diagnosis, without relapse, and with no pre-diagnosis history of neurodevelopmental disorder were compared with 36 healthy controls matched for gender, age, and parents' socio-economic status. The former patients and the healthy controls completed an extensive battery of standardized neuropsychological tests. Results: Survivors who were treated by CTO obtained significantly lower scores than did healthy controls on the domains of Copy and drawing (p = 0.001; Cohen's d 0.85; after controlling for Type 1 errors q = 0.006), Arithmetic (p = 0.001; Cohen's d 0.80; after controlling for Type 1 errors, q = 0.006), and Tactile sensory functions (p = 0.008; Cohen's d 0.65; after controlling for Type 1 errors, q = 0.03). Fifty percent of the ALL group were more than 1 SD below the control groups mean on Copy and drawing. There was an interaction between age and group (ALL vs. Control, p = 0.042) on Copy and drawing, indicating that the youngest ALL patients exhibited the worst performance. The oldest ALL patients performed equal to or better than the controls. A tendency in the same direction was seen for Arithmetic and Tactile sensory functions. The ALL survivors exhibited a steeper rising learning slope on repeated tests, with lower scores on a tactile problem-solving task, tactile sensory tests, verbal memory, and visual attention, but they performed as well as the controls when stimuli were repeated. Conclusion: The results indicate that neurocognitive long-term sequelae in ALL survivors are limited to specific domains - particularly complex drawing, arithmetic, and tactile processing, and novelty processing. Cognitive deficits are shown among the youngest ALL patients. Intervention programs and school programs should account for difficulties with processing new information and taking advantage of repetitions as a strength, which may prevent survivors from falling behind their peers.

Increased frontal electroencephalogram theta amplitude in patients with anorexia nervosa compared to healthy controls.

OBJECTIVE: To conduct a blind study of quantitative electroencephalogram-band amplitudes in patients with anorexia nervosa (AN) and healthy controls. METHODS: Twenty-one patients with AN and 24 controls were examined with eyes-closed 16-channel electroencephalogram. Main variables were absolute alpha, theta, and delta amplitudes in frontal, temporal, and posterior regions. RESULTS: There were no significant differences between the AN patients and controls regarding absolute regional band amplitudes in µV. Borderline significance was found for anterior theta (P=0.051). Significantly increased left and right frontal electrode theta amplitude was found in AN patients (F3, P=0.014; F4, P=0.038) compared to controls. Significant differences were also observed for secondary variables: lower values for relative parietooccipital delta and frontocentral alpha activity among AN patients than among controls. CONCLUSION: We observed slight excess frontal theta and lower relative alpha and delta amplitudes among AN patients than among controls. This pattern is possibly related to a slight frontal lobe dysfunction in AN, or it may reflect increased attention/vigilance or another state-related change in patients with AN compared to healthy controls.